Breast fine-needle aspiration malondialdehyde deoxyguanosine adduct in breast cancer

This study has analysed the generation of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adduct [M?dG], a biomarker of oxidative stress and lipid peroxidation, in breast fine-needle aspirate samples of 22 patients with breast cancer, at different clinical stages, in respect to 13 controls. The multivariate analysis show that M(1)dG adduct was higher in cases than in controls (Mean Ratio (MR) = 5.26, 95% CI = 3.16-8.77). Increased M?dG was observed in women with a tumour grade 3 and a pathological diameter 2 (MR = 7.61, 95% CI = 3.91-14.80 and MR = 5.75, 95% CI = 3.13-10.59, respectively). A trend with increasing tumour grade and pathological diameter was present (MR = 1.98, 95% CI = 1.57-2.50 and MR = 2.44, 95% CI = 1.71-3.48, respectively). Not significant effects of age and smoking habit were found (MR = 1.58, 95% CI = 0.92-2.72 and MR = 1.68, 95% CI 0.88-3.20, respectively). An increment over the background frequency of M?dG can contribute to breast cancer development. Increasing severity of breast tumour can influence DNA damage level.     

DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study

We evaluated the association between methylation of 9 genes, SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1, and SFN in tumor samples from 720 breast cancer cases with clinicopathological features of the tumors and survival. Logistic regression was used to estimate odds ratios (OR) of methylation and Cox proportional hazards models to estimate hazard ratios (HR) between methylation and breast cancer related mortality. Estrogen receptor (ER) and progesterone receptor (PR) positivity were associated with increased SCGB3A1 methylation among pre- and post-menopausal cases. Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1–19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4–39.9; Stage III/IV OR = 5.6, 95% CI: 1.1–29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1–0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1–0.8; Stage III/IV OR = 0.6, 95% CI: 0.1–3.4). Among postmenopausal women, methylation of SYK was associated with increased tumor size (OR = 1.7, 95% CI: 1.0–2.7) and higher nuclear grade (OR = 2.0, 95% CI 1.2–3.6). Associations between methylation and breast cancer related mortality were observed among pre- but not post-menopausal women. Methylation of SCGB3A1 was associated with reduced risk of death from breast cancer (HR = 0.41, 95% CI: 0.17–0.99) as was BRCA1 (HR = 0.41, 95% CI: 0.16–0.97). CCND2 methylation was associated with increased risk of breast cancer mortality (HR = 3.4, 95% CI: 1.1–10.5). We observed differences in methylation associated with tumor characteristics; methylation of these genes was also associated with breast cancer survival among premenopausal cases. Understanding of the associations of DNA methylation with other clinicopathological features may have implications for prevention and treatment.     

Pre-diagnostic smoking behaviour and poorer prognosis in a German breast cancer patient cohort – Differential effects by tumour subtype,NAT2 status,BMI and alcohol intake

