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1.
Arife Ulas Fatma Paksoy Turkoz Kamile Silay Saadet Tokluoglu Nilufer Avci Berna Oksuzoglu Necati Alkis 《PloS one》2014,9(12)
Purpose
We aimed to establish a laboratory prognostic index (LPI) in advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival.Patients and Methods
The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC), lactate dehydrogenase (LDH), albumin, calcium, and alkaline phosphatase (ALP), based on the results of a Cox regression analysis. The patients were classified into 3 LPI groups as follows: LPI 0: normal; LPI 1: one abnormal laboratory finding; and LPI 2: at least 2 abnormal laboratory findings.Results
The median follow up period was 44 months; the median overall survival (OS) and median progression-free survival (PFS) were 11 and 6 months, respectively. A multivariate analysis revealed that the following could be used as independent prognostic factors: an Eastern Cooperative Oncology Group performance status score (ECOG PS) ≥2, a high LDH level, serum albumin <3 g/dL, serum calcium>10.5 g/dL, number of metastases>2, presence of liver metastases, malignant pleural effusion, or receiving chemotherapy ≥4 cycles. The 1-year OS rates according to LPI 0, LPI 1, and LPI 2 were 54%, 34%, and 17% (p<0.001), respectively and 6-month PFS rates were 44%, 27%, and 15% (p<0.001), respectively. The LPI was a significant predictor for OS (Hazard Ratio (HR): 1.41; 1.05–1.88, p<0.001) and PFS (HR: 1.48; 1.14–1.93, p<0.001).Conclusion
An LPI is an inexpensive, easily accessible and independent prognostic index for advanced NSCLC and may be helpful in making individualized treatment plans and predicting survival rates when combined with clinical parameters. 相似文献2.
Aim
The benefit of nucleot(s)ide analogues (NA) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative treatment has been widely debated due to the relatively weak evidence. The objective of this systematic review was to evaluate the effect of NA on recurrence and survival after curative treatment of HBV-HCC.Methods
A systematic electronic search was performed. All controlled trials comparing NA versus placebo or no treatment were considered for inclusion. Results were expressed as Hazard Ratio for recurrence and survival with 95% confidence intervals using RevMan 5.2.Results
We included 13 trials with 6350 patients. There were significant improvements for recurrence-free survival (HR 0.66, 95% CI 0.54–0.80; p<0.0001) and overall survival (HR 0.56, 95% CI 0.43–0.73; p<0.0001) in the adjuvant NA group compared with the control group. Sensitivity analyses confirmed the robustness of the results. There were no serious adverse effects being reported. Lamivudine resistance was from 28.6% to 37.5% but could be rescued by other types of NA or combination therapy.Conclusion
Our study suggested benefits of adjuvant NA therapy following curative treatment of HBV-HCC. Since the great proven efficacy of NA in improving clinical and viral parameters besides HCC, further studies should be focused on broadening the indications for NA therapy after curative treatment of HBV-HCC. 相似文献3.
Emer Caffrey Helen Ingoldsby Deirdre Wall Mark Webber Kate Dinneen Laura S. Murillo Celine Inderhaug John Newell Sanjeev Gupta Grace Callagy 《PloS one》2013,8(12)
Background
Dicer, an RNase III-type endonuclease, is the key enzyme involved in RNA interference and microRNA pathways. Aberrant expression of Dicer is reported in several human cancers. Our aim was to assess the prognostic role of Dicer in breast cancer.Methods
The entire series comprised 666 invasive breast cancers (IBCs), 480 DCIS cases (397 associated with IBC and 83 pure DCIS) and 305 lymph node metastases. Cytoplasmic Dicer expression by immunohistochemistry was scored as negative (no staining) and positive (weak, moderate or strong staining).Results
Dicer staining was assessable in 446 IBC, 128 DCIS and 101 lymph node metastases. Expression of Dicer was observed in 33% (145/446) of IBCs, 34% (44/128) of DCIS and 57% (58/101) of lymph node metastases. Dicer expression was increased in nodal metastases compared to primary tumours (p<0.001); and was associated with ER negativity (p<0.001), HER2 positivity (p<0.001), high Ki67 labeling index (p<0.001) and expression of basal-like biomarkers (p = 0.002). Dicer positivity was more frequent in the HER2 overexpressing (p<0.001) and basal-like (p = 0.002) subtypes compared to luminal A subtype. Dicer expression was associated with reduced overall survival (OS) on univariate analysis (p = 0.058) and remained an independent predictor of OS on multivariate analysis (HR 2.84, 95% CI 1.43–5.62, p = 0.003), with nodal status (HR 2.61, 95% CI 1.18–5.80, p = 0.018) and PR (HR 0.28, 95% CI 0.13–0.59, p = 0.001). Further, moderate or strong expression of Dicer was associated with improved disease-free survival in the HER2-overexpressing subtype compared to negative or weak expression (p = 0.038).Conclusion
Deregulated Dicer expression is associated with aggressive tumour characteristics and is an independent prognostic factor for OS. Our findings suggest that Dicer is an important prognostic marker in breast cancer and that its prognostic role may be subtype specific. 相似文献4.
