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1.

Objective

Recently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis.

Patients and methods

Matched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017. Presence of the T790M mutation was simultaneously detected using amplification refractory mutation system-PCR (ARMS-PCR) assay and droplet digital PCR (ddPCR) assay.

Results

Of the 61 enrolled patients, 46 were candidates for and received TKIs treatment based on their EGFR mutation status. When these samples were assayed, ddPCR identified significantly more T790M mutations than ARMS-PCR (before TKIs treatment: 19.6% (9/46) vs. 2.2% (1/46), P?=?0.040; after TKIs treatment: 78.3% (36/46) vs. 50% (23/46), P?<?0.001, respectively). Patients with first-line TKIs treatment harboring de novo T790M mutations showed a shorter PFS compared to those without de novo T790M mutations (median, 7.0 months vs. 11.7 months, p?=?0.013). In multivariate analyses, de novo T790M mutation was an independent predictor of PFS in EGFR-mutant patients who received TKIs treatment (p?=?0.031, HR 0.310, 95% CI: 0.107-0.900).

Conclusion

The ddPCR assay is an ultra-sensitive method to detect a minor amount of de novo T790M mutations in tumor samples. The de novo T790M mutation is a relatively unfavorable prognosis factor for patients receiving first-line TKIs treatment.  相似文献   

2.

Objective

Information overload can negatively impact positive health behaviors such as cancer screening. The 8-item Cancer Information Overload (CIO) scale appears to be the only validated measure of health-related information overload. The present study assesses the validity of the CIO scale when modified for use in patients with atrial fibrillation (AF) residing in Australia.

Methods

We conducted a secondary analysis of data from a study of adult Australian patients with AF (N?=?386) in which a modified version of the CIO scale was used. In the present study, we examined the construct (convergent and divergent) validity and performed an exploratory factor analysis for the modified scale.

Results

All items on the modified-CIO scale appear to load onto a single factor. As predicted, higher education levels (rs=-.24, p?<?.001) and higher oral anticoagulant knowledge (rs=-.17, p?=?.001) were significantly associated with lower modified-CIO scores; no other demographic characteristics were significantly associated with CIO scores.

Conclusion

When adapted to the AF context, the modified-CIO scale appears to be a valid measure of information overload.

Practice Implications

A valid scale is required to measure information overload accurately. Knowledge of the interplay between information overload and various health behaviors help focus future efforts to support patient empowerment.  相似文献   

3.

Background

MFG-E8(Milk fat globule-EGF factor 8), a secreted glycoprotein, plays an exceptional role in various diseases. MFG-E8 overexpression is found in a variety of cancers. However, it remains unclear whether MFG-E8 overexpression is associated with the clinicopathological characteristics and prognosis of human breast cancer.

Materials and methods

In this study, we detected the expression and localization of MFG-E8 protein in breast cancer and cancer-adjacent tissues using immunohistochemical staining, Western blot analysis and immunofluorescence. We analyzed the association between MFG-E8 expression and clinical characteristics and outcomes of breast cancer patients with different HR and HER2 statuses.

Results

Our results confirmed that MFG-E8 expression increased significantly in breast cancer compared with cancer-adjacent tissues by immunohistochemical staining (P?<? 0.001). Similarly, the Western blot results further confirmed the increased expression of MFG-E8 in breast cancer compared with cancer-adjacent tissues (P?=? 0.001). Immunofluorescence staining showed that MFG-E8 was mainly localized in the cytoplasm and membrane of tumor cells, consistent with the immunohistochemical staining results. The high expression levels of MFG-E8 showed a greater association with lymph node metastasis, TNM stage and histological grade (P < 0.001). Moreover, high MFG-E8 expression was related to a shortened overall survival (OS) (P?<? 0.001) and disease-free survival (DFS) (P?<? 0.001). Bioinformatics analysis with a Kaplan-Meier plotter also demonstrated a strong association of MFG-E8 mRNA overexpression with a short OS and DFS compared with low MFG-E8 expression (P?=? 0.040, P?=? 0.005).

Conclusions

Our findings indicate that MFG-E8 may be a potential marker for poor prognosis and survival in breast cancer.  相似文献   

4.

Objective

To develop a patient-centered informed consent and assessment tool written at a 6th grade-level that is multimodal, affordable, transportable, and readily modifiable for protocol updates.