BackgroundInconsistent associations of smoking and breast cancer-specific mortality might be explained by subgroups of patients with different susceptibility to harmful effects of smoking.MethodsWe used a prospective cohort of 3340 postmenopausal breast cancer patients aged 50–74 and diagnosed with invasive tumours 2001–2005 in Germany, with a median follow-up time of 6 years. The effect of pre-diagnostic smoking behaviour on mortality outcomes and risk of recurrence was investigated using delayed entry Cox regression analysis. Differential effects according to N-acetyltransferase (NAT2) status, BMI, alcohol consumption, and tumour subtypes were assessed.ResultsOverall, smoking at time of breast cancer diagnosis versus never/former smoking was non-significantly associated with increased breast cancer-specific mortality and risk of recurrence (HR 1.23, 95% CI 0.93–1.64, and HR 1.29, 95% CI 0.95–1.75, respectively). Associations were consistently stronger in NAT2 slow than in fast acetylators for all mortality outcomes. Breast cancer-specific mortality was significantly increased in smokers with NAT2 slow acetylating status (HR 1.77, 95% CI 1.13–2.79) but not in those with fast acetylating status (HR 1.09, 95% CI 0.60–1.98; P_{heterogeneity} = 0.19). Smoking was associated with significantly poorer outcomes for triple negative and luminal A-like tumours (e.g. all-cause mortality: HR 1.93, 95% CI 1.02–3.65, and HR 2.08, 95% CI 1.40–3.10, respectively). Risk of recurrence was significantly increased for women with HER2 positive tumours (HR 3.64, 95% CI 1.22–10.8). There was significant heterogeneity by BMI for non-breast cancer-specific mortality (<25 kg/m²: HR 2.52, 95% CI 1.52–4.15 vs. ≥25 kg/m²: HR 0.94, 95% CI 0.38–2.36; P_{heterogeneity} = 0.04).ConclusionThe harmful effects of smoking may be particularly relevant for certain subgroups of breast cancer patients. This may include patients with NAT2 slow acetylation status or with tumour subtypes other than luminal B, such as luminal A tumours who usually have a rather good prognosis. Emphasis on smoking cessation programmes for all cancer patients should be strengthened.     

Fruit and vegetable and fried food consumption and 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α] purin-10(3H)-one deoxyguanosine adduct formation

Diet has been shown to modulate M(1)dG adduct, a biomarker of oxidative stress and lipid peroxidation. Thus, we analysed the association between diet and M(1)dG in 120 controls and 67 Map Ta Phut industrial estate workers in Rayong, Thailand, to evaluate the influence of fruit and vegetables, and fried and charcoal-grilled/barbecued food consumption on M(1)dG. M(1)dG was decreased in controls reporting to consume 14-17 servings/week of fruit and vegetables (mean ratio [MR]= 0.35, CI 0.18-0.69, p< 0.05). Conversely, a non-statistically significant M(1)dG increment was detected in controls consuming 9-18 servings/week of fried food (MR = 1.33, CI 0.88-2.00, p = 0.168). No effect of charcoal-grilled/barbecued food was found. No effect of diet was observed in workers. An association with smoking was observed in controls (MR = 1.88, CI 1.14-3.10, p < 0.05), but not in workers. M(1)dG can induce mutations and/or methylation changes within the promoter regions of cancer-related genes, thus promotion of healthy eating practices should be recommended.     

Prognostic and clinical significance of focal adhesion kinase expression in breast cancer: A systematic review and meta-analysis

BackgroundThe prognostic significance of focal adhesion kinase (FAK) in breast cancer remains controversial. Here, we conducted a meta-analysis to explore the prognostic value of FAK expression in breast cancer.Materials and methodsPossible prognostic significance of protein or mRNA expression of FAK in breast cancer was investigated with searches of electronic databases for relevant publications. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted from eligible studies.ResultsA total of eight eligible studies which included 2604 participants were analyzed in this meta-analysis. Increased expression of FAK protein was found to significantly correlate with shorter overall survival (OS) (HR = 1.43, 95% CI: 1.12–1.83; P = 0.004), and not with disease-free survival (HR = 1.31, 95% CI: 0.92–1.85; P = 0.14). Elevated FAK protein expression was also associated with negative estrogen receptor (ER) expression (OR, 1.34; 95% CI, 1.06–1.68; P = 0.01), negative progesterone receptor (PR) expression (OR, 1.54; 95% CI, 1.22–1.93; P < 0.001), positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.64; 95% CI, 1.28–2.09; P < 0.001), triple-negative breast cancer (TNBC) (OR, 1.57; 95% CI, 1.14–2.17; P = 0.006), high nuclear grade (OR, 1.70; 95% CI, 1.05–2.78; P = 0.03), high Ki-67 expression level (OR, 2.87; 95% CI, 1.94–4.24; P < 0.001), and positive p53 status (OR, 2.28; 95% CI, 1.58–3.29; P < 0.001).ConclusionOur meta-analysis identifies an association between increased FAK protein expression and worse OS among breast cancer patients. Moreover, enhanced FAK expression is associated with negative ER expression, negative PR expression, positive HER2 expression, TNBC, high nuclear grade, high Ki-67 expression level, and positive p53 status in breast carcinoma.     