Lei Zeng Yun-Ming Tian Ying Huang Xue-Ming Sun Feng-Hua Wang Xiao-Wu Deng Fei Han Tai-Xiang Lu 《PloS one》2014,9(9)
Purpose
The purpose of this retrospective study was to identify the independent prognostic factors and optimize the treatment for nasopharyngeal carcinoma (NPC) patients with distant metastasis at initial diagnosis.Methods
A total of 234 patients referred between January 2001 and December 2010 were retrospectively analyzed. Among the 234 patients, 94 patients received chemotherapy alone (CT), and 140 patients received chemoradiotherapy (CRT). Clinical features, laboratory parameters and treatment modality were examined with univariate and multivariate analyses.Results
The median overall survival (OS) time was 22 months (range, 2-125 months), and the 1-year, 2-year, 3-year overall survival rates were 82.2%, 51.3% and 34.1%. The overall response and disease control rates of metastatic lesions after chemotherapy were 56.0% and 89.8%. The factors associated with poor response were karnofsky performance score (KPS) <80, liver metastasis, lactate dehydrogenase (LDH)>245 IU/L, and number of chemotherapy cycles <4. The 3-year OS of patients receiving CRT was higher than those receiving CT alone (48.2% vs. 12.4%, p<0.001). Subgroup analysis showed that significantly improved survival was also achieved by radiotherapy of the primary tumor in patients who achieved complete remission (CR)/partial remission (PR) or stable disease (SD) of metastatic lesions after chemotherapy. Significant independent prognostic factors of OS were KPS, liver metastasis, levels of LDH, and multiple metastases. Treatment modality, response to chemotherapy and chemotherapy cycles were also associated with OS.Conclusion
A combination of radiotherapy and chemotherapy seems to have survival benefits for selected patients with distant metastases at initial diagnosis. Clinical and laboratory characteristics can help to guide treatment selection. Prospective randomized studies are needed to confirm the result. 相似文献5.
Jiwen Cheng Wanli Wang Yingjun Zhang Xi Liu Muxing Li Zheng Wu Zhengwen Liu Yi Lv Bo Wang 《PloS one》2014,9(1)
Background
Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.Methods
Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.Results
Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).Conclusion
The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration. 相似文献6.
