Alterations in human papillomavirus-related biomarkers after treatment of cervical intraepithelial neoplasia

Objective

This study aims to assess the alterations in various HPV-related biomarkers 6 months post-treatment and how these relate to various risk factors and individual characteristics; their role for the prediction of treatment failure was also evaluated.

Material and methods

Design: Prospective observational study.Population: Women planning to undergo treatment for cervical intraepithelial neoplasia.Intervention: A liquid-based cytology sample was taken pre-operatively. This was tested for HPV genotyping, Nucleic Acid Sequence Based Amplification, flow cytometric evaluation and p16 immunostaining. A repeat LBC sample was obtained 6 months post-treatment and was tested for the same biomarkers.Outcomes: The alterations of the biomarkers 6 months post-treatment were recorded. Their relation to individual characteristics and risk factors (age, smoking, sexual history, use of condom, CIN grade, excision margin status, crypt involvement) as well as their role for the prediction of residual/recurrent disease were assessed.Analysis: The accuracy parameters (sensitivity, specificity, positive and negative predictive value and the likelihood ratios) of each biomarker for the prediction of recurrent/residual CIN were calculated.

Results

A total of 190 women were recruited. All biomarkers had significantly higher negativity rates post-treatment compared to pre-treatment ones. Multivariate analysis demonstrated that consistent condom use post-treatment significantly reduces the high-risk HPV positivity rates in comparison to no use (OR = 0.18; 95% CI: 0.09-0.38). Sensitivity and specificity for all high risk HPV DNA testing were 0.5/0.62, respectively; the relevant values for only type 16 or 18 DNA typing were 0.5/0.92, for NASBA 0.5/0.94, for flow 0.5/0.85 and for p16 0.25/0.93.

Conclusion

CIN treatment reduces positivity for all HPV-related biomarkers. Consistent condom use significantly reduces high-risk HPV positivity rates. More cases of treatment failures are required in order to specify whether different combinations of HPV-related biomarkers could enhance the accuracy of follow up, possibly in the form of a Scoring System that could allow tailored post-treatment surveillance.     

子宫内膜异位症诊断标志物的研究进展

子宫内膜异位症（endometriosis,EMs）是一种好发于育龄期女性,具有恶性潜能的良性疾病,发病率约为10%。因该疾病起病隐匿,且只能通过腹腔镜和组织病理学等有创操作进行确诊,目前临床诊断上缺少敏感而特异的生物学指标,导致疾病的诊断及治疗延迟,严重影响女性的生活质量。因此,寻找无创的生物标志物对EMs的临床的诊断和治疗具有重大意义。研究发现患有EMs女性的血清、尿液及月经血等体液中存在一些诊断标志物,使用这些标志物诊断具有简便、快速且无创等优势,成为该病诊断的一个重要方向。     

PD-1抑制剂治疗肝细胞癌疗效相关生物标志物的研究现状

近年来免疫治疗在肝细胞癌辅助治疗领域取得了初步成果,而程序性死亡受体1(Programmed cell death-1,PD-1)抑制剂是目前的研究热点,然而其总反应率仍不尽如人意,因此目前急需寻找合适的生物标志物,来预测PD-1抑制剂治疗肝细胞癌患者的疗效,本文就PD-1抑制剂治疗肝细胞癌的相关生物标志物的研究进展进行综述。     

Genetic Variations in IFNGR1, BDNF and IL-10 May Predict the Susceptibility to Depression and Anxiety in Chinese Women With Breast Cancer