A systematic review and meta-analysis of higher expression of folate receptor alpha (FOLR1) predicts poor cancer prognosis

Abstract

Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR)?=?0.78, 95% confidence interval (CI)?=?0.64–0.94, p?=?0.009) and the disease-free survival (DFS) (HR?=?1.25, 95% CI?=?1.07–1.47, p?=?0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR?=?2.66, 95% CI?=?1.54–4.59, p?=?0.0005) and endometrial carcinoma (HR?=?1.30, 95% CI?=?1.05–1.61, p?=?0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.     

Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort

BackgroundMammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent.MethodsDense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses.ResultsOverall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33–1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR_1SD = 2.25; 95% CI, 1.67–3.04) than in women reporting none (OR_1SD = 1.41; 95% CI, 1.24–1.60; p_{heterogeneity} = 0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p_{heterogeneity} = 0.02) with respective ORs of 15.16 (95% CI, 4.23–54.28) vs. 3.14 (95% CI, 1.89–5.22) for ≥50% vs. <10% PMD.ConclusionsThe stronger association between mammographic density and breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density.     

A new technique for assessing arterial pressure wave forms and central pressure with tissue Doppler

Background

Arterial diameters enlarge in response to wall thickening, plaques, and many atherosclerotic risk factors. We hypothesized that right common carotid artery (RCCA) diameter would be independently associated with cardiac disease and improve risk discrimination.

Methods

In a middle-aged, biracial population (baseline n = 11225), we examined associations between 1 standard deviation increments of baseline RCCA diameter with prevalent myocardial infarction (MI) and incident cardiac events (MI or cardiac death) using logistic regression and Cox proportional hazards models, respectively. Areas under the receiver operator characteristic curve (AUC) were used to estimate model discrimination.

Results

MI was present in 451 (4%) participants at baseline (1987–89), and incident cardiac events occurred among 646 (6%) others through 1999. Adjusting for IMT, RCCA diameter was associated with prevalent MI (female OR = 2.0, 95%CI = 1.61–2.49; male OR = 1.16, 95% CI = 1.04–1.30) and incident cardiac events (female HR = 1.75, 95% CI = 1.51–2.02; male HR = 1.27, 95% CI = 1.15–1.40). Associations were attenuated but persisted after adjustment for risk factors (not including IMT) (prevalent MI: female OR = 1.73, 95% CI = 1.40–2.14; male OR = 1.14, 95% CI = 1.02–1.28, and incident cardiac events: female HR = 1.26, 95% CI = 1.08–1.48; male HR = 1.19, 95% CI = 1.08–1.32). After additional adjustment for IMT, diameter was associated with incident cardiac events in women (HR = 1.18, 95% CI = 1.00–1.40) and men (HR = 1.17, 95% CI = 1.06–1.29), and with prevalent MI only in women (OR = 1.73; 95% CI = 1.37–2.17). In women, when adjustment was limited, diameter models had larger AUC than other models.

Conclusion

RCCA diameter is an important correlate of cardiac events, independent of IMT, but adds little to overall risk discrimination after risk factor adjustment.     

