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Sample records for major prognostic impact

  1. PD-L1 expression and prognostic impact in glioblastoma

    PubMed Central

    Nduom, Edjah K.; Wei, Jun; Yaghi, Nasser K.; Huang, Neal; Kong, Ling-Yuan; Gabrusiewicz, Konrad; Ling, Xiaoyang; Zhou, Shouhao; Ivan, Cristina; Chen, Jie Qing; Burks, Jared K.; Fuller, Greg N.; Calin, George A.; Conrad, Charles A.; Creasy, Caitlin; Ritthipichai, Krit; Radvanyi, Laszlo; Heimberger, Amy B.

    2016-01-01

    Background Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. Methods Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. Results The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%–86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. Conclusions The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome. PMID:26323609

  2. Prognostic impact of microscopic positive margin in gastric cancer patients.

    PubMed

    Nagata, Tomoyuki; Ichikawa, Daisuke; Komatsu, Shuhei; Inoue, Koji; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Sakakura, Chohei; Otsuji, Eigo

    2011-11-01

    Complete resection with negative surgical margins has been a long-held surgical philosophy based on the concept that even minimal remaining cancer cells will develop recurrences. This study investigated the clinical significance of microscopic positive margin on the outcome of patients with gastric cancers. The relationships between the margin status and other clinicopathologic factors were examined in gastric cancer patients undergoing gastrectomy, and then the prognostic impact of the margin status was evaluated by univariate and multivariate analysis. The microscopic positive margin was identified in 23 patients (2.8%) by standard H&E staining. The positive margin showed a strong correlation significantly with tumor size (P < 0.05). Microscopic positive margin was found to be a significant prognostic factor on univariate analysis (5-year survival rate 51.9% vs. 82.2%, P < 0.0001), as well as multivariate analysis (risk ratio 3.24, 95% CI: 1.24-6.50, P < 0.01). Detailed analysis of margin status demonstrated that patients with positive margin in a deep site and/or in multiple layers showed poor survival. Microscopic positive margin was found to be an independent prognostic factor in gastric cancer patients. The status of the surgical margin might provide useful information for selecting additional treatments and performing intensive follow-up. Copyright © 2011 Wiley Periodicals, Inc.

  3. IDH mutations: genotype-phenotype correlation and prognostic impact.

    PubMed

    Wang, Xiao-Wei; Ciccarino, Pietro; Rossetto, Marta; Boisselier, Blandine; Marie, Yannick; Desestret, Virginie; Gleize, Vincent; Mokhtari, Karima; Sanson, Marc; Labussière, Marianne

    2014-01-01

    IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated--which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

  4. Prognostic impact of metallothionein on oral squamous cell carcinoma.

    PubMed

    Cardoso, Sérgio V; Barbosa, Hugo M; Candellori, Ignez M; Loyola, Adriano M; Aguiar, Maria Cássia F

    2002-08-01

    Metallothionein (MT), a low-molecular-weight protein with high cysteine content, seems to be related to neoplastic resistance to oncologic treatment and therefore has been studied as a prognostic factor for a variety of human malignant tumors. MT overexpression in neoplasms of ectodermal origin is usually associated with a poor prognosis. MT expression was evaluated in 60 samples of oral squamous cell carcinoma by immunohistochemistry to study its prognostic influence on oral cancer. Possible associations of MT immunoexpression were also investigated with respect to clinical stage (TNM), histological grading, and proliferation index (Ki-67) of the lesions. No significant statistical correlation was observed among these variables. The impact on overall survival was assessed by uni and multivariate statistical tests. Mean MT labeling index was 60%. High MT labeling indexes (over 76%) predicted shorter survival in univariate statistical analysis. In multivariate analysis, MT labeling index and clinical stage were independent prognostic factors. MT overexpression in oral squamous cell carcinoma seems to be related to a worse prognosis for patients.

  5. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  6. Prognostic impact of HER-2 Subclonal Amplification in breast cancer.

    PubMed

    Di Oto, Enrico; Brandes, Alba A; Cucchi, Maria C; Foschini, Maria P

    2017-06-02

    The presence of a limited number of cells with HER-2 amplification (Subclonal Amplification) in breast carcinomas is occasionally encountered, but its prognostic impact is poorly known. The purpose of this study is to evaluate the prognostic impact of HER-2 Subclonal Amplification in a retrospective series of breast cancers. Accordingly, 81 consecutive breast carcinomas showing HER-2 Subclonal Amplification were obtained from the histology files (case series). These cases were subdivided into two groups: (a) those cases in which the HER-2 Subclonal Amplification was consonant to the accepted criteria for amplification, showing clusters of amplified cells, and (b) those cases with rare HER-2 Subclonal Amplification that did not reflect the accepted criteria for amplification, showing scattered amplified cells only. The incidence of metastases and late recurrences of the case series was compared with a series composed of 109 consecutive cases, being HER-2 homogeneous (comprising 14 Amplified and 95 Non-Amplified cases), matched for grade and stage (control series). It appeared that cases showing Subclonal Amplification had an incidence of metastases intermediate between the cases Amplified and Non-Amplified. Specifically, Subclonal Amplification with clustered cells had a lower incidence of metastases than Amplified cases (12.9 versus 21.4%). On the contrary, Subclonal Amplification with scattered cells showed an incidence of metastases higher than Non-Amplified cases (14 versus 9.47%). In addition, patients Subclonal Amplification with clustered cells, who were treated with the specific monoclonal antibody, had a lower incidence of metastases than patients showing Subclonal Amplification with scattered cells, who did not receive target therapy. These data, together with those recently published, indicate that Subclonal Amplification has an impact on prognosis and should be taken into consideration to correctly plan the treatment of breast cancer patients.

  7. Impact of prognostic nutritional index on long-term outcomes in patients with breast cancer.

    PubMed

    Mohri, Tomomi; Mohri, Yasuhiko; Shigemori, Tsunehiko; Takeuchi, Kenji; Itoh, Yoshiyuki; Kato, Toshio

    2016-06-27

    Prognostic nutritional index has been shown to be a prognostic marker for various solid tumors. However, few studies have investigated the impact of the prognostic nutritional index on survival of patients with breast cancer. The aim of this study was to investigate the impact of the prognostic nutritional index on the long-term outcomes in patients with breast cancer. This study reviewed the medical records of 212 patients with breast cancer who underwent mastectomy. The prognostic nutritional index was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm(3)). Receiver operating characteristic curve analysis was performed to determine the cutoff value of the prognostic nutritional index. The survival curves were calculated by the Kaplan-Meier method. Differences between the curves were analyzed by the log-rank test. Multivariate Cox proportional hazard model was used to evaluate the prognostic significance of prognostic nutritional index in patients with breast cancer. The mean prognostic nutritional index just before the operation was 51.9, and the median follow-up after surgery was 47.7 months. The optimal cutoff value of the prognostic nutritional index for predicting the overall survival was 52.8 from the receiver operating characteristic curve analysis. The 5-year overall survival rate was 98.3 % in the prognostic nutritional index >52.8 and 92.0 % in the prognostic nutritional index <52.8 (P = 0.013). In the multivariate analysis, a low prognostic nutritional index was an independent predictor for poor overall survival (HR, 5.88; 95 % CI, 1.13-108.01; P = 0.033). The prognostic nutritional index is a simple and useful marker for predicting the long-term outcomes of breast cancer patients, independent of the tumor stage.

  8. Lunar highlands breccias generated by major impacts

    NASA Technical Reports Server (NTRS)

    James, O. B.

    1977-01-01

    The processes that may have been involved in the formation of most of the major types of lunar breccias are discussed. Some of the types of highlands breccias that may have originated in large impacts are identified.

  9. Diffuse sclerosing variant of papillary thyroid carcinoma: major genetic alterations and prognostic implications.

    PubMed

    Joung, Ji Y; Kim, Tae H; Jeong, Dae J; Park, Sun-Mi; Cho, Yoon Y; Jang, Hye W; Jung, Yoon Y; Oh, Young L; Yim, Hyun S; Kim, Yoo-Li; Chung, Jae H; Ki, Chang-Seok; Kim, Sun W

    2016-07-01

    Diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is an uncommon variant of PTC, and its prognostic significance remains controversial. The aim of this study was to investigate the major genetic alterations of DSV-PTC and their prognostic implications. We included 37 patients with DSV-PTC who underwent thyroid surgery and had formalin-fixed paraffin-embedded samples. We tested for a panel of genetic alterations, including BRAF(V) (600E) , NRAS codon 61, HRAS codon 12/13/61 and KRAS codon 12/13 point mutations as well as RET/PTC1, RET/PTC3 and PAX8/PPARγ rearrangements using reverse transcription real-time polymerase chain reaction (PCR). All genetic alterations found on PCR were confirmed by Sanger sequencing. Associations between the identified genetic alterations and clinicopathological characteristics were evaluated. Among 37 cases of DSV-PTC, 17 were positive for RET/PTC1 (46%), six for RET/PTC3 (16%) and nine for BRAF(V) (600E) (24%). All mutations/rearrangements were mutually exclusive. The remaining five cases had none of the above genetic alterations. DSV-PTC with RET/PTC3 rearrangement was associated with advanced-stage disease, including T4 and distant metastasis (P < 0.05). Patients with RET/PTC3 showed a higher frequency of persistent disease (P < 0.01). In contrast, DSV-PTC with RET/PTC1 was associated with a higher prevalence of disease remission (P < 0.05) and coexistent Hashimoto's thyroiditis (P < 0.01). Taken together, RET/PTC rearrangement was the major genetic alteration seen in patients with DSV-PTC, and the RET/PTC3 rearrangement was associated with advanced stage at diagnosis and poor clinical outcome. © 2015 John Wiley & Sons Ltd.

  10. Prognostic impact of stress testing in coronary artery disease

    SciTech Connect

    Severi, S.; Michelassi, C. )

    1991-05-01

    Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and {sup 201}Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.47 references.

  11. Prognostic impact of tumour-associated B cells and plasma cells in epithelial ovarian cancer.

    PubMed

    Lundgren, Sebastian; Berntsson, Jonna; Nodin, Björn; Micke, Patrick; Jirström, Karin

    2016-04-06

    The critical role of the immune system in controlling cancer progression has become evident and immune modulatory therapy is now approved for clinical use. However, while the majority of studies on the inflammatory tumour microenvironment have focused on the cellular immune response, in particular the prognostic and predictive role of various T cell infiltrates, the role of the humoral immune response in this context has long been overlooked. This study aimed to investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in epithelial ovarian cancer (EOC). Immunohistochemical expression of immunoglobulin kappa C (IGKC), CD20 and CD138 was analysed in tissue microarrays with tumours from 154 incident cases of EOC from two pooled prospective population-based cohorts. Subsets of corresponding benign-appearing fallopian tubes (n = 38) and omental metastases (n = 33) were also analysed. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of immune-cell specific IGKC, CD20 and CD138 expression on overall survival and ovarian cancer-specific survival. High IGKC expression correlated significantly with expression of CD20 (p = 0.001) and CD138 (p = 0.035). Expression of IGKC as well as CD138 was significantly higher in primary tumours than in fallopian tubes (p = 0.004 and p = 0.001, respectively). High CD20 and CD138 expression correlated significantly with high tumour grade (p = 0.032 and p = 0.030, respectively). CD20 and IGKC expression was not prognostic but univariable Cox regression analysis revealed high CD138 expression to correlate with a significantly reduced overall survival (HR = 2.20; 95 % CI 1.34-3.55; p-0.001) as well as ovarian cancer-specific survival (HR = 1.95; 95 % CI 1.28-2.98; p = 0.002). The prognostic impact was independent of established clinical parameters (age, grade, clinical stage) as shown in multivariable analysis (HR = 2.28; 95 % CI 1.39-3.75; p = 0.001). In

  12. Incremental prognostic value of computed tomography in stroke: rationale and design of the IMPACTS study.

    PubMed

    Lee, Ji Won; Hur, Jin; Choi, Sang Il; Chun, Eun Ju; Kang, Joon-Won; Jin, Gong Yong; Kim, Eun Young; Yong, Hwan Seok; Kang, Eun-Ju; Han, Kyunghwa; Lee, Hoon-Suk; Choi, Byoung Wook

    2016-06-01

    This study was designed to determine the prognostic value of coronary computed tomography angiography (CCTA) in ischemic stroke patients and to identify any incremental risk stratification benefits of CCTA findings compared with coronary artery calcium scoring (CACS) and traditional Framingham risk scores (FRS) in ischemic stroke patients without chest pain. IMPACTS is a prospective, multicenter, observational cohort study in which at least seven centers in Korea will participate. All participants will be enrolled in this study after providing informed consent. Nine hundred total ischemic stroke patients without chest pain will be enrolled and will undergo CACS and CCTA. All participants will be followed-up for a minimum of 24 months to determine the endpoints. The primary endpoint will be occurrence of major adverse cardiovascular events (MACEs), defined as all-cause mortality, cardiovascular death, myocardial infarction, or cardiovascular events requiring hospitalization and revascularization either by percutaneous coronary intervention or by coronary artery bypass graft after 90 days of index testing during the follow-up period. Patient enrollment should be completed within 2.5 years. We plan to analyze and identify the CCTA predictors of MACEs. In addition, we will compare several models used to assess independent relationships between the variables and MACEs using a shared frailty model and therefore determine the incremental prognostic value of CCTA findings compared with either the CACS or FRS. The results of IMPACTS will provide valuable information for risk stratification with CCTA in ischemic stroke patients without chest pain.

  13. Prognostic Impact of Autophagy Biomarkers for Cutaneous Melanoma

    PubMed Central

    Tang, Diana Y. L.; Ellis, Robert A.; Lovat, Penny E.

    2016-01-01

    Prognosis and survival for malignant melanoma is highly dependent on early diagnosis and treatment. While the American Joint Committee on Cancer (AJCC) criterion provides a means of staging melanomas and guiding treatment approaches, it is unable to identify the risk of disease progression of early stage tumors or provide reliable stratification for novel adjuvant therapies. The demand for credible prognostic/companion biomarkers able to identify high-risk melanoma subgroups as well as guide more effective personalized/precision-based therapy is therefore of paramount importance. Autophagy, the principle lysosomal-mediated process for the degradation/recycling of cellular debris, is a hot topic in cancer medicine, and observations of its deregulation in melanoma have brought its potential as a prognostic biomarker to the forefront of current research. Key regulatory proteins, including Atg8/microtubule-associated light chain 3 (LC3) and BECN1 (Beclin 1), have been proposed as potential prognostic biomarkers. However, given the dynamic nature of autophagy, their expression in vitro does not translate to their use as a prognostic biomarker for melanoma in vivo. We have recently identified the expression levels of Sequestosome1/SQSTM1 (p62) and activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) as novel independent prognostic biomarkers for early stage melanomas. While increasing followed by subsequent decreasing levels of p62 expression reflects the paradoxical role of autophagy in melanoma, expression levels additionally define a novel prognostic biomarker for AJCC stage II tumors. Conversely, loss of AMBRA1 in the epidermis overlying primary melanomas defines a novel prognostic biomarker for AJCC stage I tumors. Collectively, the definition of AMBRA1 and p62 as prognostic biomarkers for early stage melanomas provides novel and accurate means through which to identify tumors at risk of disease progression, facilitating earlier patient therapeutic

  14. Lunar highlands breccias generated by major impacts

    NASA Technical Reports Server (NTRS)

    James, O. B.

    1974-01-01

    Lunar missions are reported which have returned a variety of different types of breccias. These rocks differ greatly in their mechanisms of formation, source materials, and histories after formation; but all are related in that all were generated by impact processes. The impact processes involved in the formation of several major types of breccias are discussed. Some types that may have originated in large impacts are identified. Such breccias are extremely important. The impacts that formed them penetrated deeply into, and perhaps through the lunar crust and brought up materials that had previously experienced little or no impact modification. Detailed studies of such breccias can permit partial reconstruction of their preimpact source terranes and yield information on the nature of the early lunar crust (and possibly the upper mantle as well).

  15. The Social Impact of Majorities and Minorities.

    ERIC Educational Resources Information Center

    Latane, Bibb; Wolf, Sharon

    1981-01-01

    A new theory of social impact is proposed and related to prior work. Social influences result from forces operating in a social force field. Influence by either a majority or a minority is a multiplicative function of the strength, immediacy, and number of its members. Conformity and innovation are compared. (Author/RD)

  16. Histopathological Significance and Prognostic Impact of Tumor Budding in Colorectal Cancer.

    PubMed

    Mehta, Anurag; Goswami, Malini; Sinha, Rupal

    2017-03-01

    Colorectal cancer (CRC) is a heterogeneous disease with complex etiology. New prognostic factors for this group of disease need to be investigated. This study evaluated the histopathological significance and prognostic impact of tumor budding in CRC. A total of 60 treatment naive consecutive patients undergoing surgical resection for CRC during the period of January 2011 to December 2013 were included in the study. Details of each patient related to their demographic and tumor profile were recorded. Pan Cytokeratin immunohistochemistry was applied on chosen sections and tumor budding was assessed. The most frequent site of involvement was rectosigmoid and sigmoid colon (31.6%). The majority of the cases were moderately differentiated (75%) in morphology, and showed tumor invasion into the pericolic/subserosal fat (66.6%), and were stage III (38.3%). Nodal involvement was present in 50% cases. Correlations between tumor budding and nodal involvement (p-value 0.039) and AJCC stage (p-value 0.021) were found to be statistically significant. Tumor budding may be a promising and powerful predictor of lymphnodal metastasis and a higher stage of tumor and can be used as a marker for assessing the aggressiveness of CRC. Routine hemotoxylin-eosin staining supported by cytokeratin immunostain can aid in the grading of tumor budding in CRC. © 2017 by the Association of Clinical Scientists, Inc.

  17. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection.

    PubMed

    Beuschlein, Felix; Weigel, Jens; Saeger, Wolfgang; Kroiss, Matthias; Wild, Vanessa; Daffara, Fulvia; Libé, Rosella; Ardito, Arianna; Al Ghuzlan, Abir; Quinkler, Marcus; Oßwald, Andrea; Ronchi, Cristina L; de Krijger, Ronald; Feelders, Richard A; Waldmann, Jens; Willenberg, Holger S; Deutschbein, Timo; Stell, Anthony; Reincke, Martin; Papotti, Mauro; Baudin, Eric; Tissier, Frédérique; Haak, Harm R; Loli, Paola; Terzolo, Massimo; Allolio, Bruno; Müller, Hans-Helge; Fassnacht, Martin

    2015-03-01

    Recurrence of adrenocortical carcinoma (ACC) even after complete (R0) resection occurs frequently. The aim of this study was to identify markers with prognostic value for patients in this clinical setting. From the German ACC registry, 319 patients with the European Network for the Study of Adrenal Tumors stage I-III were identified. As an independent validation cohort, 250 patients from three European countries were included. Clinical, histological, and immunohistochemical markers were correlated with recurrence-free (RFS) and overall survival (OS). Although univariable analysis within the German cohort suggested several factors with potential prognostic power, upon multivariable adjustment only a few including age, tumor size, venous tumor thrombus (VTT), and the proliferation marker Ki67 retained significance. Among these, Ki67 provided the single best prognostic value for RFS (hazard ratio [HR] for recurrence, 1.042 per 1% increase; P < .0001) and OS (HR for death, 1.051; P < .0001) which was confirmed in the validation cohort. Accordingly, clinical outcome differed significantly between patients with Ki67 <10%, 10-19%, and ≥20% (for the German cohort: median RFS, 53.2 vs 31.6 vs 9.4 mo; median OS, 180.5 vs 113.5 vs 42.0 mo). Using the combined cohort prognostic scores including tumor size, VTT, and Ki67 were established. Although these scores discriminated slightly better between subgroups, there was no clinically meaningful advantage in comparison with Ki67 alone. This largest study on prognostic markers in localized ACC identified Ki67 as the single most important factor predicting recurrence in patients following R0 resection. Thus, evaluation of Ki67 indices should be introduced as standard grading in all pathology reports of patients with ACC.

  18. Prognostic value of major extracranial injury in traumatic brain injury: an individual patient data meta-analysis in 39,274 patients.

    PubMed

    van Leeuwen, Nikki; Lingsma, Hester F; Perel, Pablo; Lecky, Fiona; Roozenbeek, Bob; Lu, Juan; Shakur, Haleema; Weir, James; Steyerberg, Ewout W; Maas, Andrew I R

    2012-04-01

    Major extracranial injury (MEI) is common in traumatic brain injury (TBI) patients, but the effect on outcome is controversial. To assess the prognostic value of MEI on mortality after TBI in an individual patient data meta-analysis of 3 observational TBI studies (International Mission on Prognosis and Clinical Trial Design in TBI [IMPACT]), a randomized controlled trial (Corticosteroid Randomization After Significant Head Injury [CRASH]), and a trauma registry (Trauma Audit and Research Network [TARN]). MEI (extracranial injury with an Abbreviated Injury Scale ≥ 3 or requiring hospital admission) was related to mortality with logistic regression analysis, adjusted for age, Glasgow Coma Scale motor score, and pupil reactivity and stratified by TBI severity. We pooled odds ratios (ORs) with random-effects meta-analysis. We included 39,274 patients. Mortality was 25%, and 32% had MEI. MEI was a strong predictor for mortality in TARN, with adjusted odds ratios of 2.81 (95% confidence interval [CI], 2.44-3.23) in mild, 2.18 (95% CI, 1.80-2.65) in moderate, and 2.14 (95% CI, 1.95-2.35) in severe TBI patients. The prognostic effect was smaller in IMPACT and CRASH, with pooled adjusted odds ratios of 2.14 (95% CI, 0.93-4.91) in mild, 1.46 (95% CI, 1.14-1.85) in moderate, and 1.18 (95% CI, 1.03-1.55) in severe TBI. When patients who died within 6 hours after injury were excluded from TARN, the effect of MEI was comparable with IMPACT and CRASH. MEI is an important prognostic factor for mortality in TBI patients. However, the effect varies by population, which explains the controversy in the literature. The strength of the effect is smaller in patients with more severe brain injury and depends on time of inclusion in a study.

  19. Prognostic factors associated with mortality and major in-hospital complications in patients with bacteremic pneumococcal pneumonia

    PubMed Central

    Beatty, Jessica A.; Majumdar, Sumit R.; Tyrrell, Gregory J.; Marrie, Thomas J.; Eurich, Dean T.

    2016-01-01

    Abstract Bacteremic pneumococcal pneumonia (BPP) causes considerable mortality and morbidity. We aimed to identify prognostic factors associated with mortality and major in-hospital complications in BPP. A prospective, population-based clinical registry of 1636 hospitalized adult patients (≥18 years) with BPP was established between 2000 and 2010 in Northern Alberta, Canada. Prognostic factors for mortality and major in-hospital complications (e.g., cardiac events, mechanical ventilation, aspiration) were evaluated using multivariable logistic regression. Average age was 54 (standard deviation 18) years, 57% males, and 59% had high case-fatality rate (CFR) serotypes. Overall, 14% (226/1636) of patients died and 22% (315/1410) of survivors developed at least 1 complication. Independent prognostic factors for mortality were age (adjusted odds ratio [aOR], 1.5 per decade; 95% confidence interval [CI], 1.3–1.7), nursing home residence (aOR, 3.7; 95% CI 1.8–7.4), community-dwelling dementia (aOR 3.7; 95% CI, 1.6–8.6), alcohol abuse (aOR, 2.2; 95% CI, 1.4–3.4), acid-suppressing drugs (aOR, 1.5; 95% CI, 1.0–2.3), guideline-discordant antibiotics (aOR, 3.4; 95% CI, 2.4–4.8), multilobe pneumonia (aOR, 2.6; 95% CI, 1.8–3.6), and high CFR serotypes (aOR, 1.8; 95% CI, 1.2–2.8). Similar prognostic factors were observed for major in-hospital complications. Pneumococcal vaccination was associated with reduced in-hospital mortality (aOR, 0.2; 95% CI, 0.05–0.9) but not major complications (P = 0.2). Older and frailer patients, and those who abuse alcohol or take acid-suppressing drugs, are at increased risk of BPP-related mortality and complications, as are those with high CFR serotypes. Beyond identifying those at highest risk, our findings demonstrate the importance of guideline-concordant antibiotics and pneumococcal vaccination in those with BPP. PMID:27861340

  20. The prognostic impact of the log odds of positive lymph nodes in colon cancer.

    PubMed

    Arslan, N C; Sokmen, S; Canda, A E; Terzi, C; Sarioglu, S

    2014-11-01

    This study aimed to investigate the prognostic impact of the log odds of positive lymph nodes (LODDS) in colon cancer. Four hundred and forty patients with colon cancer were divided into three each groups according to their lymph node ratio (LNR) and LODDS. Survival analysis was performed. The 5-year overall survival (OS) rate was 70.2%. In univariate analysis age, pT and pN stage, tumour grade, lymphatic, venous and perineural invasion, surgical margin clearance, LNR and LODDS were significantly associated with OS. In multivariate analysis age, surgical margins, perineural invasion and LODDS were found to be independent prognostic factors. In subgroup analysis of patients with an inadequate number of examined lymph nodes (NELN) (n = 76) and node-negative patients (n = 210), LODDS retained its prognostic value, whereas the impact of LNR was not statistically significant (P = 0.063). The overall survival rates of node-negative patients in the LODDS groups 0, 1 and 2 were 81%, 74.2% and 50%, respectively (P = 0.020). LNR and LODDS classifications were both significantly associated with survival in Stage III colon cancer, but only LODDS was an independent prognostic factor. Conventional TNM staging for nodes (pN) and LNR status cannot reliably classify node-negative patients into homogeneous groups. LODDS provides more valuable information than LNR independently of the NELN. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  1. Time for initial response to steroids is a major prognostic factor in idiopathic nephrotic syndrome.

    PubMed

    Vivarelli, Marina; Moscaritolo, Eleonora; Tsalkidis, Aggelos; Massella, Laura; Emma, Francesco

    2010-06-01

    To identify early prognostic factors for idiopathic nephrotic syndrome (INS) in childhood. A retrospective analysis of 103 patients with INS at onset, all treated in a single center with the same induction protocol, was conducted. Minimum length of follow-up was 2 years; median length of follow-up was 43 months. Survival data were assessed with Cox-Mantel analysis. Predictive values were estimated with receiver operating characteristic curves. The median time of response to steroid therapy was 7 days. A significant association was found between the interval from onset of steroid therapy to remission and the risk of relapsing within 3 months after steroid therapy discontinuation (P < .0001). A similar association was found between the time to achieve remission and the risk of developing frequent relapsing or steroid-dependent nephrotic syndrome (P < .0001), the prescription of maintenance steroid therapy (P < .003), and the prescription of all other non-steroid drugs (P < .0001) during follow-up. Patients with non-relapsing and infrequent relapsing nephrotic syndrome had a median time to achieve remission <7 days; in patients with frequent relapsing and steroid-dependent nephrotic syndrome, this median was >7 days. The interval from onset of steroid therapy to remission is an accurate early prognostic factor in INS. Copyright 2010 Mosby, Inc. All rights reserved.

  2. Prognostic Impact of Immunonutritional Status Changes During Preoperative Chemoradiation in Patients With Rectal Cancer

    PubMed Central

    Lee, Yong Joon; Kim, Woo Ram; Han, Jeonghee; Han, Yoon Dae; Cho, Min Soo; Hur, Hyuk; Lee, Kang Young; Kim, Nam Kyu

    2016-01-01

    Purpose Previous studies have demonstrated the prognostic impact of the prognostic nutritional index (PNI), a proposed indicator of immunonutritional statuses of surgical patients, on patients with various gastrointestinal cancers. Although the prognostic impact of the PNI on patients with colorectal cancer has been well established, its value has not been studied in patients treated with preoperative chemoradiation (pCRT). This study aimed to evaluate the prognostic impact of PNI on patients receiving pCRT for locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent curative pCRT followed by surgical resection were enrolled. The PNI was measured in all patients before and after pCRT, and the difference in values was calculated as the PNI difference (dPNI). Patients were classified according to dPNI (<5, 5–10, and >10). Clinicopathologic parameters and long-term oncologic outcomes were assessed according to dPNI classification. Results No significant intergroup differences were observed in clinicopathologic parameters such as age, histologic grade, tumor location, tumor-node-metastasis stage, and postoperative complications. Approximately 53% of the patients had a mild dPNI (<5); only 15% had a high dPNI (>10). Univariate and multivariate analyses identified the dPNI as an independent prognostic factor for disease-free status (P < 0.01; hazard ratio [HR], 2.792; 95% confidence interval [CI], 1.577–4.942) and for cancer-specific survival (P = 0.012; HR, 2.469; 95%CI, 1.225–4.978). Conclusion The dPNI is predictive of long-term outcomes in pCRT-treated patients with LARC. Further prospective studies should investigate whether immune-nutritional status correction during pCRT would improve oncologic outcomes. PMID:28119863

  3. Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma.

    PubMed

    Unger, Ulrike; Denkert, Carsten; Braicu, Ioana; Sehouli, Jalid; Dietel, Manfred; Loibl, Sibylle; Darb-Esfahani, Silvia

    2017-02-01

    HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26-0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.

  4. The aggressiveness of neurotrauma practitioners and the influence of the IMPACT prognostic calculator.

    PubMed

    Letsinger, Joshua; Rommel, Casey; Hirschi, Ryan; Nirula, Raminder; Hawryluk, Gregory W J

    2017-01-01

    Published guidelines have helped to standardize the care of patients with traumatic brain injury; however, there remains substantial variation in the decision to pursue or withhold aggressive care. The International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic calculator offers the opportunity to study and decrease variability in physician aggressiveness. The authors wish to understand how IMPACT's prognostic calculations currently influence patient care and to better understand physician aggressiveness. The authors conducted an anonymous international, multidisciplinary survey of practitioners who provide care to patients with traumatic brain injury. Questions were designed to determine current use rates of the IMPACT prognostic calculator and thresholds of age and risk for death or poor outcome that might cause practitioners to consider withholding aggressive care. Correlations between physician aggressiveness, putative predictors of aggressiveness, and demographics were examined. One hundred fifty-four responses were received, half of which were from physicians who were familiar with the IMPACT calculator. The most frequent use of the calculator was to improve communication with patients and their families. On average, respondents indicated that in patients older than 76 years or those with a >85% chance of death or poor outcome it might be reasonable to pursue non-aggressive care. These thresholds were robust and were not influenced by provider or institutional characteristics. This study demonstrates the need to educate physicians about the IMPACT prognostic calculator. The consensus values for age and prognosis identified in our study may be explored in future studies aimed at reducing variability in physician aggressiveness and should not serve as a basis for withdrawing care.

  5. Prognostic impact of monocyte count at presentation in mantle cell lymphoma.

    PubMed

    von Hohenstaufen, Kathrin Aprile; Conconi, Annarita; de Campos, Cassio Polpo; Franceschetti, Silvia; Bertoni, Francesco; Margiotta Casaluci, Gloria; Stathis, Anastasios; Ghielmini, Michele; Stussi, Georg; Cavalli, Franco; Gaidano, Gianluca; Zucca, Emanuele

    2013-08-01

    An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

  6. Prognostic Impact of Visceral Fat Amount and Branched-Chain Amino Acids (BCAA) in Hepatocellular Carcinoma.

    PubMed

    Higashi, Takaaki; Hayashi, Hiromitsu; Kaida, Takayoshi; Arima, Kota; Takeyama, Hideaki; Taki, Katsunobu; Izumi, Daisuke; Tokunaga, Ryuma; Kosumi, Keisuke; Nakagawa, Shigeki; Okabe, Hirohisa; Imai, Katsunobu; Nitta, Hidetoshi; Hashimoto, Daisuke; Chikamoto, Akira; Beppu, Toru; Baba, Hideo

    2015-12-01

    Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI (P < 0.0001; r = 0.63) and BCAA levels (P < 0.0001; r = 0.29). Overall survival was significantly greater in the high than in the low VFA group (P = 0.002). Multivariate analyses showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and prognostic nutritional index were not. High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC.

  7. Prognostic impact of LDH levels in patients with relapsed/refractory seminoma.

    PubMed

    Powles, Tom; Bascoul-Mollevi, Caroline; Kramar, Andrew; Lorch, Anja; Beyer, Jörg

    2013-08-01

    To evaluate the impact of age and LDH levels in patients with relapsed seminoma. Data on the 204 seminoma from the International Prognostic Factor Study Group (IPFSG) were analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles. Age and LDH at relapse were assessed in addition to previously identified prognostic factors for all germ cell tumor patients from the database (J Clin Oncol 28:4906, 2010). The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥1.5 times the upper limit of normal (ULN) was significant in univariate (HR 1.96; CI 1.06-3.61) and multivariate analysis (HR 1.90; CI 1.00-3.62). Age, however, was not significant. Therefore, LDH was incorporated into a modified new IPFSG seminoma score by moving patients to the next unfavorable group for patients with LDH values ≥1.5 × ULN. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: "very low risk" (n = 23) 85.7% (95% CI 62-95), "low risk" (n = 44) 62.7 % (95% CI 46-75) and "intermediate risk" (n = 36) 35.1% (95% CI 20-51). Overall survival at 3 years: "very low risk" 88.8% (95% CI 62-97), "low risk" 71.3% (95% CI 55-83) and "intermediate risk" 51.3% (95% CI 33-67). The addition of LDH, but not age, improves the impact of the IPFSG prognostic score in seminoma patients relapsing or progressing after cisplatin-based chemotherapy.

  8. Prognostic impact of nutritional risk assessment in patients with chronic schizophrenia.

    PubMed

    Tsai, Ming-Tsun; Chang, Tien-Hao; Wu, Bo-Jian

    2017-04-22

    Protein-energy wasting is associated with poor outcome in various clinical settings. However, the prevalence of malnutrition and the prognostic impact of nutritional status are poorly understood in institutionalized patients with chronic schizophrenia. This study aimed to assess the predictive ability of the Geriatric Nutritional Risk Index and Onodera's Prognostic Nutritional Index for long-term outcomes in patients with chronic schizophrenia. All measurements, including nutritional scores, were performed at baseline after the enrollment of 542 (64.6% men, mean age 53.8±9.7years) patients with chronic schizophrenia. The median follow-up period was 408days. The endpoints were falls and infection-related hospitalizations. At study completion, 34 patients suffered falls and 40 patients were admitted to hospitals due to infection. Both indices showed significant association with infectious complications, whereas only the Onodera's Prognostic Nutritional Index was significantly associated with falls. The adjusted hazard ratios (95% confidence intervals) of low Onodera's Prognostic Nutritional Index were 2.38 (1.16-4.86) for falls and 1.99 (1.05-3.76) for infectious complications. The Onodera's Prognostic Nutritional Index is more appropriate than the Geriatric Nutritional Risk Index in identifying patients with chronic schizophrenia who are at risk for malnutrition and nutrition-related morbidity. Further studies are needed to explore whether early detection of patients with schizophrenia who are at risk for malnutrition could lead to the reduction of morbidity and mortality with the aid of appropriate interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Statistical approaches to the univariate prognostic analysis of the IMPACT database on traumatic brain injury.

    PubMed

    McHugh, Gillian S; Butcher, Isabella; Steyerberg, Ewout W; Lu, Juan; Mushkudiani, Nino; Marmarou, Anthony; Maas, Andrew I R; Murray, Gordon D

    2007-02-01

    The univariate prognostic analysis of the IMPACT database on traumatic brain injury (TBI) poses the formidable challenge of how best to summarize a highly complex set of data in a way which is accessible without being overly simplistic. In this paper, we describe and illustrate the battery of statistical methods that have been used. Boxplots, histograms, tabulations, and splines were used for initial data checking and in identifying appropriate transformations for more formal statistical modeling. Imputation techniques were used to minimize the problems associated with the analysis of incomplete data due to missing values. The associations between covariates and outcome (Glasgow Outcome Scale [GOS] assessed at 6 months) were expressed as odds ratios with supporting confidence intervals when the GOS was collapsed to a dichotomous scale. This was extended to use common odds ratios from proportional odds models to express associations over the full range of the GOS. Forest plots were used to illustrate the consistency of results from study to study within the IMPACT database. The overall prognostic strength of the prognostic factors was expressed as the proportion of variance explained (Nagelkerke's R(2) statistic). Many of our approaches are based on simple graphical displays of the data, but, where appropriate, we have also used methods that although established in the statistical literature are relatively novel in their application to TBI.

  10. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  11. The highest prognostic impact of LDH among International Prognostic Indices (IPIs): an explorative study of five IPI factors among patients with DLBCL in the era of rituximab.

    PubMed

    Park, J H; Yoon, D H; Kim, D Y; Kim, S; Seo, S; Jeong, Y; Lee, S W; Park, C S; Huh, J; Suh, C

    2014-10-01

    Although the International Prognostic Index (IPI) is considered as the current standard prognostication system for diffuse large B-cell lymphoma (DLBCL), prognostic heterogeneity is suggested to exist among the patients within the same IPI risk group. Hence, we investigated the pattern of distribution and prognostic impact of five IPI factors within the same IPI score. We retrospectively reviewed the medical records of 387 patients newly diagnosed as pathologically proven DLBCL between February 2002 and February 2010. We classified patients to IPI risk scores and categorized them according to the combinations of IPI. Then, we explored the frequency of five IPI factors and analyzed the correlation between these subgroups and efficacy outcomes: complete response (CR), event-free survival (EFS), and overall survival (OS). Survival estimates by IPI score in this cohort corresponded to the classic IPI. Elevated serum level of lactate dehydrogenase (LDH) was the most prevalently distributed factor throughout the scores, and patients with elevated serum level of LDH tended to have lower CR, inferior EFS, and/or OS irrespective of IPI scores. Particularly, among the subgroups of IPI score of 2, elevated serum level of LDH was significantly associated with inferior CR (73.1 vs 95.2 %), 3-year EFS (57 vs 87 %), and 3-year OS (58 vs 82 %). In addition, the higher serum level of LDH, particularly above 2,000 IU/L, was significantly correlated with the inferior survival outcomes (3-year EFS 78.0 vs 58.5 vs 45.5 vs 20.0 %, 3-year OS 86.0 vs 66.2 vs 58.2 vs 40.0 %). In conclusion, among five factors of IPI, elevated serum level of LDH seems to be the most frequently distributed and, more importantly, the most relevant IPI factor with the highest prognostic impact. These findings still warrant further validation in larger cohorts.

  12. Impacts of Prognostic Phenology and Agriculture on the Seasonal Cycle of Carbon Fluxes

    NASA Astrophysics Data System (ADS)

    Haynes, K. D.; Baker, I. T.; Denning, A.; Stockli, R.; Lokupitiya, E. Y.

    2011-12-01

    Since terrestrial carbon fluxes cannot be measured directly on regional and global scales, land surface models are an important tool in improving estimates of carbon sources and sinks. One common limitation in biosphere models is requiring the use of remotely sensed data to represent vegetation phenology; however, prognostic phenology models are being developed to predict the phonological timing and leaf state of both natural vegetation and crops (Stockli et al., 2008; Lokupitiya et al., 2009; Stockli et al., 2011). Simulating phenology rather than relying on data products removes the uncertainty due to satellite retrievals, allows the short yet highly productive growing season of crops to be more accurately simulated, and enables predictive capabilities. The Simple Biosphere Model (SiB) has been modified to include prognostic phenology for twenty different plant functional types, including maize, soybean and wheat. Predicting the phenology will alter carbon fluxes regionally and globally on diurnal to seasonal timescales, and this study will discuss the impact of prognostic phenology on the resulting simulated net ecosystem exchange of carbon dioxide.

  13. The Lowered Age of Majority: Its Impact on Higher Education.

    ERIC Educational Resources Information Center

    Hanson, David J.

    The impact of lowered age of majority on higher education is discussed in this report. After reviewing the concept of majority and related principles of constitutional law, four areas of possible impact are considered. The first section deals with the determination of financial need for the independent adult student, the second with the question…

  14. Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast Conserving Surgery

    PubMed Central

    Gosset, Marie; Hamy, Anne-Sophie; Mallon, Peter; Delomenie, Myriam; Mouttet, Delphine; Pierga, Jean-Yves; Lae, Marick; Fourquet, Alain; Rouzier, Roman; Reyal, Fabien; Feron, Jean-Guillaume

    2016-01-01

    Background The poor prognosis of patients who experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A short time between primary cancer and IBTR is a prognostic factor but no clinically relevant threshold was determined. Classification of IBTR may help tailor treatment strategies. Purpose We determined a specific time frame, which differentiates IBTR into early and late recurrence, and identified prognostic factors for patients with IBTR at time of the recurrence. Methods We analyzed 2209 patients with IBTR after BCS. We applied the optimal cut-points method for survival data to determine the cut-off times to IBTR. A subgroup analysis was performed by hormone receptor (HR) status. Survival analyses were performed using a Cox proportional hazard model to determine clinical features associated with distant-disease-free survival (DDFS) after IBTR. We therefor built decision trees. Results On the 828 metastatic events observed, the majority occurred within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR negative group. We found different prognostic times to IBTR: 49 months in the HR positive group, 33 in the HR negative group. After multivariate analysis, time to IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95% [0.54–0.79] and 0.42 [0.30–0.57] respectively). The other following variables were significantly correlated with the DDFS: the initial number of positive lymph nodes for both groups, the initial tumor size and grade for HR positive tumors. Conclusion A short interval time to IBTR is the strongest factor of poor prognosis and reflects occult distant disease. It would appear that prognosis after IBTR depends more on clinical and histological parameters than on surgical treatment. A prospective trial in a low-risk group of patients to validate the safety of salvage BCS instead of mastectomy in IBTR is needed. PMID:27494111

  15. Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker.

    PubMed

    Stengel, Anna; Kern, Wolfgang; Zenger, Melanie; Perglerová, Karolína; Schnittger, Susanne; Haferlach, Torsten; Haferlach, Claudia

    2016-01-01

    T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data are available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis. Genetic abnormalities were found in all 51 cases with T-PLL, most frequently involving the TCRA/D locus (86%). Deletions were detected for ATM (69%) and TP53 (31%), whereas i(8)(q10) was observed in 61% of cases. Mutations in ATM, TP53, JAK1, and JAK3 were detected in 73, 14, 6, and 21% of patients, respectively. Additionally, BCOR mutations were observed for the first time in a lymphoid malignancy (8%). Two distinct genetic subgroups of T-PLL were identified: A large subset (86% of patients) showed abnormalities involving the TCRA/D locus activating the proto-oncogenes TCL1 or MTCP1, while the second group was characterized by a high frequency of TP53 mutations (4/7 cases). Further, analyses of overall survival identified JAK3 mutations as important prognostic marker, showing a significant negative impact. © 2015 Wiley Periodicals, Inc.

  16. Prognostic Impact of ABO Blood Group on the Survival in Patients with Ovarian Cancer

    PubMed Central

    Zhou, Juan; Yang, Li-Chao; He, Zhen-Yu; Li, Fang-Yan; Wu, San-Gang; Sun, Jia-Yuan

    2015-01-01

    Purpose: The impact of ABO blood group on the survival of patients with ovarian cancer remains uncertain. The aim of this study was to evaluate the prognostic value of the ABO blood group in ovarian cancer patients. Methods: 256 ovarian cancer patients who received a cytoreductive surgery were retrospectively reviewed. The prognostic impact of the ABO blood group with respect to overall survival (OS) was analyzed. Results: The median follow-up time was 57 months and the 5-year OS was 70.1%. The 5-year OS were 55.0%, 83.3%, 82.5%, and 70.0% in patients with A, B, AB, and O blood type, respectively (p = 0.003). Patients with blood type A had a poorer 5-year OS than patients with blood type non-A (55.0% vs. 75.0%, p = 0.001), especially in patients with age > 50 years (40.0% vs. 62.5%, p = 0.004). Univariate Cox analyses showed that blood type A was significantly associated with OS than those with non-A types (hazard ratio (HR) 2.210, 95% confidence interval (CI) 1.373-3.557, p = 0.001). Blood type A remained an independent prognostic factor for OS than those with non-A blood types in multivariate analyses (HR 2.235, 95% CI 1.360-3.674, p = 0.002). Conclusion: ABO blood group is associated with survival in patients with ovarian cancer, patients with blood type A had a significantly worse OS than patients with non-A blood types, especially in patients with age > 50 years. PMID:26316893

  17. Lack of Prognostic Impact of Adjuvant Radiation on Oncologic Outcomes in Elderly Women with Breast Cancer.

    PubMed

    Omidvari, Shapour; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Moaddabshoar, Leila; Dayani, Maliheh; Mosalaei, Ahmad; Ahmadloo, Niloofar; Ansari, Mansour; Mohammadianpanah, Mohammad

    2015-01-01

    Radiotherapy plays an important role as adjuvant treatment in locally advanced breast cancer and in those patients who have undergone breast-conserving surgery. This study aimed to investigate the prognostic impact of adjuvant radiation on oncologic outcomes in elderly women with breast cancer. In this retrospective study, we reviewed and analyzed the characteristics, treatment outcome and survival of elderly women (aged ≥ 60 years) with breast cancer who were treated and followed-up between 1993 and 2014. The median follow up for the surviving patients was 38 (range 3-207) months. One hundred and seventy-eight patients with a median age of 74 (range 60-95) years were enrolled in the study. Of the total, 60 patients received postoperative adjuvant radiation (radiation group) and the remaining 118 did not (control group). Patients in the radiation group were significantly younger than those in the control group (P value=0.004). In addition, patients in radiation group had higher node stage (P value<0.001) and disease stage (P=0.003) and tended to have higher tumor grade (P=0.031) and received more frequent (P value <0.001) adjuvant and neoadjuvant chemotherapy compared to those in the control group. There was no statistically significant difference between two groups regarding the local control, disease-free survival and overall survival rates. In this study, we did not find a prognostic impact for adjuvant radiation on oncologic outcomes in elderly women with breast cancer.

  18. Career Cruising Impact on the Self Efficacy of Deciding Majors

    ERIC Educational Resources Information Center

    Smother, Anthony William

    2012-01-01

    The purpose of this study was to analyze the impact of "Career Cruising"© on self-efficacy of deciding majors in a university setting. The use of the self-assessment instrument, "Career Cruising"©, was used with measuring the career-decision making self-efficacy in a pre and post-test with deciding majors. The independent…

  19. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome

    PubMed Central

    Klusmann, Jan-Henning; Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael; Jorch, Norbert; Langebrake, Claudia; Pekrun, Arnulf; Macakova-Reinhardt, Katarina

    2008-01-01

    Approximately 10% of the neonates with Down syndrome (DS) exhibit a unique transient leukemia (TL). Though TL resolves spontaneously in most patients, early death and development of myeloid leukemia (ML-DS) may occur. Prognostic factors as well as treatment indication are currently uncertain. To resolve that issue, we prospectively collected clinical, biologic, and treatment data of 146 patients with TL. The 5-year overall survival (OS) and event-free survival (EFS) were 85% plus or minus 3% and 63% plus or minus 4%, respectively. Multivariate analysis revealed a correlation between high white blood cell (WBC) count, ascites, preterm delivery, bleeding diatheses, failure of spontaneous remission, and the occurrence of early death. Treatment with cytarabine (0.5-1.5 mg/kg) was administered to 28 patients with high WBC count, thrombocytopenia, or liver dysfunction. The therapy had a beneficial effect on the outcome of those children with risk factors for early death (5-year EFS, 52% ± 12% vs 28% ± 11% [no treatment]; P = .02). Multivariate analysis demonstrated its favorable prognostic impact. A total of 29 (23%) patients with TL subsequently developed ML-DS. Patients with ML-DS with a history of TL had a significantly better 5-year EFS (91% ± 5%) than those without documented TL (70% ± 4%), primarily due to a lower relapse rate. A history of TL may therefore define a lower-risk ML-DS subgroup. This study was registered at www.clinicaltrials.gov as no. NCT 00111345. PMID:18182574

  20. Low-level copy number changes of MYC genes have a prognostic impact in medulloblastoma.

    PubMed

    Zitterbart, Karel; Filkova, Hana; Tomasikova, Lenka; Necesalova, Eva; Zambo, Iva; Kantorova, Dagmar; Slamova, Iva; Vranova, Vladimira; Zezulkova, Dita; Pesakova, Martina; Pavelka, Zdenek; Veselska, Renata; Kuglik, Petr; Sterba, Jaroslav

    2011-03-01

    High-level amplifications of MYC genes are associated with poor outcomes in childhood medulloblastoma (MB). However, the occurrence of MYCN and MYCC copy number increases below the intense amplification pattern is rarely reported, and its clinical impact has not yet been determined. Here, we describe this phenomenon and its prognostic significance in a cohort of 29 MB patients. Using interphase fluorescence in situ hybridization (I-FISH), low-level copy number alterations, i.e. gain of MYCN, were shown in 5/27 (19%) samples, whereas amplification was revealed in only 1/27 (4%) samples. MYCC gain was revealed in 6/29 (21%) MB, while amplification was disclosed in only 2/29 (7%). Hyperploidy and co-incidence of gains in both MYC loci were frequently observed in samples with copy number aberrations. Survival analysis has clearly shown that MYC copy number increases are associated with lowered event-free survival and overall survival in MB. In the case of MYCN, this negative correlation was statistically significant. We conclude that limited numerical alterations in loci 2p24 (MYCN) and 8q24 (MYCC), as assessed by I-FISH, are present in MB with a higher frequency than high-level amplifications. Poor prognoses were observed in patients with copy number increases in MYC genes. Our data illustrate the importance of further investigations in multicenter trials to better refine the emerging genomic-based prognostic stratification in MB.