Alberto Bouzas-Mosquera Francisco J. Broullón Nemesio álvarez-García Jesús Peteiro Víctor X. Mosquera Alfonso Castro-Beiras 《PloS one》2012,7(9)
Background
Our aim was to assess the association of left ventricular mass with mortality and nonfatal cardiovascular events.Methodology/Principal Findings
Left ventricular mass was measured by echocardiography in 40138 adult patients (mean age 61.1±16.4 years, 52.5% male). The primary endpoint was all-cause mortality. Secondary endpoints included nonfatal myocardial infarction and nonfatal stroke. During a mean follow-up period of 5.6±3.9 years, 9181 patients died, 901 patients had a nonfatal myocardial infarction, and 2139 patients had a nonfatal stroke. Cumulative 10-year mortality was 26.8%, 31.9%, 37.4% and 46.4% in patients with normal, mildly, moderately and severely increased left ventricular mass, respectively (p<0.001). Ten-year rates of nonfatal myocardial infarction and stroke ranged from 3.2% and 6.7% in patients with normal left ventricular mass to 5.3% and 12.7% in those with severe increase in left ventricular mass, respectively. After multivariate adjustment, left ventricular mass remained an independent predictor of all-cause mortality (hazard ratio [HR] per 100 g increase 1.21, 95% confidence interval [CI] 1.14–1–27, p<0.001 in women, and HR 1.09, 95% CI 1.04–1–13, p<0.001 in men), myocardial infarction (HR 1.60, 95% CI 1.31–1.94, p<0.001 in women and HR 1.15, 95% CI 1.02–1.29, p = 0.019 in men) and stroke (HR 1.26, 95% CI 1.13–1.40, p<0.001 in women and HR 1.19, 95% CI 1.09–1.30, p<0.001 in men).Conclusions/Significance
Left ventricular mass has a graded and independent association with all-cause mortality, myocardial infarction and stroke. 相似文献7.
Rebecca K?rner Klaus-Dieter Preuss Natalie Fadle Darius Madjidi Frank Neumann Lennart Bergeler Stefan Gr?ber Cornelia S. L. Müller Frank Grünhage Michael Pfreundschuh Frank Lammert Thomas Vogt Claudia Pf?hler 《PloS one》2013,8(3)
Background
Autoantibodies against CD28 have been found in patients with autoimmune and atopic diseases. These antibodies may act as superagonists and activate T cells but may also be antagonistic or induce immunosuppressive effects by activating regulatory T cells. Autoimmunity in melanoma patients has been discussed controversially.Objective
We investigated 230 melanoma patients for the occurrence of CD28 antibodies and the effect of the latter on overall and progress-free survival.Methods
We constructed an ELISA assay to measure CD28 serum antibodies. 230 patients with melanoma and a control-group of 625 patients consistent of 212 patients with virus hepatitis b or c, 149 patients with allergies, 78 patients with psoriasis, 46 patients with plasmocytoma and 140 healthy blood donors were investigated for the occurrence of CD28 antibodies.Results
CD28 abs occur at a higher percentage in patients with melanoma and in patients with viral hepatitis than in other groups investigated (p<0.001). Occurrence of CD28 abs is significantly higher in patients receiving interferons independent from the underlying disease (p<0.001). In vitro CD28 serum antibodies have an inhibitory effect on the CD28 receptor as they lead to reduced stimulation of Jurkat cells. Presence of CD28 was correlated with a higher risk of dying from melanoma (p = 0.043), but not with a significantly shortened overall survival or progression-free survival.Conclusion
Interferon therapy appears to induce the production of CD28 abs. In light of reports that these CD28 abs induce immunosuppressive Tregs and – as our data show – that they are inhibitors of CD28 receptor mediated stimulation, the continuation of therapies with interferons in melanoma patients developing CD28 antibodies should be critically reconsidered, since our data indicate a worse outcome of patients with CD28 abs. 相似文献8.
Henry E. Wang Nathan I. Shapiro Russell Griffin Monika M. Safford Suzanne Judd George Howard 《PloS one》2012,7(10)
Background
We sought to determine the associations between baseline chronic medical conditions and future risk of sepsis.Methods
Longitudinal cohort study using the 30,239 community-dwelling participants of the REGARDS cohort. We determined associations between baseline chronic medical conditions and incident sepsis episodes, defined as hospitalization for an infection with the presence of infection plus two or more systemic inflammatory response syndrome criteria.Results
Over the mean observation time of 4.6 years (February 5, 2003 through October 14, 2011), there were 975 incident cases of sepsis. Incident sepsis episodes were associated with older age (p<0.001), white race (HR 1.39; 95% CI: 1.22–1.59), lower education (p<0.001) and income (p<0.001), tobacco use (p<0.001), and alcohol use (p = 0.02). Incident sepsis episodes were associated with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05–2.86), peripheral artery disease (2.16; 1.58–2.95), chronic kidney disease (1.99; 1.73–2.29), myocardial infarction 1.79 (1.49–2.15), diabetes 1.78 (1.53–2.07), stroke 1.67 (1.34–2.07), deep vein thrombosis 1.63 (1.29–2.06), coronary artery disease 1.61 (1.38–1.87), hypertension 1.49 (1.29–1.74), atrial fibrillation 1.48 (1.21–1.81) and dyslipidemia 1.16 (1.01–1.34). Sepsis risk increased with the number of chronic medical conditions (p<0.001).Conclusions
Individuals with chronic medical conditions are at increased risk of future sepsis events. 相似文献9.