Methods

This quality improvement initiative was performed in two phases on an actively-recruiting study at a pediatric diabetes clinic. In phase I, 38 volunteers underwent the standard-paper consent process, a comprehension assessment and provided feedback. Using feedback and the structure of the Plan-Do-Study-Act cycle a multimodal consent and assessment were developed. In phase II, volunteers were randomized to the standard (n?=?25) or the multimodal consent (n?=?25) and all completed the same comprehension assessment via touch-screen tablet. Primary outcomes were comparison of the individual and total comprehension assessment scores.

Results

Total comprehension scores were higher in the multimodal versus the standard consent group (p?<? 0.001) and on the elements of benefits (p?<? 0.001), risks (p?<? 0.001), volunteerism (p?<? 0.012), results (p?<? 0.001), confidentiality (p?<? 0.004) and privacy (p < 0.001).

Conclusion

A multimodal consent and assessment presented sequentially on a touch-screen tablet were patient-centered enhancements to standard consent.

Practice implications

Multimodal standardization of delivery with improved readability may strengthen the informed consent process.  相似文献   

5.

Background

LincRNA-p21 is involved in the initiation and progression of many human diseases. We aimed to investigate the expression of LincRNA-p21 in different types of liver diseases.

Methods

Serum from patients with primary liver diseases (chronic HBV or HCV infection, hepatitis B virus-related cirrhosis, hepatitis B virus-related HCC, non-HBV/HCV-related HCC, alcoholic liver disease) and HBV negative liver metastatic cancer and control healthy individuals was collected and serum lincRNA-p21 levels were determined by RT-qPCR. Clinicopathological characteristics of the patients were also recorded.

Results

Serum lincRNA-p21 levels in patients with chronic HBV infection, hepatitis B cirrhosis, hepatitis B virus-related HCC, chronic hepatitis B virus infection, non-HBV/HCV-related HCC, and alcoholic liver disease were higher than those in the control individuals (P?<?0.001, P?<?0.001, P?<?0.001, P?<?0.001, P?<?0.001 and P?=?0.002, respectively). The serum lincRNA-p21 level was not significantly different between patients with HBV negative liver metastatic cancer and the normal control (P?=?0.80). LincRNA-p21 level was negatively correlated with HBV DNA (P?=?0.02), ALT (P?=?0.01) and AST (P?=?0.01) in patients with liver disease, but not correlated with gender (P?=?0.24), age (P?=?0.11) and AFP level (P?=?0.84). Serum lincRNA-p21 in hepatocellular carcinoma patients was higher than that in liver metastatic cancer patients (P?<?0.001).

Conclusion

Serum lincRNA-p21 may serve as a potential biomarker for liver cell damage in patients with hepatitis virus infection, hepatitis B cirrhosis, HBV-related HCC and alcoholic liver disease.  相似文献   

6.

Objective

There is some evidence for biomarker feedback when combined with cessation counseling for reducing smoking in pregnancy. This randomized controlled pilot study evaluated feasibility and potential efficacy of a social-cognitive theory (SCT)-based biomarker feedback intervention among pregnant Alaska Native (AN) smokers.

Methods

Participants were randomly assigned to receive three study calls (10–20?min each): (1) biomarker feedback intervention (n?=?30) including personalized cotinine results and feedback on their baby’s likely exposure to carcinogen metabolite NNAL, or (2) contact control usual care condition based on the 5As (n?=?30). Assessments were conducted at baseline, post-treatment, and delivery.

Results

High rates of treatment compliance, study retention, and treatment acceptability were observed in both groups. 7-day point prevalence smoking abstinence rates at delivery verified with urinary cotinine were the same in both study groups (20% intent-to-treat analysis, 26% per-protocol). SCT-based measures did not change differentially from baseline by study group.

Conclusion

This trial supports the feasibility and acceptability of providing biomarker feedback within the clinical care delivery system, but the intervention did not promote increased smoking cessation during pregnancy compared to usual care.

Practice Implications

Efforts are needed to promote the usual care and to develop alternative biomarker feedback messaging for pregnant AN women.  相似文献   

7.

Introduction

Chronic spontaneous urticaria (CSU) is characterized by recurrent itchy wheals, angioedema or both, that persist for longer than six weeks. In children, up to 40% of chronic spontaneous urticaria is due to mast cells and basophils-activating autoantibodies, mostly directed against the IgE high-affinity receptor subunit (FcεRI). Indirect basophil activation test (BAT) has been proposed in the diagnosis of autoimmune urticaria.