  1. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

    PubMed Central

    Teixido, Cristina; Michels, Sebastian; Morales-Espinosa, Daniela; Viteri, Santiago; Hartmann, Wolfgang; Merkelbach-Bruse, Sabine; Fischer, Rieke; Schildhaus, Hans-Ulrich; Fassunke, Jana; Sebastian, Martin; Serke, Monika; Kaminsky, Britta; Randerath, Winfried; Gerigk, Ulrich; Ko, Yon-Dschun; Krüger, Stefan; Schnell, Roland; Rothe, Achim; Kropf-Sanchen, Cornelia; Heukamp, Lukas; Rosell, Rafael

    2015-01-01

    Background While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Patients and Methods 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. Conclusion ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC. PMID:25868855

  2. Epidemiology and clinical impact of major comorbidities in patients with COPD

    PubMed Central

    Smith, Miranda Caroline; Wrobel, Jeremy P

    2014-01-01

    Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival. There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes. Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD. Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication. The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities. Unfortunately, comorbidities are often under-recognized and under-treated. This review focuses on the epidemiology of ten major comorbidities in patients with COPD. Further, we emphasize the clinical impact upon prognosis and management considerations. This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. PMID:25210449

  3. Apolipoproteins A1, B, and other prognostic biochemical cardiovascular risk factors in patients with beta-thalassemia major.

    PubMed

    Ghorban, Khodayar; Shanaki, Mehrnoosh; Mobarra, Naser; Azad, Mehdi; Asadi, Jahanbakhsh; Pakzad, Reza; Ehteram, Hassan

    2016-03-01

    The occurrence of cardiac iron deposition is one of the late effect of iron over load which causes cardiovascular disease (CVD) in patients who are affected by beta-thalassemia major. Evaluation of some cardiovascular risk factors plays a crucial role in prediction and prevention of CVD. This study consisted of 70 young adult subjects with beta-thalassemia major (beta-TM) (aged <30 years) and 71 age- and sex-matched healthy subjects as control group in the range of 20-30 years. Hematological and biochemical laboratory parameters including apolipoprotein (Apo)A1 and ApoB, oxidative stress biomarker pro-oxidant-antioxidant balance (PAB), homocysteine, serum high-sensitivity C-reactive protein (hs-CRP), and lipid profile were evaluated. ApoA1, ApoB, lipid profiles, and homocysteine were significantly decreased in patients group (P < 0.001); however, very low-density lipoprotein and also mean corpuscular hemoglobin concentration (P > 0.05) were different. Some elements included ferritin (P < 0.001), PAB (P < 0.001), and ApoB/apoA1 ratio (P < 0.05) statistically increased in patients, whereas hs-CRP (P > 0.05) was not significantly different in study groups. Exception of high-density lipoprotein (P > 0.05), other lipid profiles, and apoB had a negative meaningful correlation with PAB (P < 0.05). Likewise, apoA1, apoB, apoB/A1 ratio with apoB and homocysteine showed a strong correlation (P < 0.05). We did not find a slight correlation between apoB/A1 ratio in the company of oxidative stress marker PAB (r = -0.366; P = 0.086). We found a statistical correlation between apoB/A1 and homocysteine (P < 0.05). Higher level of some risk factors like PAB values, apoB/A1 ratio concentration, and lipid profiles is able to involve in the prognostic pathological consequences in patients with beta-thalassemia major. Even so, they contribute toward the gradual development of CVD.

  4. Unique cytogenetic findings confirmed by FISH in a rare case of infant MDS with major prognostic implications

    SciTech Connect

    Sutcliffe, M.J.; Haag, M.M.; Dumont, D.P.

    1994-09-01

    An extremely rare finding in the young, the myelodysplastic syndrome (MDS) refractory anemia with excess blasts (RAEB), is distinguished by blood cytopenia, trilineage dyspoiesis and an increase in peripheral and bone marrow blasts. A 3-year-old male presented with arm pain of one week duration followed by progressive bruising, high fever and severe headaches. Bone marrow pathology revealed dysmyelopoietic granulocytic hyperplasia, marked reduction in megakaryocytes and increased blastosis suggestive of RAEB. Peripheral blood smear confirmed leukoerythroblastic anemia, reticulocytopenia and thyrombocytopenia. Cytogenetic bone marrow evaluation showed the majority of cells with ring (11), monosomies No. 17 and No. 20 and a derivative No. 12 chromosome. Due to the structural complexity and diagnostic and prognostic implications of accurate interpretation, analysis was confirmed using FISH COATASOME probes No. 11, No. 12 and No. 20 (Oncor, Inc.). The rearranged chromosome comprised chromosomes 12 and 20. Breakpoints in No. 12 were at p13 and q24.3. The breakpoint in chromosome 20 at q11.2 resulted in attachment of the distal 20q11.2 fragment to 12q and the centromere and p arm to 12p. C-banding confirmed two centromeres. Progression to ANLL is observed in 15-30% of patients with MDS. Distinction between RAEB and ANLL challenges diagnosis and patient management. Clonal chromosomal abnormalities due to RAEB and nonrandom ANLL changes also show considerable overlap, emphasizing their basic pathobiological similarity. However, r(11) has been described in ANLL and although the structurally rearranged No. 12 is believed to be a unique finding, the breakpoints were considered diagnostically significant. The presence of unusual cytogenetic findings may herald progression of MDS to acute leukemia before morphological classification is evident, emphasing the importance of clarifying structural abnormalities that may provide powerful evidence for clinical management.

  5. Tumor Epression of Major Vault Protein is an Adverse Prognostic Factor for Radiotherapy Outcome in Oropharyngeal Carcinoma

    SciTech Connect

    Silva, Priyamal; West, Catharine M.; Slevin, Nick F.R.C.R.; Valentine, Helen; Ryder, W. David J. Grad. I.S.; Hampson, Lynne; Bibi, Rufzan; Sloan, Philip; Thakker, Nalin; Homer, Jarrod; Hampson, Ian

    2007-09-01

    Purpose: Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport, with the major vault protein (MVP or lung resistance-related protein [LRP]) being the main component. The MVP gene is located on chromosome 16 close to the multidrug resistance-associated protein and protein kinase c-{beta} genes. The role of MVP in cancer drug resistance has been demonstrated in various cell lines as well as in ovarian carcinomas and acute myeloid leukemia, but nothing is known about its possible role in radiation resistance. Our aim was to examine this in head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Archived biopsy material was obtained for 78 patients with squamous cell carcinoma of the oropharynx who received primary radiotherapy with curative intent. Immunohistochemistry was used to detect MVP expression. Locoregional failure and cancer-specific survival were estimated using cumulative incidence and Cox multivariate analyses. Results: In a univariate and multivariate analysis, MVP expression was strongly associated with both locoregional failure and cancer-specific survival. After adjustment for disease site, stage, grade, anemia, smoking, alcohol, gender, and age, the estimated hazard ratio for high MVP (2/3) compared with low (0/1) was 4.98 (95% confidence interval, 2.17-11.42; p 0.0002) for locoregional failure and 4.28 (95% confidence interval, 1.85-9.95; p = 0.001) for cancer-specific mortality. Conclusion: These data are the first to show that MVP may be a useful prognostic marker associated with radiotherapy resistance in a subgroup of patients with HNSCC.

  6. Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study.

    PubMed

    Azumi, Motoi; Suda, Takeshi; Terai, Shuji; Akazawa, Kouhei

    2017-01-01

    Objective Radiofrequency ablation has been used widely for the local ablation of hepatocellular carcinoma, particularly in its early stages. The study aim was to identify significant prognostic factors and develop a predictive nomogram for patients with hepatocellular carcinoma who have undergone radiofrequency ablation. We also developed the formula to predict the probability of 3- and 5-year overall survival based on clinical variables. Methods We retrospectively studied 96 consecutive patients with hepatocellular carcinoma who had undergone radiofrequency ablation as a first-line treatment. Independent and significant factors affecting the overall survival were selected using a Cox proportional hazards model, and a prognostic nomogram was developed based on these factors. The predictive accuracy of the nomogram was determined by Harrell's concordance index and compared with the Cancer of the Liver Italian Program score and Japan Integrated Staging score. Results A multivariate analysis revealed that age, indocyanine green plasma disappearance rate, and log (des-gamma-carboxy prothrombin) level were independent and significant factors influencing the overall survival. The nomogram was based on these three factors. The mean concordance index of the nomogram was 0.74±0.08, which was significantly better than that of conventional staging systems using the Cancer of the Liver Italian Program score (0.54±0.03) and Japan Integrated Staging score (0.59±0.07). Conclusion This study suggested that the indocyanine green plasma disappearance rate and age at radiofrequency ablation (RFA) and des-gamma-carboxy-prothrombin (DCP) are good predictors of the prognosis in hepatocellular carcinoma patients after radiofrequency ablation. We successfully developed a nomogram using obtainable variables before treatment.

  7. Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications.

    PubMed

    Del Principe, Maria Ilaria; Buccisano, Francesco; Maurillo, Luca; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; Consalvo, Maria Irno; Sarlo, Chiara; Conti, Consuelo; De Santis, Giovanna; De Bellis, Eleonora; Di Veroli, Ambra; Palomba, Patrizia; Attrotto, Cristina; Zizzari, Annagiulia; Paterno, Giovangiacinto; Voso, Maria Teresa; Del Poeta, Giovanni; Lo-Coco, Francesco; Arcese, William; Amadori, Sergio; Venditti, Adriano

    2016-01-01

    Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients' risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help to identify patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry(MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management.

  8. Defining high, medium and low impact prognostic factors for developing multiple sclerosis.

    PubMed

    Tintore, Mar; Rovira, Àlex; Río, Jordi; Otero-Romero, Susana; Arrambide, Georgina; Tur, Carmen; Comabella, Manuel; Nos, Carlos; Arévalo, María Jesús; Negrotto, Laura; Galán, Ingrid; Vidal-Jordana, Angela; Castilló, Joaquin; Palavra, Filipe; Simon, Eva; Mitjana, Raquel; Auger, Cristina; Sastre-Garriga, Jaume; Montalban, Xavier

    2015-07-01

    [adjusted hazard ratio 0.6 (0.4-1.0)] in adjusted models. The presence of oligoclonal bands increased the risk of clinically definite multiple sclerosis [adjusted hazard ratio 1.3 (1.0-1.8)] and of disability [adjusted hazard ratio 2.0 (1.2-3.6)] independently of other factors. The presence of 10 or more brain lesions on magnetic resonance increased the risk of clinically definite multiple sclerosis [adjusted hazard ratio 11.3 (6.7-19.3)] and disability [adjusted hazard ratio 2.9 (1.4-6.0)]. Disease-modifying treatment before the second attack reduced the risk of McDonald multiple sclerosis [adjusted hazard ratio 0.6 (0.4-0.9)] and disability accumulation [adjusted hazard ratio 0.5 (0.3-0.9)]. We conclude that the demographic and topographic characteristics are low-impact prognostic factors, the presence of oligoclonal bands is a medium-impact prognostic factor, and the number of lesions on brain magnetic resonance is a high-impact prognostic factor.

  9. Prognostic impact of C-REL expression in diffuse large B-cell lymphoma.

    PubMed

    Curry, Choladda V; Ewton, April A; Olsen, Randall J; Logan, Brent R; Preti, Hector A; Liu, Yao-Chang; Perkins, Sherrie L; Chang, Chung-Che

    2009-03-01

    Diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) phenotype is believed to confer a better prognosis than DLBCL with an activated B-cell (ABC) phenotype. Previous studies have suggested that nuclear factor-kappaB (NF-kappaB) activation plays an important role in the ABC subtype of DLBCL, whereas c-REL amplification is associated with the GCB subtype. Using immunohistochemical techniques, we examined 68 newly diagnosed de novo DLBCL cases (median follow-up 44 months, range 1 to 142 months) for the expression of c-REL, BCL-6, CD10, and MUM1/IRF4. Forty-four (65%) cases demonstrated positive c-REL nuclear expression. In this cohort of patients, the GCB phenotype was associated with a better overall survival (OS) than the non-GCB phenotype (Kaplan-Meier survival (KMS) analysis, p = 0.016, Breslow-Gehan-Wilcoxon test). In general, c-REL nuclear expression did not correlate with GCB vs. non-GCB phenotype, International Prognostic Index score, or OS. However, cases with a GCB phenotype and negative nuclear c-REL demonstrated better OS than cases with a GCB phenotype and positive nuclear c-REL (KMS analysis, p = 0.045, Breslow-Gehan-Wilcoxon test), whereas in cases with non-GCB phenotype, the expression of c-REL did not significantly impact the prognosis. These results suggest that c-REL nuclear expression may be a prognostic factor in DLBCL and it may improve patient risk stratification in combination with GCB/non-GCB phenotyping.

  10. Clinical and Cost Impact Analysis of a Novel Prognostic Test for Early Detection of Preterm Birth

    PubMed Central

    Caughey, Aaron B.; Zupancic, John A. F.; Greenberg, James M.; Garfield, Susan S.; Thung, Stephen F.; Iams, Jay D.

    2016-01-01

    Objective The objective of this study was to evaluate the potential impact to the U.S. health care system by adopting a novel test that identifies women at risk for spontaneous preterm birth. Methods A decision-analytic model was developed to assess clinical and cost outcomes over a 1-year period. The use of a prognostic test to predict spontaneous preterm birth in a hypothetical population of women reflective of the U.S. population (predictive arm) was compared with the current baseline rate of spontaneous preterm birth and associated infant morbidity and mortality (baseline care arm). Results In a population of 3,528,593 births, our model predicts a 23.5% reduction in infant mortality (8,300 vs. 6,343 deaths) with use of the novel test. The rate of acute conditions at birth decreased from 11.2 to 8.1%; similarly, the rate of developmental disabilities decreased from 13.2 to 11.5%. The rate of spontaneous preterm birth decreased from 9.8 to 9.1%, a reduction of 23,430 preterm births. Direct medical costs savings was $511.7M (− 2.1%) in the first year of life. Discussion The use of a prognostic test for reducing spontaneous preterm birth is a dominant strategy that could reduce costs and improve outcomes. More research is needed once such a test is available to determine if these results are borne out upon real-world use. PMID:27917307

  11. Extracorporeal spread and its prognostic impact in stages I and II (FIGO) endometrial carcinoma.

    PubMed

    Sakuragi, N; Tanaka, T; Satoh, C; Nishiya, M; Ohkouchi, T; Tsumura, N; Takeda, N; Hirahatake, K; Sagawa, T; Ohkubo, H

    1991-09-01

    Prognostic risk factors were statistically analyzed from the histopathologic data obtained from 90 Japanese women with stages I and II endometrial carcinoma treated surgically, including systemic retroperitoneal lymph node dissection, between June 1979 and June 1989. In stage Ia endometrial carcinoma, pelvic and paraaortic nodes metastasis were seen in 13.8(4/29)% and 0.0(0/19)% of patients, respectively. In stage Ib, the incidence of pelvic and paraaortic node metastasis was 25.6(11/43)% and 9.7(3/31)%, respectively. In stage II, the incidence was 38.9(7/18)% and 13.3(2/15)%, respectively. Prognosis of patients even with deep myometrial invasion (greater than or equal to 2/3) or G3 tumor was fairly good (5-year survival rate: 87.5% and 85.7%, respectively) if the disease was histologically confined to the uterine corpus. Once the tumor spread outside the corpus uteri, the survival rate of patients was strongly affected by the grade of the tumor, moderate to marked lymph-vascular space invasion of tumor cells, or tumor invading middle or outer third of myometrium (P less than 0.05 for each factor). In summary, endometrial cancer frequently metastasize to pelvic and paraaortic lymph nodes even in the early stages, and lymph node metastasis and other extracorporeal spread of disease have a serious impact on patient survival. Prognosis of patients with extracorporeal spread of disease seems to be determined by the high grade of tumor and lymph-vascular space invasion. These results suggest that surgical exploration including paraaortic lymph node dissection to accurately evaluate the extent of the disease is essential to estimate the patient's prognostic risk and to individualize the treatment schedule.

  12. Prognostic impact of the indexation of left ventricular mass in patients undergoing dialysis.

    PubMed

    Zoccali, C; Benedetto, F A; Mallamaci, F; Tripepi, G; Giacone, G; Cataliotti, A; Seminara, G; Stancanelli, B; Malatino, L S

    2001-12-01

    Left ventricular hypertrophy (LVH) is exceedingly frequent in patients undergoing dialysis. Cardiac mass is proportional to body size, but the influence of various indexing methods has not been studied in patients with end-stage renal disease. The issue is important because malnutrition and volume expansion would both tend to distort the estimate of LV mass (LVM) in these patients. In a cohort of 254 patients, the prognostic impact on all-cause mortality and cardiovascular outcomes of LVH values, calculated according to two established methods of indexing, either body surface area (BSA) or height(2.7), was assessed prospectively. When LVM was analyzed as a categorical variable, the height(2.7)-based method identified a larger number of patients with LVH than the corresponding BSA-based method. One hundred and thirty-seven fatal and nonfatal cardiovascular events occurred during the follow-up period. Overall, 90 patients died, 51 of cardiovascular causes. In separate Cox models, both the LVM/height(2.7) and the LVM/BSA index independently predicted total and cardiovascular mortality (P < 0.001). However, the height(2.7)-based method coherently produced a closer-fitting model (P < or = 0.02) than did the BSA-based method. The height(2.7) index was also important for the subcategorization of patients according to the presence of concentric or eccentric LVH because the prognostic value of such subcategorization was apparent only when the height(2.7)-based criterion was applied. In conclusion, LVM is a strong and independent predictor of survival and cardiovascular events in patients undergoing dialysis. The indexing of LVM by height(2.7) provides more powerful prediction of mortality and cardiovascular outcomes than the BSA-based method, and the use of this index appears to be appropriate in patients undergoing dialysis.

  13. The impact and control of major southern forest diseases

    Treesearch

    A. Dan Wilson; Theodor D. Leininger; William J. Otrosina; L. David Dwinell; Nathan M. Schiff

    2004-01-01

    A variety of forest health issues, concerns, and events have rapidly changed southern forests and plantations in the past two decades. These factors have strongly impacted the ways we manage forest pests in the Southern United States. This trend will no doubt continue to shape forest pest management in the future. The major issues and events of concern include changing...

  14. Chromosomal Abnormalities Are Major Prognostic Factors in Elderly Patients With Multiple Myeloma: The Intergroupe Francophone du Myélome Experience

    PubMed Central

    Avet-Loiseau, Hervé; Hulin, Cyrille; Campion, Loic; Rodon, Philippe; Marit, Gerald; Attal, Michel; Royer, Bruno; Dib, Mamoun; Voillat, Laurent; Bouscary, Didier; Caillot, Denis; Wetterwald, Marc; Pegourie, Brigitte; Lepeu, Gerard; Corront, Bernadette; Karlin, Lionel; Stoppa, Anne-Marie; Fuzibet, Jean-Gabriel; Delbrel, Xavier; Guilhot, Francois; Kolb, Brigitte; Decaux, Olivier; Lamy, Thierry; Garderet, Laurent; Allangba, Olivier; Lifermann, Francois; Anglaret, Bruno; Moreau, Philippe; Harousseau, Jean-Luc; Facon, Thierry

    2013-01-01

    Purpose Chromosomal abnormalities, especially t(4;14) and del(17p), are major prognostic factors in patients with multiple myeloma (MM). However, this has been especially demonstrated in patients age < 66 years treated with intensive approaches. The goal of this study was to address this issue in elderly patients treated with conventional-dose chemotherapy. Patients and Methods To answer this important question, we retrospectively analyzed a series of 1,890 patients (median age, 72 years; range, 66 to 94 years), including 1,095 with updated data on treatment modalities and survival. Results This large study first showed that the incidence of t(4;14) was not uniform over age, with a marked decrease in the oldest patients. Second, it showed that both t(4;14) and del(17p) retained their prognostic value in elderly patients treated with melphalan and prednisone–based chemotherapy. Conclusion t(4;14) and del(17p) are major prognostic factors in elderly patients with MM, both for progression-free and overall survival, indicating that these two abnormalities should be investigated at diagnosis of MM, regardless of age. PMID:23796999

  15. Changes in environmental impacts of major crops in the US

    NASA Astrophysics Data System (ADS)

    Yang, Yi; Suh, Sangwon

    2015-09-01

    As with life cycle assessment (LCA) studies in general, agricultural LCAs often rely on static and outdated inventory data, but literature suggests that agricultural systems may be highly dynamic. Here, we applied life cycle impact assessment methods to investigate the trends and underlying drivers of changes in non-global environmental impacts of major crops in the US. The results show that the impact per hectare corn and cotton generated on the ecological health of freshwater systems decreased by about 50% in the last decade. This change is mainly due to the use of genetically modified (GM) crops, which has reduced the application of insecticides and relatively toxic herbicides such as atrazine. However, the freshwater ecotoxicity impact per hectare soybean production increased by 3-fold, mainly because the spread of an invasive species, soybean aphid, has resulted in an increasing use of insecticides. In comparison, other impact categories remained relatively stable. By evaluating the relative ecotoxicity potential of a large number of pesticides, our analysis offers new insight into the benefits associated with GM crops. Our study also implies that because different impact categories show different degrees of changes, it is worthwhile focusing on the rapidly changing categories when updating agricultural LCA databases under time and resource constraints.

  16. Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

    PubMed Central

    Kong, Pengfei; Wu, Ruiyan; Yang, Chenlu; Geng, Qirong; Liu, Jianjun; Chen, Shangxiang; Liu, Xuechao; Ye, Minting; He, Wenzhuo; Yang, Qiong; Xia, Liangping; Xu, Dazhi

    2016-01-01

    Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion. PMID:27381549

  17. Long-term prognostic impact of circulating tumour cells in gastric cancer patients

    PubMed Central

    Ito, Hiroaki; Sato, Jun; Tsujino, Yukio; Yamaguchi, Noriko; Kimura, Satoshi; Gohda, Keigo; Murakami, Katsuhiro; Onimaru, Manabu; Ohmori, Tohru; Ishikawa, Fumihiro; Inoue, Haruhiro

    2016-01-01

    AIM To analyse the long-term prognostic impact of circulating tumour cells (CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-mL peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerase-specific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-mL of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant (P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs (P = 0.034). CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer. PMID:28028372

  18. Paradoxical prognostic impact of TERT promoter mutations in gliomas depends on different histological and genetic backgrounds.

    PubMed

    You, Hao; Wu, Yao; Chang, Kai; Shi, Xiao; Chen, Xin-Da; Yan, Wei; Li, Rui

    2017-10-01

    The purpose of this study was to explore the clinical significance of telomerase reverse transcriptase (TERT) promoter mutations in gliomas. We used DNA sequencing data to analyze 887 gliomas for TERT promoter mutations based on histological and genetic backgrounds. TERT promoter mutations were detected in 39.6% of low-grade gliomas, 40.3% of anaplastic gliomas, 44.7% of primary glioblastomas, 29.4% of secondary glioblastomas, and in 29.7% of Proneural, 38.6% of Neural, 41.8% of Classical, and 41.6% of Mesenchymal subtypes. Frequency of C250T mutation in recurrent gliomas was approximately half that in newly diagnosed gliomas. TERT exhibited improved prognosis when co-occurred with isocitrate dehydrogenase 1 (IDH1) and 1p19q alteration, but experienced inverse survival in the Mesenchymal subtype or tumor protein p53 (TP53) and epidermal growth factor receptor (EGFR) alteration. Furthermore, the five subtypes were classified based on the prognostic impact of the TERT mutation with different genetic backgrounds of glioma. We describe the TERT promoter mutation spectrum according to the histological, genetic, and molecular subtypes of glioma, which may aid in glioma subtype classification and have clinical implications. © 2017 John Wiley & Sons Ltd.

  19. Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination, Prognostic Impact and Clinical Applications

    PubMed Central

    Del Principe, Maria Ilaria; Buccisano, Francesco; Maurillo, Luca; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; Consalvo, Maria Irno; Sarlo, Chiara; Conti, Consuelo; De Santis, Giovanna; De Bellis, Eleonora; Di Veroli, Ambra; Palomba, Patrizia; Attrotto, Cristina; Zizzari, Annagiulia; Paterno, Giovangiacinto; Voso, Maria Teresa; Del Poeta, Giovanni; Lo-Coco, Francesco; Arcese, William; Amadori, Sergio; Venditti, Adriano

    2016-01-01

    Pretreatment assessment of cytogenetic/genetic signature of acute myeloid leukemia (AML) has been consistently shown to play a major prognostic role but also to fail at predicting outcome on individual basis, even in low-risk AML. Therefore, we are in need of further accurate methods to refine the patients’ risk allocation process, distinguishing more adequately those who are likely to recur from those who are not. In this view, there is now evidence that the submicroscopic amounts of leukemic cells (called minimal residual disease, MRD), measured during the course of treatment, indicate the quality of response to therapy. Therefore, MRD might serve as an independent, additional biomarker to help to identify patients at higher risk of relapse. Detection of MRD requires the use of highly sensitive ancillary techniques, such as polymerase chain reaction (PCR) and multiparametric flow cytometry(MPFC). In the present manuscript, we will review the current approaches to investigate MRD and its clinical applications in AML management. PMID:27872732

  20. Prognostic impact of margin status in liver resections for colorectal metastases after bevacizumab.

    PubMed

    Sasaki, K; Margonis, G A; Andreatos, N; Wilson, A; Weiss, M; Wolfgang, C; Sergentanis, T N; Polychronidis, G; He, J; Pawlik, T M

    2017-06-01

    Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab. Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses. Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0 versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0 versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0 versus R1 resection; P = 0·917), but this may be due to a type II error. The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play

  1. Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013.

    PubMed

    King, Tari A; Lyman, Jaclyn P; Gonen, Mithat; Voci, Amy; De Brot, Marina; Boafo, Camilla; Sing, Amy Pratt; Hwang, E Shelley; Alvarado, Michael D; Liu, Minetta C; Boughey, Judy C; McGuire, Kandace P; Van Poznak, Catherine H; Jacobs, Lisa K; Meszoely, Ingrid M; Krontiras, Helen; Babiera, Gildy V; Norton, Larry; Morrow, Monica; Hudis, Clifford A

    2016-07-10

    The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013. TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From July 2009 to April 2012, 127 patients from 14 sites were enrolled; 109 (86%) patients had pretreatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with the 21-gene RS by using log-rank, Kaplan-Meier, and Cox regression. Median patient age was 52 years (21 to 79 years); the majority had hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (72 [66%]) or hormone receptor-positive/HER2-positive (20 [18%]) breast cancer. At a median follow-up of 29 months, median TTP was 20 months (95% CI, 16 to 26 months), and median survival was 49 months (95% CI, 40 months to not reached). An RS was generated for 101 (93%) primary tumor samples: 22 (23%) low risk (< 18), 29 (28%) intermediate risk (18 to 30); and 50 (49%) high risk (≥ 31). For all patients, RS was associated with TTP (P = .01) and 2-year OS (P = .04). In multivariable Cox regression models among 69 patients with estrogen receptor (ER)-positive/HER2-negative cancer, RS was independently prognostic for TTP (hazard ratio, 1.40; 95% CI, 1.05 to 1.86; P = .02) and 2-year OS (hazard ratio, 1.83; 95% CI, 1.14 to 2.95; P = .013). The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER-positive/HER2-negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset. © 2016 by American Society of Clinical Oncology.

  2. Frequence, Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors1234

    PubMed Central

    Kramer, K.; Wolf, S.; Mayer, B.; Schmidt, S.A.; Agaimy, A.; Henne-Bruns, D.; Knippschild, U.; Schwab, M.; Schmieder, M.

    2015-01-01

    Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months), respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%), uro-genital and breast cancers (34.1%), hematological malignancies (7.3%), skin cancer (7.3%) and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267) was 62.8% compared to 83.4% in patients without other tumors (n = 569) (P < .001, HR=0.397, 95% CI: 0.298-0.530). Five-year disease specific survival was not different between both groups (90.8% versus 90.9%). 34.2% of all deaths (n = 66 of n = 193) were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted. PMID:25622906

  3. Lactate Elevation During and After Major Cardiac Surgery in Adults: A Review of Etiology, Prognostic Value, and Management.

    PubMed

    Andersen, Lars W

    2017-03-08

    Elevated lactate is a common occurrence after cardiac surgery. This review summarizes the literature on the complex etiology of lactate elevation during and after cardiac surgery, including considerations of oxygen delivery, oxygen utilization, increased metabolism, lactate clearance, medications and fluids, and postoperative complications. Second, the association between lactate and a variety of outcomes are described, and the prognostic role of lactate is critically assessed. Despite the fact that elevated lactate is strongly associated with many important outcomes, including postoperative complications, length of stay, and mortality, little is known about the optimal management of postoperative patients with lactate elevations. This review ends with an assessment of the limited literature on this subject.

  4. Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome

    PubMed Central

    Kim, Inho; Kim, Hyeoung-Joon; Shin, Dong-Yeop; Koh, Youngil; Yoon, Sung-Soo; Min, Yoo Hong; Ahn, Jae-Sook; Kim, Yeo-Kyeoung; Lee, Yun-Gyoo; Lee, Jeong-Ok; Bang, Soo-Mee; Mun, Yeung-Chul; Seong, Chu-Myoung; Park, Yong; Kim, Byung-Soo; Hong, Junshik; Park, Jinny; Lee, Jae Hoon; Kim, Sung-Yong; Lee, Hong Ghi

    2016-01-01

    Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment. PMID:27824923

  5. The prognostic impact of the anatomical sites in the 'head and neck melanoma': scalp versus face and neck.

    PubMed

    de Giorgi, Vincenzo; Rossari, Susanna; Gori, Alessia; Grazzini, Marta; Savarese, Imma; Crocetti, Emanuele; Cervadoro, Elisa; Massi, Daniela

    2012-10-01

    Cutaneous melanoma is a malignant neoplasia with several demographic and histopathological prognostic factors. Many studies stress that the head and neck region has a worse prognosis compared with other localizations, but the reasons for this worse prognosis are unclear. Therefore, the aim of our study is to analyse the poor prognosis of head and neck melanoma (HNM) with respect to the other anatomical sites, considering the face and neck (F&N) and the scalp separately. We carried out a retrospective analysis of 757 melanoma patients. In particular, we studied the prognostic impact of different melanoma skin localizations (head and neck, trunk, upper extremities and lower extremities). Afterwards, we divided HNM into two subgroups, F&N and scalp, to evaluate their impact in the HNM prognosis. Data showed a significantly lower 5-year overall survival probability for HNM (78.9 versus 93.1% for other body sites; P=0.05). Moreover, on analysing the two anatomical areas considered among HNM, we observed a 5-year overall survival of 81.8% for F&N and 66.7% for scalp. HNM has different and worse prognostic features with respect to other sites, but this trend is not only because of scalp melanoma but is also determined by F&N melanoma, which we believe to be underestimated until now.

  6. Prognostic Impact of Subclinical Microalbuminuria in Patients With Chronic Heart Failure.

    PubMed

    Miura, Masanobu; Sakata, Yasuhiko; Miyata, Satoshi; Nochioka, Kotaro; Takada, Tsuyoshi; Tadaki, Soichiro; Ushigome, Ryoichi; Yamauchi, Takeshi; Takahashi, Jun; Shimokawa, Hiroaki

    2014-10-30

    Background:Microalbuminuria, traditionally defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g, is a risk factor for mortality even in patients with preserved glomerular filtration rate (GFR). The prognostic impact of subclinical microalbuminuria, however, remains unknown in patients with chronic heart failure (CHF).Methods and Results:In the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 Study, we enrolled 2,039 consecutive symptomatic CHF patients (median age, 67.4 years; 68.9% male) after excluding those on hemodialysis. On classification and regression tree analysis, UACR=10.2 mg/g and 27.4 mg/g were identified as the first and second discriminating points to stratify the risk for composite of death, acute myocardial infarction, HF admission and stroke, therefore subclinical microalbuminuria was defined as UACR ≥10.2 and <27.4 mg/g. There were 506 composite endpoints (24.8%) during the median follow-up of 2.69 years. On Kaplan-Meier analysis and multivariate Cox modeling, subclinical microalbuminuria was significantly associated with increased composite endpoints with hazard ratios of 1.90 (P<0.001) and 2.29 (P<0.001) in patients with preserved (>60 ml·min(-1)·1.73 m(-2), n=1,129) or mildly reduced eGFR (30-59.9 ml·min(-1)·1.73 m(-2), n=789), respectively. In patients with severely reduced GFR (eGFR <30 ml·min(-1)·1.73 m(-2), n=121), >80% had microalbuminuria or macroalbuminuria, and only 9.1% were free from any composite endpoints.Conclusions:Subclinical microalbuminuria was associated with increased risk of cardiovascular events in CHF patients with mildly reduced or preserved renal function.

  7. The prognostic impact of obesity on molecular subtypes of breast cancer in premenopausal women.

    PubMed

    Turkoz, F P; Solak, M; Petekkaya, I; Keskin, O; Kertmen, N; Sarici, F; Arik, Z; Babacan, T; Ozisik, Y; Altundag, K

    2013-01-01

    The increasing incidence of obesity throughout the world will result in expansion of the number of women at risk for developing breast cancer. Obesity is associated with adverse outcomes in postmenopausal women with breast cancer. In premenopausal women, the association is less clear. We investigated the impact of obesity on tumor features, hormonal status, recurrence and mortality in premenopausal breast cancer patients, classified according to molecular subtypes. 818 premenopausal women with nonmetastatic breast cancer were analysed. Patients were classified into 3 groups according to body mass index (BMI): i) normal body weight (BMI: 18.5-24.9 kg/m(2)); ii) overweight (BMI: 25-29.9 kg/ m(2)); and iii) obese (BMI:>30 kg/ m(2)). Clinocopathologic characteristics and survival rates were analyzed for triple negative, HER-2 overexpressing and luminal subtypes. Obese patients compared with normal-weight women were older at diagnosis (p<0.001) and more often had high grade tumor (57.1 vs 42.3%; p=0.04) with lymphovascular invasion (79.5 vs 63.9%; p=0.03). The median follow-up period after diagnosis was 29 months. According to the molecular subtypes, overall survival (OS) and disease free survival (DFS) were significantly shorter in obese patients with triple negative breast cancer (TNBC) (p=0.001 and p=0.006, respectively). Obesity (HR 1.4; 95% CI 1.0-2.1; p=0.04) and lymphovascular invasion (HR 2.1; 95% CI 1.3- 3.3; p=0.02) were found to be independent prognostic factors for TNBC mortality. Obesity is associated with estrogen (ER) and progesterone receptor (PR) negative tumors and poor OS in premenopausal women with breast cancer.

  8. Clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease.

    PubMed

    Park, Jin Kyoung; Lee, Chang Hun; Kim, In Hee; Kim, Seon Min; Jang, Ji Won; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae-Ghon

    2015-05-01

    Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na <135 mM/L, albumin <2.5 g/dL, C-reactive protein ≥20 mg/L, systemic inflammatory response syndrome (SIRS) positivity were independently associated with bacterial infection in patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P < 0.001) higher than those without infection (22.3% vs. 5.1% and 32.3% vs. 8.2%, respectively). Furthermore, bacterial infection (HR, 2.2; 95% CI, 1.049-4.579, P = 0.037), SIRS positivity (HR, 2.5; 95% CI, 1.240-4.861, P = 0.010), Maddrey's discriminant function score ≥32 (HR, 2.3; 95% CI, 1.036-5.222, P = 0.041), and hemoglobin <12 g/dL (HR, 2.4; 95% CI, 1.081-5.450, P = 0.032) were independent predictors of short-term mortality. In conclusion, bacterial infection and SIRS positivity predicted short-term prognosis in hospitalized patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.

  9. Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients.

    PubMed

    Liu, Yi-Chun; Wang, Wen-Yi; Twu, Chih-Wen; Jiang, Rong-San; Liang, Kai-Li; Wu, Ching-Te; Lin, Po-Ju; Huang, Jing-Wen; Hsieh, He-Yuan; Lin, Jin-Ching

    2017-01-01

    To investigate the prognostic impact of adjuvant chemotherapy (AdjCT) in patients with high-risk nasopharyngeal carcinoma (NPC). A total 403 NPC patients with at least one of the following criteria (1) neck node>6cm; (2) supraclavicular node metastasis; (3) skull base destruction/intracranial invasion plus multiple nodes metastasis; or (4) multiple neck nodes metastasis with one of nodal size>4cm were retrospectively reviewed. All patients finished curative radiotherapy±neoadjuvant/concurrent chemotherapy. Post-radiation AdjCT consisted of tegafur-uracil (two capsules twice daily) for 12months. We analyzed the treatment outcome between patients with (n=154) and without (n=249) AdjCT. Baseline patient characteristics at diagnosis (age, gender, pathological type, performance status, T-classification, N-classification, and overall stage) were comparable in both arms. After a median follow-up of 72months for surviving patients, 31.8% (49/154) and 42.2% (105/249) in patients with and without AdjCT developed tumor relapse respectively (P=0.0377). AdjCT improved both overall survival (HR 1.89, 95% CI 1.37-2.61, P=0.0001) and progression-free survival (HR 1.42, 95% CI 1.03-1.96, P=0.0322). There were significant reduction in distant failures (P=0.0016) but not in local (P=0.8587) or regional (P=0.8997) recurrences for patients who received AdjCT. AdjCT can reduce distant failure and improve overall survival in high-risk NPC patients after curative radiotherapy±neoadjuvant/concurrent chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

    PubMed Central

    Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

    2017-01-01

    Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

  11. Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

    PubMed

    Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

    2017-01-01

    Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

  12. Exploring prognostic factors for HER2-positive metastatic breast cancer: a retrospective cohort study in a major Swiss hospital.

    PubMed

    Bringolf, Lilian; Pestalozzi, Bernhard; Fink, Daniel; Dedes, Konstantin

    2017-01-19

    Trastuzumab (Herceptin®, Roche) has significantly improved the prognosis of patients with HER2-positive metastatic breast cancer. Some patients remain in remission for many years. However, there are no prognostic markers associated with long-term survival. This study aimed to analyse treatment patterns of HER2-positive metastatic breast cancer at a single institution and explore prognostic factors for long-term survival after HER2-targeted treatment. This was a retrospective cohort study of all patients with HER2-positive metastatic breast cancer receiving first-line treatment with HER2-targeted therapy between 2004 and 2014 at the University Hospital of Zurich (n = 81). Overall survival (OS) and other time-to-event endpoints were determined with Kaplan-Meier curves and clinicopathological factors predicting long-term outcome were identified by use of the log-rank test. The median OS for the cohort was 5.9 years (95% confidence interval [CI] 3.5-8.3). Twenty patients (28.6%) remained in complete remission after 1 year, 11 (15.7%) after 2 years and 4 (5.7%) beyond 5 years. The median progression-free survival was 13.6 months (95% CI 9.0-18.3). The objective response rate (ORR) was 60.5% with 16 (19.8%) complete responses and 33 (40.8%) partial responses. Six (7.4%) patients had brain metastases as first site of relapse and they had a median OS of 1.9 years (95% CI 1.7-2.2 years). Thirty-four of all 81 patients (42%) had developed brain metastases by the time of death or last follow-up. Median OS after diagnosis of brain metastases was 26 months (95% CI 19.9-32.0). Only primary brain metastases were found to be a prognostic marker associated with shorter overall survival. Hormone-receptor status and presence of visceral metastases at primary diagnosis were not associated with prognosis. Only four patients (4.9%) developed some degree of left ventricular dysfunction under treatment with trastuzumab. HER2-targeted treatment has improved the overall survival of

  13. Prognostic impact of body mass index stratified by smoking status in patients with esophageal squamous cell carcinoma

    PubMed Central

    Sun, Peng; Zhang, Fei; Chen, Cui; Ren, Chao; Bi, Xi-Wen; Yang, Hang; An, Xin; Wang, Feng-Hua; Jiang, Wen-Qi

    2016-01-01

    Background As smoking affects the body mass index (BMI) and causes the risk of esophageal squamous cell carcinoma (ESCC), the prognostic impact of BMI in ESCC could be stratified by smoking status. We investigated the true prognostic effect of BMI and its potential modification by smoking status in ESCC. Methods We retrospectively analyzed 459 patients who underwent curative treatment at a single institution between January 2007 and December 2010. BMI was calculated using the measured height and weight before surgery. Chi-square test was used to evaluate the relationships between smoking status and other clinicopathological variables. The Cox proportional hazard models were used for univariate and multivariate analyses of variables related to overall survival. Results BMI <18.5 kg/m2 was a significantly independent predictor of poor survival in the overall population and never smokers after adjusting for covariates, but not in ever smokers. Among never smokers, underweight patients (BMI <18.5 kg/m2) had a 2.218 times greater risk of mortality than non-underweight (BMI ≥18.5 kg/m2) patients (P=0.015). Among ever smokers, BMI <18 kg/m2 increased the risk of mortality to 1.656 (P=0.019), compared to those having BMI ≥18 kg/m2. Conclusion Our study is likely the first to show that the prognostic effect of BMI was substantial in ESCC, even after stratifying by smoking status. Furthermore, the risk of death due to low BMI would be significantly increased in never smokers. We believe that the prognostic impact of BMI is modified but not eliminated by the smoking status in ESCC. PMID:27799787

  14. Impact of misspecifying the distribution of a prognostic factor on power and sample size for testing treatment interactions in clinical trials.

    PubMed

    Reichmann, William M; LaValley, Michael P; Gagnon, David R; Losina, Elena

    2013-02-15

    Interaction in clinical trials presents challenges for design and appropriate sample size estimation. Here we considered interaction between treatment assignment and a dichotomous prognostic factor with a continuous outcome. Our objectives were to describe differences in power and sample size requirements across alternative distributions of a prognostic factor and magnitudes of the interaction effect, describe the effect of misspecification of the distribution of the prognostic factor on the power to detect an interaction effect, and discuss and compare three methods of handling the misspecification of the prognostic factor distribution. We examined the impact of the distribution of the dichotomous prognostic factor on power and sample size for the interaction effect using traditional one-stage sample size calculation. We varied the magnitude of the interaction effect, the distribution of the prognostic factor, and the magnitude and direction of the misspecification of the distribution of the prognostic factor. We compared quota sampling, modified quota sampling, and sample size re-estimation using conditional power as three strategies for ensuring adequate power and type I error in the presence of a misspecification of the prognostic factor distribution. The sample size required to detect an interaction effect with 80% power increases as the distribution of the prognostic factor becomes less balanced. Misspecification such that the actual distribution of the prognostic factor was more skewed than planned led to a decrease in power with the greatest loss in power seen as the distribution of the prognostic factor became less balanced. Quota sampling was able to maintain the empirical power at 80% and the empirical type I error at 5%. The performance of the modified quota sampling procedure was related to the percentage of trials switching the quota sampling scheme. Sample size re-estimation using conditional power was able to improve the empirical power under

  15. Clinical characteristics and prognostic impact of atrial fibrillation in patients with chronic heart failure.

    PubMed

    Gigli, Lorenzo; Ameri, Pietro; Secco, Gianmarco; De Blasi, Gabriele; Miceli, Roberta; Lorenzoni, Alessandra; Torre, Francesco; Chiarella, Francesco; Brunelli, Claudio; Canepa, Marco

    2016-11-26

    To assess the prevalence, clinical characteristics and independent prognostic impact of atrial fibrillation (AF) in chronic heart failure (CHF) patients, and the potential protective effect of disease-modifying medications, particularly beta-blockers (BB). We retrospectively reviewed the charts of patients referred to our center since January 2004, and collected all clinical information available at their first visit. We assessed mortality to the end of June 2015. We compared patients with and without AF, and assessed the association between AF and all-cause mortality by multivariate Cox regression and Kaplan-Meyer analysis, particularly accounting for ongoing treatment with BB. A total of 903 patients were evaluated (mean age 68 ± 12 years, 73% male). Prevalence of AF was 19%, ranging from 10% to 28% in patients ≤ 60 and ≥ 77 years, respectively. Besides the older age, patients with AF had more symptoms (New York Heart Association II-III 60% vs 44%), lower prevalence of dyslipidemia (23% vs 37%), coronary artery disease (28% vs 52%) and left bundle branch block (9% vs 16%). On the contrary, they more frequently presented with an idiopathic etiology (50% vs 24%), a history of valve surgery (13% vs 4%) and received overall more devices implantation (31% vs 21%). The use of disease-modifying medications (i.e., BB and ACE inhibitors/angiotensin receptor blockers) was lower in patients with AF (72% vs 80% and 71% vs 79%, respectively), who on the contrary were more frequently treated with symptomatic and antiarrhythmic drugs including diuretics (87% vs 69%) and digoxin (51% vs 11%). At a mean follow-up of about 5 years, all-cause mortality was significantly higher in patients with AF as compared to those in sinus rhythm (SR) (45% vs 34%, P value < 0.05 for all previous comparisons). However, in a multivariate analysis including the main significant predictors of all-cause mortality, the univariate relationship between AF and death (HR = 1.49, 95%CI: 1

  16. Prediction of Outcome after Moderate and Severe Traumatic Brain Injury: External Validation of the IMPACT and CRASH Prognostic Models

    PubMed Central

    Roozenbeek, Bob; Lingsma, Hester F.; Lecky, Fiona E.; Lu, Juan; Weir, James; Butcher, Isabella; McHugh, Gillian S.; Murray, Gordon D.; Perel, Pablo; Maas, Andrew I.R.; Steyerberg, Ewout W.