Risk factors of recurrence in small-sized, node negative breast cancer in young women: a retrospective study in Chinese population

We aimed to investigate risk factors of local and distant recurrence in small-sized, node negative breast cancer in women <35 years in a Chinese cohort. Between January 1994 and January 2007, 107 patients with pathologically confirmed small-sized (?1 cm), node negative breast cancer who did not receive neoadjuvant or adjuvant chemotherapy were included. The 5-year recurrence-free survival (RFS) was estimated according to different prognostic variables. With a median time of 60 months (range, 8–60 months) follow-up, local and distant recurrence were observed in 25 cases (23.4%). By univariate analysis, HER-2 positivity, triple negative (TN), and high Ki-67 index (?14%) were risk factors of a lower RFS (hazard ratio (HR) 6.680, 95% confidence interval (CI) 2.350–18.985, P<0.0001 for HER-2 positive; HR 4.769, 95%CI 1.559–14.591, P=0.006 for TN; HR 6.030, 95%CI 2.659–13.674, P<0.0001 for high Ki-67 index). Patients with grade 3 tumors had a lower RFS (HR 2.922, 95%CI 1.096–7.791, P=0.032) compared with those with grade 1 or grade 2 tumors. By multivariate analysis, HER-2 positivity (HR 10.204, 95%CI 3.391–30.704, P<0.0001), TN (HR 10.521, 95% CI 3.152–35.113, P<0.0001) and high Ki-67 index (HR 10.820, 95%CI 4.338–27.002, P<0.0001) remained risk factors of RFS. In this cohort, HER-2 positivity, triple negative and high Ki-67 index were independent risk factors of RFS in young patients with T1a,bN0 breast cancer. Subsequent pregnancy did not affect RFS.     

Genetic predisposition of six well‐defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population

Breast cancer constitutes an enormous burden in China. A strong familial clustering of breast cancer suggests a genetic component in its carcinogenesis. To examine the genetic predisposition of high mobility group box‐1/receptor for advanced glycation end products (HMGB1/RAGE) pathway to breast cancer, we genotyped six well‐defined polymorphisms in this pathway among 524 breast cancer patients and 518 cancer‐free controls from Heilongjiang province, China. There were no deviations from Hardy–Weinberg equilibrium for all polymorphisms. In single‐locus analysis, the frequency of rs1800624 polymorphism mutant A allele in RAGE gene was significantly higher in patients than in controls (24.52% versus 19.50%, P = 0.006), with the carriers of rs1800624‐A allele being 1.51 times more likely to develop breast cancer relative to those with rs1800624‐GG genotype after adjustment (95% confidence interval or CI: 1.17–1.94, P = 0.001). In HMGB1 gene, haplotype analysis did not reveal any significance, while in RAGE gene, haplotypes C‐T‐A and C‐A‐G (alleles in order of rs1800625, rs18006024, rs2070600) were significantly associated with an increased risk of breast cancer (adjusted OR = 2.72 and 10.35; 95% CI: 1.20–6.18 and 1.58–67.80; P = 0.017 and 0.015 respectively). In further genetic score analysis, per unit and quartile increments of unfavourable alleles were significantly associated with an increased risk of breast cancer after adjustment (odds ratio or OR = 1.20 and 1.26; 95% CI: 1.09–1.32 and 1.12–1.42; P < 0.001 and <0.001 respectively). Our findings altogether demonstrate a significant association between RAGE gene rs1800624 polymorphism and breast cancer risk, and more importantly a cumulative impact of multiple risk associated polymorphisms in HMGB1/RAGE pathway on breast carcinogenesis.     

Neutrophil-to-eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti-PD-1 therapy

Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil-to-eosinophil ratios (NER) as a predictive indicator in this population. In this retrospective study evaluating anti-PD-1 treated patients with advanced melanoma, progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and risk of high-grade (grade ≥3) immune-related adverse events (irAEs) were compared between groups defined by median pretreatment NLR and NER as well as median NLR and NER at 1-month post-treatment. Lower baseline NLR and NER were associated with improved OS [HR: 0.504, 95% CI: 0.328–0.773, p = .002 and HR: 0.442, 95% CI: 0.288–0.681, p < .001, respectively] on univariate testing. After accounting for multiple covariates, our multivariate analysis found that lower pretreatment NER was associated with better ORR (by irRECIST) (OR: 2.199, 95% CI: 1.071–4.582, p = .033) and improved OS (HR: 0.480, 95% CI: 0.296–0.777, p = .003). Baseline NLR, 1-month NLR, and 1-month NER were not associated with ORR, PFS, or OS outcomes; but 1-month NER correlated with lower risk of grade ≥3 irAEs (OR: 0.392, 95% CI: 0.165–0.895, p = .029). Our findings suggest baseline NER merits additional investigation as a novel prognostic marker for advanced melanoma patients receiving anti-PD-1-based regimens.     