Materials and methods

Sera from sixteen patients, aged from 2 to 15 yrs, with CSU were evaluated through indirect BAT by flow cytometry using a commercial kit (Flow CAST®, BUHLMANN Laboratories, Schonenbuch, Switzerland) according to the manufacturer’s instructions.

Results

Indirect BAT test gave a much better diagnosis in our cohort than the gold standard ASST. Six children (37.5%) showed a positive indirect BAT while we could perform ASST in only 3 patients with just one patients showing a positive ASST. The specificity of BAT positive results was confirmed by the absence of significant difference between the BAT results obtained from negative controls vs negative sera of the patient (p?=?0.65) on the basophil donors, indicating that the serum is not activating basophil per se.

Conclusions

This pilot study suggests the utility of BAT to identify the subtype of autoimmune CSU in children in clinical practice.  相似文献   

8.

Objective

Shared decision-making (SDM) measures have never been assessed for validity and feasibility in pediatric outpatient settings. We compared psychometric performance of parent adaptations of a well-established measure (SDM-Q-9) to a newer measure focusing on provider effort in facilitating SDM (CollaboRATE) in two clinics.

Methods

English (n?=?955) and Spanish (n?=?58) speaking parents of children ages 1–5 years with symptoms of acute respiratory tract infections (ARTI) completed post-visit SDM-Q-9, CollaboRATE, satisfaction items (visit, provider communication, and study participation), and qualitative feedback.

Results

Parents felt CollaboRATE was more comprehensible and relevant than SDM-Q-9, which refers to decision-making actions difficult to define in ARTI visits. Among English-speakers, both measures showed high internal consistency (α?=?0.91, α?=?0.97). SDM-Q-9 reliability was strong (split-half, r?=?0.83) and CollaboRATE weak-to-moderate (two-week test-retest, ρ?=?0.41-0.66). Convergent validity with communication and visit satisfaction was poor for SDM-Q-9 (r=0.38, r=0.34) but higher for CollaboRATE (r=0.59, r?=?0.52). Both showed divergent validity with study participation satisfaction (r=0.08, r=0.13). Spanish versions demonstrated similar results.

Conclusions

Parent preference and correlations with satisfaction support CollaboRATE over SDM-Q-9, however psychometrics were borderline acceptable.

Practice Implications

Tools like CollaboRATE that focus on provider effort appear more appropriate for routine pediatric visits where SDM outcomes may be difficult to identify, yet additional validation research is needed.  相似文献   

9.

Objective

To compare the preferences of older (≥70 years old) versus younger (<70 years old) cancer patients regarding surrogate designation and decision making.

Methods

A cross-sectional survey. Patient characteristics and information about surrogacy and involvement in decision making were collected. Associations between patient characteristics and preferences were examined.

Results

The study included 130 patients aged ≥70 years (mean age 80 years) and 102 patients aged <70 years (mean age 55) and. Factors independently associated with surrogate knowledge (66%): younger age, more children living nearby, high income; factors associated with having already designated a surrogate (62%): younger age, decreased number of daily medications; factors associated with designating a surrogate after questionnaire administration (40%): low education, metastasis. Patients requiring an informed consent for any intervention was associated with older age (adjusted OR [aOR]per year?=?1.04[95% confidence interval 1.00–1.08]), not living alone (aOR?=?2.52[1.00–6.36]), and having children (aOR?=?4.49[1.13–17.81]).

Conclusion

All cancer patients, wanted to be fully informed and 72% wanted to be involved in medical decisions. Preferences for decision control vary between age groups, depending on family members’ presence and living alone.

Practice implications

Sharing complete and clear information should be an important key in the process of cancer patients’ care, regardless of patient age.  相似文献   

10.

Objectives

The aim of this study was to investigate the link between perceived dimensions of patient centred care and the satisfaction of adolescents and young adults within the UK, USA, Australian, Italian, and Chinese healthcare systems.

Methods

One thousand and thirty-four participants (212 from China,206 from Australia,208 from UK, 202 from USA, and 206 from Italy) answered a self-report questionnaire assessing the perceived dimensions of patient centred care. Factor analysis (PFA) was conducted on the data to identify relevant dimensions. One-way ANOVAs were run to identify differences between country samples related to perceived dimensions of patient centredness, and a multi-level multiple regression model was computed to assess the link between satisfaction and dimensions of patient centred care.

Results

Countries’ mean scores on ‘Satisfaction with Care’ (PF1) and on ‘Psychosocial Context’ (PF2) were statistically significant by inspecting the ANOVAs (p?<?.05). Satisfaction with care was predicted by PF2 and clinical utilization.