Young Ju Lee Kyung Chul Moon Chang Wook Jeong Cheol Kwak Hyeon Hoe Kim Ja Hyeon Ku 《PloS one》2014,9(9)
Purpose
To investigate the prognostic significance of squamous and/or glandular differentiation in urothelial carcinoma (UC).Materials and Methods
Among 800 consecutive patients who underwent radical cystectomy or nephroureterectomy at our institution from January 1990 to December 2010, 696 patients were included for the analysis. Clinicopathologic variables were compared according to the presence of squamous and/or glandular differentiation and the tumor location.Results
A total of 51 (7.3%) patients had squamous and/or glandular differentiation. Patients with squamous and/or glandular differentiation had higher pathological T stage (p<0.001) and grade (p<0.001) than those with pure form of UC. After the median follow-up of 55.2 months, 84 (24.6%) and 82 (23.1%) died of upper urinary tract UC and UC of bladder, respectively. Patients with squamous and/or glandular differentiation in upper urinary tract UC showed poorer cancer-specific survival (CSS) (p<0.001) and overall survival (OS) (p<0.001) than those with pure form in upper urinary tract UC (p<0.001), but not in UC of bladder (p = 0.178 for CSS and p = 0.172 for OS). On multivariate Cox regression analysis, squamous and/or glandular differentiation was an independent predictor of CSS (hazard ratio [HR] 1.76; 95% confidence interval [CI] 1.08–2.85, p = 0.023), but it was not associated with OS (HR 1.52; 95% CI 1.00–2.32, p = 0.051).Conclusions
The presence of variant histology could be associated with poorer survival outcome in patients with UC. Squamous and/or glandular differentiation is associated with features of biologically aggressive disease and an independent predictor of CSS. 相似文献10.
Tsung-Hsien Lin Wen-Ter Lai Ho-Tsung Hsin Ai-Hsien Li Chun-Li Wang Chi-Tai Kuo Juey-Jen Hwang Fu-Tien Chiang Shu-Chen Chang 《PloS one》2013,8(8)
Background
The efficacy of clopidogrel is inconclusive in the chronic kidney disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD patients are prone to bleeding with antiplatelet therapy. We investigated the efficacy and safety of clopidogrel in patients with ACS and CKD.Methods
In a Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m2. The primary endpoints are the combined outcomes of death, non-fatal myocardial infarction and stroke at 12 months.Results
Overall 949 (33.7%) patients had CKD and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to 3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary endpoint at 12 months (HR 0.42, 95% CI: 0.29–0.60, p<0.01). Cox regression analysis showed that clopidogrel reduced death and primary endpoints for CKD population (HR 0.35, 95% CI: 0.21–0.61 and HR 0.48, 95% CI: 0.30–0.77, respectively, both p<0.01). Patients with clopidogrel(−)/CKD(−), clopidogrel(+)/CKD(+) and clopidogrel(−)/CKD(+) have 2.4, 3.0 and 10.4 fold risk to have primary endpoints compared with those receiving clopidogrel treatment without CKD (all p<0.01). Clopidogrel treatment was not associated with increased in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD population.Conclusion
Clopidogrel could decrease mortality and improve cardiovascular outcomes without increasing risk of bleeding in ACS patients with CKD. 相似文献11.