Intérêt de l’imagerie hybride TEMP/TDM pour la scintigraphie des récepteurs de la somatostatine dans le bilan des tumeurs endocrines gastro-entéro-pancréatiques

In this work, we have evaluated the potential of image fusion and attenuation correction (AC) of SPECT-CT imaging for the assessment of gastro-entero-pancreatic endocrine tumors by somatostatin receptor scintigraphy (SRS).MethodAfter optimisation of acquisition and reconstruction parameters, we have evaluated, in a prospective study, SRS performed over a period of one year. We have compared visual interpretations of planar and tomographic images versus SPECT/CT images to determine if anatomical localisation and diagnostic contributions are improved. In a semi-quantitative analysis of pathological foci, we have measured maximal intensity values (T_max), tumour to background ratios (T/B) and tumour contrasts (Ct) with and without AC.ResultsIn 25 SRS, visual analysis has shown anatomical localisation improvements in 60% of cases (CI95%, 39–79) and diagnostic improvements in 64% of cases (CI95%, 43–82). Doubtful foci proportion changed from 44 to 11%. In the semi-quantitative analysis of 41 pathological foci, Wilcoxon matched-pairs tests showed significantly higher T_max, T/B and Ct values after AC.ConclusionSPECT/CT imaging improves diagnostic quality of SRS thanks to a better foci localisation and a better lesional contrast in the image.     

Reproductive factors and breast cancer risk in Palestine: A case control study

BackgroundEarly age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer (breast ca). This study aims to investigate the reproductive determinants of breast cancer among women in the West Bank of Palestine.A structured questionnaire was used to collect data in a case-control study (237 registered cases and 237 controls). A multivariate analysis model was used to adjust for the association between women’s reproductive factors and breast ca risk. This study was approved by Al Quds University Ethical Research Committee and the Ministry of Health research unit.ResultsIn the multivariate analysis, menarche after 13 years of age, use of oral contraceptives for more than two months, and hormonal contraceptives use significantly doubled the risk for breast ca (Adjusted Odds Ratio (AOR) = 2.03, 95 % CI: 1.21–4.37, p < 0.011 and AOR = 2.2, 95 % CI: 1.24–4.01, p = 0.008, respectively). Women who used hormone replacement therapy (HRT) were significantly associated with higher odds (5 folds) of having breast ca versus those who did not use them (AOR 5.02, 95 % CI: 1.93–13.06, p = 0.001). Similarly, nulliparous women showed 6 times the odds of breast ca compared with women with one or more children (p = 0.005). Also, parental consanguinity marriage (AOR 2.59, 95 % CI: 1.53–4.36, p = 0.001) and positive family history (AOR 3.88, 95 % CI: 2.19–6.87, p = 0.001) of the condition can be strong determinants for breast ca in this study.ConclusionThis study provides clear evidence that the use of reproductive hormones, whether as a birth control tool or for therapeutic purposes, must be rationalized worldwide and in Palestine in particular.     

Diagnostic route is associated with care satisfaction independently of tumour stage: Evidence from linked English Cancer Patient Experience Survey and cancer registration data