    2012-01-01

    Objective The International Mission on Prognosis and Analysis of Clinical Trials (IMPACT) and Corticoid Randomisation After Significant Head injury (CRASH) prognostic models predict outcome after traumatic brain injury (TBI) but have not been compared in large datasets. The objective of this is study is to validate externally and compare the IMPACT and CRASH prognostic models for prediction of outcome after moderate or severe TBI. Design External validation study. Patients We considered 5 new datasets with a total of 9036 patients, comprising three randomized trials and two observational series, containing prospectively collected individual TBI patient data. Measurements Outcomes were mortality and unfavourable outcome, based on the Glasgow Outcome Score (GOS) at six months after injury. To assess performance, we studied the discrimination of the models (by AUCs), and calibration (by comparison of the mean observed to predicted outcomes and calibration slopes). Main Results The highest discrimination was found in the TARN trauma registry (AUCs between 0.83 and 0.87), and the lowest discrimination in the Pharmos trial (AUCs between 0.65 and 0.71). Although differences in predictor effects between development and validation populations were found (calibration slopes varying between 0.58 and 1.53), the differences in discrimination were largely explained by differences in case-mix in the validation studies. Calibration was good, the fraction of observed outcomes generally agreed well with the mean predicted outcome. No meaningful differences were noted in performance between the IMPACT and CRASH models. More complex models discriminated slightly better than simpler variants. Conclusions Since both the IMPACT and the CRASH prognostic models show good generalizability to more recent data, they are valid instruments to quantify prognosis in TBI. PMID:22511138

  17. Prognostic impact of absolute lymphocyte count/absolute monocyte count ratio and prognostic score in patients with nasal-type, extranodal natural killer/T-cell lymphoma.

    PubMed

    Li, Na; Zhang, Li; Song, Hao-Lan; Zhang, Jing; Weng, Hua-Wei; Zou, Li-Qun

    2017-05-01

    Nasal-type, extranodal natural killer/T-cell lymphoma is a heterogeneous disorder with poor prognosis, requiring risk stratification in this population. The combined value of baseline absolute lymphocyte count and absolute monocyte count provided prognostic information in some malignancies. However, the evidence requires validation in extranodal natural killer/T-cell lymphoma. Aiming to investigate the prognostic significance of absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score for extranodal natural killer/T-cell lymphoma, a retrospective research was carried out. A total of 264 patients with newly diagnosed extranodal natural killer/T-cell lymphoma were analyzed in this study. The patients' absolute lymphocyte count and absolute monocyte count tested at initial diagnosis were collected. Receiver operating curve analysis showed that the optimal cut-off values for absolute lymphocyte count and absolute monocyte count were 1.0 × 10(9) and 0.5 × 10(9)L(-1), respectively, and for absolute lymphocyte count/absolute monocyte count ratio was 2.85. After a median follow-up of 27 months (range 1-87 months), the 3-year overall survival and progression-free survival was 75.4% and 67.6%, respectively. Patients with absolute lymphocyte count/absolute monocyte count ratio ≥ 2.85 had better 3-year overall survival and progression-free survival than those with absolute lymphocyte count/absolute monocyte count ratio <2.85 (p < 0.001). According to absolute lymphocyte count/absolute monocyte count prognostic score, significant difference has been noticed in 3-year overall survival and progression-free survival (p < 0.001) and high absolute lymphocyte count/absolute monocyte count prognostic score was associated with poorer survival. The International Prognostic Index and Korean Prognostic Index were used for prognosis and showed no significant difference. When adding absolute lymphocyte count

  18. The prognostic impact of sex on surgically resected non-small cell lung cancer depends on clinicopathologic characteristics.

    PubMed

    Sterlacci, William; Tzankov, Alexandar; Veits, Lothar; Oberaigner, Wilhelm; Schmid, Thomas; Hilbe, Wolfgang; Fiegl, Michael

    2011-04-01

    The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non-small cell lung cancers (NSCLCs) using a standardized tissue microarray platform. Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less. Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.

  19. The public health impact of hurricanes and major flooding.

    PubMed

    Diaz, James H

    2004-01-01

    Accurate predictions of the public health impact of hurricanes and major flooding are hampered by the absence of a dose-response relationship between hurricane-associated flooding and human health and the imprecise, often conflicting, meteorological models of climate change and hurricane landfall. Flooding is now the most common type of disaster worldwide, and flash flooding, usually associated with tropical storms, is the leading cause of weather-related deaths in the United States. As a result of climate changes and more frequently alternating ocean oscillations, hurricanes of category 3 or greater now strike the continental US approximately every 18 months. Public health officials are obligated to educate policymakers and the public about the significant threats posed to population health and quality of life by the inexorable progression of global climate change, including more water-centered disasters, such as tropical storms and hurricanes.

  20. Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients.

    PubMed

    Choi, Seyoun; Lee, Keun-Wook; Bang, Soo-Mee; Kim, Sujung; Lee, Jeong-Ok; Kim, Yu Jung; Kim, Jee Hyun; Park, Young Soo; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Jae-Sung; Oh, Doyeun; Lee, Jong Seok

    2011-12-01

    This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.

  1. Performance status in patients with hepatocellular carcinoma: determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system.

    PubMed

    Hsu, Chia-Yang; Lee, Yun-Hsuan; Hsia, Cheng-Yuan; Huang, Yi-Hsiang; Su, Chien-Wei; Lin, Han-Chieh; Lee, Rheun-Chuan; Chiou, Yi-You; Lee, Fa-Yauh; Huo, Teh-Ia

    2013-01-01

    Performance status is included in the Barcelona Clinic Liver Cancer (BCLC) system for hepatocellular carcinoma (HCC). Few studies specifically evaluated the role of performance status in patients with HCC. This study investigated its distribution, determinants, and prognostic impact, aiming to improve the performance of the BCLC system. A total of 2,381 HCC patients were enrolled. Performance status was determined according to the Eastern Cooperative Oncology Group scale. The prognostic ability of the original and three modified BCLC systems in HCC patients was compared by the Akaike information criterion (AIC). There were 60, 17, 11, 8, and 4% of patients who were classified as performance status 0, 1, 2, 3, and 4, respectively. A worse performance status significantly correlated with age, alcoholism, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, and prothrombin time prolongation (all P < 0.001). Larger tumor burden, poorer residual liver function, more frequent vascular invasion, and diabetes mellitus were also observed in patients with worse performance status (all P < 0.001). Patients with poorer performance status more often received best supportive care (P < 0.001). In the Cox proportional hazards model, performance status was an independent prognostic predictor and the long-term survival tended to be worse in patients with progressively poor performance status (all P < 0.05). Reassigning patients with performance status 0 or 1 to stage B provided the lowest AIC among the four BCLC-based staging systems. Performance status is strongly associated with both tumoral and cirrhotic factors and accurately predicts long-term survival in HCC patients. Modification of the BCLC system based on performance status may further enhance its prognostic ability in patients with early to advanced cancer stage. Copyright © 2012 American Association for the Study of Liver Diseases.

  2. Incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with neuromuscular scoliosis

    PubMed Central

    Jia, Rui; Li, Na; Xu, Bi-Yun; Zhang, Wei; Gu, Xiao-ping; Ma, Zheng-Liang

    2017-01-01

    Abstract Factors influencing massive blood loss for neuromuscular scoliosis (NMS) patients. Despite advances in surgical and anesthetic techniques, scoliosis surgery is still associated with intraoperative massive blood loss, which can result in postoperative mortality and morbidity. The aim of this study was to assess the incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with NMS. A retrospective review of adolescents who underwent posterior spinal instrumentation and fusion for NMS was performed. Perioperative variables and data were recorded. Massive blood loss was defined as an estimated blood loss that exceeds 30% of total blood volume. We obtained data for 114 patients, of whom 63 (55%) had intraoperative massive blood loss. Compared with those without, patients with massive blood loss were more likely to be older, have lower body mass indexes (BMIs), larger Cobb angles, more fused levels, more osteotomy procedures, and prolonged duration of operation. Logistic regression analysis identified the number of fused levels to be more than 12 (P = 0.003, odds ratio = 6.614, 95% confidence interval [CI]: 1.891–23.131), BMI lower than 16.8 kg/m2 (P = 0.025, odds ratio = 3.293, 95% CI: 1.159–9.357), age greater than 15 years (P = 0.014, odds ratio = 3.505, 95% CI: 1.259–9.761), and duration of operation longer than 4.4 hours (P = 0.016, odds ratio = 3.746, 95% CI: 1.428–9.822) as influencing factors. Patients with massive blood loss are associated with more intraoperative colloids infusion and blood transfusions (red blood cell and fresh frozen plasma), as well as postoperative drainage volume. In adolescents with NMS who underwent posterior spinal instrumentation and fusion operations, intraoperative massive blood loss is common. The number of fused levels, BMI, age, and duration of operation are factors influencing intraoperative massive blood loss. PMID:28296737

  3. Patterns, predictive factors and prognostic impact of multilevel metastasis in N1b papillary thyroid carcinoma.

    PubMed

    Kim, S K; Park, I; Hur, N; Choe, J-H; Kim, J-H; Kim, J S

    2017-06-01

    The patterns, predictive factors and prognostic impact of multilevel metastasis in patients with N1b papillary thyroid carcinoma (PTC) were investigated. A retrospective review of patients with N1b PTC from a tertiary referral centre in Korea who underwent unilateral modified radical neck dissection was undertaken. Of 658 patients, multilevel metastasis was found in 73·9 per cent; the most common type was metastasis in two levels. Tumour size per 0·1-cm increment (adjusted odds ratio (OR) 1·33, 95 per cent c.i. 1·08 to 1·64), microscopic extrathyroidal extension (adjusted OR 1·72, 1·10 to 2·71), gross extrathyroidal extension (adjusted OR 2·35, 1·24 to 4·46), unilateral central lymph node metastasis (adjusted OR 2·45, 1·53 to 3·92) and bilateral central lymph node metastasis (adjusted OR 4·06, 2·29 to 7·18) were independent predictors of multilevel metastasis. Only four-level metastasis significantly increased the risk of overall locoregional recurrence (LRR) (adjusted hazard ratio (HR) 7·41, 95 per cent c.i. 2·20 to 24·53) and lateral neck LRR (adjusted HR 7·22, 1·82 to 28·65), compared with one-level metastasis. Two subgroup analyses were conducted, showing that only three-level metastasis including metastasis in level V significantly increased the risk of overall LRR (adjusted HR 5·66, 1·20 to 26·75). In addition, having level V metastasis was an independent predictor of both overall (adjusted HR 3·26, 1·72 to 6·18; P < 0·001) and lateral neck (adjusted HR 3·28, 1·50 to 7·16; P = 0·003) LRR. Level V metastasis rather than multilevel metastasis itself is associated with an increased risk of LRR. Patients with N1b PTC and level V metastasis require risk restratification and meticulous follow-up. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  4. Environmental impacts of Major Flood Events: Hurricane Katrina

    NASA Astrophysics Data System (ADS)

    Reible, D. D.

    2008-05-01

    The flooding of New Orleans by Hurricane Katrina provides many lessons for the environmental and engineering communities and raises serious public policy questions about risk management. Although serious environmental and waste management concerns were highlighted as a result of the flooding, many were not observed in the extensive environmental sampling that occurred. The potential environmental consequences were of concern because of the many chemical plants, petroleum facilities, and contaminated sites, including Superfund sites, in the areas covered by floodwaters. The potential sources of toxics and environmental contaminants included metal-contaminated soils typical of old urban areas. Compounding these concerns is the presence of hazardous chemicals commonly stored in households and commercial establishments and the fuel and motor oil in approximately 350,000 flooded automobiles. Uncontrolled biological wastes from both human and animal sources also contributed to the pollutant burden. There were concerns associated with the immediate impacts of the flooding, the disposal of the debris and wastes in the aftermath, as well as the long- term legacy associated with contaminants in homes and yards. This discussion focuses on successes and failures in responding to each of these concerns as well as lessons learned for future major flooding events. Special attention is paid to some of the unique hazards posed by Katrina, including water quality impacts associated with debris disposal, high indoor concentrations of contaminants due to fractionation from outdoor soils, and mold.

  5. The Impact of Various Platelet Indices as Prognostic Markers of Septic Shock

    PubMed Central

    Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li

    2014-01-01

    Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886

  6. Subtype-specific prognostic impact of different immune signatures in node-negative breast cancer.

    PubMed

    Heimes, A-S; Madjar, K; Edlund, K; Battista, M J; Almstedt, K; Elger, T; Krajnak, S; Rahnenführer, J; Brenner, W; Hasenburg, A; Hengstler, J G; Schmidt, M

    2017-09-01

    The role of different subtypes of immune cells is still a matter of debate. We compared the prognostic relevance for metastasis-free survival (MFS) of a B-cell signature (BS), a T-cell signature (TS), and an immune checkpoint signature (CPS) in node-negative breast cancer (BC) using mRNA expression. Microarray-based gene-expression data were analyzed in six previously published cohorts of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). The prognostic relevance of the individual immune markers was assessed using univariate analysis. The amount of independent prognostic information provided by each immune signature was then compared using a likelihood ratio statistic in the whole cohort as well as in different molecular subtypes. Univariate Cox regression in the whole cohort revealed prognostic significance of CD4 (HR 0.66, CI 0.50-0.87, p = 0.004), CXCL13 (HR 0.86, CI 0.81-0.92, p < 0.001), CD20 (HR 0.76, CI 0.64-0.89, p = 0.001), IgκC (HR 0.81, CI 0.75-0.88, p < 0.001), and CTLA-4 (HR 0.67, CI 0.46-0.97, p = 0.032). Multivariate analyses of the immune signatures showed that both TS (p < 0.001) and BS (p < 0.001) showed a significant prognostic information in the whole cohort. After accounting for clinical-pathological variables, TS (p < 0.001), BS (p < 0.05), and CPS (p < 0.05) had an independent effect for MFS. In subgroup analyses, the prognostic effect of immune cells was most pronounced in HER2+ BC: BS as well as TS showed a strong association with MFS when included first in the model (p < 0.001). Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.

  7. Impact of the pretreatment Glasgow prognostic score on treatment tolerance, toxicities, and survival in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy.

    PubMed

    Chang, Pei-Hung; Yeh, Kun-Yun; Wang, Cheng-Hsu; Chen, Eric Yen-Chao; Yang, Shih-Wei; Huang, Jen-Seng; Chou, Wen-Chi; Hsieh, Jason Chia-Hsun

    2017-10-01

    The purpose of this study was to evaluate the impact of the pretreatment Glasgow prognostic score on treatment-related toxicities, tolerance, and survival in patients with advanced head and neck cancers undergoing concurrent chemoradiotherapy (CRT). We retrospectively analyzed and compared the clinical characteristics, toxicities, and survival of 143 patients with stages III, IVA, and IVB head and neck cancer treated with concurrent CRT according to their Glasgow prognostic score between 2007 and 2010. The Glasgow prognostic score was correlated with advanced tumor stage and T/N classification. Patients with a higher Glasgow prognostic score were less likely to tolerate concurrent CRT, experienced more weight loss, required tube feeding support more frequently, and had higher percentage of grade ≥3 hematological toxicities, sepsis, and toxic death. Patients with a Glasgow prognostic score of 0 had better overall and recurrence-free survival than those with a Glasgow prognostic score of 1 or 2. Pretreatment Glasgow prognostic score predicts treatment tolerance, toxicity, and survival in patients with advanced head and neck cancer undergoing concurrent CRT. © 2017 Wiley Periodicals, Inc.

  8. Clinical characteristics and prognostic impact of atrial fibrillation in patients with chronic heart failure

    PubMed Central

    Gigli, Lorenzo; Ameri, Pietro; Secco, Gianmarco; De Blasi, Gabriele; Miceli, Roberta; Lorenzoni, Alessandra; Torre, Francesco; Chiarella, Francesco; Brunelli, Claudio; Canepa, Marco

    2016-01-01

    AIM To assess the prevalence, clinical characteristics and independent prognostic impact of atrial fibrillation (AF) in chronic heart failure (CHF) patients, and the potential protective effect of disease-modifying medications, particularly beta-blockers (BB). METHODS We retrospectively reviewed the charts of patients referred to our center since January 2004, and collected all clinical information available at their first visit. We assessed mortality to the end of June 2015. We compared patients with and without AF, and assessed the association between AF and all-cause mortality by multivariate Cox regression and Kaplan-Meyer analysis, particularly accounting for ongoing treatment with BB. RESULTS A total of 903 patients were evaluated (mean age 68 ± 12 years, 73% male). Prevalence of AF was 19%, ranging from 10% to 28% in patients ≤ 60 and ≥ 77 years, respectively. Besides the older age, patients with AF had more symptoms (New York Heart Association II-III 60% vs 44%), lower prevalence of dyslipidemia (23% vs 37%), coronary artery disease (28% vs 52%) and left bundle branch block (9% vs 16%). On the contrary, they more frequently presented with an idiopathic etiology (50% vs 24%), a history of valve surgery (13% vs 4%) and received overall more devices implantation (31% vs 21%). The use of disease-modifying medications (i.e., BB and ACE inhibitors/angiotensin receptor blockers) was lower in patients with AF (72% vs 80% and 71% vs 79%, respectively), who on the contrary were more frequently treated with symptomatic and antiarrhythmic drugs including diuretics (87% vs 69%) and digoxin (51% vs 11%). At a mean follow-up of about 5 years, all-cause mortality was significantly higher in patients with AF as compared to those in sinus rhythm (SR) (45% vs 34%, P value < 0.05 for all previous comparisons). However, in a multivariate analysis including the main significant predictors of all-cause mortality, the univariate relationship between AF and death (HR = 1

  9. Major osteoporotic fragility fractures: Risk factor updates and societal impact

    PubMed Central

    Pisani, Paola; Renna, Maria Daniela; Conversano, Francesco; Casciaro, Ernesto; Di Paola, Marco; Quarta, Eugenio; Muratore, Maurizio; Casciaro, Sergio

    2016-01-01

    Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence. PMID:27004165

  10. Prognostic factors of brain metastases from breast cancer: impact of targeted therapies.

    PubMed

    Braccini, Antoine Laurent; Azria, David; Thezenas, Simon; Romieu, Gilles; Ferrero, Jean Marc; Jacot, William

    2013-10-01

    Brain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population. Breast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study. 250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR-/HER2-), 30.8% as HR+/HER2- and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9-10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p < 0.001). Biological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Impact of sex on prognostic host factors in surgical patients with lung cancer.

    PubMed

    Wainer, Zoe; Wright, Gavin M; Gough, Karla; Daniels, Marissa G; Choong, Peter; Conron, Matthew; Russell, Prudence A; Alam, Naveed Z; Ball, David; Solomon, Benjamin

    2016-09-14

    Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors. Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women. The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012). Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men. © 2016 Royal Australasian College of Surgeons.

  12. Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

    PubMed

    Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

    2016-03-01

    The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.

  13. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy.

    PubMed

    Santacruz, Rodrigo; Villamor, Neus; Aymerich, Marta; Martínez-Trillos, Alejandra; López, Cristina; Navarro, Alba; Rozman, María; Beà, Sílvia; Royo, Cristina; Cazorla, Maite; Colomer, Dolors; Giné, Eva; Pinyol, Magda; Puente, Xose S; López-Otín, Carlos; Campo, Elías; López-Guillermo, Armando; Delgado, Julio

    2014-05-01

    A proportion of patients with chronic lymphocytic leukemia achieve a minimal residual disease negative status after therapy. We retrospectively evaluated the impact of minimal residual disease on the outcome of 255 consecutive patients receiving any front-line therapy in the context of a detailed prognostic evaluation, including assessment of IGHV, TP53, NOTCH1 and SF3B1 mutations. The median follow-up was 73 months (range, 2-202) from disease evaluation. The median treatment-free survival durations for patients achieving a complete response without or with minimal residual disease, a partial response and no response were 76, 40, 11 and 11 months, respectively (P<0.001). Multivariate analysis revealed that three variables had a significant impact on treatment-free survival: minimal residual disease (P<0.001), IGHV status (P<0.001) and β2-microglobulin levels (P=0.012). With regards to overall survival, factors predictive of an unfavorable outcome were minimal residual disease positivity (P=0.014), together with advanced age (P<0.001), unmutated IGHV status (P=0.001), TP53 mutations (P<0.001) and elevated levels of β2-microglobulin (P=0.003). In conclusion, for patients requiring front-line therapy, achievement of minimal residual disease negativity is associated with significantly prolonged treatment-free and overall survival irrespective of other prognostic markers or treatment administered.

  14. Outcome in excised thymomas: role of prognostic factors and impact of additional malignancies on survival.

    PubMed

    Granato, F; Blackhall, V; Alessandra, R; Spina, D; Luca, V; Piero, P; Mohiyaddin, S; Asif, M; Kirk, A J B; Giuseppe, Gotti

    2014-02-01

    Although the management of thymomas has been extensively evaluated, the value of prognostic factors in the outcome of these patients remains unclear. The medical records of all patients who underwent resection of thymoma between January 1985 and September 2010 at a single thoracic unit were reviewed. Patients were followed up with reference to disease recurrence and development of additional malignancies (AM). Total thymectomy was performed in all 68 cases. Mean follow-up time was four years. Mean survival was 63.9 months. Mean disease-free interval was 13 months. Factors affecting prognosis were Masaoka staging and WHO histological sub-type. Patients with thymomas had a higher risk of developing AM when compared with a control population of individuals with other tumours (p = 0.0002). Among thymomas, the cortical subtype was associated with a higher risk of AM (p = 0.047) and mortality (p = 0.001). This data confirms that Masaoka staging and WHO histologic sub-type are the most important prognostic factors in patients with thymoma. Moreover, thymomas predominantly arising from the thymic cortex are associated with a higher risk of developing other malignancies and with poorer survival. The cortical origin of thymoma could therefore be considered as a significant prognostic factor.

  15. Impact of major volcanic eruptions on stratospheric water vapour

    NASA Astrophysics Data System (ADS)

    Löffler, M.; Brinkop, S.; Jöckel, P.

    2015-12-01

    Volcanic eruptions can have significant impact on the earth's weather and climate system. Besides the subsequent tropospheric changes also the stratosphere is influenced by large eruptions. Here changes in stratospheric water vapour after the two major volcanic eruptions of El Chichón in Mexico in 1982 and Mount Pinatubo on the Philippines in 1991 are investigated with chemistry-climate model simulations. This study is based on two simulations with specified dynamics of the EMAC model, performed within the Earth System Chemistry integrated Modelling (ESCiMo) project, of which only one includes the volcanic forcing through prescribed aerosol optical properties. The results show a significant increase in stratospheric water vapour after the eruptions, resulting from increased heating rates and the subsequent changes in stratospheric and tropopause temperatures in the tropics. The tropical vertical advection and the South Asian summer monsoon are identified as important sources for the additional water vapour in the stratosphere. Additionally, volcanic influences on the tropospheric water vapour and ENSO are evident.

  16. Impact of major volcanic eruptions on stratospheric water vapour

    NASA Astrophysics Data System (ADS)

    Löffler, Michael; Brinkop, Sabine; Jöckel, Patrick

    2016-05-01

    Volcanic eruptions can have a significant impact on the Earth's weather and climate system. Besides the subsequent tropospheric changes, the stratosphere is also influenced by large eruptions. Here changes in stratospheric water vapour after the two major volcanic eruptions of El Chichón in Mexico in 1982 and Mount Pinatubo on the Philippines in 1991 are investigated with chemistry-climate model simulations. This study is based on two simulations with specified dynamics of the European Centre for Medium-Range Weather Forecasts Hamburg - Modular Earth Submodel System (ECHAM/MESSy) Atmospheric Chemistry (EMAC) model, performed within the Earth System Chemistry integrated Modelling (ESCiMo) project, of which only one includes the long-wave volcanic forcing through prescribed aerosol optical properties. The results show a significant increase in stratospheric water vapour induced by the eruptions, resulting from increased heating rates and the subsequent changes in stratospheric and tropopause temperatures in the tropics. The tropical vertical advection and the South Asian summer monsoon are identified as sources for the additional water vapour in the stratosphere. Additionally, volcanic influences on tropospheric water vapour and El Niño-Southern Oscillation (ENSO) are evident, if the long-wave forcing is strong enough. Our results are corroborated by additional sensitivity simulations of the Mount Pinatubo period with reduced nudging and reduced volcanic aerosol extinction.

  17. Long-term Prognostic Value of Major and Minor ECG Abnormalities in Latent Keshan Disease With Suspect Chronic Keshan Disease

    PubMed Central

    Zhu, Yanhe; Lai, Bingqi; Niu, Xiaolin; Wei, Jin; Tan, Wuhong; Wang, Xinfeng

    2014-01-01

    Objective This study aims to determine whether baseline electrocardiography (ECG) abnormalities, the appearance of new ECG abnormalities, or other clinical characteristics are associated with increased rates of progression to chronic Keshan disease (KD) among patients with latent KD. Methods Four hundred and fourteen new latent KD patients from a monitored population in China were diagnosed and then followed for 10 years. Baseline and 10-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict chronic KD events. Results In 414 latent KD patients with ECG abnormalities, 220 (53.1%) had minor and 194 (46.9%) had major ECG abnormalities. During the follow-up, 92 (22.2%) patients experienced chronic KD events; 32 (14.5%) and 60 (30.9%) of these chronic KD events occurred in the minor and major ECG abnormalities groups, respectively. After adjustment for baseline potential confounders, the hazard ratios and 95% confidence intervals (CIs) for progression to chronic KD in latent KD patients with major ECG abnormalities versus those with minor ECG abnormalities was 2.43 (95% CI 1.58–3.93). Conclusions Major ECG abnormalities and new ventricular premature complex abnormalities that occurred during the follow-up were both associated with an increased risk of progression to chronic KD. Atrial fibrillation and right bundle branch block with left anterior hemiblock are the most strongly predictive components of major ECG abnormalities. Depending on the model, adding ECG abnormalities to traditional risk factors was associated with improved risk prediction in latent KD. PMID:24975014

  18. Long-term prognostic value of major and minor ECG abnormalities in latent Keshan disease with suspect chronic Keshan disease.

    PubMed

    Zhu, Yanhe; Lai, Bingqi; Niu, Xiaolin; Wei, Jin; Tan, Wuhong; Wang, Xinfeng

    2014-01-01

    This study aims to determine whether baseline electrocardiography (ECG) abnormalities, the appearance of new ECG abnormalities, or other clinical characteristics are associated with increased rates of progression to chronic Keshan disease (KD) among patients with latent KD. Four hundred and fourteen new latent KD patients from a monitored population in China were diagnosed and then followed for 10 years. Baseline and 10-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict chronic KD events. In 414 latent KD patients with ECG abnormalities, 220 (53.1%) had minor and 194 (46.9%) had major ECG abnormalities. During the follow-up, 92 (22.2%) patients experienced chronic KD events; 32 (14.5%) and 60 (30.9%) of these chronic KD events occurred in the minor and major ECG abnormalities groups, respectively. After adjustment for baseline potential confounders, the hazard ratios and 95% confidence intervals (CIs) for progression to chronic KD in latent KD patients with major ECG abnormalities versus those with minor ECG abnormalities was 2.43 (95% CI 1.58-3.93). Major ECG abnormalities and new ventricular premature complex abnormalities that occurred during the follow-up were both associated with an increased risk of progression to chronic KD. Atrial fibrillation and right bundle branch block with left anterior hemiblock are the most strongly predictive components of major ECG abnormalities. Depending on the model, adding ECG abnormalities to traditional risk factors was associated with improved risk prediction in latent KD.

  19. Reduced expression of argininosuccinate synthetase 1 has a negative prognostic impact in patients with pancreatic ductal adenocarcinoma

    PubMed Central

    Liu, Qingqing; Stewart, John; Wang, Hua; Rashid, Asif; Zhao, Jun; Katz, Matthew H.; Lee, Jeffrey E.; Fleming, Jason B.; Maitra, Anirban; Wolff, Robert A.; Varadhachary, Gauri R.; Krishnan, Sunil; Wang, Huamin

    2017-01-01

    Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme for arginine biosynthesis, is expressed in many types of human malignancies. Recent studies showed that ASS1 may have tumor suppressor function and that ASS1 deficiency is associated with clinical aggressiveness in nasopharyngeal carcinoma, myxofibrosarcomas and bladder cancer. The goal of this study was to evaluate the prognostic impact of ASS1 expression in patients with pancreatic ductal adenocarcinoma (PDAC). Our study included two independent cohorts: untreated cohort, which was comprised of 135 patients with PDAC who underwent pancreatoduodenectomy (PD) without pre-operative neoadjuvant therapy, and treated cohort, which was comprised of 122 patients with PDAC who have completed neoadjuvant therapy and PD. The expression level of ASS1 was evaluated by immunohistochemistry and the results were correlated with clinicopathologic parameters and survival using SPSS statistics. Our study showed that 12% of PDAC in untreated cohort and 15% of PDAC in treated cohort has low expression of ASS1 (ASS1-low). ASS1-low was associated with higher recurrence (p = 0.045), shorter disease-free survival (DFS, 4.8 ± 1.6 months vs 15.3 ± 2.2 months, p = 0.001) and shorter overall survival (OS, 14.6 ± 6.4 months vs 26.5 ± 3.5 months, p = 0.005) in untreated cohort and shorter OS in treated cohort compared to ASS1-high tumors. In multivariate analysis, ASS1-low (HR: 0.45, 95% CI: 0.26–0.79, p = 0.005) was an independent prognostic factor for DFS in untreated cohort and an independent prognostic factor for OS (HR: 0.56, 95% CI: 0.32–0.97, p = 0.04) in treated cohort. Our results provide supporting evidence for future clinical trial using arginine deprivation agents either alone or in combination with conventional chemotherapy in treating pancreatic cancer. PMID:28187218

  20. Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

    PubMed Central

    Chang, I-Wei; Li, Chien-Feng; Lin, Victor Chia-Hsiang; He, Hong-Lin; Liang, Per-In; Wu, Wen-Jeng; Li, Ching-Chia; Huang, Chun-Nung

    2016-01-01

    Purpose: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene. Materials and Methods: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS). Results: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses. Conclusion: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs. PMID:27471570

  1. Is the negative prognostic impact of signet ring cell histology maintained in early gastric adenocarcinoma?

    PubMed

    Gronnier, Caroline; Messager, Mathieu; Robb, William B; Thiebot, Timothée; Louis, Damien; Luc, Guillaume; Piessen, Guillaume; Mariette, Christophe

    2013-11-01

    Although the signet ring cell histologic subtype (SRC) is an independent predictor of poor prognosis in advanced gastric adenocarcinomas (GA), its prognostic value in early GA remains highly controversial. The aim of the study was to evaluate the prognostic impact of SRC in mucosal and submucosal GAs. Based on a multicenter cohort of 3,010 patients operated on for GA between January 1997 and January 2010, patients with pTis or pT1 tumors were extracted and analyzed comparatively between the SRC and non-SRC groups. The primary objective was to compare the 5-year survival rate between groups. Among 421 patients with a pTis or pT1 tumor, 104 (25%) were SRC and 317 (75%) were non-SRC. Demographic variables were comparable between groups, except median age, which was less in the SRC group (59.6 vs 68.8 years; P < .001). Submucosal involvement was more frequent in the SRC group (94% vs 85%; P = .043), whereas lymph node involvement and number of invaded nodes were comparable between the 2 groups. When comparing SRC and non-SRC, recurrence rates (6% vs 9%; P = .223) and sites of recurrence were similar. The 5-year overall survival benefit in SRC patients (85% vs 76%, respectively; P = .035), was not evident when considering exclusively disease-specific survival or in multivariable analysis. Contrary to more advanced GA, SRC morphologic subtype is not a negative prognostic factor in early GA. Better survival identified in some reports may be related to the younger age in SRC patients. Copyright © 2013 Mosby, Inc. All rights reserved.

  2. Nutritional Risk in Major Abdominal Surgery: Protocol of a Prospective Observational Trial to Evaluate the Prognostic Value of Different Nutritional Scores in Pancreatic Surgery

    PubMed Central

    Probst, Pascal; Haller, Sebastian; Dörr-Harim, Colette; Bruckner, Thomas; Ulrich, Alexis; Hackert, Thilo; Diener, Markus K

    2015-01-01

    Background The influence of patients’ preoperative nutritional status on their clinical outcome has already been proven. Therefore, patients with malnutrition are in need of additional therapeutic efforts. However, for pancreatic surgery, evidence suggesting the adequacy of existing nutritional assessment scores to estimate malnutrition associated with postoperative outcome is limited. Objective The aim of the observational trial “Nutritional Risk in Major Abdominal Surgery (NURIMAS) Pancreas” is to prospectively assess and analyze different nutritional assessment scores for their prognostic value on postoperative complications in patients undergoing pancreatic surgery. Methods All patients scheduled to receive elective pancreatic surgery at the University Hospital of Heidelberg will be screened for eligibility. Preoperatively, 12 nutritional assessment scores will be collected and patients will be assigned either at risk or not at risk for malnutrition. The postoperative course will be followed prospectively and complications according to the Clavien-Dindo classification will be recorded. The prognostic value for complications will be evaluated for every score in a univariable and multivariable analysis corrected for known risk factors in pancreatic surgery. Results Final data analysis is expected to be available during Spring 2016. Conclusions The NURIMAS Pancreas trial is a monocentric, prospective, observational trial aiming to find the most predictive clinical nutritional assessment score for postoperative complications. Using the results of this protocol as a knowledge base, it is possible to conduct nutritional risk-guided intervention trials to prevent postoperative complications in the pancreatic surgical population. Trial Registration germanctr.de: DRKS00006340; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00006340 (Archived by WebCite at http://www.webcitation.org/6bzXWSRYZ) PMID:26573991

  3. Seafood prices reveal impacts of a major ecological disturbance.

    PubMed

    Smith, Martin D; Oglend, Atle; Kirkpatrick, A Justin; Asche, Frank; Bennear, Lori S; Craig, J Kevin; Nance, James M

    2017-02-14

    Coastal hypoxia (dissolved oxygen ≤ 2 mg/L) is a growing problem worldwide that threatens marine ecosystem services, but little is known about economic effects on fisheries. Here, we provide evidence that hypoxia causes economic impacts on a major fishery. Ecological studies of hypoxia and marine fauna suggest multiple mechanisms through which hypoxia can skew a population's size distribution toward smaller individuals. These mechanisms produce sharp predictions about changes in seafood markets. Hypoxia is hypothesized to decrease the quantity of large shrimp relative to small shrimp and increase the price of large shrimp relative to small shrimp. We test these hypotheses using time series of size-based prices. Naive quantity-based models using treatment/control comparisons in hypoxic and nonhypoxic areas produce null results, but we find strong evidence of the hypothesized effects in the relative prices: Hypoxia increases the relative price of large shrimp compared with small shrimp. The effects of fuel prices provide supporting evidence. Empirical models of fishing effort and bioeconomic simulations explain why quantifying effects of hypoxia on fisheries using quantity data has been inconclusive. Specifically, spatial-dynamic feedbacks across the natural system (the fish stock) and human system (the mobile fishing fleet) confound "treated" and "control" areas. Consequently, analyses of price data, which rely on a market counterfactual, are able to reveal effects of the ecological disturbance that are obscured in quantity data. Our results are an important step toward quantifying the economic value of reduced upstream nutrient loading in the Mississippi Basin and are broadly applicable to other coupled human-natural systems.

  4. Seafood prices reveal impacts of a major ecological disturbance

    PubMed Central

    Smith, Martin D.; Oglend, Atle; Kirkpatrick, A. Justin; Asche, Frank; Bennear, Lori S.; Craig, J. Kevin; Nance, James M.

    2017-01-01

    Coastal hypoxia (dissolved oxygen ≤ 2 mg/L) is a growing problem worldwide that threatens marine ecosystem services, but little is known about economic effects on fisheries. Here, we provide evidence that hypoxia causes economic impacts on a major fishery. Ecological studies of hypoxia and marine fauna suggest multiple mechanisms through which hypoxia can skew a population’s size distribution toward smaller individuals. These mechanisms produce sharp predictions about changes in seafood markets. Hypoxia is hypothesized to decrease the quantity of large shrimp relative to small shrimp and increase the price of large shrimp relative to small shrimp. We test these hypotheses using time series of size-based prices. Naive quantity-based models using treatment/control comparisons in hypoxic and nonhypoxic areas produce null results, but we find strong evidence of the hypothesized effects in the relative prices: Hypoxia increases the relative price of large shrimp compared with small shrimp. The effects of fuel prices provide supporting evidence. Empirical models of fishing effort and bioeconomic simulations explain why quantifying effects of hypoxia on fisheries using quantity data has been inconclusive. Specifically, spatial-dynamic feedbacks across the natural system (the fish stock) and human system (the mobile fishing fleet) confound “treated” and “control” areas. Consequently, analyses of price data, which rely on a market counterfactual, are able to reveal effects of the ecological disturbance that are obscured in quantity data. Our results are an important step toward quantifying the economic value of reduced upstream nutrient loading in the Mississippi Basin and are broadly applicable to other coupled human-natural systems. PMID:28137850

  5. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort.

    PubMed

    Tabouret, Emeline; Nguyen, Anh Tuan; Dehais, Caroline; Carpentier, Catherine; Ducray, François; Idbaih, Ahmed; Mokhtari, Karima; Jouvet, Anne; Uro-Coste, Emmanuelle; Colin, Carole; Chinot, Olivier; Loiseau, Hugues; Moyal, Elisabeth; Maurage, Claude-Alain; Polivka, Marc; Lechapt-Zalcman, Emmanuèle; Desenclos, Christine; Meyronet, David; Delattre, Jean-Yves; Figarella-Branger, Dominique

    2016-10-01

    The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1-84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH (mut)) (11.0 %), anaplastic astrocytoma IDH wild type (IDH (wt)) (5.3 %), glioblastoma IDH (mut) (17.1 %), and glioblastoma IDH (wt) (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p < 0.001). We did not find prognosis differences between grades III and IV for IDH (mut) 1p/19q intact and IDH (wt) gliomas in univariate and multivariate analyses. Among anaplastic astrocytoma IDH (wt), cases with chromosome arm 7p gain and 10q loss (55 %) had shorter PFS than the others (p = 0.027). In conclusion, the new WHO histomolecular classification of diffuse gliomas presented with high prognostic value. Grading was not discriminant between grade III and IV high-grade gliomas.

  6. Prognostic impact of tumour size in completely resected thymic epithelial tumours.

    PubMed

    Fukui, Takayuki; Fukumoto, Koichi; Okasaka, Toshiki; Kawaguchi, Koji; Nakamura, Shota; Hakiri, Shuhei; Ozeki, Naoki; Hirakawa, Akihiro; Tateyama, Hisashi; Yokoi, Kohei

    2016-12-01

    The T descriptor of thymic epithelial tumours proposed by the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group as well as the Masaoka-Koga system is defined by the anatomical extent of primary tumours, regardless of their size. However, the prognostic significance of tumour size in thymic epithelial tumours has not been fully elucidated. We evaluated the prognostic significance of tumour size in 154 consecutive patients with thymic epithelial tumours including 124 thymomas, 21 thymic carcinomas and 9 neuroendocrine tumours, who underwent complete resection between 2001 and 2014. Among all tumours, the median tumour size was 4.9 cm. The median thymoma, thymic carcinoma and neuroendocrine tumour sizes were 4.8, 5.7 and 5.8, respectively, although the differences were not significant. In survival analysis, the 5- and 10-year overall survival (OS) and recurrence-free survival (RFS) rates for all patients were 91 and 81%, and 80 and 69%, respectively. Under the stratification of tumour size, no trend was observed for OS, whereas RFS showed stepwise deterioration as tumour size increased. For 119 patients with Stage I disease, RFS showed deterioration as tumour size increased. Multivariate analysis revealed that tumour size >4.0 cm was an independent prognostic factor for worsening RFS (P = 0.03). Patients with tumours >4.0 cm showed significantly worse outcomes in RFS compared with those with smaller tumours. This relationship was also noted in patients with Stage I disease. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  7. Phosphorylated CXCR4 expression has a positive prognostic impact in colorectal cancer.

    PubMed

    Weixler, B; Renetseder, F; Facile, I; Tosti, N; Cremonesi, E; Tampakis, A; Delko, T; Eppenberger-Castori, S; Tzankov, A; Iezzi, G; Kettelhack, C; Soysal, S D; von Holzen, U; Spagnoli, G C; Terracciano, L; Tornillo, L; Droeser, Raoul A; Däster, S

    2017-09-21

    The CXCL12-CXCR4 chemokine axis plays an important role in cell trafficking as well as in tumor progression. In colorectal cancer (CRC), the chemokine receptor CXCR4 has been shown to be an unfavorable prognostic factor in some studies, however, the role of its activated (phosphorylated) form, pCXCR4, has not yet been evaluated. Here, we aimed to investigate the prognostic value of CXCR4 and pCXCR4 in a large cohort of CRC patients. A tissue microarray (TMA) of 684 patient specimens of primary CRCs was analyzed by immunohistochemistry (IHC) for the expression of CXCR4 and pCXCR4 by tumor cells and tumor-infiltrating immune cells (TICs). The combined high expression of CXCR4 and pCXCR4 showed a favorable 5-year overall survival rate (68%; 95%CI = 59-76%) compared to tumors showing a high expression of CXCR4 only (48%; 95%CI = 41-54%). High expression of pCXCR4 was significantly associated with a favorable prognosis in a test and validation group (p = 0.015 and p = 0.0001). Moreover, we found that CRCs with a high density of pCXCR4+ tumor-infiltrating immune cells (TICs) also showed a favorable prognosis in a test and validation group (p = 0.054 and p = 0.004). Univariate Cox regression analysis for TICs revealed that a high density of pCXCR4+ TICs was a favorable prognostic marker for overall survival (HR = 0.97,95%CI = 0.96-1.00; p = 0.01). In multivariate Cox regression survival analyses a high expression of pCXCR4 in tumor cells lost its association with a better overall survival (HR = 0.99; 95%CI = 0.99-1.00, p = 0.098). Our results show that high densities of CXCR4 and pCXCR4 positive TICs are favorable prognostic factors in CRC.

  8. Prognostic Impact of Residual Disease After Neoadjuvant Chemotherapy in 648 Patients with Triple-negative Breast Cancer.

    PubMed

    Kern, Peter; Von Minckwitz, Gunter; Puetter, Carolin; Pavlidou, Sofia; Flach, Annika; Kimmig, Rainer; Rezai, Mahdi

    2015-10-01

    In order to establish a new risk categorization system for triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy, we analyzed a large database including more than 50% of all breast cancer cases nationwide. From a database of 39,570 primary breast cancer cases, 648 patients with TNBC were treated with neoadjuvant chemotherapy (2009-2011). The primary study end-point was the impact of residual tumor burden on survival. Pathological complete response (pCR) was achieved in 199 patients; 449 patients had a non-pCR (pCR rate=30.8%). Stage ypT1 did not differ prognostically from ypT2, and likewise ypT3 not from ypT4 (in patients with N0 and N1-3 disease). Combined analysis of ypT1/2 and ypT3/4 yielded highly significant differences (p=0.000145). A partial response still conveys a substantial survival benefit. There is no linear deterioration of prognosis according to residual tumor size. Post-neoadjuvant TNM stages ypT1 and ypT2, and ypT3 and ypT4 pairwise build uniform prognostic groups in TNBC, when there is no or low axillary lymph-node involvement. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Colorectal cancer metastatic to the brain: analysis of prognostic factors and impact of KRAS mutations on presentation and outcome.

    PubMed

    Nieder, C; Hintz, M; Grosu, A L

    2016-01-01

    Treatment concepts for metastatic colorectal cancer continue to evolve. While the presence of RAS mutations impacts systemic therapy, little is known about the influence of such mutations in patients with brain metastases. Pooled retrospective analysis was conducted of 57 patients with brain metastases from colorectal cancer treated in two different institutions (2005-2013). The only mutations analyzed in a relatively large subgroup were KRAS mutations (14 wild type, 12 mutated). Mutation status was not associated with baseline characteristics such as number or location of metastases, and did not impact prognosis. Three factors were significantly associated with survival in multivariate analysis: Karnofsky Performance Status (KPS), management strategy, and systemic treatment. Median survival was 0.6 months with best supportive care, 3.0 months with initial whole-brain radiotherapy (WBRT), and 12.7 months if initial treatment included surgery or stereotactic radiosurgery (SRS), p = 0.0001. The survival difference between the WBRT and surgery/SRS groups was largest in patients with KPS 80-100. Effective local treatment was a prerequisite for improved survival. The only significant prognostic baseline factor was KPS, which forms the basis of the diagnosis-specific graded prognostic assessment (DS-GPA) score. Thus, our results validate the DS-GPA in this patient population. So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases. Studies focusing on patients who develop brain metastases early during the course of metastatic disease might be warranted, because the influence of different systemic therapies might be larger in this subgroup.

  10. Measuring the impact of major life events upon happiness.

    PubMed

    Ballas, Dimitris; Dorling, Danny

    2007-12-01

    In recent years there have been numerous attempts to define and measure happiness in various contexts and pertaining to a wide range of disciplines, ranging from neuroscience and psychology to philosophy, economics and social policy. This article builds on recent work by economists who attempt to estimate happiness regressions using large random samples of individuals in order to calculate monetary 'compensating amounts' for different life 'events'. We estimate happiness regressions using the 'major life event' and 'happiness' data from the British Household Panel Survey. The data and methods used in this article suggest that in contrast to living states such as 'being married', it is more events such as 'starting a new relationship' that have the highest positive effect on happiness. This is closely followed by 'employment-related gains' (in contrast to employment status). Also, women who become pregnant on average report higher than average levels of subjective happiness (in contrast to 'being a parent'). Other events that appear to be associated with happiness according to our analysis include 'personal education-related events' (e.g. starting a new course, graduating from University, passing exams) and 'finance/house related events' (e.g. buying a new house). On the other hand, the event that has the highest negative impact upon happiness according to our analysis is 'the end of my relationship' closely followed by 'death of a parent'. Adverse health events pertaining to the parents of the respondents also have a high negative coefficient and so does an employment-related loss. The analysis presented in this article suggests that what matters the most in people's lives in Britain is to have good dynamic interpersonal relationships and to be respected at work with that respect being constantly renewed. These 'goods' are as much reflected through dynamic events as static situations. Relationships at work appear to be of a similar order of importance to those at

  11. Prognostic impact of alkaline phosphatase measured at time of presentation in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction

    PubMed Central

    Kim, Tae-Hoon; Moon, Jeonggeun; Park, Hyun Woo; Jang, Ho-Jun; Park, Sang-Don; Kwon, Sung Woo; Suh, Jon

    2017-01-01

    Background Serum alkaline phosphatase (ALP) has been shown to be a prognostic factor in several subgroups of patients due to its promotion of vascular calcification. However, the prognostic impact of serum ALP level in ST-segment elevation myocardial infarction (STEMI) patients with a relatively low calcification burden has not been determined. We aimed to investigate the association of ALP level measured at time of presentation on clinical outcomes in patients with STEMI requiring primary percutaneous coronary intervention (PCI). Methods A total of 1178 patients with STEMI undergoing primary PCI between 2007 and 2014 were retrospectively enrolled from the INTERSTELLAR registry and classified into tertiles by ALP level (<64, 65–82, or >83 IU/L). The primary study outcome was a major adverse cardiac or cerebrovascular event (MACCE), defined as the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and ischemia-driven revascularization. Results Median follow-up duration was 25 months (interquartile range, 10–39 months). The incidence of MACCE significantly increased as ALP level increased, that is, for the <64, 65–82, and >83 IU/L tertiles incidences were 8.7%, 11.7%, and 15.7%, respectively; p for trend = 0.003). After adjustment for potential confounders, the adjusted hazard ratios for MACCE in the middle and highest tertiles were 1.69 (95% CI 1.01–2.81) and 2.46 (95% CI 1.48–4.09), respectively, as compared with the lowest ALP tertile. Conclusions Elevated ALP level at presentation, but within the higher limit of normal, was found to be independently associated with higher risk of MACCE after primary PCI in patients with STEMI. PMID:28182682

  12. The prognostic impact of SYT-SSX fusion type and histological grade in pediatric patients with synovial sarcoma treated according to the CWS (Cooperative Weichteilsarkom Studie) trials.