Pai-Chien Chou Shu-Min Lin Chun-Yu Lo Hao-Cheng Chen Chih-Wei Wang Chun-Liang Chou Chih-Teng Yu Horng-Chyuan Lin Chun-Hua Wang Han-Pin Kuo 《PloS one》2012,7(10)
Background
Current staging system for small cell lung cancer (SCLC) categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion.Methods
We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated.Results
84% (364/432) of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30–3.10), age (HR, 1.04; 95% CI, 1.03–1.06), and extensive stage (HR, 1.39; 95% CI, 1.06–1.84) were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25–0.42) was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001). Among SCLC patients of either limited (median 180 vs. 460, p<0.0001) or extensive (median 125 vs. 207, p<0.0001) stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively.Conclusion
Endobronchial mucosal involvement is an independent prognostic factor for SCLC patients and associated with decreased survival days. 相似文献12.
Tatiana Falcone Vincent Fazio Catherine Lee Barry Simon Kathleen Franco Nicola Marchi Damir Janigro 《PloS one》2010,5(6)
Background
Studies have shown that patients suffering from depression or schizophrenia often have immunological alterations that can be detected in the blood. Others reported a possible link between inflammation, a microgliosis and the blood-brain barrier (BBB) in suicidal patients. Serum S100B is a marker of BBB function commonly used to study cerebrovascular wall function.Methods
We measured levels of S100B in serum of 40 adolescents with acute psychosis, 24 adolescents with mood disorders and 20 healthy controls. Patients were diagnosed according to DSM-IV TR criteria. We evaluated suicidal ideation using the suicidality subscale of the Brief Psychiatric Rating Scale for Children (BPRS-C).Results
Serum S100B levels were significantly higher (p<0.05) and correlated to severity of suicidal ideation in patients with psychosis or mood disorders, independent of psychiatric diagnosis. Patients with a BPRS-C suicidality subscores of 1–4 (low suicidality) had mean serum S100B values +/− SEM of 0.152+/−0.020 ng/mL (n = 34) compared to those with BPRS-C suicidality subscores of 5–7 (high suicidality) with a mean of 0.354+/−0.044 ng/mL (n = 30). This difference was statistically significant (p<0.05).Conclusion
Our data support the use of S100B as an adjunctive biomarker to assess suicidal risk in patients with mood disorders or schizophrenia. 相似文献13.
Matthew C. Tattersall Ronald E. Gangnon Kunal N. Karmali Michael W. Cullen James H. Stein Jon G. Keevil 《PloS one》2013,8(4)
Background
Previous studies have demonstrated gaps in achievement of low-density lipoprotein-cholesterol (LDL-C) goals among U.S. individuals at high cardiovascular disease risk; however, recent studies in selected populations indicate improvements.Objective
We sought to define the longitudinal trends in achieving LDL-C goals among high-risk United States adults from 1999–2008. Methods We analyzed five sequential population-based cross-sectional National Health and Nutrition Examination Surveys 1999–2008, which included 18,656 participants aged 20–79 years. We calculated rates of LDL-C goal achievement and treatment in the high-risk population.Results
The prevalence of high-risk individuals increased from 13% to 15.5% (p = 0.046). Achievement of LDL-C <100 mg/dL increased from 24% to 50.4% (p<0.0001) in the high-risk population with similar findings in subgroups with (27% to 64.8% p<0.0001) and without (21.8% to 43.7%, p<0.0001) coronary heart disease (CHD). Achievement of LDL-C <70 mg/dL improved from 2.4% to 17% (p<0.0001) in high-risk individuals and subgroups with (3.4% to 21.4%, p<0.0001) and without (1.7% to 14.9%, p<0.0001) CHD. The proportion with LDL-C ≥130 mg/dL and not on lipid medications decreased from 29.4% to 18% (p = 0.0002), with similar findings among CHD (25% to 11.9% p = 0.0013) and non-CHD (35.8% to 20.8% p<0.0001) subgroups.Conclusion
The proportions of the U.S. high-risk population achieving LDL-C <100 mg/dL and <70 mg/dL increased over the last decade. With 65% of the CHD subpopulation achieving an LDL-C <100 mg/dL in the most recent survey, U.S. LDL-C goal achievement exceeds previous reports and approximates rates achieved in highly selected patient cohorts. 相似文献14.