BackgroundA large number of breast cancer survivors suffer from psychological distress. The purpose of this study was to investigate the association between genetic variations in Chinese breast cancer patients and anxiety or depression, and to screen patients who are susceptible to psychological problems.MethodsA total of 300 early-stage breast cancer patients were recruited in this prospective observational single-center cohort study. With reference to the previous literature and the mechanism concerning anxiety and depression, 9 candidate genes and 29 single-nucleotide polymorphisms (SNPs) loci were selected. The association between SNP variations and anxiety/depression were analyzed.ResultsAfter we incorporated meaningful clinicopathological and demographic factors, multivariate analysis showed that the A/G and G/G genotypes of IFNGR1 (rs2234711) and the T/C and T/T genotypes of BDNF (rs6265) were significantly associated with depression (HR 3.10, P = .008; HR 2.04, P = .03). The G/A and G/G genotypes of IL-10 (rs1554286) remained independent predictors of anxiety (HR 1.85, P = .019).ConclusionsThese findings suggested that variations in IL-10, IFNGR1 and BDNF were associated with anxious/depressive symptoms in early-stage breast cancer patients in China, which could help identify patients at high risk for psychological problems.     

Diagnostic value of intestinal fatty acid-binding protein for pneumatosis intestinalis

Background

Pneumatosis intestinalis (PI) is known as a sign of a life-threatening bowel ischemia. We aimed to evaluate the utility of intestinal fatty acid-binding protein (I-FABP) in the diagnosis of pathologic PI.

Methods

All consecutive patients who presented to our emergency department with PI were prospectively enrolled. The diagnostic performance of I-FABP for pathologic PI was compared with that of other traditional biomarkers and various parameters.

Results

Seventy patients with PI were enrolled. Pathologic PI was diagnosed in 27 patients (39%). The levels of most biomarkers were significantly higher in patients with pathologic PI than those with nonpathologic PI (P < .05). Receiver operator characteristic analysis revealed that the area under the curve (AUC) was highest for I-FABP (area under the curve = .82) in the diagnosis of pathologic PI.

Conclusions

High I-FABP value, in combination with other parameters, might be clinically useful for pathologic PI.     

Reductions in biomarkers of exposure (BoE) to harmful or potentially harmful constituents (HPHCs) following partial or complete substitution of cigarettes with electronic cigarettes in adult smokers

Changes in fifteen urine, blood and exhaled breath BoEs of HPHCs representing classes of compounds reported by FDA to be significant contributors to smoking-associated disease risks were measured in 105 clinical-confined subjects following randomization and a five-day forced-switch from usual brand conventional combustible cigarettes to: (i) exclusive commercial e-cigarette use; (ii) dual-use of commercial e-cigarettes and the subject’s usual cigarette brand; or (iii) discontinued use of all tobacco or nicotine products. Levels of urinary biomarkers in subjects that completely substituted their usual cigarette with e-cigarettes were significantly lower (29–95%) after 5 days. Percent reductions in eight of nine urinary BoEs were indistinguishable to smokers who had quit smoking, except for nicotine equivalents, which declined by 25–40%. Dual users who halved self-reported daily cigarette consumption with e-cigarettes exhibited reductions (7–38%) in eight of nine urinary biomarkers, but had increase (1–20%) in nicotine equivalents. Reductions were broadly proportional to the reduced numbers of cigarettes smoked. Dual user urinary nicotine equivalents were slightly higher, but not statistically significant. After 5 days, blood nicotine biomarker levels were lower in the cessation (75–96%) and exclusive use groups (11–83%); with dual users experiencing no significant reductions. All subjects experienced significant decreases in exhaled CO. Decreases in the cessation and exclusive groups ranged from 88–89% and 27–32% in dual users. Exhaled NO increased in the cessation and exclusive groups (46–63% respectively), whereas the dual users experienced minimal changes. Overall, smokers who completely or partially substituted conventional cigarettes with e-cigarettes over five days, experienced reductions in HPHCs.     

Prediction of cardiovascular disease events

Observational studies with incidence of cardiovascular disease (CVD) events have typically provided the information that is used. Prediction of risk is dependent on accurate and precise baseline measurements in persons without coronary disease at baseline. Follow-up of 5 to 10 years is a typical interval of interest for the prediction of coronary disease events in adults who are asymptomatic at the baseline. Performance criteria for risk estimation include discrimination, calibration, and reclassification, and newer heart disease risk factors and biomarkers can be evaluated in the context of existing risk estimation approaches.     