    PubMed

    Stegmaier, Sabine; Leuschner, Ivo; Poremba, Christopher; Ladenstein, Ruth; Kazanowska, Bernarda; Ljungman, Gustaf; Scheer, Monika; Blank, Bernd; Bielack, Stefan; Klingebiel, Thomas; Koscielniak, Ewa

    2017-01-01

    The aim of our analysis was the evaluation of the prognostic impact of SYT-SSX fusion status and histological grading in synovial sarcoma (SS) of children and adolescents in the context of the consistent multimodal treatment strategy of the CWS (Cooperative Weichteilsarkom Studie; Cooperative Soft Tissue Sarcoma Study Group) and in comparison with other risk factors. Between 1986 and 2006, out of 243 patients with SS, tumor samples from 84 patients with localized disease were available for RT-PCR analysis. Outcome depending on fusion status in the context with known clinical risk factors was analyzed. No prognostic significance was shown for SYT-SSX fusion status and for histological grade. Highest significance of negative prognostic impact was found for large tumor size in uni- and multivariate analysis (P < 0.01). Furthermore, male gender was shown to be an adverse prognostic factor in multivariate analysis (P = 0.01). Based on our results, neither histological grading nor SYT-SSX fusion status seems to be suitable for outcome prediction and risk stratification in localized SS treated according to the CWS. This is in contrast to several other publications concerning more heterogeneous age groups including children and adults, and this indicates that prognostic factors should not be interpreted apart from the particular study population and the therapeutic context. © 2016 Wiley Periodicals, Inc.

  13. The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.

    PubMed

    Merlo, Marco; Gobbo, Marco; Stolfo, Davide; Losurdo, Pasquale; Ramani, Federica; Barbati, Giulia; Pivetta, Alberto; Di Lenarda, Andrea; Anzini, Marco; Gigli, Marta; Pinamonti, Bruno; Sinagra, Gianfranco

    2016-09-01

    In this study, the authors analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of ≥72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF

  14. Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas

    PubMed Central

    Aaberg-Jessen, Charlotte; Hermansen, Simon K.; Kristensen, Bjarne W.

    2017-01-01

    Astrocytomas are the most frequent primary brain tumors in adults, and despite aggressive treatment patients often experience recurrence. Survival decreases with increasing tumor grade, and especially patients with grade IV glioblastoma have poor prognosis due to the aggressive character of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2 expression in tumor cells and blood vessels. Measurements of MMP-2 intensity increased with tumor grade, and MMP-2 expression was found to be significantly higher in glioblastomas compared to normal brain tissue (p<0.001), diffuse astrocytomas (p<0.001) and anaplastic astrocytomas (p<0.05). MMP-2 expression was associated with shorter overall survival in patients with grade II-IV astrocytic tumors (HR 1.60; 95% CI 1.03–2.48; p = 0.036). In glioblastoma, high MMP-2 was associated with poorer prognosis in patients who survived longer than 8.5 months independent of age and gender (HR 2.27; 95% CI 1.07–4.81; p = 0.033). We found a positive correlation between MMP-2 and tissue inhibitor of metalloproteinases-1 (TIMP-1), and combined MMP-2 and TIMP-1 had stronger prognostic value than MMP-2 alone also when adjusting for age and gender (HR 2.78; 95% CI 1.30–5.92; p = 0.008). These findings were validated in bioinformatics databases. In conclusion, this study indicates that MMP-2 is associated with aggressiveness in astrocytomas and may hold an unfavorable prognostic value in

  15. Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age.

    PubMed

    van den Brink, R H S; Schutter, N; Hanssen, D J C; Elzinga, B M; Rabeling-Keus, I M; Stek, M L; Comijs, H C; Penninx, B W J H; Oude Voshaar, R C

    2017-02-10

    Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age. Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender. Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders - including depression severity - but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of

  16. The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

    PubMed Central

    Nahajevszky, Sarolta; Andrikovics, Hajnalka; Batai, Arpad; Adam, Emma; Bors, Andras; Csomor, Judit; Gopcsa, Laszlo; Koszarska, Magdalena; Kozma, Andras; Lovas, Nora; Lueff, Sandor; Matrai, Zoltan; Meggyesi, Nora; Sinko, Janos; Sipos, Andrea; Varkonyi, Andrea; Fekete, Sandor; Tordai, Attila; Masszi, Tamas

    2011-01-01

    Background Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. Design and Methods Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. Results The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P=0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P=0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P=0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P=0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P=0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P=0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P=0.024) and overall survival (P=0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. Conclusions Janus

  17. Prognostic Impact of the Geriatric Nutritional Risk Index on Long-Term Outcomes in Patients Who Underwent Percutaneous Coronary Intervention.

    PubMed

    Wada, Hideki; Dohi, Tomotaka; Miyauchi, Katsumi; Doi, Shinichiro; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Ogita, Manabu; Kasai, Takatoshi; Hassan, Ahmed; Okazaki, Shinya; Isoda, Kikuo; Suwa, Satoru; Daida, Hiroyuki

    2017-03-16

    Malnutrition has been identified as an important predictor of poor clinical outcomes in patients with heart failure. The aim of this study is to examine the prognostic impact of nutritional status in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). The impact of nutrition, assessed using the geriatric nutritional risk index (GNRI) calculated by serum albumin and body mass index, was evaluated in 2,853 patients with CAD who underwent their first PCI between 2000 and 2011. Patients were assigned to tertiles based on their GNRI levels. The incidences of all-cause death and cardiac death were assessed. The median GNRI values were 101 (interquartile range 95 to 106). Lower GNRI levels were associated with older age and higher prevalence of acute coronary syndrome and chronic kidney disease. During the median follow-up period of 7.4 years, Kaplan-Meier curves showed ongoing divergence in rates of mortality among tertiles (GNRI <98: 35.1%; 98 to 104: 20.6%; ≥104: 12.1%; log-rank p <0.0001). Stratification analysis by age also showed that the lowest GNRI tertile was associated with mortality in both patients <65 years and those ≥65 years. After adjusting for established cardiovascular risk factors, lower GNRI was an independent predictor of all-cause death (hazard ratio 1.55 per 10 decrease, 95% confidence interval 1.30 to 1.84, p <0.0001) and cardiac death (hazard ratio 1.44, 95% confidence interval 1.08 to 1.90, p = 0.01). In conclusion, nutritional status was associated with long-term clinical outcomes in CAD patients after PCI. Evaluation of GNRI carries important prognostic information and may guide the therapeutic approach to such patients.

  18. Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging.

    PubMed

    Allen, Michael D; Luong, Phuong; Hudson, Chantelle; Leyton, Julius; Delage, Barbara; Ghazaly, Essam; Cutts, Rosalind; Yuan, Ming; Syed, Nelofer; Lo Nigro, Cristiana; Lattanzio, Laura; Chmielewska-Kassassir, Malgorzata; Tomlinson, Ian; Roylance, Rebecca; Whitaker, Hayley C; Warren, Anne Y; Neal, David; Frezza, Christian; Beltran, Luis; Jones, Louise J; Chelala, Claude; Wu, Bor-Wen; Bomalaski, John S; Jackson, Robert C; Lu, Yong-Jie; Crook, Tim; Lemoine, Nicholas R; Mather, Stephen; Foster, Julie; Sosabowski, Jane; Avril, Norbert; Li, Chien-Feng; Szlosarek, Peter W

    2014-02-01

    Targeted therapies have yet to have significant impact on the survival of patients with bladder cancer. In this study, we focused on the urea cycle enzyme argininosuccinate synthetase 1 (ASS1) as a therapeutic target in bladder cancer, based on our discovery of the prognostic and functional import of ASS1 in this setting. ASS1 expression status in bladder tumors from 183 Caucasian and 295 Asian patients was analyzed, along with its hypothesized prognostic impact and association with clinicopathologic features, including tumor size and invasion. Furthermore, the genetics, biology, and therapeutic implications of ASS1 loss were investigated in urothelial cancer cells. We detected ASS1 negativity in 40% of bladder cancers, in which multivariate analysis indicated worse disease-specific and metastasis-free survival. ASS1 loss secondary to epigenetic silencing was accompanied by increased tumor cell proliferation and invasion, consistent with a tumor-suppressor role for ASS1. In developing a treatment approach, we identified a novel targeted antimetabolite strategy to exploit arginine deprivation with pegylated arginine deiminase (ADI-PEG20) as a therapeutic. ADI-PEG20 was synthetically lethal in ASS1-methylated bladder cells and its exposure was associated with a marked reduction in intracellular levels of thymidine, due to suppression of both uptake and de novo synthesis. We found that thymidine uptake correlated with thymidine kinase-1 protein levels and that thymidine levels were imageable with [(18)F]-fluoro-L-thymidine (FLT)-positron emission tomography (PET). In contrast, inhibition of de novo synthesis was linked to decreased expression of thymidylate synthase and dihydrofolate reductase. Notably, inhibition of de novo synthesis was associated with potentiation of ADI-PEG20 activity by the antifolate drug pemetrexed. Taken together, our findings argue that arginine deprivation combined with antifolates warrants clinical investigation in ASS1-negative urothelial

  19. Prognostic impact of MYH9 expression on patients with acute myeloid leukemia

    PubMed Central

    Hu, Chao; Ma, Qiuling; Li, Xia; Yin, Xiufeng; Huang, Jiansong; Zhang, Ting; Ma, Zhixin; Zhou, Yile; Li, Chenying; Chen, Feifei; Chen, Jian; Wang, Yungui; Pan, Hanzhang; Wang, Dongmei; Jin, Jie

    2017-01-01

    MYH9 expression has previously been demonstrated as an independent predictor of clinical outcome in solid tumors. However, the prognostic relevance of MYH9 expression in acute myeloid leukemia is still unclear. Here, we found high MYH9 expressers were seen more frequently in females and more frequently in M4 morphology. We also found high MYH9 expressers had lower percentage of bone marrow blasts. In addition, overexpression of MYH9 was associated with an inferior overall survival. Notably, distinct microRNA signatures were seen in high MYH9 expressers. These results were also validated in an independent cohort of AML patients using the published data. In conclusion, gene of MYH9 expression might serve as a reliable predictor for overall survival in AML patients. PMID:27437869

  20. The prognostic impact of lymph-node dissection on lobectomy for pulmonary metastasis.

    PubMed

    Shiono, Satoshi; Matsutani, Noriyuki; Okumura, Sakae; Nakajima, Jun; Horio, Hirotoshi; Kohno, Mitsutomo; Ikeda, Norihiko; Kawamura, Masafumi

    2015-10-01

    The prevalence and characteristics of lymph-node metastasis have not been thoroughly investigated in patients with pulmonary metastases from various primary neoplasms. The necessity of performing lymph-node dissection with pulmonary metastasectomy is unknown. We retrospectively reviewed the database of the Metastatic Lung Tumor Study Group of Japan. Between November 1980 and June 2013, 4363 patients underwent resection of pulmonary metastases. After selecting for patients who underwent lobectomy, 683 patients (16%) were analysed. The presence of lymph-node metastasis, outcomes and prognoses were investigated. The primary tumour site was colorectal in 350 patients, head and neck in 73 patients, kidney in 41 patients, uterus in 41 patients and bone/soft tissue in 31 patients. The overall 5-year survival rate after pulmonary metastasectomy was 50.1%, and the 10-year survival rate was 36.4%. Lymph-node metastasis was more frequently found in uterine (27%) and head and neck cancers (29%). Five-year survival rates were 53.8% in patients without lymph-node metastasis, 39.4% in patients with hilar lymph-node metastasis and 30.8% in patients with mediastinal lymph-node metastasis. The extent of lymph-node dissection was not related to survival. Univariate analysis revealed that tumour size, the presence of lymph-node metastasis, the presence of multiple lesions, a disease-free interval of 24 months or less and incomplete resection were significant predictors of poor prognosis. Multivariate analysis confirmed these prognostic factors. Retrospective analysis of lobectomy for pulmonary metastasis demonstrated that lymph-node metastasis is a significant prognostic factor predicting poor outcome. Lymph-node sampling or dissection is therefore warranted to predict patient prognosis. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Prognostic impact of chromosomal aberrations and GNAQ, GNA11 and BAP1 mutations in uveal melanoma.

    PubMed

    Staby, Kjersti M; Gravdal, Karsten; Mørk, Sverre J; Heegaard, Steffen; Vintermyr, Olav K; Krohn, Jørgen

    2017-04-26

    To evaluate clinico-pathological and molecular prognostic factors in a well-defined series of posterior uveal melanoma (UM) with focus on chromosomal aberrations and mutations in the GNAQ, GNA11 and BRCA1-associated protein 1 (BAP1) genes. Formalin-fixed paraffin-embedded (FFPE) tissue samples were obtained from 50 consecutive eyes enucleated for UM between 1993 and 2005. The material was tested for loss of chromosome 3 and gain of chromosome 8q gene signatures by selective molecular gene markers using multiplex ligation-dependent probe amplification (MLPA), and for DNA mutations in the GNAQ, GNA11 and BAP1 genes. After a mean follow-up of 83 months (range, 8-205 months), 21 patients had died of metastatic UM and 16 patients of other causes. Tumour diameter, ciliary body involvement, mixed/epithelioid cell types, mitotic index, Ki-67 proliferation index, loss of chromosome 3 and gain of chromosome 8q showed statistically significant associations with metastatic disease. There were no significant differences in the prevalence of GNAQ and GNA11 mutations between patients with or without metastatic disease. Mutational analysis of the BAP1 gene was performed in 32 primary UM and in five UM liver metastases. Nine different BAP1 missense mutations were identified. BAP1 mutations were not more common in metastasizing than in nonmetastasizing UM. The molecular gene markers showing loss of chromosome 3 and gain of 8q gene signatures were associated with an increased risk of metastatic disease. BRCA1-associated protein 1 (BAP1) gene mutation status had no prognostic significance. The frequency and spectrum of BAP1 mutations in UM may be more dependent on ethnicity and demographic variables than hitherto considered. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  2. Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer

    PubMed Central

    Borgquist, Signe; Jögi, Annika; Pontén, Fredrik; Rydén, Lisa; Brennan, Donal J; Jirström, Karin

    2008-01-01

    Introduction We have previously reported that tumour-specific expression of the rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR), in the mevalonate pathway is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up. Methods The expression of HMG-CoAR was assessed by immunohistochemistry on tissue microarrays with tumour specimens from 498 consecutive cases of breast cancer with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the rate of recurrence-free survival (RFS) and breast cancer specific survival (BCSS). Results In line with our previous findings, tumour-specific HMG-CoAR expression was associated with low grade (p < 0.001), small size (p = 0.007), oestrogen receptor (ER) positive (p = 0.01), low Ki-67 (p = 0.02) tumours. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS, even when adjusted for established prognostic factors (relative risk [RR] = 0.60, 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In ER-negative tumours, however, there was a trend, that was not significantly significant, towards a shorter RFS in HMG-CoAR expressing tumours. Conclusions HMG-CoAR expression is an independent predictor of a prolonged RFS in primary breast cancer. This may, however, not be true for ER-negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status. PMID:18808688

  3. Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

    PubMed Central

    2014-01-01

    Background New biomarkers are needed for the prognosis of advanced colorectal cancer, which remains incurable by conventional treatments. O6-methylguanine DNA methyltransferase (MGMT) methylation and protein expression have been related to colorectal cancer treatment failure and tumor progression. Moreover, the presence in these tumors of cancer stem cells, which are characterized by CD133 expression, has been associated with chemoresistance, radioresistance, metastasis, and local recurrence. The objective of this study was to determine the prognostic value of CD133 and MGMT and their possible interaction in colorectal cancer patients. Methods MGMT and CD133 expression was analyzed by immunohistochemistry in 123 paraffin-embedded colorectal adenocarcinoma samples, obtaining the percentage staining and intensity. MGMT promoter methylation status was obtained by using bisulfite modification and methylation-specific PCR (MSP). These values were correlated with clinical data, including overall survival (OS), disease-free survival (DFS), tumor stage, and differentiation grade. Results Low MGMT expression intensity was significantly correlated with shorter OS and was a prognostic factor independently of treatment and histopathological variables. High percentage of CD133 expression was significantly correlated with shorter DFS but was not an independent factor. Patients with low-intensity MGMT expression and ≥50% CD133 expression had the poorest DFS and OS outcomes. Conclusions Our results support the hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133 expression may be a predictive biomarker of DFS. Thus, MGMT and CD133 may both be useful for determining the prognosis of colorectal cancer patients and to identify those requiring more aggressive adjuvant therapies. Future studies will be necessary to determine its clinical utility. PMID:25015560

  4. The prognostic impact of age in different molecular subtypes of breast cancer.

    PubMed

    Liedtke, Cornelia; Rody, Achim; Gluz, Oleg; Baumann, Kristin; Beyer, Daniel; Kohls, Eva-Beatrice; Lausen, Kerstin; Hanker, Lars; Holtrich, Uwe; Becker, Sven; Karn, Thomas

    2015-08-01

    Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.

  5. Prognostic impact of intensive statin therapy on N-terminal pro-BNP level in non-ST-segment elevation acute myocardial infarction patients.

    PubMed

    Shehata, Mohamed; Samir, Ayman; Dardiri, May

    2017-08-15

    This study explored the impact of intensive daily dosing of atorvastatin on in-hospital N-terminal pro-B-type natriuretic peptide level, left ventricular systolic function and incidence of major adverse cardiac events in non-ST-segment elevation myocardial infarction patients. Several studies showed that early initiation of statin therapy in acute coronary syndrome patients has a favorable prognostic impact. Hundred statin naive patients were prospectively enrolled. Once eligible, patients were randomly assigned to receive either a moderate daily dose that is, 20 mg (Group A) or an intensified daily dose that is, 80 mg (Group B) of atorvastatin, in addition to an equally divided loading dose given 24 and 12 h before coronary angiography (80 mg each). N-terminal pro-B-type natriuretic peptide levels were recorded before and after coronary intervention. Collected data after 3 months included; N-terminal pro-B-type natriuretic peptide levels, left ventricle systolic function and major adverse cardiac events. Mean age of the study cohort was 55 ± 10 years, 68% being males. There was no significant difference between both groups concerning procedural data. Group B patients showed a significantly lower N-terminal pro-B-type natriuretic peptide levels at both sampling occasions, i.e., after coronary intervention and 3 months later (P < 0.001). After 3 months, the same group showed higher left ventricle ejection fraction (P < 0.05), with no significant difference between both groups regarding incidence of major adverse cardiac events. Intensive atorvastatin therapy in non-ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention is associated with; lower in-hospital N-terminal pro BNP level and higher LVEF after 3 months. © 2017, Wiley Periodicals, Inc.

  6. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention.

    PubMed

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness.

  7. Prognostic factors in cancer.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

  8. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

    PubMed

    Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

    2016-12-01

    Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD.

  9. Major intrinsic proteins (MIPs) in plants: a complex gene family with major impacts on plant phenotype.

    PubMed

    Forrest, Kerrie L; Bhave, Mrinal

    2007-10-01

    The ubiquitous cell membrane proteins called aquaporins are now firmly established as channel proteins that control the specific transport of water molecules across cell membranes in all living organisms. The aquaporins are thus likely to be of fundamental significance to all facets of plant growth and development affected by plant-water relations. A majority of plant aquaporins have been found to share essential structural features with the human aquaporin and exhibit water-transporting ability in various functional assays, and some have been shown experimentally to be of critical importance to plant survival. Furthermore, substantial evidence is now available from a number of plant species that shows differential gene expression of aquaporins in response to abiotic stresses such as salinity, drought, or cold and clearly establishes the aquaporins as major players in the response of plants to conditions that affect water availability. This review summarizes the function and regulation of these genes to develop a greater understanding of the response of plants to water insufficiency, and particularly, to identify tolerant genotypes of major crop species including wheat and rice and plants that are important in agroforestry.

  10. Relocation Impacts of a Major Release from SRTC

    SciTech Connect

    Blanchard, A.

    1999-05-17

    The relocation impacts of an accidental release, scenario 1-RD-3 , are evaluated for the Savannah River Technology Center. The extent of the area potentially contaminated to a level that would result in doses exceeding the relocation protective action guide is calculated.

  11. Prognostic impact of standard laboratory values on outcome in patients with sudden sensorineural hearing loss

    PubMed Central

    2014-01-01

    Background Aim of the present study was to evaluate prognostic factors, in particular standard laboratory parameters, for better outcome after idiopathic sudden sensorineural hearing loss (SSNHL). Methods Using a retrospective review, 173 patients were included presenting between 2006 and 2009 with unilateral SSNHL, ≥30 dB bone conduction in three succeeding frequencies between 0.125 to 8 kHz in pure tone audiometry (PTA), and a time interval between first symptoms and diagnostics ≤ 4 weeks. Hearing gain of <10 dB versus ≥10 dB in the affected ear in 6PTA values was the primary outcome criterion. Univariate and multivariate statistical tests were used to analyze predictors for better outcome. Results The initial hearing loss was 50.6 ± 27.2 dB. The absolute hearing gain was 15.6 ± 20.1 dB. Eighty-one patients (47%) had a final hearing gain of ≥10 dB. Low-frequency hearing loss (p <0.0001); start of inpatient treatment <4 days after onset (p = 0.018); first SSNHL (versus recurrent SSNHL, p = 0.001); initial hearing loss ≥ 60 dB (p < 0.0001); an initial quick value lower than the reference values (p = 0.040); and a pretherapeutic hyperfibrinogenemia (p = 0.007) were significantly correlated to better outcome (≥10 dB absolute hearing gain). Multivariate analysis revealed that first SSNHL (p = 0.004), start of treatment <4 days after onset (p = 0.015), initial hearing loss ≥ 60 dB (p = 0.001), and hyperfibrinogenemia (p = 0.032) were independent prognostic factors for better hearing recovery. Conclusion Better hearing gain in patients with hyperfibrinogenemia might be explained by the rheological properties of the applied therapy and supports the hypothesis that SSNHL is caused in part by vascular factors. PMID:25028570

  12. Mir-21–Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact

    PubMed Central

    Sathyan, Pratheesh; Zinn, Pascal O.; Marisetty, Anantha L.; Liu, Bin; Kamal, Mohamed Mostafa; Singh, Sanjay K.; Bady, Pierre; Lu, Li; Wani, Khalida M.; Veo, Bethany L.; Gumin, Joy; Kassem, Dina Hamada; Robinson, Frederick; Weng, Connie; Baladandayuthapani, Veerabhadran; Suki, Dima; Colman, Howard; Bhat, Krishna P.; Sulman, Erik P.; Aldape, Ken; Colen, Rivka R.; Verhaak, Roel G.W.; Lu, Zhimin; Fuller, Gregory N.; Huang, Suyun; Lang, Frederick F.; Sawaya, Raymond; Hegi, Monika

    2015-01-01

    Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21–Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21–Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21–Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not

  13. The Impact of New Major Offerings on Student Retention

    ERIC Educational Resources Information Center

    Sauer, Paul L.; O'Donnell, Joseph B.

    2006-01-01

    A strategy used by industry to retain customers and remain competitive is the design and launch of new products. One might then question whether the launch of new courses and new majors by colleges and universities has the potential of reducing student attrition. Combining survey data from matriculating freshmen with administrative data taken from…

  14. Prognostic impact of DNA ploidy pattern, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) in patients with primary gastric lymphoma.

    PubMed

    Belessi, Chrysoula J; Parasi, Aikaterini S; Manioudaki, Helen S; Laoutaris, Nikolaos P; Legakis, Nikolaos C; Peros, Georgios Th; Androulakis, Georgios A

    2003-04-01

    DNA ploidy, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) are considered to be significant prognostic factors in non-Hodgkin lymphomas. However, reports on their prognostic importance in gastric lymphoma patients are relatively lacking. In the present study, we retrospectively studied the above-mentioned parameters in 29 patients with primary gastric lymphoma; 11/29 had B-low grade mucosa associated lymphoid tissue lymphoma (B-MALT), while 18/29 had diffuse large B-cell lymphoma (DLBCL), according to WHO classification. Proliferative activity was studied by staining against PCNA; in addition, the prognostic significance of DNA ploidy and SPF, as determined by flow cytometry, were investigated and compared to the results of the PCNA stainings. Seven out of 29 patients were found to have aneuploid tumors; DNA index values were >1 for all aneuploid lymphomas. There was no difference in DNA aneuploidy in MALT vs. DLBCL. The mean percentage of SPF was 11.4. SPF was found significantly lower in MALT vs. DLBCL (P < 0.05). The mean percentage of PCNA positive tumor cells was 52.6. PCNA protein expression was significantly lower in MALT vs. DLBCL (P < 0.0001). There was a significant positive correlation between PCNA score and SPF (P < 0.01, by Spearman analysis). DNA ploidy had no impact on survival in the present study. Both SPF and PCNA expression were important prognostic factors in the univariate analysis; however, in the multivariate analysis, the only independent prognostic factor for survival was PCNA expression. These findings indicate that SPF and PCNA are significant prognostic factors in patients with primary gastric lymphomas. However, in the present study, DNA ploidy had no impact on survival in patients with primary gastric lymphomas. Copyright 2003 Wiley-Liss, Inc.

  15. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

    SciTech Connect

    Twu, C.-W.; Wang, W.-Y.; Liang, W.-M.; Jan, J.-S.; Jiang, R.-S.; Chao, Jeffrey; Jin, Y.-T.; Lin, J.-C. . E-mail: jclin@vghtc.gov.tw

    2007-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

  16. Incidence and Prognostic Impact of DNMT3A Mutations in Korean Normal Karyotype Acute Myeloid Leukemia Patients

    PubMed Central

    Park, Sang Hyuk; Choi, Jae-Cheol; Kim, Shine Young; Yi, Jongyoun; Oh, Seung Hwan; Kim, In-Suk; Kim, Hyung-Hoi; Chang, Chulhun Ludgerus; Lee, Eun Yup; Song, Moo-Kon; Shin, Ho-Jin; Chung, Joo Seop

    2015-01-01

    Background. DNA methyltransferase 3A (DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact of DNMT3A mutations in Korean NK AML patients. Methods. Total 67 NK AML patients diagnosed during the recent 10 years were enrolled. DNMT3A mutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based on in silico analysis results. Clinical features and prognosis were compared with respect to DNMT3A mutation status. Results. Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs. DNMT3A NSVs, DMs, and R882 mutation were identified in 14.9%–17.9%, 10.3%–10.4%, and 7.5% of patients, respectively. DNMT3A mutations were frequently detected in FLT3 ITD mutated patients (P = 0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly. Conclusions. Incidences of DNMT3A NSVs, DMs, and R882 mutation are 14.9%–17.9%, 10.3%–10.4%, and 7.5%, respectively, in Korean NK AML patients. DNMT3A mutations are associated with FLT3 ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients. PMID:25650308

  17. p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

    PubMed Central

    Silva, S.D.; Nonogaki, S.; Soares, F.A.; Kowalski, L.P.

    2012-01-01

    CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis. PMID:22948376

  18. Prognostic impact of Wilms tumor gene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype.

    PubMed

    Zidan, Magda Abdel Aziz; Kamal Shaaban, Howyda M; Elghannam, Doaa M

    2014-07-01

    The Wilms' tumor (WT1) gene mutations were detected in patients with most forms of acute leukemia. However, the biological significance and the prognostic impact of WT1 mutation in Egyptian patients with acute myeloid leukemia with normal karyotype (AML-NK) are still uncertain. We aimed to evaluate the incidence and clinical relevance of WT1 gene mutations in acute myeloid leukemia with normal karyotype (AML-NK). Exons 7 and 9 of WT1 were screened in samples from 216 adult NK-AML using polymerase chain reaction single-strand conformation polymorphism techniques. Twenty-three patients (10.6%) harbored WT1 mutations. Younger ages and higher marrow blasts were significantly associated with WT1 mutations (P = 0.006 and 0.003 respectively). Complete remission rates were significantly lower in patients with WT1 mutations than those with WT1 wild-type (P = 0.015). Resistance, relapse, and mortality rates were significantly higher in patients with WT1 mutations than those without (P = 0.041, 0.016, and 0.008 respectively). WT1 mutations were inversely associated with NPM1 mutations (P = 0.007). Patients with WT1 mutations had worse disease-free survival (P < 0.001) and overall survival (P < 0.001) than patients with WT1 wild-type. In multivariable analyses, WT1 mutations independently predicted worse DFS (P < 0.001; hazard ratio [HR] 0.036) and overall survival (P = 0.001; HR = 0.376) when controlling for age, total leukocytic count (TLC), and NPM1 mutational status. In conclusion, WT1 mutations are a negative prognostic indicator in intensively treated patients with AML-NK, may be a part of molecularly based risk assessment and risk-adapted treatment stratification of patients with AML-NK.

  19. Impact of Age and Target-Organ Damage on Prognostic Value of 24-Hour Ambulatory Blood Pressure.

    PubMed

    Olesen, Thomas B; Stidsen, Jacob V; Blicher, Marie K; Pareek, Manan; Rasmussen, Susanne; Vishram-Nielsen, Julie K K; Olsen, Michael H

    2017-09-11

    Markers of target-organ damage and 24-hour ambulatory blood pressure (BP) measurement improve cardiovascular risk stratification. The prevalence of target-organ damage and raised BP increases with aging. The study aim was to evaluate the impact of age and target-organ damage on the prognostic value of ambulatory BP. Markers of target-organ damage and ambulatory BP were measured in 1408 healthy people aged 41 or 51 (middle-aged group), and 61 or 71 (older group) years. The primary outcome was cardiovascular events after 16 years of follow-up, with data obtained from national registries. The prognostic value of BP was evaluated with Cox regression models, adjusted for traditional risk factors and target-organ damage, including left ventricular mass, pulse wave velocity, carotid plaques, and urine albumin/creatinine ratio. A total of 323 events were observed. In comparison with traditional risk factors, adding systolic BP and presence of target-organ damage improved risk stratification by increasing concordance index from 0.711 to 0.728 (P=0.01). In middle-aged subjects with target-organ damage, increment in pulse pressure (hazard ratio, 1.70; 95% confidence interval, 1.31-2.21; P<0.01) and increment in average real variability (hazard ratio, 1.29; 95% confidence interval, 1.05-1.59; P=0.02) were associated with a greater risk of cardiovascular disease compared with subjects without target-organ damage: hazard ratio, 1.04 (95% confidence interval, 0.74-1.46; P=0.81); P for interaction, 0.02; and hazard ratio, 0.89 (95% confidence interval, 0.69-1.14; P=0.36); P for interaction, 0.01. Target-organ damage may be a marker of individual susceptibility to the harmful effects of pulse pressure and BP variability on the cardiovascular system in middle-aged individuals. © 2017 American Heart Association, Inc.

  20. Chemical consequences of major impact events on earth

    NASA Technical Reports Server (NTRS)

    Lewis, J. S.; Watkins, G. H.; Hartman, H.; Prinn, R. G.

    1982-01-01

    Violent cometary or asteroidal impact events comparable to that which terminated the Cretaceous era must produce large amounts of nitrogen oxides, sufficient to provide NOx mole fractions much larger than 100 ppm over areas of millions of square kilometers. Rapid production of NO2, and subsequent rainout of HNO3 and other strong acids can acidify surface waters, selectively destroying CaCO3 shells. This scenario holds the promise of explaining both the scope of Cretaceous biological extinctions and their extraordinary selectivity.

  1. Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies

    PubMed Central

    Tiu, Ramon V.; Gondek, Lukasz P.; O'Keefe, Christine L.; Elson, Paul; Huh, Jungwon; Mohamedali, Azim; Kulasekararaj, Austin; Advani, Anjali S.; Paquette, Ronald; List, Alan F.; Sekeres, Mikkael A.; McDevitt, Michael A.

    2011-01-01

    Single nucleotide polymorphism arrays (SNP-As) have emerged as an important tool in the identification of chromosomal defects undetected by metaphase cytogenetics (MC) in hematologic cancers, offering superior resolution of unbalanced chromosomal defects and acquired copy-neutral loss of heterozygosity. Myelodysplastic syndromes (MDSs) and related cancers share recurrent chromosomal defects and molecular lesions that predict outcomes. We hypothesized that combining SNP-A and MC could improve diagnosis/prognosis and further the molecular characterization of myeloid malignancies. We analyzed MC/SNP-A results from 430 patients (MDS = 250, MDS/myeloproliferative overlap neoplasm = 95, acute myeloid leukemia from MDS = 85). The frequency and clinical significance of genomic aberrations was compared between MC and MC plus SNP-A. Combined MC/SNP-A karyotyping lead to higher diagnostic yield of chromosomal defects (74% vs 44%, P < .0001), compared with MC alone, often through detection of novel lesions in patients with normal/noninformative (54%) and abnormal (62%) MC results. Newly detected SNP-A defects contributed to poorer prognosis for patients stratified by current morphologic and clinical risk schemes. The presence and number of new SNP-A detected lesions are independent predictors of overall and event-free survival. The significant diagnostic and prognostic contributions of SNP-A–detected defects in MDS and related diseases underscore the utility of SNP-A when combined with MC in hematologic malignancies. PMID:21285439

  2. Prognostic impact of GATA binding protein-3 expression in primary lung adenocarcinoma.

    PubMed

    Hashiguchi, Toshihiro; Miyoshi, Hiroaki; Nakashima, Kazutaka; Yokoyama, Shintaro; Matsumoto, Ryoichi; Murakami, Daigo; Mitsuoka, Masahiro; Takamori, Shinzo; Akagi, Yoshito; Ohshima, Koichi

    2017-05-01

    GATA binding protein-3 (GATA3) is a transcription factor that regulates cell differentiation and maintenance in some types of normal cells. This study aimed to investigate the association between GATA3 expression and primary lung adenocarcinoma and to clarify the clinical significance of GATA3 expression in lung adenocarcinoma. Immunohistochemical GATA3 expression was evaluated using completely resected lung adenocarcinoma samples from 95 cases. GATA3 immunohistochemical staining was performed and scored. Associations between clinicopathological factors and GATA3 expression were analyzed by using the χ(2) test and Fisher exact test. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS). Forty-nine cases expressed high levels of GATA3, which were associated with lymphatic invasion (P=.003). In univariate and multivariate analyses, vascular invasion (P<.001) and high GATA3 expression (P=.023) were identified as independent risk factors for OS. Higher pathological stages (P=.012), vascular invasion (P=.010), and high GATA3 expression (P=.009) were identified as independent risk factors for DFS. The high GATA3 expression group exhibited statistically worse OS (P=.031) and DFS (P=.011) than the low-expression group based on the Kaplan-Meier curves. In resected lung adenocarcinoma, high GATA3 expression is associated with poorer prognosis for both OS and DFS. Therefore, the immunohistochemical evaluation of GATA3 represents a potentially useful prognostic tool for postoperative patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Prognostic impact of psychoactive substances use during hospitalization for intentional drug overdose.

    PubMed

    Tournier, M; Molimard, M; Abouelfath, A; Cougnard, A; Begaud, B; Gbikpi-Benissan, G; Verdoux, H

    2005-08-01

    To assess whether current use of psychoactive substance(s) is a prognostic factor during hospitalization for intentional drug overdose (IDO). Current intoxication with psychoactive substance(s) [cannabis, opiate, buprenorphine, amphetamine/ecstasy, cocaine, lysergic acid diethylamide (LSD)] was identified using toxicological urinalysis in 671 patients with IDO. An IDO was a priori defined as serious if associated with one of the following events: death, hospitalization in intensive care unit longer than 48 h, respiratory support, use of vasopressive drugs, cardiac massage or dialysis. Subjects positive for toxicological assays were twice as likely to present with serious IDO (OR = 1.9, 95% CI: 1.3-2.8, P = 0.001), independently from a large range of confounding factors. The risk of serious IDO was especially marked in subjects using LSD, buprenorphine or opiates. Systematic investigation of substance use could be important to adapt medical management of subjects with IDO in general hospital, but also in primary care and psychiatric settings. Copyright 2005 Blackwell Munksgaard.

  4. Impact Constraints on Major Events in Early Mars History

    NASA Technical Reports Server (NTRS)

    Frey, H. V.

    2004-01-01

    MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

  5. Psychosocial impact of prognostic genetic testing in the care of uveal melanoma patients: protocol of a controlled prospective clinical observational study.

    PubMed

    Erim, Yesim; Scheel, Jennifer; Breidenstein, Anja; Metz, Claudia Hd; Lohmann, Dietmar; Friederich, Hans-Christoph; Tagay, Sefik

    2016-07-07

    Uveal melanoma patients with a poor prognosis can be detected through genetic analysis of the tumor, which has a very high sensitivity. A large number of patients with uveal melanoma decide to receive information about their individual risk and therefore routine prognostic genetic testing is being carried out on a growing number of patients. It is obvious that a positive prediction for recidivism in the future will emotionally burden the respective patients, but research on the psychosocial impact of this innovative method is lacking. The aim of the current study is therefore to investigate the psychosocial impact (psychological distress and quality of life) of prognostic genetic testing in patients with uveal melanoma. This study is a non-randomized controlled prospective clinical observational trial. Subjects are patients with uveal melanoma, in whom genetic testing is possible. Patients who consent to genetic testing are allocated to the intervention group and patients who refuse genetic testing form the observational group. Both groups receive cancer therapy and psycho-oncological intervention when needed. The psychosocial impact of prognostic testing is investigated with the following variables: resilience, social support, fear of tumor progression, depression, general distress, cancer-specific and general health-related quality of life, attitude towards genetic testing, estimation of the perceived risk of metastasis, utilization and satisfaction with psycho-oncological crisis intervention, and sociodemographic data. Data are assessed preoperatively (at initial admission in the clinic) and postoperatively (at discharge from hospital after surgery, 6-12 weeks, 6 and 12 months after initial admission). Genetic test results are communicated 6-12 weeks after initial admission to the clinic. We created optimal conditions for investigation of the psychosocial impact of prognostic genetic testing. This study will provide information on the course of disease and

  6. Relocation impacts of a major release from SRTC

    SciTech Connect

    Blanchard, A.; Thompson, E.A.; Thompson, J.M.

    1999-06-01

    The relocation impacts of an accidental release, scenario 1-RD-3 , are evaluated for the Savannah River Technology Center. The extent of the area potentially contaminated to a level that would result in doses exceeding the relocation protective action guide(PAG)is calculated. The maximum calculated distance downwind from the accident at which the relocation PAG is exceeded is also determined. The consequences of the particulate portion of the release are evaluated using the HOTSPOT model and an EXCEL spreadsheet. The consequences of the tritium release are evaluated using UFOTRI.

  7. Prognostic Impact of Discordant Results from Cytogenetics and Flow Cytometry in Patients with Acute Myeloid Leukemia Undergoing Hematopoietic Cell Transplantation

    PubMed Central

    Fang, Min; Store, Barry; Wood, Brent; Gyurkocza, Boglarka; Sandmaier, Brenda M.; Appelbaum, Frederick R.

    2012-01-01

    BACKGROUND Cytogenetics and multicolor flow cytometry (MFC) are useful tools for monitoring outcome of treatment in acute myeloid leukemia (AML). However, no data are available regarding the meaning of results when the two tests do not agree. METHODS We analyzed 1464 pairs of concurrent cytogenetics and flow results from 424 patients, both pre- and post- hematopoietic cell transplantation (HCT), and compared the prognostic impact of discordant and concordant results. RESULTS Informative discordant results were found in 22% of patients. Compared with patients with double negative testing results, either positive result had a significant impact on overall survival (OS) and relapse-free survival (RFS). The hazard ratios (HR) with either cytogenetics or MFC positive pre-transplant were 3.1 (P = 0.009) and 2.5 (P = 0.0008), respectively, for reduced OS, and 2.7 (P = 0.01) and 4.1 (P < 0.0001), respectively, for decreased RFS. Similar findings were obtained post-transplant. Molecular cytogenetics, i.e. fluorescence in situ hybridization (FISH), further added value to the evaluation of discordant cases. CONCLUSION Detection of residual disease of AML by either cytogenetics or flow cytometry in HCT patients predicts early relapse and shortened survival. PMID:21928360

  8. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukaemia definition.

    PubMed

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara M; Teixidó, Montserrat; Gimenez, Maria Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Blade, Joan; Fernández de Larrea, Carlos

    2017-03-02

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the present study, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analysed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukaemia were reviewed and patients were classified in four categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20% and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%) respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95%CI 2.6-9.3) independently of age, creatinine, Durie-Salmon and international stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86x109/L vs. 214x109/L, p<0.0001) and higher bone marrow plasma cells (median 53% vs. 36%, p=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has similar adverse prognostic impact as plasma cell leukemia.

  9. Prognostic Impact of Neuropilin-1 Expression in Egyptian Children with B-lineage Acute Lymphoblastic Leukemia

    PubMed Central

    Hagag, Adel A; Nosair, Nahla A

    2015-01-01

    Background Neuropilins are transmembrane glycoproteins that act as receptors for vascular endothelial growth factors and are involved in the process of tumor angiogenesis. Objective The aim of this work was to study the prognostic value of Neuropilin-1 (NRP-1) expression in Egyptian children with B-lineage acute lymphoblastic leukemia (ALL). Patients and methods This study was conducted on fifty children with newly diagnosed B-lineage ALL, admitted to Oncology Unit, Pediatric Department, Tanta University Hospitals in the period from August 2010 to March 2014. This series included 32 males and 18 females with ages ranging from 3–17 years and a mean value of 9 ± 3.5 years. Twenty healthy children, age and sex matched, were also included in this study as a control group. For all patients, the following examens were done: Bone marrow aspiration, cytochemistry, immunophenotyping and estimation of Neuropilin-1 expression on blast cells by flow cytometry. Results The present study revealed highly significant differences in Neuropilin-1 expression between B-lineage ALL lymphoblasts and control lymphocytes. A significant higher Neuropilin-1 expression was found in pre-B ALL (74.04%) compared with early pre-B (23.55%). Neuropilin-1 positive expression was associated with significantly higher white blood cells count (Mean = 69.3±18.53 ×103/mm3 versus 32.5±11.64 ×103/mm3 and p=0.003), bone marrow blasts percentage (Mean=76.12±21.4 % versus 41.2±19.71% and p= 0.003), serum lactate dehydrogenase levels (Mean=1992.2 ± 58.6 unit/L versus 955.1± 234.7 unit/L and p=0.001) at diagnosis compared with negative Neuropilin-1 expression. The levels of Neuropilin-1 on BM blasts at diagnosis were higher in patients who subsequently relapsed (Mean=53.8 ± 27.1) or later died (Mean=81.51 ± 9.94) during the period of follow-up compared to those who achieved and maintained complete remission (Mean=18.17 ± 10.4) with p value of 0.001. Furthermore, patients with higher Neuropilin-1

  10. Female STEM majors wanted: The impact of certain factors on choice of a college major

    NASA Astrophysics Data System (ADS)

    Conrad, Walter Michael

    Although females have made significant strides in educational achievements and substantial inroads into academic majors, such as business and medicine, they have made considerably less progress in the science, technology, engineering, and math (STEM) fields. This translates into a smaller number of female graduates prepared to work in the science career fields and results in American industry looking to other countries for its educated workforce. A mixed-methods research design was used to explore and understand the lived experiences and perceptions of faculty members and working STEM professionals in Northern and Central Virginia. Results indicated that although females are attaining STEM degrees and entering STEM fields in record numbers, obstacles such as a challenging STEM curriculum, bias, feelings of insecurity, lack of female role models, and inadequate preparation for the STEM workforce could impede the progress females have made. This research makes recommendations to the academic community and industry which may be used as retention and recruitment strategies for females considering a career in STEM. The ultimate goal is to significantly increase the number of highly skilled female graduates entering STEM fields, leading the U.S. to regain its previous position atop the world in technological innovation and leadership.

  11. Prognostic factors and impact of antibiotherapy in 117 cases of anaerobic bacteraemia.

    PubMed

    Robert, R; Deraignac, A; Le Moal, G; Ragot, S; Grollier, G

    2008-08-01

    Bacteraemia due to anaerobic bacteria occurs infrequently, making the systematic use of an anaerobic blood sample bottle in patients with sepsis controversial. We retrospectively reviewed the clinical and microbiological data from all cases of anaerobic bacteraemia in a teaching hospital over 2 years and determined the prognostic factors and antibiotic management. With the goal of evaluating the morbidity and mortality of bacteraemia due to anaerobic bacteria, a case-control study was also performed. One hundred eighty-four blood cultures from 125 patients grew at least one anaerobic bacterium, representing 0.5% of all and 7.0% of the positive blood cultures. One hundred seventeen patients were studied. In 24 cases, anaerobic blood cultures were associated with concomitant aerobic bacteria isolation. The most frequently isolated anaerobic species were Bacteroides sp. (n = 62), Clostridium sp. (n = 25), and Fusobacterium sp. (n = 12). The most frequent site of origin was the digestive tract (n = 61). In 51 cases, patients did not receive adequate empirical antianaerobic therapy. The mortality rate was 27%. Age [odds ratio (OR) 1.059; 95% confidence interval (CI) 1.021-1.100], cancer history (OR 3.21, 95% CI 1.126-9.156), and ineffective definitive antibiotherapy (OR 19.292, 95% CI 5.330-69.832) were independently associated with increased hospital mortality. The 72 patients that could be matched with patients without anaerobic bacteria according to their primary diagnosis had a longer hospitalisation and a trend toward increased mortality (P = 0.08). Anaerobic bacteraemia contributed significantly to the morbidity of the patients, and adequate empirical antibiotherapy may play an important role in the clinical outcomes.

  12. Renal Outcomes in Patients with AL Amyloidosis: Prognostic Factors, Renal response and the Impact of Therapy.

    PubMed

    Kastritis, Efstathios; Gavriatopoulou, Maria; Roussou, Maria; Migkou, Magdalini; Fotiou, Despina; Ziogas, Dimitrios C; Kanellias, Nikos; Eleutherakis-Papaiakovou, Evangelos; Panagiotidis, Ioannis; Giannouli, Stavroula; Psimenou, Erasmia; Marinaki, Smaragdi; Apostolou, Theofanis; Gakiopoulou, Hariklia; Tasidou, Anna; Papassotiriou, Ioannis; Terpos, Evangelos; Dimopoulos, Meletios A

    2017-03-28

    A staging system for patients with renal AL amyloidosis, based on eGFR (<50 ml/min/1.73 m(2) ) and proteinuria (≥5gr/day) at diagnosis, as well as criteria for renal progression (≥25% eGFR reduction) and response (≥30% reduction of proteinuria without renal progression) were recently proposed. We validated these criteria in a cohort of 125 patients with renal AL amyloidosis, mostly treated with bortezomib or lenalidomide. We confirmed the prognostic value of the renal staging system but also identified the limitations of renal progression criteria which are based only on eGFR reduction. We identified the ratio of 24h proteinuria to eGFR as a sensitive marker of renal risk which also accounts for changes in both proteinuria and eGFR: 24h proteinuria/eGFR ratio <30 (in mg/ml/min/1.73 m(2) ) was associated with a 2-year progression to dialysis rate of 0% compared to 9% for a ratio of 31-99 and 35% for a ratio ≥100 (p<0.001). In landmark analysis, patients who achieved a reduction of this ratio by at least 25% or ≤100 (if initially >100) at 3 months had a 2-year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (p=0.001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib-based therapy was more effective than lenalidomide-based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival. This article is protected by copyright. All rights reserved.

  13. Major coastal impact induced by a 1000-year storm event

    PubMed Central

    Fruergaard, Mikkel; Andersen, Thorbjørn J.; Johannessen, Peter N.; Nielsen, Lars H.; Pejrup, Morten

    2013-01-01

    Extreme storms and storm surges may induce major changes along sandy barrier coastlines, potentially causing substantial environmental and economic damage. We show that the most destructive storm (the 1634 AD storm) documented for the northern Wadden Sea within the last thousand years both caused permanent barrier breaching and initiated accumulation of up to several metres of marine sand. An aggradational storm shoal and a prograding shoreface sand unit having thicknesses of up to 8 m and 5 m respectively were deposited as a result of the storm and during the subsequent 30 to 40 years long healing phase, on the eroded shoreface. Our results demonstrate that millennial-scale storms can induce large-scale and long-term changes on barrier coastlines and shorefaces, and that coastal changes assumed to take place over centuries or even millennia may occur in association with and be triggered by a single extreme storm event.