Benjamin Weide Christine Faller Margrit Els?sser Petra Büttner Annette Pflugfelder Ulrike Leiter Thomas Kurt Eigentler Jürgen Bauer Friedegund Meier Claus Garbe 《PloS one》2013,8(6)
Background
A direct comparison of prognosis between patients with regional lymph node metastases (LNM) detected synchronously with the primary melanoma (primary LNM), patients who developed their first LNM subsequently (secondary LNM) and those with initial LNM in melanoma with unknown primary site (MUP) is missing thus far.Patients and Methods
Survival of 498 patients was calculated from the time point of the first macroscopic LNM using Kaplan Meier and multivariate Cox hazard regression analysis.Results
Patients with secondary LNM (HR = 0.67; p = 0.009) and those with initial LNM in MUP (HR = 0.45; p = 0.008) had a better prognosis compared to patients with primary LNM (median survival time 52 and 65 vs. 24 months, respectively). A high number of involved nodes, the presence of in-transit/satellite metastases and male gender had an additional independent unfavourable effect.Conclusions
Survival of patients with LNM in MUP and with secondary LNM is similar and considerably more favourable compared to those with primary LNM. This difference needs to be considered during patient counselling and for stratification purposes in clinical trials. The assumption of an immune privilege of patients with MUP which is responsible for rejection of the primary melanoma, and results in a favourable prognosis is not supported by our data. 相似文献15.
Emil Ivan Nigel J. Crowther Eugene Mutimura Lawrence Obado Osuwat Saskia Janssen Martin P. Grobusch 《PLoS neglected tropical diseases》2013,7(8)
Background
Within sub-Saharan Africa, helminth and malaria infections cause considerable morbidity in HIV-positive pregnant women and their offspring. Helminth infections are also associated with a higher risk of mother-to-child HIV transmission. The aim of this study was to determine the prevalence of, and the protective and risk factors for helminth and malaria infections in pregnant HIV-positive Rwandan women receiving anti-retroviral therapy (ART).Methodology and principle findings
Pregnant females (n = 980) were recruited from health centres in rural and peri-urban locations in the central and eastern provinces of Rwanda. Helminth infection was diagnosed using the Kato Katz method whilst the presence of Plasmodium falciparum was identified from blood smears. The prevalence of helminth infections was 34.3%; of malaria 13.3%, and of co-infections 6.6%. Helminth infections were more common in rural (43.1%) than peri-urban (18.0%; p<0.0005) sites. A CD4 count ≤350 cells/mm3 was associated with a higher risk of helminth infections (odds ratio, 3.39; 95% CIs, 2.16–5.33; p<0.0005) and malaria (3.37 [2.11–5.38]; p<0.0005) whilst helminth infection was a risk factor for malaria infection and vice versa. Education and employment reduced the risk of all types of infection whilst hand washing protected against helminth infection (0.29 [0.19–0.46]; p<0.0005);). The TDF-3TC-NVP (3.47 [2.21–5.45]; p<0.0005), D4T-3TC-NVP (2.47 [1.27–4.80]; p<0.05) and AZT-NVP (2.60 [1.33–5.08]; p<0.05) regimens each yielded higher helminth infection rates than the AZT-3TC-NVP regimen. Anti-retroviral therapy had no effect on the risk of malaria.Conclusion/significance
HIV-positive pregnant women would benefit from the scaling up of de-worming programs alongside health education and hygiene interventions. The differential effect of certain ART combinations (as observed here most strongly with AZT-3TC-NVP) possibly protecting against helminth infection warrants further investigation. 相似文献16.