BackgroundWhether diagnostic route (e.g. emergency presentation) is associated with cancer care experience independently of tumour stage is unknown.MethodsWe analysed data on 18 590 patients with breast, prostate, colon, lung, and rectal cancers who responded to the 2014 English Cancer Patient Experience Survey, linked to cancer registration data on diagnostic route and tumour stage at diagnosis. We estimated odds ratios (OR) of reporting a negative experience of overall cancer care by tumour stage and diagnostic route (crude and adjusted for patient characteristic and cancer site variables) and examined their interactions with cancer site.ResultsAfter adjustment, the likelihood of reporting a negative experience was highest for emergency presenters and lowest for screening-detected patients with breast, colon, and rectal cancers (OR versus two-week-wait 1.51, 95% confidence interval [CI] 1.24–1.83; 0.88, 95% CI 0.75–1.03, respectively). Patients with the most advanced stage were more likely to report a negative experience (OR stage IV versus I 1.37, 95% CI 1.15–1.62) with little confounding between stage and route, and no evidence for cancer-stage or cancer-route interactions.ConclusionsThough the extent of disease is strongly associated with ratings of overall cancer care, diagnostic route (particularly emergency presentation or screening detection) exerts important independent effects.     

Ultrasound settings significantly alter arterial lumen and wall thickness measurements

Background

Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk.

Methods

We investigated cross-sectional (baseline 1987–89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period.

Results

Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47–1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28–1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04–1.18; progression HR = 1.11, 95% CI = 1.03–1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50^th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47–2.0; men HR = 1.88, 95% CI = 1.48–2.39; women HR = 1.59, 95% CI = 1.31–1.95) while RCCA IMT or diameter alone in the upper 50^th percentile produced significantly lower estimated risks.

Conclusion

RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.     

Mendelian randomization supports causality between overweight status and accelerated aging

It is reported that overweight may lead to accelerated aging. However, there is still a lack of evidence on the causal effect of overweight and aging. We collected genetic variants associated with overweight, age proxy indicators (telomere length, frailty index and facial aging), etc., from genome-wide association studies datasets. Then we performed MR analyses to explore associations between overweight and age proxy indicators. MR analyses were primarily conducted using the inverse variance weighted method, followed by various sensitivity and validation analyses. MR analyses indicated that there were significant associations of overweight on telomere length, frailty index, and facial aging (β = −0.018, 95% CI = −0.033 to −0.003, p = 0.0162; β = 0.055, 95% CI = 0.030–0.079, p < 0.0001; β = 0.029, 95% CI = 0.013–0.046, p = 0.0005 respectively). Overweight also had a significant negative causality with longevity expectancy (90th survival percentile, β = −0.220, 95% CI = −0.323 to −0.118, p < 0.0001; 99th survival percentile, β = −0.389, 95% CI = −0.652 to −0.126, p = 0.0038). Moreover, the findings tend to favor causal links between body fat mass/body fat percentage on aging proxy indicators, but not body fat-free mass. This study provides evidence of the causality between overweight and accelerated aging (telomere length decreased, frailty index increased, facial aging increased) and lower longevity expectancy. Accordingly, the potential significance of weight control and treatment of overweight in combating accelerated aging need to be emphasized.     

PETER PHAN: An MRI phantom for the optimisation of radiomic studies of the female pelvis

PurposeTo develop a phantom for methodological radiomic investigation on Magnetic Resonance (MR) images of female patients affected by pelvic cancer.MethodsA pelvis-shaped container was filled with a MnCl₂ solution reproducing the relaxation times (T₁, T₂) of muscle surrounding pelvic malignancies. Inserts simulating multi-textured lesions were embedded in the phantom. The relaxation times of muscle and tumour were measured on an MR scanner on healthy volunteers and patients; T₁ and T₂ of MnCl₂ solutions were evaluated with a relaxometer to find the concentrations providing a match to in vivo relaxation times. Radiomic features were extracted from the phantom inserts and the patients’ lesions. Their repeatability was assessed by multiple measurements.ResultsMuscle T₁ and T₂ were 1128 (806–1378) and 51 (40–65) ms, respectively. The phantom reproduced in vivo values within 13% (T₁) and 12% (T₂). T₁ and T₂ of tumour tissue were 1637 (1396–2121) and 94 (79–101) ms, respectively. The phantom insert best mimicking the tumour agreed within 7% (T₁) and 24% (T₂) with in vivo values. Out of 1034 features, 75% (95%) had interclass correlation coefficient greater than 0.9 on T₁ (T₂)-weighted images, reducing to 33% (25%) if the phantom was repositioned. The most repeatable features on phantom showed values in agreement with the features extracted from patients’ lesions.ConclusionsWe developed an MR phantom with inserts mimicking both relaxation times and texture of pelvic tumours. As exemplified with repeatability assessment, such phantom is useful to investigate features robustness and optimise the radiomic workflow on pelvic MR images.     