  14. Prognostic impact of chronic total occlusion in a nonculprit artery in patients with acute myocardial infarction undergoing primary angioplasty.

    PubMed

    Ariza-Solé, Albert; Teruel, Luis; di Marco, Andrea; Lorente, Victòria; Sánchez-Salado, José C; Sánchez-Elvira, Guillermo; Romaguera, Rafael; Gómez-Lara, Josep; Gómez-Hospital, Joan A; Cequier, Angel

    2014-05-01

    The prognostic value of chronic total occlusion in nonculprit coronary arteries in patients with myocardial infarction undergoing primary angioplasty remains controversial. Several publications have described different methodologies and conflicting findings. In addition, causes of death were not reported. Our aim is to analyze the prognostic impact of chronic total occlusion in nonculprit coronary arteries and the role of left ventricular ejection fraction in this analysis. Prospective inclusion of consecutive patients with ST-segment elevation myocardial infarction who underwent primary angioplasty. We recorded baseline characteristics, in-hospital clinical course, and mortality and its causes during follow-up. We assessed the impact of chronic total occlusion on mortality using Cox regression analysis. Chronic total occlusion in nonculprit arteries was present in 125 of 1176 patients (10.6%); in 79 of these 125 patients, chronic total occlusion was present in the proximal segments. The mean follow-up was 339 days; 64 (5.8%) patients died during the first 6 months. Patients with chronic total occlusions had more comorbidities, poorer ventricular function, and higher mortality (hazard ratio=2.79; 95% confidence interval, 1.71-4.56). Chronic total occlusion was also associated with noncardiac death (hazard ratio=3.83; 95% confidence interval, 2.10-7.01). Chronic total occlusion in proximal segments was associated with both cardiac (hazard ratio=3.22; 95% confidence interval, 1.42-7.30) and noncardiac deaths (hazard ratio=3.43; 95% confidence interval, 1.67-7.06). The multivariate analysis performed without including left ventricular ejection fraction showed a significant association between chronic total occlusion and mortality. However, when left ventricular ejection fraction was included in the analysis, this association was nonsignificant (hazard ratio=1.76; 95% confidence interval, 0.85-3.65; P=.166). Chronic total occlusion in this clinical setting identified

  15. Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma

    PubMed Central

    Peng, Hai-Hua; Huang, Wen-Jin; Cai, Long-Mei; Zhou, Tong-Chong

    2017-01-01

    Background Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. Methods Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical–pathological parameters was examined. Univariate and multivariate survival analyses were performed. Findings The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. Conclusion The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant

  16. Significance Analysis of Prognostic Signatures

    PubMed Central

    Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

    2013-01-01

    A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated

  17. Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Ujiie, Hideki; Buitrago, Daniel H.; Woo, Kaitlin M.; Sima, Camelia S.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Introduction We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma. Methods We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999 to 2009) that were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, IL-7R, and IL-12Rβ2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. Results Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10+ neutrophils were associated with worse prognoses in the training cohort (P = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10+ neutrophil and low CD20+ lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; P < 0.001); this was confirmed in the validation cohort (P = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (HR = 1.61, P = 0.006) and validation cohort (HR = 1.75; P = 0.043). Conclusions High CD10+/low CD20+ immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma. PMID:26291010

  18. Prognostic impact of WT1 expression prior to hematopoietic stem cell transplantation in children with malignant hematological diseases.

    PubMed

    Woehlecke, Caroline; Wittig, Susan; Arndt, Clemens; Gruhn, Bernd

    2015-03-01

    Malignant hematological diseases represent the most common pediatric cancer. As they cannot always be cured by chemotherapy alone, leukemia and myelodysplastic syndrome (MDS) are frequent medical indications for hematopoietic stem cell transplantation, yet even this treatment is not capable of preventing relapse for certain. Therefore, molecular markers are used to monitor minimal residual disease (MRD) to be enabled to react early to an impeding relapse. As specific markers are not always available, Wilms' tumor gene 1 (WT1) has been suggested as a universal marker, but has not yet been established clinically. We determined the level of WT1 gene expression in 130 children, adolescents and young adults with malignant hematological diseases prior to transplantation and evaluated its impact on patients' outcome. A real-time quantitative RT-PCR was used for this purpose. The relationship between a high level of WT1 and the cumulative incidence of relapse, event-free survival and overall survival proved to be highly significant in univariate and multivariate analyses. Forty-eight percent of all patients with high WT1 levels suffered from a relapse, whereas only eight percent showing normal WT1 levels before transplantation relapsed. The most convincing result was found for acute myeloid leukemia (AML) and MDS. We conclude that WT1 expression prior to transplantation qualifies as an independent prognostic factor and should be further evaluated for MRD monitoring. It might especially be useful for patients with AML or MDS missing specific markers.

  19. Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

    PubMed

    Pallesen, Lars-Peder; Gerber, Johannes; Dzialowski, Imanuel; van der Hoeven, Erik J R J; Michel, Patrik; Pfefferkorn, Thomas; Ozdoba, Christoph; Kappelle, L Jaap; Wiedemann, Baerbel; Khomenko, Andrei; Algra, Ale; Hill, Michael D; von Kummer, Ruediger; Demchuk, Andrew M; Schonewille, Wouter J; Puetz, Volker

    2015-01-01

    The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality. Copyright © 2014 by the American Society of Neuroimaging.

  20. Peripheral blood eosinophilia has a favorable prognostic impact on transplant outcomes after allogeneic peripheral blood stem cell transplantation.

    PubMed

    Kim, Dong Hwan; Popradi, Gizelle; Xu, Wei; Gupta, Vikas; Kuruvilla, John; Wright, Janice; Messner, Hans A; Lipton, Jeffrey H

    2009-04-01

    Peripheral eosinophilia after allogeneic stem cell transplant (ASCT) may reflect the activation of the Th2 cytokine pathway. A retrospective analysis was performed to evaluate the impact of early- (before day 100: EEo) or late-onset (beyond day 100: LEo) eosinophilia (> or =0.5 x 10(9)/L in peripheral blood) on transplant outcomes after peripheral blood SCT (PBSCT) in 237 patients. The incidence of EEo and LEo was 43% at day 100 and 62% at 2 years, respectively. Compared with patients without LEo, improved transplant outcomes were observed in patients with LEo: better overall survival (OS; 86% versus 41%, P = 5 x 10(-11)), lower nonrelapse mortality (NRM; 10% versus 37%, P = 3 x 10(-6)), lower relapse incidence (11% versus 31%, P = 3 x 10(-5)), and higher GVHD-specific survival (GSS; 90% versus 64%, P = 1 x 10(-6)) were observed. In addition, similar finding was observed when transplant outcomes were analyzed according to the occurrence of eosinophilia at the onset of cGVHD. The multivariate analyses confirmed a favorable implication of LEo on OS, NRM, and GSS. LEo was associated with: (1) less severe chronic GVHD (cGVHD), (2) higher prevalence of autoantibodies, and (3) rapid lymphocyte count recovery after ASCT. In summary, the development of eosinophila after allogeneic PBSCT seemed to be a prognostic marker for improving transplant outcome.

  1. Prognostic impact of renal dysfunction does not differ according to the clinical profiles of patients: insight from the acute decompensated heart failure syndromes (ATTEND) registry.

    PubMed

    Inohara, Taku; Kohsaka, Shun; Sato, Naoki; Kajimoto, Katsuya; Keida, Takehiko; Mizuno, Masayuki; Takano, Teruo

    2014-01-01

    Renal dysfunction associated with acute decompensated heart failure (ADHF) is associated with impaired outcomes. Its mechanism is attributed to renal arterial hypoperfusion or venous congestion, but its prognostic impact based on each of these clinical profiles requires elucidation. ADHF syndromes registry subjects were evaluated (N = 4,321). Logistic regression modeling calculated adjusted odds ratios (OR) for in-hospital mortality for patients with and without renal dysfunction. Renal dysfunction risk was calculated for subgroups with hypoperfusion-dominant (eg. cold extremities, a low mean blood pressure or a low proportional pulse pressure) or congestion-dominant clinical profiles (eg. peripheral edema, jugular venous distension, or elevated brain natriuretic peptide) to evaluate renal dysfunction's prognostic impact in the context of the two underlying mechanisms. On admission, 2,150 (49.8%) patients aged 73.3 ± 13.6 years had renal dysfunction. Compared with patients without renal dysfunction, those with renal dysfunction were older and had dominant ischemic etiology jugular venous distension, more frequent cold extremities, and higher brain natriuretic peptide levels. Renal dysfunction was associated with in-hospital mortality (OR 2.36; 95% confidence interval 1.75-3.18, p<0.001), and the prognostic impact of renal dysfunction was similar in subgroup of patients with hypoperfusion- or congestion-dominant clinical profiles (p-value for the interaction ranged from 0.104-0.924, and was always >0.05). Baseline renal dysfunction was significantly associated with in-hospital mortality in ADHF patients. The prognostic impact of renal dysfunction was the same, regardless of its underlying etiologic mechanism.

  2. Prognostic Impact of Anemia in Patients With Chronic Heart Failure- With Special Reference to Clinical Background: Report From the CHART-2 Study.

    PubMed

    Yamauchi, Takeshi; Sakata, Yasuhiko; Takada, Tsuyoshi; Nochioka, Kotaro; Miura, Masanobu; Tadaki, Soichiro; Ushigome, Ryoichi; Sato, Kenjiro; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Takahashi, Jun; Miyata, Satoshi; Shimokawa, Hiroaki

    2015-01-01

    We aimed to elucidate the prognostic impact of anemia with special reference to the clinical background of patients with chronic heart failure (CHF). We examined 4,646 consecutive patients with Stage C/D CHF registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). Among them, 1,627 (35%) had anemia and were characterized by higher age (74 vs. 66 years), lower estimated glomerular filtration rate (52.8 vs. 66.1 ml/min/1.73 m(2)) and higher B-type natriuretic peptide levels (154.5 vs. 81.8 pg/ml) (all P<0.001) but comparable left ventricular ejection fraction (LVEF; 57.5 vs. 56.7%). Anemic patients were more frequently treated with diuretics (55.1 vs. 42.3%) but less often treated with β-blockers (45.4 vs. 51.1%) (both P<0.001). During a median follow-up of 3.8 years, 371 and 272 patients died with and without anemia, respectively (22.8 vs. 9.0%, adjusted hazard ratio 1.40; 95% confidence interval 1.15-1.71, P=0.001). Subgroup analysis revealed that the prognostic impact of anemia was comparable in terms of age, sex, renal function and double product, but differed by LVEF level and CHF etiology (both, P for interaction <0.001). In particular, a difference in the prognostic impact of LVEF level was noted in patients with ischemic heart disease. These results indicate that the prognostic impact of anemia is evident in CHF patients with preserved EF and it differs by CHF etiology.

  3. Anaplastic astrocytoma: prognostic factors and survival in 4807 patients with emphasis on receipt and impact of adjuvant therapy.

    PubMed

    Shin, Jacob Y; Diaz, Aidnag Z

    2016-09-01

    To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

  4. Prognostic impact of EGFR mutation in non-small-cell lung cancer patients with family history of lung cancer.

    PubMed

    Kim, Jung Soo; Cho, Min Seong; Nam, Jong Hyeon; Kim, Hyun-Jung; Choi, Kyeng-Won; Ryu, Jeong-Seon

    2017-01-01

    A family history can be a valuable tool in the era of precision medicine. Although a few studies have described an association of family history of lung cancer with EGFR activating mutation, their impact on survival of lung cancer patients is unclear. The study included consecutive 829 non-small-cell lung cancer patients who received analysis of EGFR mutation in a prospective lung cancer cohort. Family history of lung cancer was obtained by face-to-face interviews at the time of diagnosis. An association of EGFR activating mutation with a family history of lung cancer in first-degree relatives was evaluated with multivariate logistic regression analysis, and its association with survival was estimated with Cox's proportional hazards model. Seventy five (9.0%) patients had family history of lung cancer. The EGFR mutation was commonly observed in patients with positive family history compared to those with no family history (46.7% v 31.3%, χ2 p = 0.007). The family history was significantly associated with the EGFR mutation (aOR and 95% CI: 2.01 and 1.18-3.60, p = 0.011). Patients with the positive family history survived longer compared to those without (MST, 17.9 v 13.0 months, log-rank p = 0.037). The presence of the EGFR mutation was associated with better survival in patients without the family history (aHR and 95% CI: 0.72 and 0.57-0.90, p = 0.005). However, this prognostic impact was not observed in patients with the positive family history (aHR and 95% CI: 1.01 and 0.50-2.36, p = 0.832). In comparison to patients without the family history, EGFR activating mutation was common, and it did not affect prognosis in patients with positive family history.

  5. Prognostic impact of mechanical ventilation after liver transplantation: A national database study

    PubMed Central

    Yuan, Hui; Tuttle-Newhall, Janet E.; Chawa, Vikram; Schnitzler, Mark A.; Xiao, Huiling; Axelrod, David; Dzebisashvili, Nino; Lentine, Krista L.

    2015-01-01

    Background The impact of mechanical ventilator support (MCVS) on mortality and graft loss after liver transplantation (LT) is not well-described. Methods Multivariate analysis of a novel database linking national transplant registry and Medicare claims data was used to assess the impact of early MCVS on mortality and graft survival following LTs performed between 2002–2008. Results Among 10,517 LT recipients, 6.9% (n=726) required post-operative MCVS, 25.6% of who required < 96 hrs, 24.2% ≥ 96 hrs, and 50.1% an unspecified duration. Significant predictors of prolonged MCVS included older age, female gender, pre-transplant dialysis requirement and ascites. After multivariate adjustment, MCVS ≥96hrs was associated with nearly 3-times the adjusted hazard ratio (aHR) of mortality (2.95, P=<0.001), while MCVS <96 hrs was not significantly associated with mortality (aHR 0.88, P=0.55). Conclusions Recognition of LT patients at-risk for prolonged MCVS may help to reduce the incidence and consequences of this complication. PMID:25151187

  6. Predictors and prognostic impact of new left bundle branch block after surgical aortic valve replacement.

    PubMed

    Khounlaboud, Moukda; Flécher, Erwan; Fournet, Maxime; Le Breton, Hervé; Donal, Erwan; Leclercq, Christophe; Mabo, Philippe; Leguerrier, Alain; Daubert, Claude

    2017-09-27

    Left bundle branch block (LBBB) induces mechanical dyssynchrony that may lead to left ventricular systolic dysfunction. To evaluate the incidence, predictors and clinical impact of new LBBB in patients undergoing surgical aortic valve replacement (SAVR). After exclusion of patients with pre-existing LBBB, a previous pacemaker or a paced rhythm at hospital discharge, 547 consecutive patients undergoing SAVR were included. All-cause death, cardiovascular death and the combined outcome of all-cause death or a first heart failure event were assessed at 3months and 1year. Patients with and without new LBBB were compared. New LBBB occurred in 4.6% of patients after SAVR (compared with 16.4% of patients treated by transcatheter aortic valve implantation during the study period). Previous valve surgery and an immediate postoperative paced rhythm were independent predictors of new LBBB. At 1-year follow-up, there were no significant differences in all-cause death, cardiovascular death, or the combined outcome of all-cause death or a first heart failure event between patients with and without new LBBB. However, new LBBB was associated with a trend towards functional deterioration and more heart failure events at 1year. At 1-year follow-up, new LBBB did not have a significant impact on clinical outcome, but was associated with worse functional status and more heart failure events. Copyright © 2017. Published by Elsevier Masson SAS.

  7. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study.

    PubMed

    Azim, Hatem A; Kroman, Niels; Paesmans, Marianne; Gelber, Shari; Rotmensz, Nicole; Ameye, Lieveke; De Mattos-Arruda, Leticia; Pistilli, Barbara; Pinto, Alvaro; Jensen, Maj-Britt; Cordoba, Octavi; de Azambuja, Evandro; Goldhirsch, Aron; Piccart, Martine J; Peccatori, Fedro A

    2013-01-01

    We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC-pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC-pregnancy interval did not seem to impact the risk of relapse. Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

  8. Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

    PubMed Central

    Azim, Hatem A.; Kroman, Niels; Paesmans, Marianne; Gelber, Shari; Rotmensz, Nicole; Ameye, Lieveke; De Mattos-Arruda, Leticia; Pistilli, Barbara; Pinto, Alvaro; Jensen, Maj-Britt; Cordoba, Octavi; de Azambuja, Evandro; Goldhirsch, Aron; Piccart, Martine J.; Peccatori, Fedro A.

    2013-01-01

    Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence. PMID:23169515

  9. Progression of a Fracture Site Impaction as a Prognostic Indicator of Impacted Femoral Neck Fracture Treated with Multiple Pinning

    PubMed Central

    Yoon, Pil Whan; Shin, Young Ho; Yoo, Jeong Joon; Yoon, Kang Sup

    2012-01-01

    Background We evaluated the clinical and radiologic results of impacted femoral neck fractures treated with multiple pinning and determined the influence of the progression of impaction at the fracture site on clinical outcome. Methods There were 34 patients with a mean age of 65.5 years. The mean follow-up period was 3.4 years. Progression of fracture site impaction was measured using an articulo-trochanteric distance index and the percentage decrease in the articulo-trochanteric distance index between follow-up intervals. The failure of treatment was clarified as non-union and avascular necrosis. Other characteristics of the patients, including mean waiting time for surgery, preoperative Singh index score, and body mass index, were also measured to evaluate the influence on the clinical outcome of surgery. Results There were 6 fractures which were not treated successfully (3 non-union, 8.8% and 3 avascular necrosis, 8.8%). The mean percentage decrease of the articulo-trochanteric distance index within the first 6 weeks after surgery was 4.5% in the successful group and 25.1% in the failure group (p < 0.001). There was also a significant mean percentage decrease in the articulo-trochanteric distance index between 6 weeks and 3 months (p < 0.001). Conclusions Primary stabilization with Knowles pins for impacted femoral neck fractures had a reasonable clinical outcome with low morbidity. Despite a significant difference of a mean percentage decrease in the articulo-trochanteric distance index between the successful group and the failure group, we could not verify it as a risk factor for failure of treatment because the odds ratio was not statistically significant. PMID:22379557

  10. Progression of a fracture site impaction as a prognostic indicator of impacted femoral neck fracture treated with multiple pinning.

    PubMed

    Yoon, Pil Whan; Shin, Young Ho; Yoo, Jeong Joon; Yoon, Kang Sup; Kim, Hee Joong

    2012-03-01

    We evaluated the clinical and radiologic results of impacted femoral neck fractures treated with multiple pinning and determined the influence of the progression of impaction at the fracture site on clinical outcome. There were 34 patients with a mean age of 65.5 years. The mean follow-up period was 3.4 years. Progression of fracture site impaction was measured using an articulo-trochanteric distance index and the percentage decrease in the articulo-trochanteric distance index between follow-up intervals. The failure of treatment was clarified as non-union and avascular necrosis. Other characteristics of the patients, including mean waiting time for surgery, preoperative Singh index score, and body mass index, were also measured to evaluate the influence on the clinical outcome of surgery. There were 6 fractures which were not treated successfully (3 non-union, 8.8% and 3 avascular necrosis, 8.8%). The mean percentage decrease of the articulo-trochanteric distance index within the first 6 weeks after surgery was 4.5% in the successful group and 25.1% in the failure group (p < 0.001). There was also a significant mean percentage decrease in the articulo-trochanteric distance index between 6 weeks and 3 months (p < 0.001). Primary stabilization with Knowles pins for impacted femoral neck fractures had a reasonable clinical outcome with low morbidity. Despite a significant difference of a mean percentage decrease in the articulo-trochanteric distance index between the successful group and the failure group, we could not verify it as a risk factor for failure of treatment because the odds ratio was not statistically significant.

  11. Prognostic impact of the time of admission and discharge from the intensive care unit

    PubMed Central

    Moreira, Héctor Eduardo; Verga, Federico; Barbato, Marcelo; Burghi, Gastón

    2017-01-01

    Objective To determine the impact of the day and time of admission and discharge from the intensive care unit on mortality. Methods Prospective observational study that included patients admitted to the intensive care unit of the Hospital Maciel in Montevideo between April and November 2014. Results We analyzed 325 patients with an average age of 55 (36 - 71) years and a SAPS II value of 43 (29 - 58) points. No differences were found in the mortality of patients in the intensive care unit when time of admission (35% on the weekend versus 31% on weekdays, p = ns) or the hour of entry (35% at night versus 31% in the daytime, p = ns) were compared. The time of discharge was associated with higher hospital mortality rates (57% for weekend discharges versus 14% for weekday discharges, p = 0.000). The factors independently associated with hospital mortality after discharge from the intensive care unit were age > 50 years (OR 2.4, 95%CI, 1.1 - 5.4) and weekend discharge (OR 7.7, 95%CI, 3.8-15.6). Conclusion This study identified the time of discharge from the intensive care unit as a factor that was independently associated with hospital mortality. PMID:28444074

  12. The prognostic impact of bone marrow micrometastases in women with breast cancer.

    PubMed

    Braun, Stephan; Auer, Doris; Marth, Christian

    2009-07-01

    Metastasis is the overwhelming cause of mortality in patients with breast cancer and our understanding of its cellular and molecular determinants is limited. Among cellular determinants, disseminated (DTC) tumor cells undoubtedly are key players in the metastatic cascade. In the past, several models have been constructed to explain the presence of individual tumor cells in secondary organs and their influence on the subsequent course of the disease. According to most recent transcriptome and genome analyses, DTCs are viewed as rare and much earlier indicators of metastasis than generally assumed from the typical course of breast cancer. Despite the observation that the numerous genetic alterations in such cells are rarely identical or even similar, characterization of the long interval between dissemination and clinically manifested metastases, the resistance to chemotherapy and significant effect on disease progression despite the low abundance in secondary organs, support the idea that some of these cells might be progenitor cells with self-renewing properties that give rise to most of the tumor mass that is dealt with clinically. Here, we review evidence from translational research and data from observational studies on DTCs to elucidate their potential impact for both future clinical trial design and, in the long run, decision-making in our daily patient management.

  13. [Prognostic Impact of Radiation Therapy and Molecular Classification of Infant Atypical Teratoid/Rhabdoid Tumors].

    PubMed

    Otani, Yoshihiro; Ichikawa, Tomotsugu; Kurozumi, Kazuhiko; Yasuhara, Takao; Washio, Kana; Shimada, Akira; Katayama, Norihisa; Katsui, Kuniaki; Yanai, Hiroyuki; Date, Isao

    2017-02-01

    Atypical teratoid/rhabdoid tumor(AT/RT)is a rare and lethal childhood cancer. Although radiation therapy in children less than three years of age is generally deferred because of its neural toxicity, recent studies have shown that multimodal therapies, including radiation therapy, are effective in pediatric patients with AT/RT less than three years of age. We treated four infant AT/RT patients and investigated the impact of radiation therapy and genetic classification on the prognosis. The mean age at the time of the operation was 9.3 months and all patients were female. All patients underwent surgical resection. Of the four patients, two received combined irradiation and chemotherapy. Specifically, one patient received conformal craniospinal radiation therapy and the other received craniospinal irradiation with proton beams. Immunohistochemical analyses of tumor specimens revealed that the two patients were positive for ASCL1, a regulator of Notch signaling. Patients who received radiation therapy and exhibited ASCL1-positive tumors had a better prognosis. We conclude that radiation therapy may prolong survival in AT/RT patients who are less than 3 years of age. However, further study is required to evaluate long-term functional outcomes.

  14. [Negative prognostic impact of female gender on oncological outcomes following radical cystectomy].

    PubMed

    Dabi, Y; Rouscoff, Y; Delongchamps, N B; Sibony, M; Saighi, D; Zerbib, M; Peyraumore, M; Xylinas, E

    2016-02-01

    To confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy. We conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer. Impact of gender on recurrence rate, specific and non-specific mortality rate were evaluated using Cox regression models in univariate and multivariate analysis. We collected data on 553 males (78.9%) and 148 females (21.1%) between 1998 and 2011. Both groups were comparable at inclusion regarding age, pathologic stage, nodal status and lymphovascular invasion. Mean follow-up time was 45 months (interquartile 23-73) and by that time, 163 patients (23.3%) had recurrence of their tumor and 127 (18.1%) died from their disease. In multivariable Cox regression analyses, female gender was independently associated with disease recurrence (RR: 1.73; 95% CI 1.22-2.47; P=0.02) and cancer-specific mortality (RR=2.50, 95% CI=1.71-3.68; P<0.001). We confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Prognostic impact of anaemia on patients with ST-elevation myocardial infarction treated by primary PCI.

    PubMed

    Rathod, Krishnaraj S; Jones, Daniel A; Rathod, Vrijraj S; Bromage, Daniel; Guttmann, Oliver; Gallagher, Sean M; Mohiddin, Saidi; Rothman, Martin T; Knight, Charles; Jain, Ajay K; Kapur, Akhil; Mathur, Anthony; Timmis, Adam D; Amersey, Rajiv; Wragg, Andrew

    2014-01-01

    The aim of this study was to investigate the effects of baseline anaemia on the outcome in patients treated by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. This study was a retrospective cohort study of 2418 patients with ST-elevation myocardial infarction treated by PPCI between January 2004 and August 2010 at a single centre. We investigated the outcome in patients with anaemia compared with that in patients with a normal haemoglobin (Hb) level. Anaemia was defined according to the WHO definition as an Hb level less than 12 g/dl for female individuals and less than 13 g/dl for male individuals. We also calculated hazard ratios using a stratified model according to the Hb level. A total of 471 (19%) patients were anaemic at presentation. The anaemic cohort was older (72.2 vs. 62.4 years, P<0.0001) and had a higher incidence of diabetes (28 vs. 16%, P<0.0001), hypertension (57 vs. 43%, P=0.01), hypercholesterolaemia (48 vs. 40%, P=0.007), previous PCI (15 vs. 9%, P<0.0001), previous myocardial infarction (23 vs. 12%, P=0.002), and cardiogenic shock (12 vs. 5%, P<0.0001). Over a mean follow-up period of 3 years there was significantly higher all-cause mortality in the anaemic group compared with the normal Hb group (20.4 vs. 13.5%, P<0.0001). However, after adjustment for all variables using multivariate analysis, anaemia (on the basis of the WHO definitions) was found not to be an independent predictor of mortality or major adverse cardiac events over the follow-up period. Further, when we used a model stratified by g/dl, we found that there was an increased risk for adverse outcomes among men with low Hb levels. There appeared to be a threshold value of Hb (13 g/dl) associated with increased risk. Although a similar trend was observed among women, no significant difference was observed. Patients with anaemia undergoing PPCI are at a higher risk of an adverse outcome. Anaemia is a simple and powerful marker of poor

  16. Case studies of major DST-6 sounding impacts with the GLAS model

    NASA Technical Reports Server (NTRS)

    Atlas, R.

    1979-01-01

    Two case studies of DST-6 sounding impacts are presented. In each of these cases, major improvements to the GLAS model's forecasts of specific synoptic features resulted from including satellite-sounding data in the initial analysis.

  17. Prognostic Impact of the Timing of Recurrence of Infarct-Related Ventricular Tachycardia After Catheter Ablation.

    PubMed

    Siontis, Konstantinos C; Kim, Hyungjin Myra; Stevenson, William G; Fujii, Akira; Bella, Paolo Della; Vergara, Pasquale; Shivkumar, Kalyanam; Tung, Roderick; Do, Duc H; Daoud, Emile G; Okabe, Toshimasa; Zeppenfeld, Katja; Riva Silva, Marta de; Hindricks, Gerhard; Arya, Arash; Weber, Alexander; Kuck, Karl-Heinz; Metzner, Andreas; Mathew, Shibu; Riedl, Johannes; Yokokawa, Miki; Jongnarangsin, Krit; Latchamsetty, Rakesh; Morady, Fred; Bogun, Frank M

    2016-12-01

    Recurrence of ventricular tachycardia (VT) after ablation in patients with previous myocardial infarction is associated with adverse prognosis. However, the impact of the timing of VT recurrence on outcomes is unclear. We analyzed data from a multicenter collaborative database of patients who underwent catheter ablation for infarct-related VT. Multivariable Cox regression analyses investigated the effect of the timing of VT recurrence on the composite outcome of death or heart transplantation using VT recurrence as a time-varying covariate. A total of 1412 patients were included (92% men; age: 66.7±10.7 years), and 605 patients (42.8%) had a recurrence after median 116 days (188 [31.1%] within 1 month, 239 [39.5%] between 1 and 12 months, and 178 [29.4%] after 12 months). At median follow-up of 670 days, 375 patients (26.6%) experienced death or heart transplantation. The median time from recurrence to death or heart transplantation was 65 and 198.5 days in patients with recurrence ≤30 days and >30 days post ablation, respectively. The adjusted hazard ratio (95% confidence interval) for the effect of VT recurrence occurring immediately post ablation on death or heart transplantation was 3.45 (2.33-5.11) in reference to no recurrence. However, the magnitude of this effect decreased statistically significantly (P<0.001) as recurrence occurred later in the follow-up period. The respective risk estimates for VT recurrence at 30 days, 6 months, 1 year, and 2 years were 3.36 (2.29-4.93), 2.94 (2.09-4.14), 2.50 (1.85-3.37), and 1.81 (1.37-2.40). VT recurrence post ablation is associated with a mortality risk that is highest soon after the ablation and decreases gradually thereafter. © 2016 American Heart Association, Inc.

  18. Prognostic impact of heart rate in elderly with systolic heart failure and concomitant atrial fibrillation.

    PubMed

    Barywani, Salim; Petzold, Max

    2017-08-01

    The present study aimed to investigate the impact of resting heart rate (HR) on 5-year all-cause mortality in patients ≥80 years with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant atrial fibrillation (AF) after optimal up-titration of beta-blockers (BBs). Patients (n = 185) aged ≥80 years with HF and left ventricular ejection fraction ≤40% were included between January 2000 and January 2008 from two university hospitals, Sahlgrenska and Östra and retrospectively studied from January 2 to May 30, 2013. Up-titrations of guideline recommended medications were performed at HF outpatient clinics. Of whole study population, 54% (n= 100) had AF. After optimal up-titration of BBs and angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), mean HR in patients with AF was 73 ± 15 beats/minute (bpm), 36% had resting HR ≤65 bpm. Five-year all-cause mortality among patients with AF was significantly lower in patients with HR ≤65 bpm (63%) compared to HR >65 (80%). Cox proportional-hazard regression analysis adjusted for clinically important baseline variables and doses of ACEIs/ARBs and BBs demonstrated resting HR ≤65 bpm as an independent predictor of improved survival compared to resting HR >65 bpm (HR 0.3, 95%CI 0.1-0.7, P 0.005). In octogenarians with HFrEF and concomitant AF, lowering resting HR to levels as low as HR ≤65 bpm was still associated with improved survival from all-cause mortality. Our data indicate that mortality in AF became comparable to SR when patients were on maximally up-titrated beta-blocker doses with HR as low as 75 bpm.

  19. Chronotropic Incompetence During Exercise in Type 2 Diabetes: Aetiology, Assessment Methodology, Prognostic Impact and Therapy.

    PubMed

    Keytsman, Charly; Dendale, Paul; Hansen, Dominique

    2015-07-01

    During incremental exercise tests, chronotropic incompetence (CI), which is the inability of the heart rate (HR) to rise in proportion to an increase in metabolic demand, is often observed in patients with type 2 diabetes mellitus (T2DM). Despite the fact that CI is associated with exercise intolerance and elevated risks of development of cardiovascular disease and premature death, this clinical anomaly is often ignored or overlooked by clinicians and physiologists. CI is, however, a significant clinical abnormality that deserves further attention, examination and treatment. The aetiology of CI in T2DM remains poorly understood and is complex. Certain T2DM-related co-morbidities or physiological anomalies may contribute to development of CI, such as altered blood catecholamine and/or potassium levels during exercise, structural myocardial abnormalities, ventricular and/or arterial stiffness, impaired baroreflex sensitivity and cardiovascular autonomic neuropathy. Clinicians should thus be aware of the potential presence of yet undetected anomalies or diseases in T2DM patients who experience CI during exercise testing. However, an effective treatment for CI in T2DM is yet to be developed. Exercise training programmes seem to be the only potentially effective and feasible interventions for partial restoration of the chronotropic response in T2DM, but it remains poorly understood how these interventions lead to restoration of the chronotropic response. Studies are thus warranted to elucidate the aetiology of CI and develop an effective treatment for CI in T2DM. In particular, the impact of (different) exercise interventions on CI in T2DM deserves greater attention in future studies.

  20. AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for early cancer detection.

    PubMed

    Garczyk, Stefan; von Stillfried, Saskia; Antonopoulos, Wiebke; Hartmann, Arndt; Schrauder, Michael G; Fasching, Peter A; Anzeneder, Tobias; Tannapfel, Andrea; Ergönenc, Yavuz; Knüchel, Ruth; Rose, Michael; Dahl, Edgar

    2015-01-01

    Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.

  1. Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer.

    PubMed

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär-Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

    2008-04-11

    Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC.

  2. Prognostic Impact of Array-based Genomic Profiles in Esophageal Squamous Cell Cancer

    PubMed Central

    Carneiro, Ana; Isinger, Anna; Karlsson, Anna; Johansson, Jan; Jönsson, Göran; Bendahl, Pär-Ola; Falkenback, Dan; Halvarsson, Britta; Nilbert, Mef

    2008-01-01

    Background Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers. Methods A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival. Results Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis. Conclusion aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC. PMID:18405350

  3. Prognostic impact of second primary tumors in head and neck cancer.

    PubMed

    Patrucco, Marta S; Aramendi, Marina V

    2016-07-01

    The incidence of Second Primary Tumors in the upper aerodigestive tract varies from 5 to 30 %. Most of them are located either in the same anatomical region or in the lungs, and are related to a poor overall survival. Our objective is to assess the incidence of Second Primary Tumors, factors related to its outcome, frequent associations, and impact on overall survival. 27 patients with Second Primary Tumors were reviewed out of 307 with head and neck cancer, between 2002 and 2011. Patients had a minimum follow-up period of 3 years, or until their death after the last treatment. Sex: 85.2 % were male; male:female ratio of 23:4. The mean age of appearance for the primary tumor was 66.8 years. Only 1 patient had a synchronous Second Primary Tumor, while 26 had metachronous Second Primary Tumors. Second neoplasms were grouped into synchronous and metachronous for statistical analysis. The following parameters were considered: age at diagnosis of the first tumor, gender, smoking and persistence of the habit, primary tumor's location in the larynx, association between two squamous cell carcinomas (index and second primary tumor), and radiotherapy for the primary tumor. The incidence of Second Primary Tumors was 8.79 %. Overall survival of metachronous tumors was 95 months (7.9 years). The primary tumor's location that prevailed when developing a Second Primary Tumor was the larynx. Regarding the histology, the most common association was head and neck squamous cell carcinoma with head and neck squamous cell carcinoma (9 patients). The Second Primary Tumor was the cause of death in 51.9 % of the patients and its most frequent location was the lungs. 19 patients underwent radiotherapy. Second Primary Tumors are common in the head and neck. The authors would like to enforce the importance of an extended follow-up, since second neoplasms worsen considerably the patient's prognosis. Patients who keep on smoking after treatment decrease even more their overall survival.

  4. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment

    PubMed Central

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels. PMID:26469350

  5. Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment.

    PubMed

    Rodier, Marion; Quirié, Aurore; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2015-01-01

    The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.

  6. Prognostic Impact of Physician Specialty on the Prognosis of Outpatients With Heart Failure: Propensity Matched Analysis of the REDINSCOR and RICA Registries.

    PubMed

    Álvarez-García, Jesús; Salamanca-Bautista, Prado; Ferrero-Gregori, Andreu; Montero-Pérez-Barquero, Manuel; Puig, Teresa; Aramburu-Bodas, Óscar; Vázquez, Rafael; Formiga, Francesc; Delgado, Juan; Arias-Jiménez, José Luis; Vives-Borrás, Miquel; Cerqueiro González, J Manuel; Manzano, Luis; Cinca, Juan

    2017-05-01

    The specialty treating patients with heart failure (HF) has a prognostic impact in the hospital setting but this issue remains under debate in the ambulatory environment. We aimed to compare the clinical profile and outcomes of outpatients with HF treated by cardiologists or internists. We analyzed the clinical, electrocardiogram, laboratory, and echocardiographic data of 2 prospective multicenter Spanish cohorts of outpatients with HF treated by cardiologists (REDINSCOR, n=2150) or by internists (RICA, n=1396). Propensity score matching analysis was used to test the influence of physician specialty on outcome. Cardiologist-treated patients were often men, were younger, and had ischemic etiology and reduced left ventricular ejection fraction (LVEF). Patients followed up by internists were predominantly women, were older, and a higher percentage had preserved LVEF and associated comorbidities. The 9-month mortality was lower in the REDINSCOR cohort (11.6% vs 16.9%; P<.001), but the 9-month HF-readmission rates were similar (15.7% vs 16.9%; P=.349). The propensity matching analysis selected 558 pairs of comparable patients and continued to show significantly lower 9-month mortality in the cardiology cohort (12.0% vs 18.8%; RR, 0.64; 95% confidence interval [95%CI], 0.48-0.85; P=.002), with no relevant differences in the 9-month HF-readmission rate (18.1% vs 17.2%; RR, 0.95; 95%CI, 0.74-1.22; P=.695). Age, sex, LVEF and comorbidities were major determinants of specialty-related referral in HF outpatients. An in-depth propensity matched analysis showed significantly lower 9-month mortality in the cardiologist cohort. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  7. The Impact of Major-Job Mismatch on College Graduates' Early Career Earnings: Evidence from China

    ERIC Educational Resources Information Center

    Zhu, Rong

    2014-01-01

    This paper assesses the impact of the mismatch between a college major and job on college graduates' early career earnings using a sample from China. On average, a major-job mismatched college graduate is found to suffer from an income loss that is much lower than the penalty documented in previous studies. The income losses are also found to be…

  8. Numerical Simulation of Major Debris-Cloud Features Produced by Projectile Hypervelocity Impact on Bumper

    NASA Astrophysics Data System (ADS)

    Ma, W. L.; Pang, B. J.; Zhang, W.; Gai, B. Z.

    All spacecrafts in low orbit are subjected to hypervelocity impacting by meteoroids and space debris These impacts can damage spacecraft flight-critical systems leading to catastrophic failure of the spacecraft In order to protect the safety of an orbiting spacecraft the shield for meteoroids and space debris becomes an indispensable factor in the design of a spacecraft especially those with long orbital life and large size structures Because the major debris-cloud represents the most severe threat to rear wall integrity researches on the major debris-cloud features are very important In this paper the numerical simulations for major debris-cloud features produced by a sphere projectile normal impacting on a single-sheet bumper at hypervelocity have been carried out using the SPH technique of AUTODYN The major debris-cloud features include the effects of debris-cloud morphology normalized axial velocity and radial velocity These features vary with bumper-thickness-to-projectile-diameter ratios t D and impact velocities The impact velocities are from 1 to 14km s The bumper and projectile materials are aluminum The ratio t d is from 0 0105 to 0 525 Effects of impact velocity and t d on the major debris-cloud features have been investigated It is shown that the major debris-cloud features have remarkable differences with various t d and impact velocities As the t D ratio is increased and impact velocity is constant the major debris-cloud morphology varies The diameter of center element and the radial debris-cloud velocities increases At the same time

  9. Impact of lymph node ratio as a valuable prognostic factor in gallbladder carcinoma, focusing on stage IIIB gallbladder carcinoma

    PubMed Central

    Choi, Byung-Gwan; Kim, Choong-Young; Cho, Seung-Hyun; Kim, Hee-Joon; Koh, Yang-Seok; Kim, Jung-Chul; Cho, Chol-Kyoon; Kim, Hyun-Jong

    2013-01-01

    Purpose It is increasingly being recognized that the lymph node ratio (LNR) is an important prognostic factor for gallbladder carcinoma patients. The present study evaluated predictors of tumor recurrence and survival in a large, mono-institutional cohort of patients who underwent surgical resection for gallbladder carcinoma, focusing specifically on the prognostic value of lymph node (LN) status and of LNR in stage IIIB patients. Methods Between 2004 and 2011, 123 patients who underwent R0 radical resection for gallbladder carcinoma at the Chonnam National University Hwasun Hospital were reviewed retrospectively. Patients were staged according to the American Joint Committee on Cancer 7th edition, and prognostic factors affecting disease free survival, such as age, sex, comorbidity, body mass index, presence of preoperative symptoms, perioperative blood transfusion, postoperative complications, LN dissection, tumor size, differentiation, lymph-vascular invasion, perineural invasion, T stage, presence of LN involvement, N stage, numbers of positive LNs, LNR and implementation of adjuvant chemotherapy, were statistically analyzed. Results LN status was an important prognostic factor in patients undergoing curative resection for gallbladder carcinoma. The total number of LNs examined was implicated with prognosis, especially in N0 patients. LNR was a powerful predictor of disease free survival even after controlling for competing risk factors, in curative resected gallbladder cancer patients, and especially in stage IIIB patients. Conclusion LNR is confirmed as an independent prognostic factor in curative resected gallbladder cancer patients, especially in stage IIIB gallbladder carcinoma. PMID:23487246

  10. Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival.

    PubMed

    Souwer, Yuri; Chamuleau, Martine E D; van de Loosdrecht, Arjan A; Tolosa, Eva; Jorritsma, Tineke; Muris, Jettie J F; Dinnissen-van Poppel, Marion J; Snel, Sander N; van de Corput, Lisette; Ossenkoppele, Gert J; Meijer, Chris J L M; Neefjes, Jacques J; Marieke van Ham, S

    2009-05-01

    In human B cells, effective major histocompatibility complex (MHC) class II-antigen presentation depends not only on MHC class II, but also on the invariant chain (CD74 or Ii), HLA-DM (DM) and HLA-DO (DO), the chaperones regulating the antigen loading process of MHC class II molecules. We analysed immediate ex vivo expression of HLA-DR (DR), CD74, DM and DO in B cell chronic lymphocytic leukaemia (B-CLL). Real-time reverse transcription polymerase chain reaction demonstrated a highly significant upregulation of DRA, CD74, DMB, DOA and DOB mRNA in purified malignant cells compared to B cells from healthy donors. The increased mRNA levels were not translated into enhanced protein levels but could reflect aberrant transcriptional regulation. Indeed, upregulation of DRA, DMB, DOA and DOB mRNA correlated with enhanced expression of class II transactivator (CIITA). In-depth analysis of the various CIITA transcripts demonstrated a significant increased activity of the interferon-gamma-inducible promoter CIITA-PIV in B-CLL. Comparison of the aberrant mRNA levels with clinical outcome identified DOA mRNA as a prognostic indicator for survival. Multivariate analysis revealed that the prognostic value of DOA mRNA was independent of the mutational status of the IGHV genes. Thus, aberrant transcription of DOA forms a novel and additional prognostic indicator for survival in B-CLL.

  11. The Impact of Serosal Invasion on Prognosis after Curative Hepatectomy for Hepatocellular Carcinoma: Invasion to Adjacent Organs and Rupture of Tumor Were Crucial Tumor-Related Prognostic Factors Needed for Survival.

    PubMed

    Kato, Yoshiyasu; Okamura, Yukiyasu; Sugiura, Teiichi; Ito, Takaaki; Yamamoto, Yusuke; Ashida, Ryo; Uesaka, Katsuhiko

    2017-08-09

    Several tumor factors seem to be related to the hepatocellular carcinoma (HCC) prognosis, but they are not definitive, except for major vascular invasion. We analyzed the impact of serosal invasion, which is histologically classified into four groups according to the definition of the Liver Cancer Study Group of Japan - S0: no tumor invasion of serosa, S1: tumor invasion of serosa, S2: tumor invasion of adjacent organs, S3: tumor rupture with intraperitoneal bleeding. This retrospective study included 421 consecutive patients who underwent hepatectomy as an initial treatment for HCC between September 2002 and December 2014. Kaplan-Meier analysis and log-rank tests revealed that both recurrence-free survival (RFS) and disease-specific survival (DSS) worsened as the serosal invasion status advanced. Multivariate analyses showed that S2/S3 was independently correlated with RFS (hazard ratio [HR] 3.52; p  < 0.001) and DSS (HR 2.58; p  = 0.039). Another multivariate analysis showed that serosal invasion (S1-S3) was independently correlated with RFS (HR 1.70; p = 0.015) but not with DSS (HR 1.38; p = 0.27). Invasion to adjacent organs and tumor rupture were crucial prognostic factors for both DSS and RFS. Serosal invasion was an independent prognostic factor only for RFS. © 2017 S. Karger AG, Basel.

  12. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

    PubMed Central

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsaker, Bard; Pawinski, Adam

    2017-01-01

    Background The aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment. Methods This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months). Results The median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3. Conclusions Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model. PMID:28179964

  13. Diaphragm dysfunction on admission to the intensive care unit. Prevalence, risk factors, and prognostic impact-a prospective study.

    PubMed

    Demoule, Alexandre; Jung, Boris; Prodanovic, Hélène; Molinari, Nicolas; Chanques, Gerald; Coirault, Catherine; Matecki, Stefan; Duguet, Alexandre; Similowski, Thomas; Jaber, Samir

    2013-07-15

    Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans. To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission. Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim). Eighty-five consecutive patients aged 62 (54-75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44-68]). On Day 1, Ptr,stim was 8.2 (5.9-12.3) cm H2O and 64% of patients had Ptr,stim less than 11 cm H2O. Independent predictors of low Ptr,stim were sepsis (linear regression coefficient, -3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, -0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr,stim (9.7 [6.3-13.8] vs. 7.3 [5.5-9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3-13.5] vs. 7.8 [5.5-10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr,stim were similar. A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis. Clinical trial registered with www.clinicaltrials.gov (NCT 00786526).

  14. Prognostic impact of ΔTAp73 isoform levels and their target genes in colon cancer patients.

    PubMed

    Soldevilla, Beatriz; Díaz, Raquel; Silva, Javier; Campos-Martín, Yolanda; Muñoz, Concepción; García, Vanesa; García, José M; Peña, Cristina; Herrera, Mercedes; Rodriguez, Marta; Gómez, Irene; Mohamed, Nagat; Marques, Margarita M; Bonilla, Félix; Domínguez, Gemma

    2011-09-15

    Cumulative data support the role of ΔTAp73 variants in tumorigenic processes such as drug resistance. We evaluate the impact of TP73 isoforms and their putative target genes ABCB1, HMGB1, and CASP1 on the survival of colon cancer patients and the correlation between their expressions. We determined in 77 colon cancer patients the expression of ΔEx2p73, ΔEx2/3p73, ΔNp73, TAp73, ABCB1, HMGB1, and CASP1 by quantitative real-time reverse transcriptase-PCR. Tumor characteristics, disease-free survival, and overall survival (OS) were examined in each patient. Functional experiments were carried out to check whether ectopic expression of ΔNp73 modifies the proliferation, drug resistance, migration, and invasion properties of colon tumor cells and the expression of ABCB1, HMGB1, and CASP1. Positive correlations were observed between the expression levels of ΔTAp73 variants and HMGB1. Furthermore, a trend was observed for ABCB1. Overexpression of ΔEx2/3p73 and ΔNp73 isoforms was significantly associated with advanced stages (P = 0.04 and P = 0.03, respectively) and predicted shortened OS (P = 0.04 and P = 0.05, respectively). High levels of ABCB1 and HMGB1 were associated with shorter OS (P = 0.04 and P = 0.05, respectively). Multivariate analysis showed that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS (P = 0.008). Ectopic expression of ΔNp73 was associated with an increase in proliferation and drug resistance. The positive correlation between ΔTAp73 variants and HMGB1 and ABCB1 expression supports them as TP73 targets. The fact that upregulation of ΔTAp73 isoforms was associated with shortened OS, increase in proliferation, and drug resistance confirms their oncogenic role and plausible value as prognostic markers. ABCB1 and HMGB1, putative ΔTAp73 target genes, strongly predict OS in an independent manner, making clear the importance of studying downstream TP73 targets that could predict the outcome of colon cancer

  15. Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study

    PubMed Central

    2010-01-01

    Introduction Since data regarding new-onset atrial fibrillation (AF) in septic shock patients are scarce, the purpose of the present study was to evaluate the incidence and prognostic impact of new-onset AF in this patient group. Methods We prospectively studied all patients with new-onset AF and all patients suffering from septic shock in a non-cardiac surgical intensive care unit (ICU) during a 13 month period. Results During the study period, 687 patients were admitted to the ICU, of which 58 patients were excluded from further analysis due to pre-existing chronic or intermittent AF. In 49 out of the remaining 629 patients (7.8%) new-onset AF occurred and 50 out of the 629 patients suffered from septic shock. 23 out of the 50 patients with septic shock (46%) developed new-onset AF. There was a steady, significant increase in C-reactive protein (CRP) levels before onset of AF in septic shock patients. ICU mortality in septic shock patients with new-onset AF was 10/23 (44%) compared with 6/27 (22%) in septic shock patients with maintained sinus rhythm (SR) (P = 0.14). During a 2-year follow-up there was a trend towards an increased mortality in septic shock patients with new-onset AF, but the difference did not reach statistical significance (P = 0.075). The median length of ICU stay among surviving patients was longer in patients with new-onset AF compared to those with maintained SR (30 versus 17 days, P = 0.017). The success rate to restore SR was 86%. Failure to restore SR was associated with increased ICU mortality (71.4% versus 21.4%, P = 0.015). Conclusions AF is a common complication in septic shock patients and is associated with an increased length of ICU stay among surviving patients. The increase in CRP levels before onset of AF may support the hypothesis that systemic inflammation is an important trigger for AF. PMID:20537138

  16. Long-term prognostic impact of the Great East Japan Earthquake in patients with cardiovascular disease - Report from the CHART-2 Study.