Primary graft dysfunction

Primary graft dysfunction (PGD) is the most important cause of early morbidity and mortality following lung transplantation. PGD affects up to 25% of all lung transplant procedures and currently has no proven preventive therapy. Lung transplant recipients who recover from PGD may have impaired long-term function and an increased risk of bronchiolitis obliterans syndrome. This article aims to provide a state-of-the-art review of PGD epidemiology, outcomes, and risk factors, and to summarize current efforts at biomarker development and novel strategies for prevention and treatment.     

Caloric restriction or resveratrol supplementation and ageing in a non-human primate: first-year outcome of the RESTRIKAL study in Microcebus murinus

A life-long follow-up of physiological and behavioural functions was initiated in 38-month-old mouse lemurs (Microcebus murinus) to test whether caloric restriction (CR) or a potential mimetic compound, resveratrol (RSV), can delay the ageing process and the onset of age-related diseases. Based on their potential survival of 12 years, mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake and a RSV group (200 mg/kg.day^–1) fed ad libitum. Since this prosimian primate exhibits a marked annual rhythm in body mass gain during winter, animals were tested throughout the year to assess body composition, daily energy expenditure (DEE), resting metabolic rate (RMR), physical activity and hormonal levels. After 1 year, all mouse lemurs seemed in good health. CR animals showed a significantly decreased body mass compared with the other groups during long day period only. CR or RSV treatments did not affect body composition. CR induced a decrease in DEE without changes in RMR, whereas RSV induced a concomitant increase in DEE and RMR without any obvious modification of locomotor activity in both groups. Hormonal levels remained similar in each group. In summary, after 1 year of treatment CR and RSV induced differential metabolic responses but animals successfully acclimated to their imposed diets. The RESTRIKAL study can now be safely undertaken on a long-term basis to determine whether age-associated alterations in mouse lemurs are delayed with CR and if RSV can mimic these effects.     

Candidate placental biomarkers for intrauterine alcohol exposure

Background: Fetal alcohol spectrum disorder (FASD) is a leading cause of nongenetic mental retardation and other neurodevelopmental deficits. Earlier diagnosis of FASD would greatly improve prognosis for individuals and families affected by this disorder. Here, we identify candidate placental biomarkers in an animal model of FASD that recapitulates many aspects of human FASD. Methods: Pregnant Sprague‐Dawley (SD) females were assigned to 1 of 3 diet groups on gestation day 8 (G8): Ethanol (E), Pair‐fed (PF) or Control (C). E dams received ethanol‐containing liquid diet and PF dams received isocaloric liquid diet in an amount that matched the paired E dam’s diet consumption the previous day. Control dams received laboratory chow and water ad libitum. Whole placentae from individual fetuses were collected on gestational day 21 (G21) for analyses. Western blotting and quantitative real‐time RT‐PCR were used to measure protein and mRNA levels of placental iodothyronine deiodinase III (Dio3), thyroid hormone receptor α1 (TRα1), and glucocorticoid receptor (GR). Placental mRNA levels of insulin‐like growth factor 2 (Igf‐2), pleckstrin homology‐like domain family A member 2 (Phlda2), and cyclin‐dependent kinase inhibitor 1C (Cdkn1c) were also measured. Results: Placental protein and mRNA levels from ethanol (E)‐consuming dams showed the following changes: increased Dio3, decreased TRα1, and decreased GR compared to both C and PF dams. Placental mRNA levels of intrauterine growth restriction (IUGR) markers Igf‐2, Phlda2, and Cdkn1c were altered similarly in PF and E dams. Conclusions: We propose the specific pattern of increased Dio3 and decreased TRα1 and GR protein levels in the placenta as selective biomarker for intrauterine alcohol exposure.