Epidemiology of asthma and associated factors in an urban Pakistani population: adult asthma study-Karachi

Background

This study was conducted in order to determine the prevalence of asthma and associated risk factors in the adult population of Karachi, Pakistan.

Methods

This multi-stage, cross-sectional survey was conducted from May 2014–August 2015; comprising 1629 adults in 75 randomly selected clusters in Karachi, Pakistan. Definitions included: ‘self-reported asthma’, ‘reversibility in FEV₁^’ and ‘respiratory symptoms and reversibility in FEV₁’.

Results

Prevalence of asthma was 1.8% (self-reported) (95% CI: 1.0–2.6), 11.3% (reversibility in FEV₁) (95% CI: 9.4–13.3) and 6.6% (symptoms and reversibility in FEV₁) (95% CI: 5.1–8.1). Asthmatics were more likely to belong to the age group ≥38?years according to ‘reversibility in FEV₁’ and ‘respiratory symptoms and reversibility in FEV₁’ (AOR: 1.9, 95% CI: 1.2–3.3) and (AOR: 2.1, 95% CI: 1.1–4.2), respectively. Asthmatics were more likely to report history of allergies (AOR: 1.9, 95% CI: 1.2–2.9) and (AOR: 2.8, 95% CI: 1.7–4.8); and were exposed to environmental tobacco smoke (AOR: 1.6, 95% CI: 1.1–2.5) and (AOR: 1.9, 95% CI: 1.1–3.3) according to ‘reversibility in FEV₁’ and ‘respiratory symptoms and reversibility in FEV₁’, respectively. Asthmatics were more likely to report pack years of smoking ≥5 (AOR: 2.3, 95% CI: 1.1–4.7) according to ‘respiratory symptoms and reversibility in FEV₁’.

Conclusion

This study reports a high prevalence of asthma among Pakistani adults and calls for developing appropriate public health policies for prevention and control of asthma in the country. Further studies should be conducted to determine the national prevalence as well as follow-up studies to identify preventable causes for adult asthma.

     

Adducts formed between deoxyguanosine and cis-Dichlorodiammineplatinum(II): Separation by means of cation-exchange chromatography

The interaction between deoxyguanosine (dG) and cis-dichlorodiammineplatinum(II) (cis-Pt) leads to the 2:1 and the 1:1 dG-Pt adducts. These adducts were separated on an Aminex A6 cationexchange column by use ot 0.01 M K₂CO₃ (pH 11) as an eluent. The stoichiometry of the adducts was determined from the ^195mPt radioactivity and from the absorbance of the guanine chromophore at 280 nm. Time-course studies show that dG reacts initially with cis-Pt to form the 1:1 adduct, which then interacts with a second molecule of dG to form the 2:1 adduct. Acid hydrolysis (100°C in 88% formic acid for 5–15 min) of the 1:1 and 2:1 adducts results in their conversion to two new products, which elute differently from the column but which still contain Pt bound in the same stoichiometric ratio to dG as in the nonhydrolyzed adducts. The hydrolyzed adducts show a negative diphenylamine reaction indicative ot cleavage of the glycosidic bond. It is concluded that mild acid hydrolysis converts the 1:1 and 2:1 dG-Pt adducts into the corresponding guanine-Pt adducts, which are chromatographically distinguishable. This acid hydrolysis-high pressure liquid chromatography (HPLC) procedure has application to the identification of the Pt adducts formed in DNA.