Purpose
Breast cancer remains a major cause of death in women worldwide, and tumor metastasis is the leading cause of death in breast cancer patients after conventional treatment. Chronic inflammation is often related to the occurrence and growth of various malignancies. This study evaluated the prognosis of breast cancer patients based on contributors to the innate immune response: myeloid differentiation primary response 88 (MyD88) and Toll-like receptor 4 (TLR4).Methods
We analyzed data from 205 breast invasive ductal carcinoma (IDC) patients who were treated at the Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, from 2002 to 2006. Overall survival (OS) and disease-free survival (DFS) were compared.Results
In total, 152 patients (74.15%) were disease-free without relapse or metastasis, whereas 53 (25.85%) patients developed recurrence or metastasis. A significant positive correlation was observed between MyD88 and TLR4 expression (p<0.001). Patients with high expression were more likely to experience death and recurrence/metastasis events (p<0.05). Patients with low MyD88 or TLR4 expression levels had better DFS and OS than patients with high expression levels (log-rank test: p<0.001). Patients with low MyD88 and TLR4 expression levels had better DFS and OS than patients with high expression levels of either (log-rank test: p<0.001). In a multivariate analysis, high MyD88 expression was an independent predictive factor for decreased DFS (adjusted HR, 3.324; 95% CI, 1.663–6.641; p = 0.001) and OS (adjusted HR, 4.500; 95% CI, 1.546–13.098; p = 0.006).Conclusions
TLR4-MyD88 signaling pathway activation or MyD88 activation alone may be a risk factor for poor prognosis in breast cancer. Therefore, TLR4-MyD88 signaling pathway activation in tumor biology provides a novel potential target for breast cancer therapy. 相似文献17.
Pascal Meier Emmanouil S. Brilakis Roberto Corti Guido Knapp Mehdi H. Shishehbor Hitinder S. Gurm 《PloS one》2010,5(6)
Background
Saphenous vein grafts develop an aggressive atherosclerotic process and the efficacy of drug eluting stents (DES) in treating saphenous vein graft (SVG) lesions has not been convincingly demonstrated. The aim of this study was to review and analyze the current literature for controlled studies comparing DES versus bare metal stents (BMS) for treatment of SVG stenoses.Methodology/Principal Findings
We searched several scientific databases and conference proceedings up to March 15, 2010 for controlled studies comparing target vessel revascularization (TVR) between DES and BMS. Summary odds ratios (OR) for the primary endpoint TVR and secondary endpoints infarction, stent thrombosis and death were calculated using random-effect models. A total of 29 studies (3 randomized controlled trials RCT) involving 7549 (202 in RCT) patients were included. The need for target vessel revascularization in the DES group tended to be lower compared to BMS for the 3 RCT (OR 0.50 [0.24–1.00]; p = 0.051) and for observational studies (0.62 [0.49–0.79]; p<0.001). There was no significant difference in the risk for myocardial infarction in the RCT (OR 1.25 [0.22–6.99]; p = 0.250) but a lower risk for DES based on the observational studies 0.68 [0.49–0.95]; p = 0.023. The risk for stent thrombosis was found to be non-different in the RCT (OR 0.78 [0.03–21.73], p = 0.885) while it was in favor of DES in the observational studies (0.58 [0.38 – 0.84]; p<0.001). The mortality was not significantly different between DES and BMS in the RCT''s (OR 2.22 [0.17 – 29.50]; p = 0.546) while the observation studies showed a decreased mortality in the DES group (0.69 [0.55–0.85]; p<0.001).Conclusion
DES may decrease TVR rate in treatment of SVG stenoses. No differences in reinfarction rate, stent thrombosis or mortality was found between the DES and BMS groups in the RCT''s while the observational data showed lower risk for myocardial infarction, stent thrombosis and death in the DES group. This may be a result of patient selection bias in the observational studies or represent a true finding that was not the detected in the RCT analysis due to limited statistical power. 相似文献18.