    PubMed

    Miyata, Satoshi; Sakata, Yasuhiko; Miura, Masanobu; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Sato, Masayuki; Nochioka, Kotaro; Shiroto, Takashi; Takahashi, Jun; Shimokawa, Hiroaki

    2017-09-01

    We and others have previously reported that the Great East Japan Earthquake (GEJE) caused a significant but transient increase in cardiovascular diseases and deaths in the disaster area. However, it remains to be examined whether the GEJE had a long-term prognostic influence in large-scale cohort studies. This point is important when analyzing the data before and after the GEJE in the cohort studies in the disaster area. We examined 8676 patients registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219) between 2006 and 2010 and were alive after March 10, 2011. There were 48 GEJE-related deaths, causing a sharp and transient increase in all-cause death within a month after the GEJE. However, after excluding the GEJE-related deaths, the cubic polynomial spline smoothing showed no significant increase in all-cause death, heart failure admission, non-fetal acute myocardial infarction, or non-fetal stroke during the median 3-year follow-up after the GEJE. The extrapolation curves beyond the GEJE, which were obtained by the parametric survival models based on the survival data censored on the GEJE, were not significantly different from the Kaplan-Meier curves estimating the survival functions of deaths and cardiac events during the total follow-up period without considering the impacts of the GEJE. Furthermore, the multivariate Cox proportional hazard model applied to the matched cohort of the baseline data and the data after the GEJE showed no significant differences in the impacts of prognostic factors on all-cause mortality before and after the GEJE. These results indicate that the GEJE had no significant long-term prognostic impact after the earthquake in cardiovascular patients in the disaster area. Copyright © 2016. Published by Elsevier Ltd.

  17. Histopathological features and their prognostic impact in nodular lymphocyte-predominant Hodgkin lymphoma--a matched pair analysis from the German Hodgkin Study Group (GHSG).

    PubMed

    Hartmann, Sylvia; Eichenauer, Dennis A; Plütschow, Annette; Mottok, Anja; Bob, Roshanak; Koch, Karoline; Bernd, Heinz-Wolfram; Cogliatti, Sergio; Hummel, Michael; Feller, Alfred C; Ott, German; Möller, Peter; Rosenwald, Andreas; Stein, Harald; Hansmann, Martin-Leo; Engert, Andreas; Klapper, Wolfram

    2014-10-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity. We performed a matched-pair analysis to evaluate the prognostic impact of several histopathological features in this distinct Hodgkin lymphoma subtype. Lymph node samples of NLPHL patients were tested for CD15, IgD, phosphorylated STAT6, ICOS and Epstein-Barr virus status of the malignant lymphocyte-predominant cells as well as epithelioid cell clusters and activated T cells in the microenvironment. None of these features was associated with a particular clinical outcome. However, patients presenting with epithelioid cell clusters showed a non-significant trend towards a lower relapse rate, justifying further evaluation of this marker.

  18. Acute renal failure requiring renal replacement therapy in the intensive care unit: impact on prognostic assessment for shared decision making.

    PubMed

    Johnson, Robert F; Gustin, Jillian

    2011-07-01

    A 69-year-old female was receiving renal replacement therapy (RRT) for acute renal failure (ARF) in an intensive care unit (ICU). Consultation was requested from the palliative medicine service to facilitate a shared decision-making process regarding goals of care. Clinician responsibility in shared decision making includes the formulation and expression of a prognostic assessment providing the necessary perspective for a spokesperson to match patient values with treatment options. For this patient, ARF requiring RRT in the ICU was used as a focal point for preparing a prognostic assessment. A prognostic assessment should include the outcomes of most importance to a discussion of goals of care: mortality risk and survivor functional status, in this case including renal recovery. A systematic review of the literature was conducted to document published data regarding these outcomes for adult patients receiving RRT for ARF in the ICU. Forty-one studies met the inclusion criteria. The combined mean values for short-term mortality, long-term mortality, renal-function recovery of short-term survivors, and renal-function recovery of long-term survivors were 51.7%, 68.6%, 82.0%, and 88.4%, respectively. This case example illustrates a process for formulating and expressing a prognostic assessment for an ICU patient requiring RRT for ARF. Data from the literature review provide baseline information that requires adjustment to reflect specific patient circumstances. The nature of the acute primary process, comorbidities, and severity of illness are key modifiers. Finally, the prognostic assessment is expressed during a family meeting using recommended principles of communication.

  19. Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors.

    PubMed

    Pasea, Laura; Chung, Sheng-Chia; Pujades-Rodriguez, Mar; Moayyeri, Alireza; Denaxas, Spiros; Fox, Keith A A; Wallentin, Lars; Pocock, Stuart J; Timmis, Adam; Banerjee, Amitava; Patel, Riyaz; Hemingway, Harry

    2017-04-07

    The aim of this study is to develop models to aid the decision to prolong dual antiplatelet therapy (DAPT) that requires balancing an individual patient's potential benefits and harms. Using population-based electronic health records (EHRs) (CALIBER, England, 2000-10), of patients evaluated 1 year after acute myocardial infarction (MI), we developed (n = 12 694 patients) and validated (n = 5613) prognostic models for cardiovascular (cardiovascular death, MI or stroke) events and three different bleeding endpoints. We applied trial effect estimates to determine potential benefits and harms of DAPT and the net clinical benefit of individuals. Prognostic models for cardiovascular events (c-index: 0.75 (95% CI: 0.74, 0.77)) and bleeding (c index 0.72 (95% CI: 0.67, 0.77)) were well calibrated: 3-year risk of cardiovascular events was 16.5% overall (5.2% in the lowest- and 46.7% in the highest-risk individuals), while for major bleeding, it was 1.7% (0.3% in the lowest- and 5.4% in the highest-risk patients). For every 10 000 patients treated per year, we estimated 249 (95% CI: 228, 269) cardiovascular events prevented and 134 (95% CI: 87, 181) major bleeding events caused in the highest-risk patients, and 28 (95% CI: 19, 37) cardiovascular events prevented and 9 (95% CI: 0, 20) major bleeding events caused in the lowest-risk patients. There was a net clinical benefit of prolonged DAPT in 63-99% patients depending on how benefits and harms were weighted. Prognostic models for cardiovascular events and bleeding using population-based EHRs may help to personalise decisions for prolonged DAPT 1-year following acute MI.

  20. Personalising the decision for prolonged dual antiplatelet therapy: development, validation and potential impact of prognostic models for cardiovascular events and bleeding in myocardial infarction survivors

    PubMed Central

    Pasea, Laura; Chung, Sheng-Chia; Pujades-Rodriguez, Mar; Moayyeri, Alireza; Denaxas, Spiros; Fox, Keith A.A.; Wallentin, Lars; Pocock, Stuart J.; Timmis, Adam; Banerjee, Amitava; Patel, Riyaz

    2017-01-01

    Aims The aim of this study is to develop models to aid the decision to prolong dual antiplatelet therapy (DAPT) that requires balancing an individual patient’s potential benefits and harms. Methods and results Using population-based electronic health records (EHRs) (CALIBER, England, 2000–10), of patients evaluated 1 year after acute myocardial infarction (MI), we developed (n = 12 694 patients) and validated (n = 5613) prognostic models for cardiovascular (cardiovascular death, MI or stroke) events and three different bleeding endpoints. We applied trial effect estimates to determine potential benefits and harms of DAPT and the net clinical benefit of individuals. Prognostic models for cardiovascular events (c-index: 0.75 (95% CI: 0.74, 0.77)) and bleeding (c index 0.72 (95% CI: 0.67, 0.77)) were well calibrated: 3-year risk of cardiovascular events was 16.5% overall (5.2% in the lowest- and 46.7% in the highest-risk individuals), while for major bleeding, it was 1.7% (0.3% in the lowest- and 5.4% in the highest-risk patients). For every 10 000 patients treated per year, we estimated 249 (95% CI: 228, 269) cardiovascular events prevented and 134 (95% CI: 87, 181) major bleeding events caused in the highest-risk patients, and 28 (95% CI: 19, 37) cardiovascular events prevented and 9 (95% CI: 0, 20) major bleeding events caused in the lowest-risk patients. There was a net clinical benefit of prolonged DAPT in 63–99% patients depending on how benefits and harms were weighted. Conclusion Prognostic models for cardiovascular events and bleeding using population-based EHRs may help to personalise decisions for prolonged DAPT 1-year following acute MI. PMID:28329300

  1. Prognostic Value of Functional Variables as Assessed by Gated Thallium-201 Myocardial Perfusion Single Photon Emission Computed Tomography for Major Adverse Cardiac Events in Patients with Coronary Artery Disease.

    PubMed

    Shen, Thau-Yun; Chang, Ming-Che; Hung, Guang-Uei; Kao, Chia-Hung; Hsu, Bailing

    2013-05-01

    Gated single photon emission computed tomography (SPECT) using thallium-201 (Tl-201) has the capacity to evaluate the earlier post-stress (PS) function compared to technetium-99m labeled tracers, and may be more sensitive in detecting transient ventricular dysfunction caused by stress-induced ischemia. The purpose of this study was to assess the prognostic value of functional variables obtained from Tl-201 gated SPECT as a predictor of major adverse cardiac events (MACE). Four hundred and thirty-eight subjects who had known or suspected coronary artery disease and underwent clinically indicated dipyridamole-stress electrocardiography-gated Tl-201 SPECT were included in this study. Functional variables, including PS-ejection fraction (EF), PS-end systolic volume (ESV), PS-regional wall motion abnormality (RWA), reversible RWA and EF worsening, were generated to study the correlation with MACE (cardiac death, nonfatal infarction, unstable angina and coronary revascularization). Sixty-eight of the total 438 patients (15.5%) had MACE during the period of follow-up (a median time of 31 months), including 2 cardiac deaths, 9 non-fatal infarctions, 9 unstable angina and 48 coronary revascularizations. These events occurred significantly more frequently in patients with reversible RWA (28.8% vs. 7.1%, p < 0.0001), EF worsening (34.8% vs. 12.1%, p < 0.0001), PS-RWA (29.9% vs. 11.4%, p < 0.0001) and PS-EF < 45% (27.8% vs. 14.4%, p = 0.034). Using the Cox proportional hazards regression analysis, reversible RWA and EF worsening were two independent predictors of MACE, providing incremental prognostic value over clinical and perfusion-alone information. The functional assessment with Tl-201 gated SPECT was a useful prognosticator for patients who had known or suspected coronary artery disease. Coronary artery disease; Gated SPECT; Major adverse cardiac events; Tl-201.

  2. Crustal evolution of the early earth: The role of major impacts

    NASA Technical Reports Server (NTRS)

    Frey, H.

    1979-01-01

    The role of major impact basins (such as those which formed on the moon before 4 billion years ago) is examined to determine the effects of such impacts on the early crustal evolution of the earth. Specifically addressed is the fundamental problem of what is the origin of the earth's fundamental crustal dichotomy of low density continental and high density oceanic crust and its relationship to the superficially similar highlands/maria crustal dichotomies of the moon, Mercury and Mars.

  3. Comparing the evidence relevant to impact and flood basalt at times of major mass extinctions.

    PubMed

    Alvarez, Walter

    2003-01-01

    The five major mass extinctions identified in 1982 by Raup and Sepkoski have expanded to six, with the suggestion that the Permian-Triassic extinction was a double event. Is there a general explanation for great mass extinctions, or can they result from different triggers, or even from internal system instabilities? The two most-discussed candidates for a general extinction mechanism are impacts and flood-basalt eruptions. A compilation of evidence for impact at the times of mass extinctions shows that this cause is abundantly confirmed in the case of the Cretaceous-Tertiary extinction and the late Eocene, which is a time of minor and gradual extinction, but little or no evidence connects other major extinctions to impact. On the other hand, there is a remarkable time correlation between flood basalts and four major extinctions, but no other evidence that flood basalts cause mass extinctions. The evidence for an impact-extinction linkage is strikingly different from that for a connection between flood basalts and extinctions. Flood basalts cover larger areas than craters and their associated thick ejecta blankets, which are thus less likely to be found. Impacts distribute proxies globally at instantaneous time horizons, whereas flood-basalt events are extended in time, and no remote proxies have been recognized. Many global killing mechanisms have been proposed in the case of impacts, but few have been suggested for flood basalts. It is possible that flood basalts are triggered by impact, but it is not obvious how impacts could result from anything other than chance. The hypothesis that impacts are the general cause of mass extinctions has not received supporting evidence, but has not been falsified. The hypothesis that flood basalts are the general cause of mass extinctions is supported by evidence from timing, but is not susceptible to falsification. Other candidates for general extinction causes, especially sea-level changes and system instabilities, would

  4. Prognostic impact of Bcl-2 depends on tumor histology and expression of MALAT-1 lncRNA in non-small-cell lung cancer.

    PubMed

    Schmidt, Lars Henning; Görlich, Dennis; Spieker, Tilmann; Rohde, Christian; Schuler, Martin; Mohr, Michael; Humberg, Julia; Sauer, Tim; Thoenissen, Nils H; Huge, Andreas; Voss, Reinhard; Marra, Alessandro; Faldum, Andreas; Müller-Tidow, Carsten; Berdel, Wolfgang E; Wiewrodt, Rainer

    2014-09-01

    Apoptosis is a crucial pathway in tumor growth and metastatic development. Apoptotic proteins regulate the underlying molecular cascades and are thought to modulate the tumor response to chemotherapy and radiation. However, the prognostic value of the expression of apoptosis regulators in localized non-small-cell lung cancer (NSCLC) is still unclear. We investigated the protein expression of apoptosis regulators Bcl-2, Bcl-xl, Mcl-1, and pp32/PHAPI, and the expression of the lncRNA MALAT-1 in tumor samples from 383 NSCLC patients (median age: 65.6 years; 77.5% male; paraffin-embedded tissue microarrays). For statistical analysis correlation tests, Log rank tests and Cox proportional hazard models were applied. Tumor histology was significantly associated with the expression of Bcl-2, Bcl-xl and Mcl-1 (all p < 0.001). Among the tested apoptotic markers only Bcl-2 demonstrated prognostic impact (hazard ratio = 0.64, p = 0.012). For NSCLC patients with non-adenocarcinoma histology, Bcl-2 expression was associated with increased overall survival (p = 0.036). Besides tumor histology, prognostic impact of Bcl-2 was also found to depend on MALAT-1 lncRNA expression. Gene expression analysis of A549 adenocarcinoma cells with differential MALAT-1 lncRNA expression demonstrated an influence on the expression of Bcl-2 and its interacting proteins. Bcl-2 expression was specifically associated with superior prognosis in localized NSCLC. An interaction of Bcl-2 with MALAT-1 lncRNA expression was revealed, which merits further investigation for risk prediction in resectable NSCLC patients.

  5. Lexical Collocations and Their Impact on the Online Writing of Taiwanese College English Majors and Non-English Majors

    ERIC Educational Resources Information Center

    Hsu, Jeng-yih

    2007-01-01

    The present study investigates the use of English lexical collocations and their relation to the online writing of Taiwanese college English majors and non-English majors. Data for the study were collected from 41 English majors and 21 non-English majors at a national university of science and technology in southern Taiwan. Each student was asked…

  6. Predicting long-term neurological outcomes after severe traumatic brain injury requiring decompressive craniectomy: A comparison of the CRASH and IMPACT prognostic models.

    PubMed

    Honeybul, Stephen; Ho, Kwok M

    2016-09-01

    Predicting long-term neurological outcomes after severe traumatic brain (TBI) is important, but which prognostic model in the context of decompressive craniectomy has the best performance remains uncertain. This prospective observational cohort study included all patients who had severe TBI requiring decompressive craniectomy between 2004 and 2014, in the two neurosurgical centres in Perth, Western Australia. Severe disability, vegetative state, or death were defined as unfavourable neurological outcomes. Area under the receiver-operating-characteristic curve (AUROC) and slope and intercept of the calibration curve were used to assess discrimination and calibration of the CRASH (Corticosteroid-Randomisation-After-Significant-Head injury) and IMPACT (International-Mission-For-Prognosis-And-Clinical-Trial) models, respectively. Of the 319 patients included in the study, 119 (37%) had unfavourable neurological outcomes at 18-month after decompressive craniectomy for severe TBI. Both CRASH (AUROC 0.86, 95% confidence interval 0.81-0.90) and IMPACT full-model (AUROC 0.85, 95% CI 0.80-0.89) were similar in discriminating between favourable and unfavourable neurological outcome at 18-month after surgery (p=0.690 for the difference in AUROC derived from the two models). Although both models tended to over-predict the risks of long-term unfavourable outcome, the IMPACT model had a slightly better calibration than the CRASH model (intercept of the calibration curve=-4.1 vs. -5.7, and log likelihoods -159 vs. -360, respectively), especially when the predicted risks of unfavourable outcome were <80%. Both CRASH and IMPACT prognostic models were good in discriminating between favourable and unfavourable long-term neurological outcome for patients with severe TBI requiring decompressive craniectomy, but the calibration of the IMPACT full-model was better than the CRASH model. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  7. Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: Impact of tumor volume

    SciTech Connect

    Basaki, Kiyoshi . E-mail: basaki-rad@umin.ac.jp; Abe, Yoshinao; Aoki, Masahiko; Kondo, Hidehiro; Hatayama, Yoshiomi; Nakaji, Shigeyuki

    2006-02-01

    Purpose: To investigate the impact of tumor volume on overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). Methods and Materials: Between May 1997 and February 2003, 71 patients with Stage III NSCLC were treated with radiation therapy of 60 Gy or more. The total target dose was between 60 and 77 Gy (average, 66.3 Gy). Chemotherapy was used in 45 cases. The primary tumor and nodal volume were identified in pretreatment computed tomography scans. Univariate and multivariate analyses were used to evaluate the impact of tumor volume on survival after RT. Results: The overall 2-year survival rate was 23%, with a median survival time of 14 months. The median survival times were 10 months and 19 months with large primary tumor volume more than median volume and smaller primary tumor volume, respectively. At a univariate analysis, the total tumor volume (TTV) (p < 0.0003) and the primary tumor volume (p < 0.00008) were significant and the nodal volume was not. At multivariate analyses, both the TTV and the primary tumor volume were significant prognostic factors. Conclusion: The primary tumor volume as well as TTV is a significant prognostic factor on survival in patients with Stage III NSCLC treated with RT and should be recorded in clinical results when the survivals are compared among clinical studies.

  8. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism.

    PubMed

    Batista, Rui; Cruvinel-Carloni, Adriana; Vinagre, João; Peixoto, Joana; Catarino, Telmo A; Campanella, Nathalia Cristina; Menezes, Weder; Becker, Aline Paixão; de Almeida, Gisele Caravina; Matsushita, Marcus M; Clara, Carlos; Neder, Luciano; Viana-Pereira, Marta; Honavar, Mrinalini; Castro, Lígia; Lopes, José Manuel; Carvalho, Bruno; Vaz, Rui Manuel; Máximo, Valdemar; Soares, Paula; Sobrinho-Simões, Manuel; Reis, Rui Manuel; Lima, Jorge

    2016-07-15

    Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients carrying the rs2853669 A allele and not in those carrying the G allele. In conclusion, the presence of TERTp mutations was associated with worse prognosis in GBM patients, although such association depended on the status of the rs2853669 SNP. The status of the rs2853669 SNP should be taken in consideration when assessing the prognostic value of TERTp mutations in GBM patients. TERTp mutations and the rs2853669 SNP can be used in the future as biomarkers of glioma prognosis. © 2016 UICC.

  9. Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer.

    PubMed

    Sang, Yulan; Bi, Xin; Liu, Yan; Zhang, Wei; Wang, Dongjie

    2017-01-01

    Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals. By using chi-square (χ(2)) test and Fisher's exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan-Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients.

  10. Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer

    PubMed Central

    Sang, Yulan; Bi, Xin; Liu, Yan; Zhang, Wei; Wang, Dongjie

    2017-01-01

    Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals. By using chi-square (χ2) test and Fisher’s exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan–Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients. PMID:28331344

  11. Negative prognostic impact of low absolute CD4(+) T cell counts in peripheral blood in mantle cell lymphoma.

    PubMed

    Zhang, Xin-Yu; Xu, Ji; Zhu, Hua-Yuan; Wang, Yan; Wang, Li; Fan, Lei; Wu, Yu-Jie; Li, Jian-Yong; Xu, Wei

    2016-10-01

    Tumor microenvironment and host immunity are closely related to outcome in patients with mantle cell lymphoma (MCL). However, few researchers have focused on the prognostic value of peripheral blood lymphocyte subsets counts. The purpose of this study was to investigate the prognostic value of lymphocyte subsets and absolute monocyte counts. Sixty-eight patients were analyzed retrospectively. Absolute CD4(+) T cell counts (ACD4C), CD8(+) T cell counts, nature killer cell counts, and CD4/CD8 ratios were assessed by peripheral blood flow cytometry and correlated with clinical parameters and long-term outcomes. The median follow-up for all patients was 21 months and the median survival time was 44 months. The overall survival (OS) rate at 1, 3, and 5 years was 80%, 51%, and 41%, respectively. In our cohort, high absolute monocyte count, and low ACD4C and CD4/CD8 ratio were associated with unfavorable OS (P = 0.029, P = 0.027, and P = 0.045, respectively) by univariate analysis. Multivariate analysis indicated that low ACD4C was a significant predictor of unfavorable OS (P = 0.004) independent of the simplified MCL International Prognostic Index (P = 0.048) in patients treated with or without rituximab (P = 0.011). Low CD4(+) T cell counts proved to be a significant predictor of unfavorable OS in patients with MCL.

  12. Impact of a Sophomore Seminar on the Desire of STEM Majors to Pursue a Science Career

    ERIC Educational Resources Information Center

    Sweeder, Ryan D.; Strong, Philip E.

    2012-01-01

    This study focuses on the impact of a sophomore seminar on STEM majors desire to pursue a science career. This seminar was a component in a broader scholarship program and focused on helping students gain a broader understanding of the process of science, expose students to a range of career options and provide opportunities for outside of class…

  13. 40 CFR 1502.4 - Major Federal actions requiring the preparation of environmental impact statements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Major Federal actions requiring the preparation of environmental impact statements. 1502.4 Section 1502.4 Protection of Environment COUNCIL ON..., could significantly affect the quality of the human environment. Statements shall be prepared on such...

  14. 40 CFR 1502.4 - Major Federal actions requiring the preparation of environmental impact statements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Major Federal actions requiring the preparation of environmental impact statements. 1502.4 Section 1502.4 Protection of Environment COUNCIL ON..., could significantly affect the quality of the human environment. Statements shall be prepared on such...

  15. Apollo 16 impact-melt splashes - Petrography and major-element composition

    NASA Technical Reports Server (NTRS)

    See, Thomas H.; Horz, Friedrich; Morris, Richard V.

    1986-01-01

    Petrographic and major-element analyses are applied to 50 Apollo 16 impact-melt splash (IMS) samples in order to determine their origin and assess the nature of the subregolith source. The macroscopic analyses reveal that the IMSs exhibit a glassy appearance, but the textures range from holohyaline to hyalopilitic. Schlieren-rich glasses dominate the holohyaline areas, and the crystalline areas are mainly spherulitic. It is observed that most IMSs contain feldspathic monomineralic and lithic clasts and no regolithic materials. It is detected that the chemistry of most IMSs is not like the local regolith and appears to represent varied mixtures of VHA impact-melt breccias and anorthosite; the host rocks are mainly dimict breccias. It is concluded that the Cayley Formation is a polymict deposit composed of VHA impact-melt breccias and anorthosites. Tables revealing the macroscopic characteristics of the IMSs and the major-element composition of IMSs and various host rock are presented.

  16. Apollo 16 impact-melt splashes - Petrography and major-element composition

    NASA Astrophysics Data System (ADS)

    See, Thomas H.; Horz, Friedrich; Morris, Richard V.

    1986-11-01

    Petrographic and major-element analyses are applied to 50 Apollo 16 impact-melt splash (IMS) samples in order to determine their origin and assess the nature of the subregolith source. The macroscopic analyses reveal that the IMSs exhibit a glassy appearance, but the textures range from holohyaline to hyalopilitic. Schlieren-rich glasses dominate the holohyaline areas, and the crystalline areas are mainly spherulitic. It is observed that most IMSs contain feldspathic monomineralic and lithic clasts and no regolithic materials. It is detected that the chemistry of most IMSs is not like the local regolith and appears to represent varied mixtures of VHA impact-melt breccias and anorthosite; the host rocks are mainly dimict breccias. It is concluded that the Cayley Formation is a polymict deposit composed of VHA impact-melt breccias and anorthosites. Tables revealing the macroscopic characteristics of the IMSs and the major-element composition of IMSs and various host rock are presented.

  17. Concussions experienced by Major League Baseball catchers and umpires: field data and experimental baseball impacts.

    PubMed

    Beyer, Jeffrey A; Rowson, Steven; Duma, Stefan M

    2012-01-01

    Some reports have shown that head injuries in baseball may comprise up to 18.5% of all competitive sports-related head injuries. The objective of this study was to evaluate the response of catcher and umpire masks to impacts at these different regions to discover the impact conditions that represent the greatest risk of injury. A series of 10 events in which a catcher or umpire in Major League Baseball, who experienced a foul ball to the mask that resulted in a concussion, were analyzed through video and data on pitch characteristics. It was found that the impacts were distributed across the face, and the median plate speed was approximately 38 m/s (84 mph). To determine the relative severity of each identified impact location, an instrumented Hybrid III head outfitted with a catcher or umpire mask was impacted with baseballs. Testing at 27 and 38 m/s (60 and 84 mph) suggested that impacts to the center-eyebrow and chin locations were the most severe. Peak linear and rotational accelerations were found to be lower than the suggested injury thresholds. While impacts to a mask result in head accelerations which are near or below levels commonly associated with the lower limits for head injury, the exact injury mechanism is unclear, as concussions are still experienced by the mask wearers.

  18. Prognostic impact of serum albumin levels on the recurrence of stage I non-small cell lung cancer.

    PubMed

    Jin, Ying; Zhao, Li; Peng, Fang

    2013-05-01

    Patients with stage I non-small cell lung cancer who have undergone complete surgical resection harbor a 30% risk for tumor recurrence. Thus, the identification of factors that are predictive for tumor recurrence is urgently needed. The aim of this study was to test the prognostic value of serum albumin levels on tumor recurrence in patients with stage I non-small cell lung cancer. Stage I non-small cell lung cancer patients who underwent complete surgical resection of the primary tumor at Zhejiang Hospital were analyzed in this study. Serum albumin levels were measured before surgery and once again after surgery in 101 histologically diagnosed non-small cell lung cancer patients. Correlations between the pre- and post-operative serum albumin levels and various clinical demographics and recurrence-free survival rates were analyzed. Patients with pre-operative hypoalbuminemia (<3.5 g/dl) had a significantly worse survival rate than patients with normal pre-operative serum albumin levels (≥3.5 g/dl) (p=0.008). Patients with post-operative hypoalbuminemia had a worse survival rate when compared with patients with normal post-operative serum albumin levels (p=0.001). Cox multivariate analysis identified pre-operative hypoalbuminemia, post-operative hypoalbuminemia and tumor size over 3 cm as independent negative prognostic factors for recurrence. Serum albumin levels appear to be a significant independent prognostic factor for tumor recurrence in patients with stage I non-small cell lung cancer who have undergone complete resection. Patient pre-treatment and post-treatment serum albumin levels provide an easy and early means of discrimination between patients with a higher risk for recurrence and patients with a low risk of recurrence.

  19. Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor.

    PubMed

    Ohara, Masahiro; Akimoto, Etsushi; Noma, Midori; Matsuura, Kazuo; Doi, Mihoko; Kagawa, Naoki; Itamoto, Toshiyuki

    2015-11-01

    Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m(2) (high, H) or <25 kg/m(2) (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR- and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR- tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2- breast cancer in patients treated with adjuvant aromatase inhibitors.

  20. Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis.

    PubMed

    Veronese, N; Nottegar, A; Pea, A; Solmi, M; Stubbs, B; Capelli, P; Sergi, G; Manzato, E; Fassan, M; Wood, L D; Scarpa, A; Luchini, C

    2016-01-01

    The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer. Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with colorectal cancer, comparing participants with the presence of ENE (ENE+) versus only intranodal extension (ENE-) were eligible. Data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) together with 95% confidence intervals (CIs) for time-dependent risk related to ENE+, adjusted for potential confounders. Thirteen studies including 1336 patients were identified with a median follow-up of 4.7 years. ENE was associated with a higher T stage and tumor grading. In addition, ENE was associated with a significantly increased risk of all-cause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I(2) = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I(2) = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I(2) = 47%; HR = 2.31, 95% CI 1.54-3.44, P < 0.0001, I(2) = 48%). Based of these results, in colorectal cancer, ENE should be considered from the gross sampling to the pathology report, as well as in future oncologic staging systems. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. Prognostic Differences for Functional Recovery after Major Lower Limb Amputation: Effects of the Timing and Type of Inpatient Rehabilitation Services in the Veterans Health Administration

    PubMed Central

    Stineman, Margaret G.; Kwong, Pui L.; Xie, Dawei; Kurichi, Jibby E.; Ripley, Diane Cowper; Brooks, David M.; Bidelspach, Douglas E.; Bates, Barbara E.

    2010-01-01

    specialized rehabilitation can be expected to make comparatively higher gains than patients who receive consultative services, regardless of timing and clinical complexity. Findings highlight the need for clinicians to adjust prognostic expectations to both clinical severity and the type of rehabilitation patients receive. PMID:20430324

  2. Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer.

    PubMed

    Miura, Takuya; Yoshizawa, Tadashi; Hirai, Hideaki; Seino, Hiroko; Morohashi, Satoko; Wu, Yunyan; Wakiya, Taiichi; Kimura, Norihisa; Kudo, Daisuke; Ishido, Keinosuke; Toyoki, Yoshikazu; Kijima, Hiroshi; Hakamada, Kenichi

    2017-01-01

    The aim of this study was to examine the clinicopathological influence of tumor-infiltrating cluster of differentiation (CD) 163(+) macrophages and CD8(+) T-cells, and to clarify the prognostic effects of these cells in patients with invasive extrahepatic bile duct cancer (EHBC). The numbers of CD8(+) T-cells in cancer cell nests and CD163(+) macrophages in tumor stroma were evaluated using immunohistochemistry in 101 resected EHBC specimens. Correlations with clinicopathological variables and overall survival were analyzed. Perihilar EHBC and perineural invasion were significantly associated with a low number of tumor-infiltrating CD8(+) T-cells. Poorly- differentiated histology and nodal metastasis were significantly associated with a high number of tumor-infiltrating CD163(+) macrophages. A combination of high number of CD8(+) T-cells and low number of CD163(+) macrophages was independently related to better overall survival in the whole patient cohort (hazard ratio=0.127, p<0.001) and in patients treated with adjuvant chemotherapy (hazard ratio=0.139, p=0.021). Infiltrating CD163(+) macrophages in tumor stroma and CD8(+) T-cells in cancer cell nests have a prognostic impact in patients with EHBC following resection and also after adjuvant chemotherapy. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. [Major depression in primary care and clinical impacts of treatment strategies: a literature review].

    PubMed

    Beaucage, Clément; Cardinal, Lise; Kavanagh, Mélanie; Aubé, Denise

    2009-01-01

    Major or clinical depression represents a frequent mental illness that is often associated with a high level of morbidity and mortality. Yet, major depression remains under-diagnosed and under-treated. On the level of treatment, it would appear desirable for reasons of better prognosis, to aim more than the simple reduction of depressive symptoms and target their remission resolutely and the fastest return to the individual's optimal functioning. This article presents a systematic review of the literature relating to the clinical impacts of treatment strategies aiming at the improvement of services offered to people who suffer of clinical depression and who consult in primary care. The authors summarize results drawn from 41 studies that include a measurement of the clinical impacts (reduction of symptoms, response, remission and functioning) of various treatment strategies. It appears that using complex treatment strategies favour positive outcomes. The authors propose various paths of research to further increase current knowledge.

  4. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    SciTech Connect

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  5. Prognostic variables for shockwave lithotripsy (SWL) treatment success: no impact of body mass index (BMI) using a third generation lithotripter.

    PubMed

    Hatiboglu, Gencay; Popeneciu, Valentin; Kurosch, Martin; Huber, Johannes; Pahernik, Sascha; Pfitzenmaier, Jesco; Haferkamp, Axel; Hohenfellner, Markus

    2011-10-01

    • To investigate the effect of different variables including body mass index (BMI) on therapy outcome in patients with upper urinary tract stones treated with a third generation lithotripter, as BMI has been reported to be an independent predictor for stone-free status after extracorporeal shockwave lithotripsy (SWL) performed with first or second generation lithotripters. • In all, 172 patients with kidney stones with a mean (range) size of 9.2 (3.0-32.0) mm were included in the study. • In all, 91 patients (52.9%) were treated with a ureteric stent in situ. • For SWL therapy a third generation, electromagnetic lithotripter (Siemens Lithoskop™) was used. Stone-free status was reached, when no more treatable stones were present (no stone or stone < 3 mm). • BMI, stone size and localization, age, gender, treatment parameters and ureteric stent in situ were evaluated for their prognostic relevance on therapy success. • The mean (range) BMI of all patients was 27.8 (19.0-58.6) kg/m(2). • Patients were categorized into two groups: A) patients that were stone free after one treatment; B) patients with residual stones. The mean (sd) BMI was 27.4 (4.6) kg/m(2) and 28.4 (6.1) kg/m(2) for A and B, respectively. • Univariate and multivariate analysis for freedom of stones showed that only stone size (P < 0.01) and presence of a ureteric stent (P = 0.01) were independent prognostic variables. • BMI had no significant influence on therapy outcome (P = 0.51). • Using a third generation lithotripter, BMI was not an independent predictor of stone-free rate after SWL therapy of kidney stones. • This effect might be attributed to a greater penetration depth of the shockwave energy. Stone size and a ureteric stent in situ were the only variables with prognostic significance. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

  6. Prognostic impact of circulating tumor cells assessed with the CellSearch System™ and AdnaTest Breast™ in metastatic breast cancer patients: the DETECT study

    PubMed Central

    2012-01-01

    Introduction There is a multitude of assays for the detection of circulating tumor cells (CTCs) but a very limited number of studies comparing the clinical relevance of results obtained with different test methods. The DETECT trial for metastatic breast cancer patients was designed to directly compare the prognostic impact of two commercially available CTC assays that are prominent representatives of immunocytochemical and RT-PCR based technologies. Methods In total, 254 metastatic breast cancer patients were enrolled in this prospective multicenter trial. CTCs were assessed using both the AdnaTest Breast Cancer and the CellSearch system according to the manufacturers' instructions. Results With the CellSearch system, 116 of 221 (50%) evaluable patients were CTC-positive based on a cut-off level at 5 or more CTCs. The median overall survival (OS) was 18.1 months in CTC-positive patients. (95%-CI: 15.1-22.1 months) compared to 27 months in CTC-negative patients (23.5-30.7 months; p<0.001). This prognostic impact for OS was also significant in the subgroups of patients with triple negative, HER2-positive and hormone receptor-positive/HER2-negative primary tumors. The progression free survival (PFS) was not correlated with CTC status in our cohort receiving different types and lines of systemic treatment (p = 0.197). In multivariate analysis, the presence of CTCs was an independent predictor for OS (HR: 2.7, 95%-CI: 1.6-4.2). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC-positive. CTC-positivity assessed by the AdnaTest Breast had no association with PFS or OS. Conclusions The prognostic relevance of CTC detection in metastatic breast cancer patients depends on the test method. The present results indicate that the CellSearch system is superior to the AdnaTest Breast Cancer in predicting clinical outcome in advanced breast cancer. Trial registration Current Controlled Trials Registry number ISRCTN59722891. PMID:22894854

  7. Prognostic Impact of Extent, Severity, and Heterogeneity of Abnormalities on (18)F-FDG PET Scans for Suspected Cardiac Sarcoidosis.

    PubMed

    Sperry, Brett W; Tamarappoo, Balaji K; Oldan, Jorge D; Javed, Omair; Culver, Daniel A; Brunken, Richard; Cerqueira, Manuel D; Hachamovitch, Rory

    2017-08-11

    This study sought to evaluate the incremental value of quantifying the extent and severity of myocardial perfusion and (18)F-labeled fluorodeoxyglucose (FDG) abnormalities in predicting adverse outcomes among patients with suspicion for cardiac sarcoidosis (CS). Positron emission tomography (PET) with FDG is a key component of the noninvasive assessment of patients with suspected CS. However, the optimal method for image interpretation has not been defined. A retrospective analysis was performed of 203 patients who underwent perfusion and FDG-PET imaging to evaluate for CS. Imaging findings were scored by conventional 3-category methods (normal perfusion and metabolism, abnormal perfusion or metabolism, abnormal perfusion and metabolism) and by summed scores using the 17-segment model to represent extent and severity of disease. Heterogeneity of metabolism was quantified using the coefficient of variation (standard deviation divided by the mean) of FDG uptake. Multivariable Cox models were developed to assess associations between imaging findings and adverse events (death, heart transplant, or ventricular arrhythmia requiring defibrillation). The indication for FDG-PET was ventricular arrhythmia in 69 (34%), heart block in 16 (8%), cardiomyopathy in 54 (27%), and other indications in 64 (32%). There were 63 patients who developed adverse events over a mean follow-up of 1.8 years. After robust adjustment, only the summed score in segments with a perfusion-metabolism mismatch and the coefficient of variation were important prognostically (p = 0.029 and p = 0.041, respectively). Quantitative measures of extent and severity of perfusion-metabolism mismatch and coefficient of variation of FDG uptake provide an incremental prognostic advantage in patients undergoing FDG-PET for CS. These results support the use of a more detailed analysis of imaging findings, as is conventional in coronary artery disease. Copyright © 2017 American College of Cardiology Foundation

  8. Prognostic impact of Ki-67 in patients with gastric cancer-the importance of depth of invasion and histologic differentiation.

    PubMed

    Ko, Gyung Hyuck; Go, Se-Il; Lee, Won Sup; Lee, Jeong-Hee; Jeong, Sang-Ho; Lee, Young-Joon; Hong, Soon Chan; Ha, Woo Song

    2017-06-01

    Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic biomarker has not been established in gastric cancer. The present study was performed to investigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC).With tissue microarray for 320 patients with gastric cancer, we performed immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. For validation, we performed bootstrap resampling.The median follow-up duration was 72 months (range: 3-120 months). Ki-67-high group showed worse prognosis than Ki-67-low group in EGC (5-YSR, 78.9% vs 92.0%, P  =  .018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs 59.2%, P  =  .951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-high group was considerably worse than that for Ki-67-low group (5-YSR, 67.0% vs 94.4%, P  =  .012), but not in those with moderately differentiated (P  =  .504) and poorly differentiated histology (P  =  .905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r  =  0.215, P  =  .002). Multivariate analysis also revealed that the high-Ki-67 expression serves as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397-13.515, P  =  .011), especially in the well-differentiated histology, but not in all the patients (P  =  .171). Bootstrap resampling internally validated this result (P  =  .011).This study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC with well-differentiated histologic type.

  9. Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer

    PubMed Central

    Radke, I; Götte, M; Kersting, C; Mattsson, B; Kiesel, L; Wülfing, P

    2006-01-01

    The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n=7) and nonmalignant (n=7) cryoconserved breast tissue samples as well as in eight breast cancer cell lines by RT–PCR. Furthermore, protein expression of PRL-3 was analysed semiquantitatively by immunohistochemistry in ductal breast carcinoma in situ (n=135) and invasive breast cancer (n=147) by use of tissue microarray technology (TMA). In 24 lymph node-positive patients we selected the corresponding lymph node metastases for analysis of PRL-3 expression, and a validation set (n=99) of invasive breast cancer samples was examined. Staining results were correlated with clinicopathological parameters and long-term follow-up. PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue. For PRL-1 and PRL-2 expression no significant differences were observed. Staining of TMAs showed PRL-3 expression in 85.9% ductal carcinoma in situ and 75.5% invasive breast carcinomas. Analysis of survival parameters revealed a shorter disease-free survival (DFS) in patients with PRL-3-positive carcinomas, and in particular a significantly shorter DFS in nodal-positive patients with PRL-3 overexpressing tumours as compared to PRL-3-negative breast carcinomas (66±7 months (95% CI, 52–80) vs 97±9 months (95% CI, 79–115); P=0.032). Moreover, we found a more frequent expression of PRL-3 in lymph node metastases as compared to the primary tumours (91.7 vs 66.7%; P=0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome. PMID:16832410

  10. Major Impact of Fleet Renewal Over Airports Located in the Most Important Region of Brazil

    NASA Technical Reports Server (NTRS)

    Maters, Rafael Waltz; deRoodeTorres, Roberta; Santo, Respicio A. Espirito, Jr.

    2003-01-01

    The present article discusses and analyses the major impacts of the Brazilian carriers fleet renewal regarding Brazilian airport infrastructure in the most important region of the country, the Southeast (SE). A brief historical overview of the country's airline fleet will be presented, demonstrating the need for its renewal (m fact, Brazilian carriers started a major fleet renewal program m the last five years), while analyzing the periods in which a new breed of aircraft was put into service by the major carriers operating in the SE region. The trend of operating the classic regional jets plus the forthcoming entry into service of the "large regional jets" (LRJ, 70-115 seaters) in several point-to-point routes are presented along with the country's carriers" reality of operating these former aircraft in several high-capacity and medium-range routes. The article will focus on the ability of four of the major Southeast's airports to cope with the fleet modernization, mainly due to the fact that the region studied is the most socioeconomic developed, by far, with the largest demand for air transportation, thus making the impacts much more perceptible for the communities and the airport management involved. With the emergence of these impacts, several new projects and investments are being discussed and pushed forward, despite budgetary constrains being a reality in almost every Brazilian city, even in the SE region. In view of this, the paper presents how the general planning could be carried out in order to adapt the airports' infrastructures in function of the proposed (and in some cases, necessary) fleet renewal. Ultimately, we will present the present picture and two future scenarios m order to determine the level of service in the existent passenger terminal facilities in the wake of the possible operation of several new aircraft. Keywords: Airline fleet planning, Airport planning, Regional development, Regional Jets.

  11. Impact of Gender on the Prognostic Value of Coronary Artery Calcium in Symptomatic Patients With Normal Single-Photon Emission Computed Tomography Myocardial Perfusion.

    PubMed

    Engbers, Elsemiek M; Timmer, Jorik R; Ottervanger, Jan Paul; Mouden, Mohamed; Knollema, Siert; Jager, Pieter L

    2016-12-01

    The coronary artery calcium (CAC) score provides independent prognostic value on top of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). We sought to determine whether the prognostic value of the CAC score in patients with normal SPECT MPI is gender specific. We studied 3,705 consecutive symptomatic patients without a history of coronary artery disease with normal SPECT MPI. All patients underwent concomitant CAC scoring, which was categorized as CAC score 0, 1 to 99, 100 to 399, 400 to 999, or ≥1,000. Major adverse cardiac events were defined as revascularization, nonfatal myocardial infarction, or all-cause mortality. The median CAC score was 9 in women (interquartile range 0 to 113) and 47 in men (interquartile range 1 to 307, p <0.001). The annual event rate was lower in women than in men (1.6% and 2.7%, respectively, p <0.001). When stratified by CAC score, annual event rates were similar (for women and men, respectively: CAC score 0, 0.6% and 0.5%, p = 0.95; CAC score 1 to 99, 0.9% and 1.2%, p = 0.45; CAC score 100 to 399, 2.7% and 3.8%, p = 0.23; CAC score 400 to 999, 3.8% and 5.3%, p = 0.34; CAC score ≥1,000, 8.4% and 8.7%, p = 0.99). The CAC score was an independent predictor of major adverse cardiac events in both genders (CAC score ≥1,000: hazard ratio for women 8.5, 95% confidence interval 4.0 to 18.1; hazard ratio for men 14.8, 95% confidence interval 5.3 to 41.1). In conclusion, risk for events is similar for both genders when stratified by CAC score, wherein a high CAC score carries a high risk for events despite normal SPECT MPI. Our findings do not reveal a gender-specific prognostic value of the CAC score.

  12. The past impact of climate change on the yield of major crops

    NASA Astrophysics Data System (ADS)

    Sakurai, G.; Iizumi, T.; Nishimori, M.; Okada, M.; Yokozawa, M.

    2014-12-01

    Understanding the relationship between climate change and crop production is of paramount importance for food security. Previous statistical analyses of historical data have revealed the important impact of temperature increases on past crop yields. However, the direct effect of the [CO2] increase, known as CO2 fertilization effect, is difficult to estimate by simple statistical analysis because the average atmospheric [CO2] does not vary widely over space and time. Moreover, it is also difficult to estimate each climatic effect on crop yields with completely removing correlation among climatic factors. Although non-statistical approaches using process-based crop models may overcome these problems, the results of simple simulation studies may be misleading because of the uncertainty of the model parameters. In the present study, we applied a Bayesian statistical approach to estimate the parameters of a basic process-based model of crop growth (PRYSBI-2) and the past effect of each climatic factor on yields of major crops. The spatial variability of model parameters was considered by estimating the posterior distribution of the parameters from historical yield data by using the Markov-chain Monte Carlo (MCMC) method. The datasets of maize, soybean, rice, and wheat yields during 1982-2006 with a spatial resolution of 1.125° × 1.125° were used for this purpose (Iizumi et al. 2013). The posterior distributions of model parameters were estimated for each spatial grid with 30 000 MCMC steps of 7 chains. Using this model, we produced maps of the estimated past impact of each climatic factor (including CO2 effect) on crop yields (see Figure for the effect of temperature changes on maize yield as an example). The results suggested large variations of the impact of the change in average temperature on major crop yields. The results also suggested a large impact of CO2 increase on C3 crops such as soybean, rice, and wheat. In some regions, the positive impact of CO2

  13. Extent of alcohol prohibition in civil policy in Muslim majority countries: the impact of globalization.

    PubMed

    Al-Ansari, Basma; Thow, Anne-Marie; Day, Carolyn A; Conigrave, Katherine M

    2016-10-01

    Many policies have been introduced to reduce alcohol harm in different countries. However, Muslim majority countries (MMCs), where the major religion (Islam) prohibits alcohol consumption, have less well-developed civil alcohol policies. Overall, MMCs have low prevalence of alcohol consumption, although recently most MMCs have been undergoing transition, which has sometimes increased pressure for alcohol availability and impacted on social practices, alcohol policies and broader public health. Globalization, the influence of the global alcohol industry, recent governmental transition or political instability and the presence of immigrants from non-Muslim countries can all affect civil alcohol policy. In this context, consumption overall has increased compared with two decades ago. This paper presents an overview of current civil alcohol policy, with regard to the presence or absence of alcohol prohibition, and provides an insight into the legal availability of alcohol in MMCs and the challenges facing policymakers. English, Arabic and Persian language sources were examined, using PubMed, government websites for each country and the World Health Organization (WHO). Some of the challenges MMCs may face in developing alcohol policies are explored, including the need to interact with the global economy and the potential influence of the alcohol industry. Muslim majority countries have adopted a range of civil alcohol policies in recent decades. There is a pressing need for better data and to support Muslim majority countries in alcohol policy development. Lessons from Muslim majority countries can help to inform other parts of the world. © 2015 Society for the Study of Addiction.