Conclusion

An online survey collected meaningful data on perceptions of healthcare received by respondents from five countries. This initial international study highlights important associations worthy of closer investigation.

Practice implications

Healthcare providers should assess comprehensively the psychosocial context of young patients during consultations.  相似文献   

11.

Objective

To identify how and why infertility patients’ communication with health care providers relates to their continuity of care within infertility treatment.

Method

A grounded theory analysis was conducted for 25 in-depth interviews across three coding phases, where we remained open to all themes present in the data, narrowed to most prominent themes, and found the connections between the themes.

Results

Based on our identified themes, we created a conceptual model that explains why infertility patients (dis)continued care with one or more clinician. Through this model, we describe two infertility identity transitions for patients: Transition 1: “Infertility as Temporary” to “Infertility as Enduring”; and Transition 2: “Infertility as Enduring” to “Infertility as Integrated.”

Conclusion

The study explains how and why patients’ view of their infertility affects their communication, and thus their continuity of care, with clinicians.

Practice implications

To provide patient-centered care within infertility treatment, providers can recognize how patients’ view of their infertility, and thus their needs, goals, and expectations, shift throughout their infertility experience.  相似文献   

12.

Objectives

To figure out that if there is a consistency relationship of the BRAFV600E mutation in matched-lymph node metastasis and original papillary thyroid carcinoma (PTC) specimen for the same patient.

Methods

We collected the specimen of thyroids and matched-lymph node metastases of PTCs and tested the BRAFV600E mutation status with amplification refractory mutation system (ARMS) PCR.

Results

20 patients with PTC and metastasis lymph node were hired. In this cohort, 16 (80%) patients had the same BRAF genetic mutation status in thyroid and metastasis, and the other 4 (20%) had an inconsistent situation.

Conclusions

Within our cohort, the data suggested that wild-type BRAFV600E oncogene in thyroid primary tumor does not rule out its mutation in lymph node metastasis, and vice versa.  相似文献   

13.

Background

Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP).

Methods

A total of 19 patients with genital C. trachomatis infection and 10 age-matched healthy controls were recruited for the study. Peripheral blood mononuclear cells (PBMCs) isolated from genital C. trachomatis-infected females were cultured in the presence of CPAF, HSP60 and MOMP antigens, and cytokines were measured by ELISA assay.

Results

We reported that pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Notably, CPAP and MOMP were more potent in triggering IL-1β, as compared to HSP60. Elevated levels of the proinflammatory cytokines were also noted in the samples infected with plasmid-bearing C. trachomatis as compared to those infected with plasmid-free strains.

Conclusions

Our study highlights distinct ability of chlamydial antigens in triggering pro-inflammatory response in the host immune cells.  相似文献   

14.

Background

GPR110 is a member of the adhesion G protein-coupled receptor family, which has been identified as an oncogene in various cancers, including hepatocellular carcinoma, lung cancer, prostatic cancer and glioma. Whereas the expression and the clinical relevance of GPR110 in gastric cancer has not been investigated. The research purpose of this study was to explore the expression pattern of GPR110 and evaluate its clinical-pathological and prognostic value in gastric cancer.

Methods

In this study, the expression of GPR110 was detected in 117 paired gastric cancer tissues and adjacent non-tumorous tissues by using qRT-PCR and immunohistochemical assays. Univariate Kaplan-Meier and multivariate Cox analysis were used to determine the prognostic value of GPR110 in GC.

Results

We demonstrated that the mRNA and protein levels of GPR110 in GC tissues were overexpressed than the adjacent non-tumorous tissues. Furthermore, elevated GPR110 protein expression was correlated with decreased overall and recurrence-free survival (P?=?0.001 and P?=?0.000, respectively). Univariate and multivariate analysis indicated that GPR110 protein level may serve as an independent prognostic indicator for determining prognosis of GC patients.

Conclusions

Our study revealed that high expression of GPR110 predicts the poor prognosis of GC patients, and GPTR110 may function as a potential biomarker for the diagnosis of GC.  相似文献   

15.
16.

Objective

The aim of this study was to elucidate the clinicopathological significance and prognostic role of loss of claudin-1 in colorectal cancer (CRC).

Methods

The correlations between claudin-1 expression and clinicopathological characteristics, including survival rates, were assessed using immunohistochemistry on 260 archival, paraffin-embedded CRC tissues. In addition, the correlations between cludin-1 and nuclear factor-kappa B (NF-κB), epithelial-mesenchymal transition markers and tumor-infiltrating lymphocytes were investigated.