Christopher Fuller Susan Michie Joanne Savage John McAteer Sarah Besser Andre Charlett Andrew Hayward Barry D. Cookson Ben S. Cooper Georgia Duckworth Annette Jeanes Jenny Roberts Louise Teare Sheldon Stone 《PloS one》2012,7(10)
Introduction
Achieving a sustained improvement in hand-hygiene compliance is the WHO’s first global patient safety challenge. There is no RCT evidence showing how to do this. Systematic reviews suggest feedback is most effective and call for long term well designed RCTs, applying behavioural theory to intervention design to optimise effectiveness.Methods
Three year stepped wedge cluster RCT of a feedback intervention testing hypothesis that the intervention was more effective than routine practice in 16 English/Welsh Hospitals (16 Intensive Therapy Units [ITU]; 44 Acute Care of the Elderly [ACE] wards) routinely implementing a national cleanyourhands campaign). Intervention-based on Goal & Control theories. Repeating 4 week cycle (20 mins/week) of observation, feedback and personalised action planning, recorded on forms. Computer-generated stepwise entry of all hospitals to intervention. Hospitals aware only of own allocation. Primary outcome: direct blinded hand hygiene compliance (%).Results
All 16 trusts (60 wards) randomised, 33 wards implemented intervention (11 ITU, 22 ACE). Mixed effects regression analysis (all wards) accounting for confounders, temporal trends, ward type and fidelity to intervention (forms/month used).Intention to Treat Analysis
Estimated odds ratio (OR) for hand hygiene compliance rose post randomisation (1.44; 95% CI 1.18, 1.76;p<0.001) in ITUs but not ACE wards, equivalent to 7–9% absolute increase in compliance.Per-Protocol Analysis for Implementing Wards
OR for compliance rose for both ACE (1.67 [1.28–2.22]; p<0.001) & ITUs (2.09 [1.55–2.81];p<0.001) equating to absolute increases of 10–13% and 13–18% respectively. Fidelity to intervention closely related to compliance on ITUs (OR 1.12 [1.04, 1.20];p = 0.003 per completed form) but not ACE wards.Conclusion
Despite difficulties in implementation, intention-to-treat, per-protocol and fidelity to intervention, analyses showed an intervention coupling feedback to personalised action planning produced moderate but significant sustained improvements in hand-hygiene compliance, in wards implementing a national hand-hygiene campaign. Further implementation studies are needed to maximise the intervention’s effect in different settings.Trial Registration
Controlled-Trials.com ISRCTN65246961 相似文献19.
Elahe A. Mostaghel Andrew Morgan Xiaotun Zhang Brett T. Marck Jing Xia Rachel Hunter-Merrill Roman Gulati Stephen Plymate Robert L. Vessella Eva Corey Celestia S. Higano Alvin M. Matsumoto R. Bruce Montgomery Peter S. Nelson 《PloS one》2014,9(10)
Background
Factors influencing differential responses of prostate tumors to androgen receptor (AR) axis-directed therapeutics are poorly understood, and predictors of treatment efficacy are needed. We hypothesized that the efficacy of inhibiting DHT ligand synthesis would associate with intra-tumoral androgen ratios indicative of relative dependence on DHT-mediated growth.Methods
We characterized two androgen-sensitive prostate cancer xenograft models after androgen suppression by castration in combination with the SRD5A inhibitor, dutasteride, as well as a panel of castration resistant metastases obtained via rapid autopsy.Results
In LuCaP35 tumors (intra-tumoral T:DHT ratio 2∶1) dutasteride suppressed DHT to 0.02 ng/gm and prolonged survival vs. castration alone (337 vs.152 days, HR 2.8, p = 0.0015). In LuCaP96 tumors (T:DHT 10∶1), survival was not improved despite similar DHT reduction (0.02 ng/gm). LuCaP35 demonstrated higher expression of steroid biosynthetic enzymes maintaining DHT levels (5-fold higher SRD5A1, 41 fold higher, 99-fold higher RL-HSD, p<0.0001 for both), reconstitution of intra-tumoral DHT (to ∼30% of untreated tumors), and ∼2 fold increased expression of full length AR. In contrast, LuCaP96 demonstrated higher levels of steroid catabolizing enzymes (6.9-fold higher AKR1C2, 3000-fold higher UGT2B15, p = 0.002 and p<0.0001 respectively), persistent suppression of intra-tumoral DHT, and 6–8 fold induction of full length AR and the ligand independent V7 AR splice variant. Human metastases demonstrated bio-active androgen levels and AR full length and AR splice-variant expression consistent with the range observed in xenografts.Conclusions
Intrinsic differences in basal steroidogenesis, as well as variable expression of full length and splice-variant AR, associate with response and resistance to pre-receptor AR ligand suppression. Expression of steroidogenic enzymes and AR isoforms may serve as potential biomarkers of sensitivity to potent AR-axis inhibition and should be validated in additional models. 相似文献20.
《PloS one》2014,9(12)