  14. Antipodal Hotspots on the Earth: Vestiges of Major Oceanic Bolide Impacts?

    NASA Astrophysics Data System (ADS)

    Hagstrum, J. T.

    2003-12-01

    The distribution of hotspots on the Earth has a distinct antipodal character, which has previously been shown to be statistically significant (p<0.05) for one long (117) and two short ( ˜40-50) hotspot lists [1]. One possible mechanism for the creation of antipodal hotspot pairs is the focusing of seismic energy from a major bolide impact at its antipode. Reflected tensile body waves would converge along the axis beneath the antipode possibly causing fracturing to depth [2], and the greatest focusing of seismic energy from fundamental-mode surface waves has been shown to occur in the antipodal asthenosphere where seismic attenuation is greatest [3]. A major impact, therefore, might produce hotspot volcanism at the impact site (particularly on oceanic crust [4]), and produce flood basalts and a second hotspot from the focused disruption at its antipode. In this study, three predictions of this model are tested. (1) All `primary' hotspots on Earth initially had near-antipodal hotspots or impact structures. (2) Volcanic activity at both antipodal hotspots of a given pair began at about the same time. And (3), antipodal hotspot pairs have only one flood basalt province and/or impact site between them. A list of 54 primary hotspots is constructed from five commonly cited short hotspot lists. Of these, 28 form near-antipodal pairs mostly within conservative limits for hotspot drift rates from initial antipodality ( ˜20 mm/yr). Of the remaining 26, 14 are nearly antipodal to `secondary' hotspots from the long (117) hotspot list [5] or other volcanic features. Another primary hotspot (Comores, ˜10 Ma) was antipodal to the proposed Ewing impact structure ( ˜7-11 Ma) in the Pacific Ocean. Many antipodal hotspots have similar ages (e.g. Galápagos, ˜85 Ma; Nikitin, ˜80 Ma), and no contradictions to this prediction have been found. Only two primary hotspots (Hawai`i, Louisville) have continental antipodal sites where no volcanic features exist. These two hotspots

  15. The impact of day of surgery on the length of stay for major urological procedures

    PubMed Central

    Nason, Gregory J.; O’Connor, Eabhann M.; O’Neill, Cathleen; Izzeldin, Omer; Considine, Shane W.; O’Brien, M. Frank

    2016-01-01

    Introduction Surgery performed later in the week has been associated with longer length of stay (LOS). The aim of this study was to assess if the day of the surgery impacted the LOS for two major urological procedures in a tertiary referral university teaching hospital. Methods A retrospective review was performed of two major urological procedures consecutively performed by a single surgeon in our unit from March 2012 to December 2015. Patient demographics, histopathological characteristics, operative details, and LOS were obtained from the patients’ medical records. Procedures performed on Monday or Tuesday were defined as early in the week and procedures performed on Wednesday, Thursday, or Friday were defined as late in the week. Results During the study period, 140 open radical prostatectomy (ORP) and 42 open partial nephrectomy (OPN) procedures were performed. There was a significant difference in median LOS for major urological procedures performed early in the week compared to late in the week (3 [3–4] days vs. 4 [4–5] days; p= 0.0001). There was a significant difference in median LOS for ORP performed early in the week compared to late in the week (3 [3–4] days vs. 4 [4–5] days; p= 0.0004). There was a similar significant difference in OPN performed early in the week compared to late in the week (4 [3–5.5] days vs. 5 [4–5] days; p= 0.029). Conclusions The day of surgery impacts LOS for major urological procedures. Major procedures should be performed early in the week, when it is feasible to facilitate prompt safe discharge and better use of hospital resources. PMID:28096920

  16. Comparative impacts of two major hurricane seasons on the Neuse River and western Pamlico Sound ecosystems

    PubMed Central

    Burkholder, JoAnn; Eggleston, David; Glasgow, Howard; Brownie, Cavell; Reed, Robert; Janowitz, Gerald; Posey, Martin; Melia, Greg; Kinder, Carol; Corbett, Reide; Toms, David; Alphin, Troy; Deamer, Nora; Springer, Jeffrey

    2004-01-01

    Ecosystem-level impacts of two hurricane seasons were compared several years after the storms in the largest lagoonal estuary in the U.S., the Albemarle–Pamlico Estuarine System. A segmented linear regression flow model was developed to compare mass-water transport and nutrient loadings to a major artery, the Neuse River Estuary (NRE), and to estimate mean annual versus storm-related volume delivery to the NRE and Pamlico Sound. Significantly less water volume was delivered by Hurricane Fran (1996), but massive fish kills occurred in association with severe dissolved oxygen deficits and high contaminant loadings (total nitrogen, total phosphorus, suspended solids, and fecal bacteria). The high water volume of the second hurricane season (Hurricanes Dennis, Floyd, and Irene in 1999) delivered generally comparable but more dilute contaminant loads, and no major fish kills were reported. There were no discernable long-term adverse impacts on water quality. Populations of undesirable organisms, such as toxic dinoflagellates, were displaced down-estuary to habitats less conducive for growth. The response of fisheries was species-dependent: there was no apparent impact of the hurricanes on commercial landings of bivalve molluscs or shrimp. In contrast, interacting effects of hurricane floodwaters in 1999 and intensive fishing pressure led to striking reductions in blue crabs. Overall, the data support the premise that, in shallow estuaries frequently disturbed by hurricanes, there can be relatively rapid recovery in water quality and biota, and benefit from the scouring activity of these storms. PMID:15199179

  17. Impacts of El Niño Southern Oscillation on the global yields of major crops.

    PubMed

    Iizumi, Toshichika; Luo, Jing-Jia; Challinor, Andrew J; Sakurai, Gen; Yokozawa, Masayuki; Sakuma, Hirofumi; Brown, Molly E; Yamagata, Toshio

    2014-05-15

    The monitoring and prediction of climate-induced variations in crop yields, production and export prices in major food-producing regions have become important to enable national governments in import-dependent countries to ensure supplies of affordable food for consumers. Although the El Niño/Southern Oscillation (ENSO) often affects seasonal temperature and precipitation, and thus crop yields in many regions, the overall impacts of ENSO on global yields are uncertain. Here we present a global map of the impacts of ENSO on the yields of major crops and quantify its impacts on their global-mean yield anomalies. Results show that El Niño likely improves the global-mean soybean yield by 2.1-5.4% but appears to change the yields of maize, rice and wheat by -4.3 to +0.8%. The global-mean yields of all four crops during La Niña years tend to be below normal (-4.5 to 0.0%). Our findings highlight the importance of ENSO to global crop production.

  18. Comparative impacts of two major hurricane seasons on the Neuse River and western Pamlico Sound ecosystems.

    PubMed

    Burkholder, JoAnn; Eggleston, David; Glasgow, Howard; Brownie, Cavell; Reed, Robert; Janowitz, Gerald; Posey, Martin; Melia, Greg; Kinder, Carol; Corbett, Reide; Toms, David; Alphin, Troy; Deamer, Nora; Springer, Jeffrey

    2004-06-22

    Ecosystem-level impacts of two hurricane seasons were compared several years after the storms in the largest lagoonal estuary in the U.S., the Albemarle-Pamlico Estuarine System. A segmented linear regression flow model was developed to compare mass-water transport and nutrient loadings to a major artery, the Neuse River Estuary (NRE), and to estimate mean annual versus storm-related volume delivery to the NRE and Pamlico Sound. Significantly less water volume was delivered by Hurricane Fran (1996), but massive fish kills occurred in association with severe dissolved oxygen deficits and high contaminant loadings (total nitrogen, total phosphorus, suspended solids, and fecal bacteria). The high water volume of the second hurricane season (Hurricanes Dennis, Floyd, and Irene in 1999) delivered generally comparable but more dilute contaminant loads, and no major fish kills were reported. There were no discernable long-term adverse impacts on water quality. Populations of undesirable organisms, such as toxic dinoflagellates, were displaced down-estuary to habitats less conducive for growth. The response of fisheries was species-dependent: there was no apparent impact of the hurricanes on commercial landings of bivalve molluscs or shrimp. In contrast, interacting effects of hurricane floodwaters in 1999 and intensive fishing pressure led to striking reductions in blue crabs. Overall, the data support the premise that, in shallow estuaries frequently disturbed by hurricanes, there can be relatively rapid recovery in water quality and biota, and benefit from the scouring activity of these storms.

  19. Impacts of El Nino Southern Oscillation on the Global Yields of Major Crops

    NASA Technical Reports Server (NTRS)

    Iizumi, Toshichika; Luo, Jing-Jia; Challinor, Andrew J.; Sakurai, Gen; Yokozawa, Masayuki; Sakuma, Hirofumi; Brown, Molly Elizabeth; Yamagata, Toshio

    2014-01-01

    The monitoring and prediction of climate-induced variations in crop yields, production and export prices in major food-producing regions have become important to enable national governments in import-dependent countries to ensure supplies of affordable food for consumers. Although the El Nino/Southern Oscillation (ENSO) often affects seasonal temperature and precipitation, and thus crop yields in many regions, the overall impacts of ENSO on global yields are uncertain. Here we present a global map of the impacts of ENSO on the yields of major crops and quantify its impacts on their global-mean yield anomalies. Results show that El Nino likely improves the global-mean soybean yield by 2.15.4 but appears to change the yields of maize, rice and wheat by -4.3 to +0.8. The global-mean yields of all four crops during La Nina years tend to be below normal (-4.5 to 0.0).Our findings highlight the importance of ENSO to global crop production.

  20. Tracking Particulate Organic Matter Characteristics in Major Arctic Rivers: Indicators of Watershed-Scale Climate Impacts

    NASA Astrophysics Data System (ADS)

    McClelland, J. W.; Griffin, C. G.; Holmes, R. M.; Peterson, B. J.; Raymond, P. A.; Spencer, R. G.; Striegl, R. G.; Tank, S. E.

    2015-12-01

    Six large rivers, including the Yukon and Mackenzie in North America and the Yenisey, Ob', Lena, and Kolyma in Eurasia, drain the majority of the watershed area surrounding the Arctic Ocean. Parallel sampling programs were initiated at downstream locations on these rivers in 2003 to improve estimates of fluvial export and track large-scale perturbations associated with climate change. Over a decade later, synthesis of water chemistry data from these ongoing sampling efforts provides an unprecedented opportunity to 1) examine similarities and differences among the major Arctic rivers, and 2) think critically about how changes in various water chemistry parameters may or may not inform us about climate change impacts. River-borne organic matter characteristics may be particularly telling because mass flux values and composition/source indicators vary with hydrology and permafrost coverage. However, separating climate impacts that occur within river corridors from those that occur beyond them may be difficult, especially when considering changes in particulate organic matter (POM) loads. Data on suspended POM yields, C:N ratios, stable isotope ratios, and radiocarbon content in the major Arctic rivers show marked spatial, seasonal, and interannual variability that is helpful for thinking about how climate change effects may manifest in the future, but it will be challenging to separate changes in POM related to bank erosion and suspension/deposition of in situ sediment stocks from changes in POM that may be linked to processes such as permafrost thaw occurring across the broader landscape.

  1. Prognostic value of myocardial perfusion single photon emission computed tomography for major adverse cardiac cerebrovascular and renal events in patients with chronic kidney disease: results from first year of follow-up of the Gunma-CKD SPECT multicenter study.

    PubMed

    Kasama, Shu; Toyama, Takuji; Sato, Makito; Sano, Hirokazu; Ueda, Tetsuya; Sasaki, Toyoshi; Nakahara, Takehiro; Higuchi, Tetsuya; Tsushima, Yoshito; Kurabayashi, Masahiko

    2016-02-01

    Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. We examined whether stress myocardial perfusion single photon emission computed tomography (SPECT) provides reliable prognostic markers for these patients. In this multicenter, prospective cohort trial from the Gunma-CKD SPECT study protocol, patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml per 1.73 m(2)] undergoing stress (99m)Tc-tetrofosmin SPECT for suspected or possible ischemic heart disease were initially followed for 1 year, with the following study endpoints: primary, the occurrence of cardiac deaths (CDs), and secondary, major adverse cardiac, cerebrovascular, and renal events (MACCREs). The summed stress score (SSS), summed rest score, and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Left ventricular end-diastolic volume, end-systolic volume (ESV), and ejection fraction were measured using electrocardiogram-gated SPECT. During the first year of follow-up, 69 of 299 patients experienced MACCREs (CD, n = 7; non-fatal myocardial infarction, n = 3; hospitalization for heart failure, n = 13; cerebrovascular accident, n = 1; need for revascularization, n = 38; and renal failure, i.e., hemodialysis initiation, n = 7). ESV and SSS were associated with CDs (p < 0.05), and eGFR and SDS were associated with MACCREs (p < 0.05), in multivariate logistic analysis. Patients with high ESV and high SSS had a significantly higher CD rate during the first year than the other CKD patient subgroups (p < 0.05). Patients with low eGFR and high SDS had a significantly higher MACCRE rate than the other subgroups (p < 0.05). Myocardial perfusion SPECT can provide reliable prognostic markers for patients with CKD.

  2. Land Area Change and Overview of Major Hurricane Impacts in Coastal Louisiana, 2004-08

    USGS Publications Warehouse

    Barras, John A.

    2009-01-01

    The U.S. Geological Survey (USGS) assessed changes in land and water coverage in coastal Louisiana within 2 months of Hurricane Gustav (September 1, 2008) and Hurricane Ike (September 13, 2008) by using Landsat Thematic Mapper (TM) satellite imagery. The purpose of this study was twofold: (1) to provide preliminary information on land-water area changes in coastal Louisiana shortly after Hurricanes Ike and Gustav made landfall and (2) to contrast these changes with prior, widespread land area changes caused by Hurricane Katrina (August 29, 2005) and Hurricane Rita (September 24, 2005) 3 years earlier. Hurricane Gustav's physical surge impacts were not as severe as those observed from Hurricane Katrina. The largest observed changes were the reversion of recovery vegetation in Upper Breton Sound to an immediate post-Katrina appearance. Hurricane Ike's surge impacts were similar, although of somewhat lesser magnitude than Hurricane Rita's surge impacts. Major surge-removed marsh occurred in similar locations with similar morphologies from the two westward tracking storms. Although the net reduction in land from 2004 to 2008 (849.5 km2) exceeded that from 1978 to 2004 (743.3 km2), it is likely that the 2004-08 estimate will decrease, given time for the coast to recover from those hurricane seasons. Nevertheless, it is likely that the cumulative loss from these hurricane seasons will remain significant. Estimation of permanent losses cannot be made until several growing seasons have passed and the transitory impacts of the hurricanes are accounted for.

  3. Oxegen 2004: the impact of a major music festival on the workload of a local hospital.

    PubMed

    Nix, C M; Khan, I J; Hoban, M; Little, G; Keye, G; O'Connor, H J

    2006-06-01

    This prospective observational study was undertaken to assess the impact of a major music festival on the workload of a local hospital. Data were collected on all attendances at Naas General Hospital from the nearby Oxegen 2004 music festival. Patient demographics, disposition and diagnoses were recorded. Emergency department activity levels were compared before, during and after the festival. Seventy-two attendees were referred to Naas emergency department over a 3-day period, representing a 45% increase in the hospital's emergency department attendance rate. Thirty-seven of these attendees (51%) required inpatient or tertiary centre services. Thirty-four attendees (47%) were noted as having consumed alcohol and/or used illicit substances. We conclude that despite the provision of on-site medical facilities, major music events are associated with a significant increase in local health care activity and expenditure.

  4. Burn Severities, Fire Intensities, and Impacts to Major Vegetation Types from the Cerro Grande Fire

    SciTech Connect

    Balice, Randy G.; Bennett, Kathryn D.; Wright, Marjorie A.

    2004-12-15

    The Cerro Grande Fire resulted in major impacts and changes to the ecosystems that were burned. To partially document these effects, we estimated the acreage of major vegetation types that were burned at selected burn severity levels and fire intensity levels. To accomplish this, we adopted independently developed burn severity and fire intensity maps, in combination with a land cover map developed for habitat management purposes, as a basis for the analysis. To provide a measure of confidence in the acreage estimates, the accuracies of these maps were also assessed. In addition, two other maps of comparable quality were assessed for accuracy: one that was developed for mapping fuel risk and a second map that resulted from a preliminary application of an evolutionary computation software system, called GENIE.

  5. Prognostic impact of education level of patients with advanced non-small cell lung cancer enrolled in clinical trials.

    PubMed

    Di Maio, Massimo; Signoriello, Simona; Morabito, Alessandro; Rossi, Antonio; Maione, Paolo; Piantedosi, Francovito; Bilancia, Domenico; Cigolari, Silvio; Barbera, Santi; Gebbia, Vittorio; Daniele, Bruno; Robbiati, Sergio Federico; Illiano, Alfonso; Ceribelli, Anna; Carrozza, Francesco; Favaretto, Adolfo; Piazza, Elena; Piccirillo, Maria Carmela; Daniele, Gennaro; Giordano, Pasqualina; Costanzo, Raffaele; Sandomenico, Claudia; Rocco, Gaetano; Gallo, Ciro; Perrone, Francesco; Gridelli, Cesare

    2012-06-01

    longer in patients with high education, after adjustment for PS and other prognostic factors. The exact underlying mechanisms of the independent prognostic role of education level are substantially unknown, but lead-time bias (anticipation in diagnosis and time to inclusion in the trial), differences in adherence to care outside the trial procedures, differences in comorbidities and life-style factors may all contribute. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Predictive and prognostic impact of tumour-infiltrating lymphocytes in triple-negative breast cancer treated with neoadjuvant chemotherapy.

    PubMed

    Herrero-Vicent, Carmen; Guerrero, Angel; Gavilá, Joaquin; Gozalbo, Francisco; Hernández, Abraham; Sandiego, Sergio; Algarra, Maria Asunción; Calatrava, Ana; Guillem-Porta, Vicente; Ruiz-Simón, Amparo

    2017-01-01

    be an independent prognostic marker of DFS. Tumour-infiltrating lymphocytes could be routinely used in locally advanced TNBC treated with anthracycline and taxane, such as biomarker, to be enabled the identification of different two subgroups: LPBC patients have a very high response to NAC pCR 88%, meanwhile non-LPBC patients only achieve 9%. Moreover, non-LPBC patients have a worse prognosis than LPBC patients. This data verified the predictive and prognostic value of TIL.

  7. The impact of complications on costs of major surgical procedures: a cost analysis of 1200 patients.

    PubMed

    Vonlanthen, René; Slankamenac, Ksenija; Breitenstein, Stefan; Puhan, Milo A; Muller, Markus K; Hahnloser, Dieter; Hauri, Dimitri; Graf, Rolf; Clavien, Pierre-Alain

    2011-12-01

    To assess the impact of postoperative complications on full in-hospital costs per case. Rising expenses for complex medical procedures combined with constrained resources represent a major challenge. The severity of postoperative complications reflects surgical outcomes. The magnitude of the cost created by negative outcomes is unclear. Morbidity of 1200 consecutive patients undergoing major surgery from 2005 to 2008 in a tertiary, high-volume center was assessed by a validated, complication score system. Full in-hospital costs were collected for each patient. Statistical analysis was performed using a multivariate linear regression model adjusted for potential confounders. This study population included 393 complex liver/bile duct surgeries, 110 major pancreas operations, 389 colon resections, and 308 Roux-en-Y gastric bypasses. The overall 30-day mortality rate was 1.8%, whereas morbidity was 53.8%. Patients with an uneventful course had mean costs per case of US$ 27,946 (SD US$ 15,106). Costs increased dramatically with the severity of postoperative complications and reached the mean costs of US$ 159,345 (SD US$ 151,191) for grade IV complications. This increase in costs, up to 5 times the cost of a similar operation without complications, was observed for all types of investigated procedures, although the magnitude of the increase varied, with the highest costs in patients undergoing pancreas surgery. This study demonstrates the dramatic impact of postoperative complications on full in-hospital costs per case and that complications are the strongest indicator of costs. Furthermore, the study highlights a relevant savings capacity for major surgical procedures, and supports all efforts to lower negative events in the postoperative course.

  8. The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients.

    PubMed

    König, Lisa; Kasimir-Bauer, Sabine; Hoffmann, Oliver; Bittner, Ann-Kathrin; Wagner, Bettina; Manvailer, Luis Felipe Santos; Schramm, Sabine; Bankfalvi, Agnes; Giebel, Bernd; Kimmig, Rainer; Horn, Peter A; Rebmann, Vera

    2016-09-01

    The non-classical human leukocyte antigen G (HLA-G) molecule and its soluble forms exert multiple immune suppressive regulatory functions in malignancy and in stem cells contributing to immune escape mechanisms. HLA-G can be secreted as free soluble HLA-G molecules or via extracellular vesicles (EVs). Here we evaluated these soluble HLA-G forms as prognostic marker for prediction of the clinical outcome of neoadjuvant chemotherapy (NACT) treated breast cancer (BC) patients. Plasma samples of BC patients procured before (n=142) and after (n=154) NACT were quantified for total soluble HLA-G (sHLA-Gtot) and HLA-G levels in ExoQuick™ derived EV fractions (sHLA-GEV) by ELISA. The corresponding increments were specified as free sHLA-G (sHLA-Gfree). Total and free sHLA-G were significantly increased in NACT treated BC patients compared to healthy controls (n=16). High sHLA-Gfree levels were exclusively associated to estrogen receptor expression before NACT. Importantly, high sHLA-GEV levels before NACT were related to disease progression and the detection of stem cell-like circulating tumor cells, but high sHLA-Gfree levels indicated an improved clinical outcome. Thus, this study demonstrates for the first time that the different sHLA-G subcomponents represent dissimilar qualitative prognostic impacts on the clinical outcome of NACT treated BC patients, whereas the total sHLA-G levels without separating into subcomponents are not related to clinical outcome.

  9. Prognostic impact of clinic and ambulatory blood pressure components in high-risk type 2 diabetic patients: the Rio de Janeiro Type 2 Diabetes Cohort Study.

    PubMed

    Salles, Gil F; Leite, Nathalie C; Pereira, Basílio B; Nascimento, Emilia M; Cardoso, Claudia R L

    2013-11-01

    The prognostic importance of tight clinic blood pressure (BP) control is controversial in diabetic patients. The objective was to investigate the prognostic impact of clinic and ambulatory BPs for cardiovascular morbidity and mortality in type 2 diabetes. In a prospective cohort study, 565 type 2 diabetic patients had clinical, laboratory and ambulatory BP monitoring (ABPM) data obtained at baseline and during follow-up. The primary endpoints were a composite of fatal and nonfatal cardiovascular events and all-cause mortality. Multivariable Cox survival and splines regression analyses assessed associations between each BP component [SBP, DBP and pulse pressure (PP)] and the endpoints. After a median follow-up of 5.75 years, 88 total cardiovascular events and 70 all-cause deaths occurred. After adjustments for cardiovascular risk factors, clinic SBP and DBPs were predictive of the composite endpoint but not of all-cause mortality, whereas all ambulatory BP components were predictors of both endpoints. Ambulatory systolic and PPs were the strongest predictors and achieved ambulatory BPs during follow-up improved risk prediction in relation to baseline values. When categorized at clinically relevant cut-off values, risk began only at clinic BPs at least 140/90 mmHg, whereas for ambulatory BPs it began at lower values (≥120/75 mmHg for the 24-h period). ABPM provides more valuable information regarding cardiovascular risk stratification than office BPs and should be performed, if possible, in every high-risk type 2 diabetic patient. Achieved 24-h ambulatory BPs less than 120/75 mmHg are associated with significant cardiovascular protection and, if confirmed by other studies, may be considered as BP treatment targets.

  10. Prognostic impact of fat tissue loss and cachexia assessed by computed tomography scan in elderly patients with diffuse large B-cell lymphoma treated with immunochemotherapy.

    PubMed

    Camus, Vincent; Lanic, Helene; Kraut, Jerôme; Modzelewski, Romain; Clatot, Florian; Picquenot, Jean M; Contentin, Nathalie; Lenain, Pascal; Groza, Luminata; Lemasle, Emilie; Fronville, Carole; Cardinael, Nathalie; Fontoura, Marie-Laure; Chamseddine, Ali; Brehar, Oana; Stamatoullas, Aspasia; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

    2014-07-01

    Approximately 30% of DLBCL patients are older than 70 yr. This study evaluated the prognostic impact of a cachexia score (CS) including fat tissue loss (adipopenia) and sarcopenia as assessed by computed tomography (CT scan) in elderly DLBCL patients treated with chemotherapy and rituximab (R). This retrospective analysis included 80 DLBCL patients older than 70 yr treated with R-CHOP or R-miniCHOP. Skeletal muscle (SM) and visceral (V) and subcutaneous (S) adipose (A) tissues were measured by analysing CT images at the third lumbar (L3) level. The median age of the patients was 78 yr. Forty-four and 46 patients were considered sarcopenic and adipopenic, respectively. The median progression-free survival (PFS) was 13.6 months in the adipopenic group and 49.4 months in the non-adipopenic group [hazard ratio (HR) = 2.27; 95% confidence interval (CI): 1.3-4; P = 0.0042]. The median overall survival (OS) was 25.7 months in the adipopenic group and 57.1 months in the non-adipopenic group (HR = 1.93; 95% CI: 1.05-3.55; P = 0.0342). A two-point CS including adipopenia and sarcopenia was created and defined two distinct risk groups with differences in outcomes that were highly significant. The CS was predictive of the prognosis in a multivariate analysis including body mass index (BMI) (< or ≥ 25 kg/m(2) ), age (< or ≥ 80 yr), international prognostic index (IPI) and albuminaemia (HR = 3.67; 95% CI = 1.93-6.97; P < 0.0001). A CS including sarcopenia and adipopenia, assessed by a single CT scan slice, predicts outcome independent of BMI and the IPI. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Prognostic and predictive impact of central necrosis and fibrosis in early breast cancer. Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy

    PubMed Central

    Maiorano, Eugenio; Regan, Meredith M.; Viale, Giuseppe; Mastropasqua, Mauro G.; Colleoni, Marco; Castiglione-Gertsch, Monica; Price, Karen N.; Gelber, Richard D.; Goldhirsch, Aron; Coates, Alan S.

    2013-01-01

    Purpose A minority of early invasive breast cancers show a pattern of central necrosis and fibrosis (CNF). Previous studies have documented an adverse prognostic impact and association with other adverse pathological features, but its predictive importance for therapy selection is unknown. Methods We examined the prognostic and predictive value of CNF in two randomized clinical trials comparing chemoendocrine therapy with endocrine therapy alone in patients with node-negative breast cancer. A total of 1850 patients randomly assigned to treatment groups comparing endocrine with chemoendocrine therapy, and with centrally-assessed CNF, ER, PgR and HER2 were included in the analytic cohort. The median follow up was 10 years. Results CNF was present in 84 of 1850 trial patients (4.5%). It was associated with tumor characteristics suggesting poor outcome, but was an independent adverse factor for disease-free survival. In the presence of CNF outcome was worse regardless of tumor grade, whereas in the absence of CNF, patients with grade 3 tumors had poorer outcome than those with grade 1-2 tumors. Among patients with estrogen receptor-absent tumors chemoendocrine therapy was superior to endocrine therapy alone only in the absence of CNF [HR (chemoendocrine:endocrine)=0.46 in CNF-absent, 0.90 in CNF-present], while among those with receptor-positive disease chemoendocrine therapy was beneficial only in the presence of CNF [HR=0.34 CNF-present, 0.96 CNF-absent]. Conclusion The results suggest that the presence of CNF reflects a biological difference in early breast cancer that is important in modulating the efficacy of standard therapies. Accordingly we believe that its presence should be routinely reported. PMID:19280340

  12. The Prognostic Impact of Controlling Nutritional Status (CONUT) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study.

    PubMed

    Miyata, Tatsunori; Yamashita, Yo-Ichi; Higashi, Takaaki; Taki, Katsunobu; Izumi, Daisuke; Kosumi, Keisuke; Tokunaga, Ryuma; Nakagawa, Shigeki; Okabe, Hirohisa; Imai, Katsunori; Hashimoto, Daisuke; Chikamoto, Akira; Baba, Hideo

    2017-09-08

    Several studies have examined controlling nutritional status (CONUT), which is one of the useful biomarkers for predicting patients' prognosis following cancer treatment. The aim of this study was to evaluate the value of CONUT as a postoperative prognostic marker in patients with intrahepatic cholangiocarcinoma (ICC) following curative hepatectomy. We retrospectively analyzed 71 patients who underwent curative hepatectomy for ICC between May 2002 and November 2016. Patients were divided into two groups according to their preoperative CONUT score (i.e., CONUT ≧ 2 or CONUT < 2). The number of patients assigned to the normal, mild, moderate, or severe malnutrition groups was 40, 28, two, and one, respectively. The high CONUT group (CONUT ≧ 2) consisted of 31 patients (43.7%) and had a poor prognosis with regard to overall survival (OS) (p = 0.0149). A high CONUT score is also identified as one of the independent predictors of poor prognosis in OS (hazard ratio 3.02; 95% confidence interval 1.4-6.8; p = 0.007). However, in the current study, a high CONUT score was not associated with postoperative complications (Clavien-Dindo classification ≧ III or more). CONUT may be useful for the preoperative assessment of prognosis in patients with ICC who have undergone curative hepatectomy.

  13. Prognostic impact of nutritional status assessed by the Controlling Nutritional Status score in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

    PubMed

    Wada, Hideki; Dohi, Tomotaka; Miyauchi, Katsumi; Doi, Shinichiro; Konishi, Hirokazu; Naito, Ryo; Tsuboi, Shuta; Ogita, Manabu; Kasai, Takatoshi; Okazaki, Shinya; Isoda, Kikuo; Suwa, Satoru; Daida, Hiroyuki

    2017-06-20

    Recently, malnutrition has been shown to be related to worse clinical outcomes in patients with heart failure. However, the association between nutritional status and clinical outcomes in patients with coronary artery disease (CAD) remains unclear. We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT; range 0-12, higher = worse, consisting of serum albumin, cholesterol and lymphocytes) score in patients with CAD. The CONUT score was measured on admission in a total of 1987 patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) between 2000 and 2011. Patients were divided into two groups according to their CONUT score (0-1 vs. ≥2). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. The median CONUT score was 1 (interquartile range 0-2). During the median follow-up of 7.4 years, 342 MACE occurred (17.2%). Kaplan-Meier curves revealed that patients with high CONUT scores had higher rates of MACE (log-rank p < 0.0001). High CONUT scores showed a significant increase in the incidence of MACE compared with low CONUT scores, even after adjusting for confounding factors (hazard ratio: 1.64, 95% confidence interval 1.30-2.07, p < 0.0001). Adding CONUT scores to a baseline model with established risk factors improved the C-index (p = 0.02), net reclassification improvement (p = 0.004) and integrated discrimination improvement (p = 0.0003). Nutritional status assessed by the CONUT score was significantly associated with long-term clinical outcomes in patients with CAD. Pre-PCI assessment of the CONUT score may provide useful prognostic information.

  14. Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.

    PubMed

    Pinto, Emilia Modolo; Rodriguez-Galindo, Carlos; Choi, John Kim; Pounds, Stanley; Liu, Zhifa; Neale, Geoffrey; Finkelstein, David; Hicks, John M; Pappo, Alberto S; Figueiredo, Bonald C; Ribeiro, Raul C; Zambetti, Gerard P

    2016-12-15

    Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor. The impact of MHC class II gene expression on outcome was determined in a cohort of uniformly treated children with adrenocortical carcinomas. We analyzed the expression of MHC class II and a selected cluster of differentiation genes in 63 pediatric adrenocortical tumors by Affymetrix Human U133 Plus 2.0 or HT HG-U133+PM gene chip analyses. Cells expressing MHC class II were identified by morphologic and immunohistochemical assays. MHC class II expression was significantly greater in adrenocortical adenomas than in carcinomas (P = 4.8 ×10(-6)) and was associated with a higher progression-free survival (PFS) estimate (P = 0.003). Specifically, HLA-DPA1 expression was most significantly associated with PFS after adjustment for tumor weight and stage. HLA-DPA1 was predominantly expressed by hematopoietic infiltrating cells and undetectable in tumor cells in 23 of 26 cases (88%). MHC class II expression, which is produced by tumor-infiltrating immune cells, is an indicator of disease aggressiveness in pediatric adrenocortical tumor. Our results suggest that immune responses modulate adrenocortical tumorigenesis and may allow the refinement of risk stratification and treatment for this disease. Clin Cancer Res; 22(24); 6247-55. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. Examining prognostic factors and patterns of failure in nasopharyngeal carcinoma following concomitant radiotherapy and chemotherapy: impact on future clinical trials.

    PubMed

    Cheng, S H; Yen, K L; Jian, J J; Tsai, S Y; Chu, N M; Leu, S Y; Chan, K Y; Tan, T D; Cheng, J C; Hsieh, C Y; Huang, A T

    2001-07-01

    Concomitant chemotherapy and radiotherapy (CCRT), followed by adjuvant chemotherapy, has improved the outcome of nasopharyngeal carcinoma (NPC). However, the prognosis and patterns of failure after this combined-modality treatment are not yet clear. In this report, the prognostic factors and failure patterns we observed with CCRT may shed new light in the design of future trials. One hundred forty-nine (149) patients with newly diagnosed and histologically proven NPC were prospectively treated with CCRT followed by adjuvant chemotherapy between April 1990 and December 1997. One hundred and thirty-three (89.3%) patients had MRI of head and neck for primary evaluation before treatment. Radiotherapy was delivered either at 2 Gy per fraction per day up to 70 Gy or 1.2 Gy per fraction, 2 fractions per day, up to 74.4 Gy. Chemotherapy consisted of cisplatin and 5-fluorouracil. According to the AJCC 1997 staging system, 32 patients were in Stage II, 53 in Stage III, and 64 in Stage IV (M0). Univariate analysis revealed that WHO (World Health Organization) Type II histology, T4 classification, and parapharyngeal extension were poor prognostic factors for locoregional control. Multivariate analysis revealed that T4 disease was the most important adverse factor that affects locoregional control, the risk ratio being 5.965 (p = 0.02). Univariate analysis for distant metastasis revealed that T4 and N3 classifications, serum LDH level > 410 U/L (normal range, 180-460), parapharyngeal extension, and infiltration of the clivus were significantly associated with poor prognosis. Multivariate analysis, however, revealed that T4 classification and N3 category were the only two factors that predicted distant metastasis; the risk ratios were 3.994 (p = 0.02) and 3.390 (p = 0.01), respectively. Therefore, based on the risk factor analysis, we were able to identify low-, intermediate-, and high-risk patients. Low-risk patients were those without the risk factors mentioned above. They

  16. Ventricular Dysfunction in Patients with Acute Coronary Syndrome Undergoing Coronary Surgical Revascularization: Prognostic Impact on Long-Term Outcomes

    PubMed Central

    Popovic, Batric; Agrinier, Nelly; Voilliot, Damien; Elfarra, Mazen; Villemot, Jean Pierre; Maureira, Pablo

    2016-01-01

    Background Patients with non-ST elevation acute coronary syndrome complicated by left ventricular dysfunction (LVEF) are a poor prognosis group. The aim of our study was to assess the short and long term LEVF prognostic value in a cohort of NSTE-ACS patients undergoing surgical revascularization. Methods We performed elective and isolated CABG on a cohort of 206 consecutive patients with LVEF≤0.40 complicating acute coronary syndrome. The case cohort was compared with a cohort of controls (LVEF>0.40) randomly selected (2:1) among patients who underwent the procedure during this period. Results The Kaplan-Meier 5-year estimated survival rates for patients in the low and normal LVEF groups were 70.8% (95% confidence interval CI: 64.2–77.4) and 81.7% (95%CI: 77.8–85.6), respectively. A low LVEF was associated with both a higher all-cause (HR [95%CI] = 1.84[1.18–2.86]) and a higher cardiovascular mortality (HR = 2.07 [1.27–3.38]) during the first 12 months of follow-up. After adjustment for potential confounders, a low LVEF remained associated with a higher cardiovascular mortality only (1.87[1.03–3.38]) during the first 12 months of follow-up. After 12 months of follow-up, a low LVEF was no more associated with all-cause, nor cardiovascular mortality. Conclusion Patients with low LVEF might require more intensive care than patients with normal LVEF during the year after the surgical procedure, but once the first postoperative year over, the initial low LVEF was no more associated with long term mortality. PMID:28005944

  17. Prognostic impact of electrocardiographic signs in patients with Type 2 diabetes and cardiovascular disease: results from the PROactive study.

    PubMed

    Pfister, R; Cairns, R; Erdmann, E; Schneider, C A

    2011-10-01

    Although a resting electrocardiograph is broadly applied in clinical practice for evaluating patients with Type 2 diabetes and cardiovascular disease, the independent prognostic relevance of electrocardiographic signs has not thoroughly been examined. Baseline 12-lead electrocardiographs available in 5231 of the 5238 participants of the PROactive trial were analysed for heart rate, heart rate corrected QT-interval, presence of atrial fibrillation/flutter, left axis deviation, right and left bundle branch block. The association of electrocardiographic signs with total mortality, the principal secondary composite endpoint (death, myocardial infarction and stroke) and serious adverse heart failure events was examined by Cox-regression analysis. Two hundred and twenty-three (4.3%) patients showed atrial fibrillation/flutter, 213 (4.1%) patients had right bundle branch block, 111 (2.1%) patients had left bundle branch block and 706 (13.5%) patients had left axis deviation. Mean cQT-interval was 418 ms (± 25 ms) and mean heart rate was 72/min (± 14/min). In multivariate adjusted analyses, heart rate and cQT-interval were significantly associated with mortality, the composite secondary endpoint and heart failure, whereas right and left bundle branch blocks were significantly associated with heart failure only. Left axis deviation was associated with heart failure and atrial fibrillation/flutter was associated with mortality and heart failure in univariate but not multivariate analyses. Easily assessable electrocardiographic signs such as heart rate, cQT-interval and bundle branch blocks were predictive for adverse outcome independently of multiple risk factor adjustment and should be considered in clinical care. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  18. The prognostic impact of tumour-associated macrophages and Reed-Sternberg cells in paediatric Hodgkin lymphoma.

    PubMed

    Gupta, Sumit; Yeh, Stacy; Chami, Rose; Punnett, Angela; Chung, Catherine

    2013-10-01

    Tumour-associated macrophages (TAM) are associated with treatment failure in adults with Hodgkin lymphoma (HL). Equivalent data in paediatric HL are sparse. We aimed to determine the prognostic significance of TAM and Reed-Sternberg (RS) cells in paediatric HL. All children aged 0-18 with HL between 1980 and 2009 with available diagnostic biopsy material were identified. A treatment failure-enriched cohort was assembled. Demographic, disease and outcome data were abstracted. Tissue microarrays with duplicate cores were constructed from diagnostic biopsy material and stained with immunohistochemical markers for TAM (CD68, CD163) and RS (CD30). A high score was defined as >5% positive cells relative to overall cellularity in any core. The association of candidate variables with event-free survival (EFS) was determined using Cox proportional hazards. The final study cohort comprised 96 patients with a median age of 14 years (interquartile range 11-15). Agreement on scores between cores from the same biopsy revealed weighted kappas of 0.60, 0.68 and 0.73 for CD30, CD68 and CD163 respectively, indicating moderate tumour heterogeneity. In univariate analysis, a high CD30 score was significantly associated with treatment failure (hazard ratio (HR) 2.27; 95th confidence interval 1.01-5.11; p<0.05). High CD68 and CD163 scores were not associated with EFS. Unlike adult HL, a higher percentage of RS cells was associated with poor outcome, while a higher percentage of TAM was not. Adult HL findings may not extend to paediatric HL. Cooperative group trials of paediatric HL should prospectively determine the association of different components of the tumour microenvironment with outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The Prognostic Importance of Impaired Systolic Function in Heart Failure with Preserved Ejection Fraction and the Impact of Spironolactone

    PubMed Central

    Shah, Amil M.; Claggett, Brian; Sweitzer, Nancy K.; Shah, Sanjiv J.; Anand, Inder S.; Liu, Li; Pitt, Bertram; Pfeffer, Marc A.; Solomon, Scott D.

    2015-01-01

    Background Impairment in left ventricular (LV) systolic function has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined whether LV longitudinal strain (LS) is predictive of cardiovascular (CV) outcomes in HFpEF beyond clinical and conventional echocardiographic measures. Methods and Results LS was assessed by 2D speckle-tracking echocardiography at baseline in 447 HFpEF patients enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 (IQR 1.5–3.9) years, 115 patients experienced the primary composite outcome of CV death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS<15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted HR 2.14, 95% CI 1.26–3.66; p=0.005), CV death alone (adjusted HR 3.20, 95% CI 1.44–7.12; p=0.004), and HF hospitalization alone (adjusted HR 2.23, 95% CI 1.16–4.28; p=0.016) after adjusting for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12–18 months demonstrated a trend towards improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia. Conclusions Impaired LV systolic function is a powerful predictor of HF hospitalization, CV death, or aborted cardiac arrest in HFpEF, independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify HFpEF patients at particularly high risk for CV morbidity and mortality. Clinical Trial Registration Information Clinicaltrials.gov. Identifier NCT00094302. PMID:26130119

  20. Impact of pulmonary rehabilitation on the major dimensions of dyspnea in COPD.

    PubMed

    Wadell, Karin; Webb, Katherine A; Preston, Megan E; Amornputtisathaporn, Naparat; Samis, Lorelei; Patelli, Jennifer; Guenette, Jordan A; O'Donnell, Denis E

    2013-08-01

    The evaluation of dyspnea and its responsiveness to therapy in COPD should consider the multidimensional nature of this symptom in each of its sensory-perceptual (intensity, quality), affective and impact domains. To gain new insights into mechanisms of dyspnea relief following pulmonary rehabilitation (PR), we examined effects on the major domains of dyspnea and their interaction with physiological training effects. This randomized, controlled study was conducted in 48 subjects with COPD. Subjects received either 8-weeks of PR or usual care (CTRL). Pre- and post-intervention assessments included: sensory-perceptual (i.e., exertional dyspnea intensity, dyspnea descriptors at end-exercise), affective (i.e., intensity of breathing-related anxiety during exercise, COPD self-efficacy, walking self-efficacy) and impact (i.e., activity-related dyspnea measured by the Baseline/Transition Dyspnea Index, Chronic Respiratory Questionnaire dyspnea component, St. George's Respiratory Disease Questionnaire activity component) domains of dyspnea; functional performance (i.e., 6-minute walk, endurance shuttle walk); pulmonary function; and physiological measurements during constant work rate cycle exercise at 75% of the peak incremental work rate. Forty-one subjects completed the study: PR (n = 17) and CTRL (n = 24) groups were well matched for age, sex, body size and pulmonary function. There were no significant between-group differences in pre- to post-intervention changes in pulmonary function or physiological parameters during exercise. After PR versus CTRL, significant improvements were found in the affective and impact domains but not in the sensory-perceptual domain of dyspnea. In conclusion, clinically meaningful improvements in the affective and impact domains of dyspnea occurred in response to PR in the absence of consistent physiological training effects.

  1. Dispersion of repolarization and beta-thalassemia major: the prognostic role of QT and JT dispersion for identifying the high-risk patients for sudden death.

    PubMed

    Russo, Vincenzo; Rago, Anna; Pannone, Bruno; Papa, Andrea A; Di Meo, Federica; Mayer, Maria C; Spasiano, Anna; Russo, Maria G; Golino, Paolo; Calabrò, Raffaele; Nigro, Gerardo

    2011-04-01

    Patients with beta-thalassemia major (β-TM) are at increased risk for sudden cardiac death (SCD). Heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias. QT dispersion (QTc-D) and JT dispersion (JTc-D) are electrocardiographic parameters indicative of heterogeneity of ventricular repolarization. The aim of our study was to evaluate the heterogeneity of ventricular repolarization in patients with beta-thalassemia and to test the hypothesis that an abnormal QTc and JTc dispersion may predict SCD in this population.  The study involved 51 patients with β-TM (age 33.9±8.4; 33M) and 51 healthy subjects used as controls, matched for age, gender, and body mass index (BMI). Among the β-TM group, 14 patients with β-TM (age 27±6.64; 11M) died from SCD during follow-up. For each patient, QTD and JTD intervals were calculated. Compared to the healthy control group, β-TM group presented increased values of the QTc-D (65.36±33.95 vs. 37, 62±17.65; P<0.003) and JTc-D (74.64±33.27 vs. 40.32±12.45; P<0.001). In the β-TM sudden death group, QTc-D and JTc-D were significantly greater than in survived β-TM group (92.70±44.24 vs. 56.14±23.80, P=0.0001; 101.54±47.93 vs. 64.47±17.90, P=0.0001). A cutoff value of 70ms for QTc-D had a sensitivity and specificity of 77% in identifying patients at risk for SCD. A cutoff value of 100ms for JTc-D had a sensitivity of 65% and a specificity of 94% in identifying this category of patients. β-TM is associated with significant changes in heterogeneity of ventricular repolarization. QTc and JTc dispersion are useful markers of risk of SCD in patients with β-TM. © 2011 John Wiley & Sons A/S.