Results

Claudin-1 expression was markedly lost in 42.7% of the 260 CRCs analyzed. Loss of claudin-1 expression significantly correlated with larger tumor size, vascular invasion, higher pT stage, and high metastatic lymph node ratio. In addition, loss of claudin-1 expression significantly correlated with NF-κB activation (P?<?0.001), high SNAI (P?<?0.001), and low E-cadherin (P?<?0.001) expressions. Patients with high immunoscores showed significantly lower rates of claudin-1 expression loss (P?=?0.020). In detail, loss of claudin-1 expression were frequently found in CRCs low CD3- and CD8-positive lymphocytes. There were significant correlations between claudin-1 expression loss and poor overall and recurrence-free survivals (P?<?0.001 and P?<?0.001, respectively).

Conclusion

Taken together, our results suggest that the loss of claudin-1 expression significantly correlates with aggressive tumor behaviors, high SNAI expression, lower immunoscore, and poor prognoses.  相似文献   

17.

Background

Increased body fat may be associated with an increased risk of developing an underlying pro-inflammatory state, thus leading to greater risk of developing certain chronic conditions. Immunoglobulin G has the ability to exert both anti- and pro-inflammatory effects, and the N-glycosylation of the fragment crystallisable portion is involved in mediating this process. Body mass index, a rudimentary yet gold standard indication for body fat, has been shown to be associated with agalactosylated immunoglobulin G N-glycans.

Aim

We aimed to determine the association between increased body fat and the immunoglobulin G glycosylation features, comparing body mass index to other measures of body fat distribution.

Methods

We investigated a sample of 637 community-based 45–69?year olds, with mixed phenotypes, residing in Busselton, Western Australia. Body mass index and the waist-to-hip and waist-to-height ratios were calculated using anthropometry, while dual-energy x-ray absorptiometry was performed to gain an accurate measure of total and area specific body fat. Serum immunoglobulin GN-glycans were analysed by ultra-performance liquid chromatography.

Results

Twenty-two N-glycan peaks were found to be associated with at least one of the fat measures. While the previous association of body mass index to agalactosylated immunoglobulin G was replicated, measures of central adiposity explained the most variation in the immunoglobulin G glycome.

Conclusion

Central adiposity is associated with an increased pro-inflammatory fraction of immunoglobulin G, suggesting that the android/gynoid ratio or waist-to-height ratio instead be considered when controlling for adiposity in immunoglobulin G glycome biomarker studies.  相似文献   

18.

Objective

To investigate role of β-catenin and lncRNA MALAT1/miR-217 axis to converge into the regulation of ZEB-1 in hepatocyte growth factor (HGF)-induced hepatocytes differentiated from bone marrow mesenchymal stem cells (BM-MSCs).

Methods

BM-MSCs were isolated and HGF was used to induce the differentiation of BM-MSCs into hepatocytes. HSC-T6 cells, BRL-3?A cells and differentiated BM-MSCs were treated by lipopolysaccharide(LPS). shRNAs were used to silence β-catenin and recombinant plasmids were used to over-express ZEB1. Measurement of cell viability was conducted using MTT assay and Hoechst 33342 staining. RNA immunoprecipitation (RIP) assay was used to determine binding of miR-217-3p and MALAT1.

Results

BM-MSCs successfully differentiated into hepatocytes by HGF treatment. Expression of β-catenin, ZEB-1 and TERT was up-regulated to a higher level in hepatocytes differentiated from BM-MSCs than HSC-T6 cells and BRL-3?A cells after LPS stimulation. When β-catenin was knocked down in all cell lines, expression of β-catenin, ZEB-1 and TERT was significantly decreased as well as telomerase activity. While when ZEB1 was over-expressed, expression of TERT and telomerase activity was all significantly up-regulated. In hepatocytes differentiated from BM-MSCs, miR-217 was down-regulated and lncRNA MALAT1 was up-regulated. RIP analysis showed MALAT1 was physically associated with miR-217 and might function in the regulation of ZEB-1, further enhancing the expression of TERT so as to augment telomerase activity.

Conclusion

We successfully used HGF to mediate differentiation of BM-MSCs into hepatocytes, and found that β-catenin-coordinated MALAT1/miR-217 axis could up-regulate expression of ZEB-1 and further enhanced the telomerase activity through regulation of TERT in BM-MSCs differentiating into hepatocytes.  相似文献   

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