  2. The health and socioeconomic impacts of major multi-sport events: systematic review (1978-2008)

    PubMed Central

    Thomas, Sian; Thomson, Hilary; Scott, John; Hamilton, Val; Hanlon, Phil; Morrison, David S; Bond, Lyndal

    2010-01-01

    Objective To assess the effects of major multi-sport events on health and socioeconomic determinants of health in the population of the city hosting the event. Design Systematic review. Data sources We searched the following sources without language restrictions for papers published between 1978 and 2008: Applied Social Science Index and Abstracts (ASSIA), British Humanities Index (BHI), Cochrane database of systematic reviews, Econlit database, Embase, Education Resources Information Center (ERIC) database, Health Management Information Consortium (HMIC) database, International Bibliography of the Social Sciences (IBSS), Medline, PreMedline, PsycINFO, Sociological Abstracts, Sportdiscus, Web of Knowledge, Worldwide Political Science Abstracts, and the grey literature. Review methods Studies of any design that assessed the health and socioeconomic impacts of major multi-sport events on the host population were included. We excluded studies that used exclusively estimated data rather than actual data, that investigated host population support for an event or media portrayals of host cities, or that described new physical infrastructure. Studies were selected and critically appraised by two independent reviewers. Results Fifty four studies were included. Study quality was poor, with 69% of studies using a repeat cross-sectional design and 85% of quantitative studies assessed as being below 2+ on the Health Development Agency appraisal scale, often because of a lack of comparison group. Five studies, each with a high risk of bias, reported health related outcomes, which were suicide, paediatric health service demand, presentations for asthma in children (two studies), and problems related to illicit drug use. Overall, the data did not indicate clear negative or positive health impacts of major multi-sport events on host populations. The most frequently reported outcomes were economic outcomes (18 studies). The outcomes used were similar enough to allow us to perform a

  3. The health and socioeconomic impacts of major multi-sport events: systematic review (1978-2008).

    PubMed

    McCartney, Gerry; Thomas, Sian; Thomson, Hilary; Scott, John; Hamilton, Val; Hanlon, Phil; Morrison, David S; Bond, Lyndal

    2010-05-20

    To assess the effects of major multi-sport events on health and socioeconomic determinants of health in the population of the city hosting the event. Systematic review. We searched the following sources without language restrictions for papers published between 1978 and 2008: Applied Social Science Index and Abstracts (ASSIA), British Humanities Index (BHI), Cochrane database of systematic reviews, Econlit database, Embase, Education Resources Information Center (ERIC) database, Health Management Information Consortium (HMIC) database, International Bibliography of the Social Sciences (IBSS), Medline, PreMedline, PsycINFO, Sociological Abstracts, Sportdiscus, Web of Knowledge, Worldwide Political Science Abstracts, and the grey literature. Review methods Studies of any design that assessed the health and socioeconomic impacts of major multi-sport events on the host population were included. We excluded studies that used exclusively estimated data rather than actual data, that investigated host population support for an event or media portrayals of host cities, or that described new physical infrastructure. Studies were selected and critically appraised by two independent reviewers. Fifty four studies were included. Study quality was poor, with 69% of studies using a repeat cross-sectional design and 85% of quantitative studies assessed as being below 2+ on the Health Development Agency appraisal scale, often because of a lack of comparison group. Five studies, each with a high risk of bias, reported health related outcomes, which were suicide, paediatric health service demand, presentations for asthma in children (two studies), and problems related to illicit drug use. Overall, the data did not indicate clear negative or positive health impacts of major multi-sport events on host populations. The most frequently reported outcomes were economic outcomes (18 studies). The outcomes used were similar enough to allow us to perform a narrative synthesis, but the overall

  4. The impact of cognitive challenges in major depression: the role of the primary care physician.

    PubMed

    Mattingly, Gregory; Anderson, Richard H; Mattingly, Stephen G; Anderson, Elizabeth Q

    2016-09-01

    Nearly 1 in 5 Americans will struggle with major depression in their lives; some will have recurring bouts. Recent psychiatric research has given new attention to the prevalence of cognitive deficits in major depression and the impact such deficits have on remission and overall life functioning. When depression is partially treated i.e., leaving residual symptoms, patients have higher rates of relapse and lower functional outcomes. Impaired cognitive functioning is a frequent residual symptom, persisting in about 45% of patients even when emotional symptoms have improved, and results in a disproportionate share of the functional impairment, particularly in the workplace. Patients with depression have disrupted circuitry in brain regions responsible for cognition and it is therefore important to screen depressed patients for cognitive as well as emotional symptoms. Cognitive dysfunction should be evaluated in every mood disordered patient with validated self-report scales such as the Patient Health Questionnaire-9 or the Beck Depression Inventory and objective measures of cognitive function are also very very useful. Two easily administered tests are the Trails B Test and the Digit Symbol Substitution Test. Each take less than two minutes and measure working memory, executive function, and processing speed and can track cognitive improvement in depressed patients. Treatment of cognitive dysfunction in major depression is complicated by the 'serotonin conundrum': SSRI's frequently do not treat to full remission, and can cause cognitive blunting-actually adding to cognitive problems. Based on recent data including results from a recently completed meta-analysis by McIntyre and colleagues, an evidence-based algorithm for treating cognitive symptoms in depression is presented. A hierarchy of antidepressants and augmentation strategies based on the best available evidence is discussed. In conclusion, cognitive symptoms in major depressive disorder have been recognized as

  5. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

    PubMed Central

    Min, James K.; Labounty, Troy M.; Gomez, Millie J.; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor; Chinnaiyan, Kavitha M.; Chow, Benjamin; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jorg; Kaufmann, Philipp; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y.; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J.; Villines, Todd C.; Berman, Daniel S.

    2015-01-01

    Background Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Methods From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification. Results Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of

  6. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals.

    PubMed

    Min, James K; Labounty, Troy M; Gomez, Millie J; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Cheng, Victor; Chinnaiyan, Kavitha M; Chow, Benjamin; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jorg; Kaufmann, Philipp; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Berman, Daniel S

    2014-02-01

    Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1-49%, 50-69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) - inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) - and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification. Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61-3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75-3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09-1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18-2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29-2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05-1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0

  7. Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study

    PubMed Central

    Alessandrino, Emilio Paolo; Porta, Matteo Giovanni Della; Bacigalupo, Andrea; Malcovati, Luca; Angelucci, Emanuele; Van Lint, Maria Teresa; Falda, Michele; Onida, Francesco; Bernardi, Massimo; Guidi, Stefano; Lucarelli, Barbarella; Rambaldi, Alessandro; Cerretti, Raffaella; Marenco, Paola; Pioltelli, Pietro; Pascutto, Cristiana; Oneto, Rosi; Pirolini, Laura; Fanin, Renato; Bosi, Alberto

    2010-01-01

    Background Transfusion-dependency affects the natural history of myelodysplastic syndromes. Secondary iron overload may concur to this effect. The relative impact of these factors on the outcome of patients with myelodysplastic syndrome receiving allogeneic stem-cell transplantation remains to be clarified. Design and Methods We retrospectively evaluated the prognostic effect of transfusion history and iron overload on the post-transplantation outcome of 357 patients with myelodysplastic syndrome reported to the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) registry between 1997 and 2007. Results Transfusion-dependency was independently associated with reduced overall survival (hazard ratio=1.48, P=0.017) and increased non-relapse mortality (hazard ratio=1.68, P=0.024). The impact of transfusion-dependency was noted only in patients receiving myeloablative conditioning (overall survival: hazard ratio=1.76, P=0.003; non-relapse mortality: hazard ratio=1.70, P=0.02). There was an inverse relationship between transfusion burden and overall survival after transplantation (P=0.022); the outcome was significantly worse in subjects receiving more than 20 red cell units. In multivariate analysis, transfusion-dependency was found to be a risk factor for acute graft-versus-host disease (P=0.04). Among transfusion-dependent patients undergoing myeloablative allogeneic stem cell transplantation, pre-transplantation serum ferritin level had a significant effect on overall survival (P=0.01) and non-relapse mortality (P=0.03). This effect was maintained after adjusting for transfusion burden and duration, suggesting that the negative effect of transfusion history on outcome might be determined at least in part by iron overload. Conclusions Pre-transplantation transfusion history and serum ferritin have significant prognostic value in patients with myelodysplastic syndrome undergoing myeloablative allogeneic stem cell transplantation, inducing a significant increase of non

  8. Some Analysis of Major Impact of Geothermal Fluid Components in Power Plant Equipment

    NASA Astrophysics Data System (ADS)

    Buzăianu, A.; Csaki, I.; Moţoiu, P.; Leósson, K.; Serghiuţă, S.; Arnbjornsson, A.; Moţoiu, V.; Popescu, G.; Guðlaugsson, S.; Guðmundsson, D.

    2016-06-01

    This paper presents the results from a some analysis and major impact of geothermal fluid composition on the equipment in use in geothermal power plant. The structural analysis of material deposition improve the direct influenced of chemical composition of stem and waters included CaO, MgO, Al2O3 and SiO2 incorporated in the molten phase and the deposits in the scales formed due to equipment. The steam turbine corrosion damage, particularly of blades, discs and pomps, has long been recognized as a leading causes of reduced availability in the geothermal power plant. The corrosion process depends on temperature, pressure, chemisty and vaporous carryover by diversity of impurity. The experimental analysis procedure involves characterization of the fluid geothermal composition. Detailed information about surfaces morphological modification of the power plant components are obtained by electron microprobe analysis EDX and SEM investigation. References selection are obtaining by X-ray diffractometer patterns of the specimen.

  9. The major impacts of James Black's drug discoveries on medicine and pharmacology.

    PubMed

    Walker, Michael J A

    2011-04-01

    James Black has many claims to pharmacological fame as the creator of two new classes of drugs (beta-blockers and H2 antihistamines) and as a tireless innovator in drug discovery strategies and analytical procedures. The latter attributes in particular assisted Black in the invention of the prototypes for the two major classes of drugs for which he is best known, propranolol and cimetidine. The clinical impact of these drugs on both morbidity and mortality has been profound. In addition, the application of his analytical approach to drug discovery and pharmacology led others in the field to create many other new classes of drugs. Shortly before he died in 2010, Black wrote a retrospective review of his research career that provides insight into his innovative thinking and career success. This overview affords readers a very personal picture of the man, his ideas and his contributions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Interpersonal impacts mediate the association between personality and treatment response in major depression.

    PubMed

    Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

    2016-07-01

    Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record

  11. Geographical Detector-Based Identification of the Impact of Major Determinants on Aeolian Desertification Risk.

    PubMed

    Du, Ziqiang; Xu, Xiaoming; Zhang, Hong; Wu, Zhitao; Liu, Yong

    2016-01-01

    Arid and semi-arid areas in North China are facing the challenge of a rising aeolian desertification risk (ADR) due to the intertwined effects of complex natural processes and intensified anthropogenic activities. An accurate quantitative assessment of the relationship between ADR and its determinants is beneficial for understanding the driving mechanisms of aeolian desertification and for controlling future desertification. Previous studies have failed to quantify the relative role of determinants driving ADR and have been limited in assessing their interactive impacts. In this study, a spatial variance analysis-based geographical detector methodology is used to quantify the effects of geological, physical, and human factors on the occurrence of ADR in an area characterized by mountains and hills in northern China. It is found that soil type, precipitation, and wind velocity are the major determinants of ADR, which implies that geological and physical elements (e.g., soil attribute) and climatic factors (e.g., precipitation and wind velocity) rather than human activities have played a greater role in the incidence of ADR. Particularly, the results show that the interaction of various determinants causes significant non-linearly enhanced impacts on the ADR. The findings of our study will assist local inhabitants and policy makers in developing measures for wind prevention and sand control to mitigate the effects of desertification in the region.

  12. Geographical Detector-Based Identification of the Impact of Major Determinants on Aeolian Desertification Risk

    PubMed Central

    Du, Ziqiang; Xu, Xiaoming; Zhang, Hong; Wu, Zhitao; Liu, Yong

    2016-01-01

    Arid and semi-arid areas in North China are facing the challenge of a rising aeolian desertification risk (ADR) due to the intertwined effects of complex natural processes and intensified anthropogenic activities. An accurate quantitative assessment of the relationship between ADR and its determinants is beneficial for understanding the driving mechanisms of aeolian desertification and for controlling future desertification. Previous studies have failed to quantify the relative role of determinants driving ADR and have been limited in assessing their interactive impacts. In this study, a spatial variance analysis-based geographical detector methodology is used to quantify the effects of geological, physical, and human factors on the occurrence of ADR in an area characterized by mountains and hills in northern China. It is found that soil type, precipitation, and wind velocity are the major determinants of ADR, which implies that geological and physical elements (e.g., soil attribute) and climatic factors (e.g., precipitation and wind velocity) rather than human activities have played a greater role in the incidence of ADR. Particularly, the results show that the interaction of various determinants causes significant non-linearly enhanced impacts on the ADR. The findings of our study will assist local inhabitants and policy makers in developing measures for wind prevention and sand control to mitigate the effects of desertification in the region. PMID:26987114

  13. The impact of educational status on the clinical features of major depressive disorder among Chinese women.

    PubMed

    Gan, Zhaoyu; Li, Yihan; Xie, Dong; Shao, Chunhong; Yang, Fuzhong; Shen, Yuan; Zhang, Ning; Zhang, Guanghua; Tian, Tian; Yin, Aihua; Chen, Ce; Liu, Jun; Tang, Chunling; Zhang, Zhuoqiu; Liu, Jia; Sang, Wenhua; Wang, Xumei; Liu, Tiebang; Wei, Qinling; Xu, Yong; Sun, Ling; Wang, Sisi; Li, Chang; Hu, Chunmei; Cui, Yanping; Liu, Ying; Li, Ying; Zhao, Xiaochuan; Zhang, Lan; Sun, Lixin; Chen, Yunchun; Zhang, Yueying; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Zhang, Jinbei

    2012-02-01

    Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. The impact of educational status on the clinical features of major depressive disorder among Chinese women

    PubMed Central

    Gan, Zhaoyu; Li, Yihan; Xie, Dong; Shao, Chunhong; Yang, Fuzhong; Shen, Yuan; Zhang, Ning; Zhang, Guanghua; Tian, Tian; Yin, Aihua; Chen, Ce; Liu, Jun; Tang, Chunling; Zhang, Zhuoqiu; Liu, Jia; Sang, Wenhua; Wang, Xumei; Liu, Tiebang; Wei, Qinling; Xu, Yong; Sun, Ling; Wang, Sisi; Li, Chang; Hu, Chunmei; Cui, Yanping; Liu, Ying; Li, Ying; Zhao, Xiaochuan; Zhang, Lan; Sun, Lixin; Chen, Yunchun; Zhang, Yueying; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Zhang, Jinbei

    2012-01-01

    Background Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Methods Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Results Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Limitations Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. Conclusions The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD. PMID:21824664

  15. Impact of early and recent stress on white matter microstructure in major depressive disorder.

    PubMed

    Sara, Poletti; Veronica, Aggio; Silvia, Brioschi; Irene, Bollettini; Andrea, Falini; Cristina, Colombo; Francesco, Benedetti

    2018-01-01

    Major Depressive Disorder (MDD) is a worldwide-spread pathology, characterized by lifetime-recurrent episodes. Adverse childhood experiences (ACE) increase the lifetime risk of developing depression and affect the structure of the brain. Recent stressful events (RSE) can trigger the onset of depressive episodes, and affect grey matter volume. The aim of our study is to analyse the effect of both early and recent stress events on white matter microstructure in MDD patients and healthy volunteers. Sixty-five MDD inpatients and fifty-nine healthy controls underwent MRI acquisition of diffusion tensor images with a 3.0T scanner. Severity of ACE and RSE was rated, respectively, on the Risky Families Questionnaire and on the Social Readjustment Rating Scale. A significant effect of diagnosis was observed, with MDD subjects showing reduced fractional anisotropy (FA) and axial diffusivity (AD) compared to healthy controls in all the major association, projection and commissural tracts. In patients with MDD, but not in healthy controls, both ACE and RSE correlated with measures of WM microstructure: ACE correlated negatively with AD and MD, whereas RSE correlated negatively with FA. The two diagnostic groups differed for age and education, previous and current medications, and treatment periods. Exposure to both early and recent stress exerts a widespread effect on WM microstructure of MDD patients, with a different impact possibly depending from the developmental period in which the stress has occurred. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Discontinuity of Medicaid Coverage: Impact on Cost and Utilization Among Adult Medicaid Beneficiaries With Major Depression.

    PubMed

    Ji, Xu; Wilk, Adam S; Druss, Benjamin G; Lally, Cathy; Cummings, Janet R

    2017-08-01

    Gaps in Medicaid coverage may disrupt access to and continuity of care. This can be detrimental for beneficiaries with chronic conditions, such as major depression, for whom disruptions in access to outpatient care may lead to increased use of acute care. However, little is known about how Medicaid coverage discontinuities impact acute care utilization among adults with depression. Examine the relationship between Medicaid discontinuities and service utilization among adults with major depression. A total of 139,164 adults (18-64) with major depression was identified using the 2003-2004 Medicaid Analytic eXtract Files. We used generalized linear and two-part models to examine the effect of Medicaid discontinuity on service utilization. To establish causality in this relationship, we used instrumental variables analysis, relying on exogenous variation in a state-level policy for identification. Emergency department (ED) visits, inpatient episodes, inpatient days, and Medicaid-reimbursed costs. Approximately 29.4% of beneficiaries experienced coverage disruptions. In instrumental variables models, those with coverage disruptions incurred an increase of $650 in acute care costs per-person per Medicaid-covered month compared with those with continuous coverage, evidenced by an increase in ED use (0.1 more ED visits per-person-month) and inpatient days (0.6 more days per-person-month). The increase in acute costs contributed to an overall increase in all-cause costs by $310 per-person-month (all P-values<0.001). Among depressed adults, those experiencing coverage disruptions have, on average, significantly greater use of costly ED/inpatient services than those with continuous coverage. Maintenance of continuous Medicaid coverage may help prevent acute episodes requiring high-cost interventions.

  17. Impact of obesity on recovery and pulmonary functions of obese women undergoing major abdominal gynecological surgeries.

    PubMed

    Moustafa, Ahmed A M; Abdelazim, Ibrahim A

    2016-06-01

    To determine impact of obesity on recovery parameters and pulmonary functions of women undergoing major abdominal gynecological surgeries. Eighty women undergoing major gynecological surgeries were included in this study. Anesthesia was induced by remifentanil bolus, followed by propofol and cisatracurium to facilitate oro-tracheal intubation and was maintained by balanced anesthesia of remifentanil intravenous infusion and sevoflurane in oxygen and air. Time from discontinuation of maintenance anesthesia to fully awake were recorded at 1-min intervals and time from discontinuation of anesthesia until patient was transferred to post-anesthesia care unit (PACU) and discharged from PACU was also recorded. Pulmonary function tests were performed before surgery and repeated 4 h, days 1, 2 and 3 post-operative for evaluation of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate. Occurrence of post-operative complications, re-admission to ICU, hospital stay and morbidities were also recorded. Induction of anesthesia using remifentanil bolus injection resulted in significant decrease of heart rate and arterial pressures compared to pre-operative and pre-induction values. Recovery times were significantly shorter in obese compared to morbidly obese women. Post-operative pulmonary function tests showed significant deterioration compared to pre-operative measures but showed progressive improvement through first 3 post-operative days. Hospital stay was significantly shorter for obese compared to morbid obese women. Obesity delays recovery from general anesthesia, adversely affects pulmonary functions and increases post-operative complications. Remifentanil infusion and sevoflurane could be appropriate combination for obese and morbidly obese women undergoing major surgeries.

  18. Favorable Prognostic Impact of NPM1 Mutations in Older Patients With Cytogenetically Normal De Novo Acute Myeloid Leukemia and Associated Gene- and MicroRNA-Expression Signatures: A Cancer and Leukemia Group B Study

    PubMed Central

    Becker, Heiko; Marcucci, Guido; Maharry, Kati; Radmacher, Michael D.; Mrózek, Krzysztof; Margeson, Dean; Whitman, Susan P.; Wu, Yue-Zhong; Schwind, Sebastian; Paschka, Peter; Powell, Bayard L.; Carter, Thomas H.; Kolitz, Jonathan E.; Wetzler, Meir; Carroll, Andrew J.; Baer, Maria R.; Caligiuri, Michael A.; Larson, Richard A.; Bloomfield, Clara D.

    2010-01-01

    Purpose To analyze the prognostic significance of NPM1 mutations, and the associated gene- and microRNA-expression signatures in older patients with de novo, cytogenetically normal acute myeloid leukemia (CN-AML) treated with intensive chemotherapy. Patients and Methods One hundred forty-eight adults age ≥ 60 years with de novo CN-AML, enrolled onto Cancer and Leukemia Group B protocols 9720 and 10201, were studied at diagnosis for NPM1, FLT3, CEBPA, and WT1 mutations, and gene- and microRNA-expression profiles. Results Patients with NPM1 mutations (56%) had higher complete remission (CR) rates (84% v 48%; P < .001) and longer disease-free survival (DFS; P = .047; 3-year rates, 23% v 10%) and overall survival (OS; P < .001; 3-year rates, 35% v 8%) than NPM1 wild-type patients. In multivariable analyses, NPM1 mutations remained independent predictors for higher CR rates (P < .001) and longer DFS (P = .004) and OS (P < .001), after adjustment for other prognostic clinical and molecular variables. Unexpectedly, the prognostic impact of NPM1 mutations was mainly observed in patients ≥ 70 years. Gene- and microRNA-expression profiles associated with NPM1 mutations were similar across older patient age groups and similar to those in younger (< 60 years) patients with CN-AML. These profiles were characterized by upregulation of HOX genes and their embedded microRNAs and downregulation of the prognostically adverse MN1, BAALC, and ERG genes. Conclusion NPM1 mutations have favorable prognostic impact in older patients with CN-AML, especially those age ≥ 70 years. The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups. PMID:20026798

  19. Impact cratering as a major process in planet formation: Projectile identification of meteorite craters

    NASA Astrophysics Data System (ADS)

    Schmidt, G.; Kratz, K.

    2009-12-01

    Ancient surfaces of solid planets show that impact cratering is a major process in planet formation. Understanding origin and influence of impactors on the chemical composition of planets (core, mantle and crust) it is important to know the relative abundances of highly siderophile elements (Os, Ir, Ru, Pt, Rh, Pd) in the silicate mantle and crust of planets and meteorites. Refractory highly siderophile elements, such as Os and Ir, are abundant in most meteorites but depleted in crustal rocks (low target/meteorite ratios) and thus the most reliable elements for projectile identification. However, target/meteorite ratios are high if target rocks consist of mantle rocks. In such cases elements are enriched in impactites due to relatively high abundances (ng/g level) in target rocks to make the identification of projectile types difficult (e.g., Gardnos impact structure in Norway). The Ru/Ir ratio is the most reliable key ratio that rules out Earth primitive upper mantle (PUM) derived refractory highly siderophile element components in impactites. The well established Ru/Ir ratio of the Earth mantle of 2.0 ± 0.1 (e.g. Schmidt and Kratz 2004) is significantly above the chondritic ratios varying from 1.4 to 1.6. On Earth Rh/Ir, Ru/Ir, Pd/Ir, and Pt/Os derived from PUM match the ratios of group IV irons with fractionated trace element patterns. The question raise if HSE in mantle rocks are added to the accreting Earth by a late bombardment of pre-differentiated objects or the cores of these objects (magmatic iron meteorites as remnants of the first planetesimals, e.g. Kleine et al. 2009) or some unsampled inner solar system materials from the Mercury-Venus formation region, not sampled through meteorite collections (Schmidt 2009). The PGE and Ni systematics of the upper continental crust (UCC) closely resembles group IIIAB iron meteorites with highly fractionated refractory trace element patterns, pallasites, and the evolved suite of Martian meteorites (representing

  20. The Impact of Letter Grades on Student Effort, Course Selection, and Major Choice: A Regression-Discontinuity Analysis

    ERIC Educational Resources Information Center

    Main, Joyce B.; Ost, Ben

    2014-01-01

    The authors apply a regression-discontinuity design to identify the causal impact of letter grades on student effort within a course, subsequent credit hours taken, and the probability of majoring in economics. Their methodology addresses key issues in identifying the causal impact of letter grades: correlation with unobservable factors, such as…

  1. Prognostic Impact of Deficient DNA Mismatch Repair in Patients With Stage III Colon Cancer From a Randomized Trial of FOLFOX-Based Adjuvant Chemotherapy

    PubMed Central

    Sinicrope, Frank A.; Mahoney, Michelle R.; Smyrk, Thomas C.; Thibodeau, Stephen N.; Warren, Robert S.; Bertagnolli, Monica M.; Nelson, Garth D.; Goldberg, Richard M.; Sargent, Daniel J.; Alberts, Steven R.

    2013-01-01

    Purpose The association of deficient DNA mismatch repair (dMMR) with prognosis in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy remains unknown. Patients and Methods Resected, stage III colon carcinomas from patients (N = 2,686) randomly assigned to FOLFOX ± cetuximab (North Central Cancer Treatment Group N0147 trial) were analyzed for mismatch repair (MMR) protein expression and mutations in BRAFV600E (exon 15) and KRAS (codons 12 and 13). Association of biomarkers with disease-free survival (DFS) was determined using Cox models. A validation cohort (Cancer and Leukemia Group B 88903 trial) was used. Results dMMR was detected in 314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAFV600E or KRAS mutations, respectively. MMR status was not prognostic overall (adjusted hazard ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions were found between MMR and primary tumor site (Pinteraction = .009) and lymph node category (N1 v N2; Pinteraction = .014). Favorable DFS was observed for dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P = .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056), adjusting for mutations and covariates. Any survival benefit of dMMR was lost in N2 tumors. Mutations in BRAFV600E (HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P < .001) were independently associated with worse DFS. The observed MMR by tumor site interaction was validated in an independent cohort of stage III colon cancers (Pinteraction = .037). Conclusion The prognostic impact of MMR depended on tumor site, and this interaction was validated in an independent cohort. Among dMMR cancers, proximal tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF or KRAS mutations were independently associated with adverse outcome. PMID:24019539

  2. Prognostic relevance of minimal residual disease in colorectal cancer

    PubMed Central

    Bork, Ulrich; Grützmann, Robert; Rahbari, Nuh N; Schölch, Sebastian; Distler, Marius; Reissfelder, Christoph; Koch, Moritz; Weitz, Jürgen

    2014-01-01

    Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options. PMID:25132746

  3. Climate-Change Impacts on Major Societal and Environmental Sectors: a National View

    NASA Astrophysics Data System (ADS)

    Melillo, J. M.

    2009-05-01

    The U.S. Climate Change Science Program's Unified Synthesis Product reports on extant and possible future impacts of climate change for seven sectors at the national level - water resources, energy supply and use, transportation, agriculture, ecosystems, human health and society. The sectoral analyses provide an integrated national picture of the climate-change consequences, now and in the future, for society and the environment, albeit a picture with regional texture. Major report findings for each sector will be presented. In addition to the specific sectoral findings, several overarching messages emerge from this component of the synthesis activity. First, it is important to think about interactions between and among sectors with regard to climate impacts. For example, the projected changes in the timing and amount of precipitation, and hence water supply, will very likely have significant implications for other sectors considered in the report. Changes in water supply have the potential to affect hydropower generation, river transportation, crop timing and management, in-stream ecosystem services including fish habitat, and human health issues related to links between heavy rains ad water-borne diseases. Second, the report concludes that climate-change impacts on the sectors must be considered in the context of a range of environmental and social factors including pollution, population growth, over use of resources, and urbanization. The multi-factor analysis provides insight into our understanding of where, when and how climate change combines with other environmental and social changes to affect the sectors. It also provides some understanding of how these interactions can either amplify or dampen climate-change impacts. This message has profound implications for the design of research programs and information systems at the national, regional and local levels. Furthermore, it demands that a true partnership be forged between the natural and social sciences

  4. Genetic Background Has a Major Impact on Differences in Sleep Resulting from Environmental Influences in Drosophila

    PubMed Central

    Zimmerman, John E.; Chan, May T.; Jackson, Nicholas; Maislin, Greg; Pack, Allan I.

    2012-01-01

    Study Objectives: To determine the effect of different genetic backgrounds on demographic and environmental interventions that affect sleep and evaluate variance of these measures; and to evaluate sleep and variance of sleep behaviors in 6 divergent laboratory strains of common origin. Design: Assessment of the effects of age, sex, mating status, food sources, and social experience using video analysis of sleep behavior in 2 different strains of Drosophila, white1118ex (w1118ex) and white Canton-S (wCS10). Sleep was also determined for 6 laboratory strains of Canton-S and 3 inbred lines. The variance of total sleep was determined for all groups and conditions. Measurements and Results: The circadian periods and the effects of age upon sleep were the same between w1118ex and wCS10 strains. However, the w1118ex and wCS10 strains demonstrated genotype-dependent differences in the effects upon sleep of sex, mating status, social experience, and being on different foods. Variance of total sleep was found to differ in a genotype dependent manner for interventions between the w1118ex and wCS10 strains. Six different laboratory Canton-S strains were found to have significantly different circadian periods (P < 0.001) and sleep phenotypes (P < 0.001). Three inbred lines showed reduced variance for sleep measurements. Conclusions: One must control environmental conditions in a rigorously consistent manner to ensure that sleep data may be compared between experiments. Genetic background has a significant impact upon changes in sleep behavior and variance of behavior due to demographic factors and environmental interventions. This represents an opportunity to discover new genes that modify sleep/wake behavior. Citation: Zimmerman JE; Chan MT; Jackson N; Maislin G; Pack AI. Genetic background has a major impact on differences in sleep resulting from environmental influences in Drosophila. SLEEP 2012;35(4):545-557. PMID:22467993

  5. The Impact of Heat Waves on Mortality in Seven Major Cities in Korea

    PubMed Central

    Son, Ji-Young; Lee, Jong-Tae; Anderson, G. Brooke

    2012-01-01

    Background: Understanding the health impacts of heat waves is important, especially given anticipated increases in the frequency, duration, and intensity of heat waves due to climate change. Objectives: We examined mortality from heat waves in seven major Korean cities for 2000 through 2007 and investigated effect modification by individual characteristics and heat wave characteristics (intensity, duration, and timing in season). Methods: Heat waves were defined as ≥ 2 consecutive days with daily mean temperature at or above the 98th percentile for the warm season in each city. We compared mortality during heat-wave days and non-heat-wave days using city-specific generalized linear models. We used Bayesian hierarchical models to estimate overall effects within and across all cities. In addition, we estimated effects of heat wave characteristics and effects according to cause of death and examined effect modification by individual characteristics for Seoul. Results: Overall, total mortality increased 4.1% [95% confidence interval (CI): –6.1%, 15.4%] during heat waves compared with non-heat-wave days, with an 8.4% increase (95% CI: 0.1%, 17.3%) estimated for Seoul. Estimated mortality was higher for heat waves that were more intense, longer, or earlier in summer, although effects were not statistically significant. Estimated risks were higher for women versus men, older versus younger residents, those with no education versus some education, and deaths that occurred out of hospitals in Seoul, although differences among strata of individual characteristics were not statistically significant. Conclusions: Our findings support evidence of mortality impacts from heat waves and have implications for efforts to reduce the public health burden of heat waves. PMID:22266672

  6. Simulated Near-term Climate Change Impacts on Major Crops across Latin America and the Caribbean

    NASA Astrophysics Data System (ADS)

    Gourdji, S.; Mesa-Diez, J.; Obando-Bonilla, D.; Navarro-Racines, C.; Moreno, P.; Fisher, M.; Prager, S.; Ramirez-Villegas, J.

    2016-12-01

    Robust estimates of climate change impacts on agricultural production can help to direct investments in adaptation in the coming decades. In this study commissioned by the Inter-American Development Bank, near-term climate change impacts (2020-2049) are simulated relative to a historical baseline period (1971-2000) for five major crops (maize, rice, wheat, soybean and dry bean) across Latin America and the Caribbean (LAC) using the DSSAT crop model. No adaptation or technological change is assumed, thereby providing an analysis of existing climatic stresses on yields in the region and a worst-case scenario in the coming decades. DSSAT is run across irrigated and rain-fed growing areas in the region at a 0.5° spatial resolution for each crop. Crop model inputs for soils, planting dates, crop varieties and fertilizer applications are taken from previously-published datasets, and also optimized for this study. Results show that maize and dry bean are the crops most affected by climate change, followed by wheat, with only minimal changes for rice and soybean. Generally, rain-fed production sees more severe yield declines than irrigated production, although large increases in irrigation water are needed to maintain yields, reducing the yield-irrigation productivity in most areas and potentially exacerbating existing supply limitations in watersheds. This is especially true for rice and soybean, the two crops showing the most neutral yield changes. Rain-fed yields for maize and bean are projected to decline most severely in the sub-tropical Caribbean, Central America and northern South America, where climate models show a consistent drying trend. Crop failures are also projected to increase in these areas, necessitating switches to other crops or investment in adaptation measures. Generally, investment in agricultural adaptation to climate change (such as improved seed and irrigation infrastructure) will be needed throughout the LAC region in the 21st century.

  7. Impact of Location of Readmission on Outcomes After Major Cancer Surgery.

    PubMed

    Stitzenberg, Karyn B; Chang, YunKyung; Smith, Angela B; Meyers, Michael O; Nielsen, Matthew E

    2017-02-01

    The burden of readmissions after major cancer surgery is high. Prior work suggests that one-third of readmitted patients are readmitted to a different hospital than where the surgery was performed. The impact of this location of readmission needs to be more thoroughly understood. This retrospective cohort study was performed on Surveillance, Epidemiology, and End Results (SEER)-Medicare patients with bladder, esophagus, lung, or pancreas cancer diagnosed from 2001 to 2007 who underwent extirpative surgery and were readmitted within 90 days. Readmission location was classified as 'index' if readmission was at the hospital where surgery was performed, or 'different' if readmission was elsewhere. Outcomes including complications, reoperations, in-hospital mortality, 90-day mortality, and 90-day total costs were compared based on the location of readmission using a propensity score inverse probability treatment weight analysis. Overall, 7903 (28 %) patients were readmitted within 90 days of index hospitalization. Thirty-three percent were readmitted to a different hospital (bladder 30 %, esophagus 34 %, lung 34 %, pancreas 34 %). Ninety-day mortality and total costs of care were not significantly different between the readmission location groups (all p > 0.05); however, substantial differences in the types of patients, and timing of and reasons for readmission were observed between the two groups. Patients readmitted to different hospitals after major cancer surgery are a different group of patients than those readmitted to the index hospital. Accounting for this, we did not find significant differences in short-term clinical outcomes or costs of care based on readmission location; however, differences in long-term outcomes were observed that should be further explored in future studies.

  8. The impact of anesthesia providers on major morbidity following screening colonoscopies

    PubMed Central

    Lubarsky, David A; Guercio, Jason R; Hanna, John W; Abreu, Maria T; Ma, Qianli; Uribe, Claudia; Birnbach, David J; Sinclair, David R; Candiotti, Keith A

    2015-01-01

    Background and aims Few studies evaluate the impact of anesthesia providers during procedures, such as colonoscopy, on low-risk patients. The objective of this study was to compare the effect of anesthesia providers on several outcome variables, including major morbidity, following screening colonoscopies. Methods A propensity-matched cohort study of 14,006 patients who enrolled with a national insurer offering health maintenance organization (HMO), preferred provider organization (PPO), and Medicare Advantage plans for a screening colonoscopy between July 1, 2005 and June 30, 2007 were studied. Records were evaluated for completion of the colonoscopy, new cancer diagnosis (colon, anal, rectal) within 6 months of the colonoscopy, new primary diagnosis of myocardial infarction (MI), new primary diagnosis of stroke, hospital admission within 7 days of the colonoscopy, and adherence to guidelines for use of anesthesia providers. Results The presence of an anesthesia provider did not affect major morbidity or the percent of completed exams. Overall morbidity within 7 days was very low. When an anesthesia provider was present, a nonsignificant trend toward greater cancer detection within 6 months of the procedure was observed. Adherence to national guidelines regarding the use of anesthesia providers for low-risk patients was poor. Conclusion A difference in outcome associated with the presence or absence of an anesthesia provider during screening colonoscopy in terms of MI, stroke, or hospital admission within 7 days of the procedure was not observed. Adherence to published guidelines for the use of anesthesia providers is low. The incidence of completed exams was unaffected by the presence of an anesthesia provider. However, a nonstatistically significant trend toward increased cancer detection requires further study. PMID:26060404

  9. Observations of the impact of a major Saharan dust storm on the atmospheric radiation balance

    SciTech Connect

    Slingo, A.; Ackerman, Thomas P.; Allan, R. P.; Kassianov, Evgueni I.; McFarlane, Sally A.; Robinson, G. J.; Barnard, James C.; Miller, Mark; Harries, J. E.; Russell, J. E.; Dewitte, S.

    2006-12-01

    Saharan dust storms transport large quantities of material across the African continent and beyond, causing widespread disruption and hazards to health. The dust may be deposited into the Atlantic Ocean, where it provides an important source of nutrients1, and may be carried as far as the West Indies. Such events may also influence the growth of Atlantic tropical cyclones. Satellite observations have enabled estimates to be made of the effect of the dust on the radiation budget seen from space, but only limited in situ observations have hitherto been made at the surface. Here we present the first simultaneous and continuous observations of the effect of a major dust storm in March 2006 on the radiation budget both at the top of the atmosphere (TOA) and at the surface. We combine data from the Geostationary Earth Radiation Budget (GERB) broadband radiometer and the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) on the Meteosat-8 weather satellite with remote sensing and in situ measurements from a new Mobile Facility located in Niamey, Niger (13{sup o} 29'N, 2{sup o} 10'E), operated by the US Atmospheric Radiation Measurement (ARM) program. We show that the dust produced major perturbations to the radiation budget seen from space and from the surface. By combining the two datasets, we estimate the impact on the radiation budget of the atmosphere itself. Using independent data from the Mobile Facility, we derive the optical properties of the dust and input these and other information into radiation codes to simulate the radiative fluxes. Comparisons with the observed fluxes provides a stringent test of the ability of the codes to represent the radiative properties of this important component of the global aerosol burden.

  10. The impact of anesthesia providers on major morbidity following screening colonoscopies.

    PubMed

    Lubarsky, David A; Guercio, Jason R; Hanna, John W; Abreu, Maria T; Ma, Qianli; Uribe, Claudia; Birnbach, David J; Sinclair, David R; Candiotti, Keith A

    2015-01-01

    Few studies evaluate the impact of anesthesia providers during procedures, such as colonoscopy, on low-risk patients. The objective of this study was to compare the effect of anesthesia providers on several outcome variables, including major morbidity, following screening colonoscopies. A propensity-matched cohort study of 14,006 patients who enrolled with a national insurer offering health maintenance organization (HMO), preferred provider organization (PPO), and Medicare Advantage plans for a screening colonoscopy between July 1, 2005 and June 30, 2007 were studied. Records were evaluated for completion of the colonoscopy, new cancer diagnosis (colon, anal, rectal) within 6 months of the colonoscopy, new primary diagnosis of myocardial infarction (MI), new primary diagnosis of stroke, hospital admission within 7 days of the colonoscopy, and adherence to guidelines for use of anesthesia providers. The presence of an anesthesia provider did not affect major morbidity or the percent of completed exams. Overall morbidity within 7 days was very low. When an anesthesia provider was present, a nonsignificant trend toward greater cancer detection within 6 months of the procedure was observed. Adherence to national guidelines regarding the use of anesthesia providers for low-risk patients was poor. A difference in outcome associated with the presence or absence of an anesthesia provider during screening colonoscopy in terms of MI, stroke, or hospital admission within 7 days of the procedure was not observed. Adherence to published guidelines for the use of anesthesia providers is low. The incidence of completed exams was unaffected by the presence of an anesthesia provider. However, a nonstatistically significant trend toward increased cancer detection requires further study.

  11. Epidemiology and Impact of Abdominal Oblique Injuries in Major and Minor League Baseball

    PubMed Central

    Camp, Christopher L.; Conte, Stan; Cohen, Steven B.; Thompson, Matthew; D’ Angelo, John; Nguyen, Joseph T.; Dines, Joshua S.

    2017-01-01

    Background: Oblique injuries are known to be a common cause of time out of play for professional baseball players, and prior work has suggested that injury rates may be on the rise in Major League Baseball (MLB). Purpose: To better understand the current incidence of oblique injuries, determine their impact based on time out of play, and to identify common injury patterns that may guide future injury prevention programs. Study Design: Descriptive epidemiological study. Methods: Using the MLB Health and Injury Tracking System, all oblique injuries that resulted in time out of play in MLB and Minor League Baseball (MiLB) during the 2011 to 2015 seasons were identified. Player demographics such as age, position/role, and handedness were included. Injury-specific factors analyzed included the following: date of injury, timing during season, days missed, mechanism, side, treatment, and reinjury status. Results: A total of 996 oblique injuries occurred in 259 (26%) MLB and 737 (74%) MiLB players. Although the injury rate was steady in MiLB, the MLB injury rate declined (P = .037). A total of 22,064 days were missed at a mean rate of 4413 days per season and 22.2 days per injury. The majority of these occurred during batting (n = 455, 46%) or pitching (n = 348, 35%), with pitchers losing 5 days more per injury than batters (P < .001). The leading side was injured in 77% of cases and took 5 days longer to recover from than trailing side injuries (P = .009). Seventy-nine (7.9%) players received either a corticosteroid or platelet-rich plasma injection, and the mean recovery time was 11 days longer compared with those who did not receive an injection (P < .001). Conclusion: Although the rate of abdominal oblique injuries is on the decline in MLB, this is not the case for MiLB, and these injuries continue to represent a significant source of time out of play in professional baseball. The vast majority of injuries occur on the lead side, and these injuries result in the

  12. Impacts of future climate change on potential yields of major crops in China

    NASA Astrophysics Data System (ADS)

    Yin, Y.; Tang, Q.; Liu, X.

    2014-05-01

    Climate change may affect crop development and yield, and consequently cast a shadow of doubt over China's food self-sufficiency efforts. In this study we used the model projections of a couple of global gridded crop models (GGCMs) to assess the effects of future climate change on the potential yields of the major crops (i.e. wheat, rice, maize and soybean) over China. The GGCMs were forced with the bias-corrected climate data from 5 global climate models (GCMs) under the Representative Concentration Pathways (RCP) 8.5 which were made available by the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP). The results show that the potential yields of rice may increase over a large portion of China. Climate change may benefit food productions over the high-altitude and cold regions where are outside current main agricultural area. However, the potential yield of maize, soybean and wheat may decrease in a large portion of the current main crop planting areas such as North China Plain. Development of new agronomic management strategy may be useful for coping with climate change in the areas with high risk of yield reduction.

  13. Major cellular and physiological impacts of ocean acidification on a reef building coral.

    PubMed

    Kaniewska, Paulina; Campbell, Paul R; Kline, David I; Rodriguez-Lanetty, Mauricio; Miller, David J; Dove, Sophie; Hoegh-Guldberg, Ove

    2012-01-01

    As atmospheric levels of CO(2) increase, reef-building corals are under greater stress from both increased sea surface temperatures and declining sea water pH. To date, most studies have focused on either coral bleaching due to warming oceans or declining calcification due to decreasing oceanic carbonate ion concentrations. Here, through the use of physiology measurements and cDNA microarrays, we show that changes in pH and ocean chemistry consistent with two scenarios put forward by the Intergovernmental Panel on Climate Change (IPCC) drive major changes in gene expression, respiration, photosynthesis and symbiosis of the coral, Acropora millepora, before affects on biomineralisation are apparent at the phenotype level. Under high CO(2) conditions corals at the phenotype level lost over half their Symbiodinium populations, and had a decrease in both photosynthesis and respiration. Changes in gene expression were consistent with metabolic suppression, an increase in oxidative stress, apoptosis and symbiont loss. Other expression patterns demonstrate upregulation of membrane transporters, as well as the regulation of genes involved in membrane cytoskeletal interactions and cytoskeletal remodeling. These widespread changes in gene expression emphasize the need to expand future studies of ocean acidification to include a wider spectrum of cellular processes, many of which may occur before impacts on calcification.

  14. Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability.

    PubMed

    Carrapita, Jorge; Abrantes, Ana Margarida; Campelos, Sofia; Gonçalves, Ana Cristina; Cardoso, Dulce; Sarmento-Ribeiro, Ana Bela; Rocha, Clara; Santos, Jorge Nunes; Botelho, Maria Filomena; Tralhão, José Guilherme; Farges, Olivier; Barbosa, Jorge Maciel

    2016-10-11

    It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.

  15. Major Cellular and Physiological Impacts of Ocean Acidification on a Reef Building Coral

    PubMed Central

    Kaniewska, Paulina; Campbell, Paul R.; Kline, David I.; Rodriguez-Lanetty, Mauricio; Miller, David J.

    2012-01-01

    As atmospheric levels of CO2 increase, reef-building corals are under greater stress from both increased sea surface temperatures and declining sea water pH. To date, most studies have focused on either coral bleaching due to warming oceans or declining calcification due to decreasing oceanic carbonate ion concentrations. Here, through the use of physiology measurements and cDNA microarrays, we show that changes in pH and ocean chemistry consistent with two scenarios put forward by the Intergovernmental Panel on Climate Change (IPCC) drive major changes in gene expression, respiration, photosynthesis and symbiosis of the coral, Acropora millepora, before affects on biomineralisation are apparent at the phenotype level. Under high CO2 conditions corals at the phenotype level lost over half their Symbiodinium populations, and had a decrease in both photosynthesis and respiration. Changes in gene expression were consistent with metabolic suppression, an increase in oxidative stress, apoptosis and symbiont loss. Other expression patterns demonstrate upregulation of membrane transporters, as well as the regulation of genes involved in membrane cytoskeletal interactions and cytoskeletal remodeling. These widespread changes in gene expression emphasize the need to expand future studies of ocean acidification to include a wider spectrum of cellular processes, many of which may occur before impacts on calcification. PMID:22509341

  16. Impact of rehabilitation programs on dependency and functional performance of patients with major lower limb amputations

    PubMed Central

    AlSofyani, Mohammad A.; AlHarthi, Abdulaziz S.; Farahat, Fayssal M.; Abuznadah, Wesam T.

    2016-01-01

    Objectives: To determine pattern and impact of physical rehabilitation on dependency and functional performance of patients. Methods: This retrospective chart review was carried out between July and August 2012 at King Abdulaziz Medical City, Jeddah, Saudi Arabia. Data were collected using demographic, clinical, and dependency assessment checklists. Results: Patients who underwent major lower limb amputations between January 2007 and April 2012 (n=121) were included in the study. There were 84 (69.4%) male and 37 (30.6%) female patients with a mean ± standard deviation of 63.3±17.4 years old. Diabetes mellitus was the most frequent cause in 63.6% of patients. Only one-third of the amputees (32.2%) have records of completion of their rehabilitation programs, although 20.7% of them completed the <50% of the scheduled rehabilitation sessions, 17.2% attended between 50% and 80%, and the remaining 62.1% attended more than 80% of the scheduled sessions. Muscle power scores in each side of the upper and lower limbs were significantly better following rehabilitation (p<0.0001). Basic functions of mobility and transfer have also significantly improved (p<0.05). Conclusions: Overall dependency and functional performance were significantly better following implementation of the physical rehabilitation programs. A multidisciplinary team approach is mandatory to improve compliance of patients toward the rehabilitation programs. PMID:27652362

  17. Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability

    PubMed Central

    Carrapita, Jorge; Abrantes, Ana Margarida; Campelos, Sofia; Gonçalves, Ana Cristina; Cardoso, Dulce; Sarmento-Ribeiro, Ana Bela; Rocha, Clara; Santos, Jorge Nunes; Botelho, Maria Filomena; Tralhão, José Guilherme; Farges, Olivier; Barbosa, Jorge Maciel

    2016-01-01

    It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours. PMID:27725728

  18. Impact of a major hurricane on surgical services in a university hospital.

    PubMed

    Norcross, E D; Elliott, B M; Adams, D B; Crawford, F A

    1993-01-01

    Hurricane Hugo struck Charleston, South Carolina, on September 21, 1989. This report analyzes the impact this storm had upon surgical care at a university medical center. Although disaster planning began on September 17, hurricane damage by high winds and an 8.7-foot tidal surge led to loss of emergency power and water. Consequently, system failures occurred in air conditioning, vacuum suction, steam and ethylene oxide sterilization, plumbing, central paging, lighting, and refrigeration. The following surgical support services were affected. In the blood bank, lack of refrigeration meant no platelet packs for 2 days. In radiology, loss of electrical power damaged CT/MRI scanners and flooding ruined patient files, resulting in lost information. In the intensive care unit, loss of electricity meant no monitors and hand ventilation was used for 4 hours. In the operating room, lack of temperature and humidity control (steam, water, and suction supply) halted elective surgery until October 2. Ground and air transportation were limited by unsafe landing sites, impassable roads, and personnel exhaustion. Surgical planning for a major hurricane should include: 1) a fail-safe source of electrical power, 2) evacuation of as many critically ill patients as possible before the storm, 3) cancellation of all elective surgery, and 4) augmented ancillary service staffing with some, although limited, physician support.

  19. Neurotrophic tyrosine kinase polymorphism impacts white matter connections in patients with major depressive disorder.

    PubMed

    Murphy, Melissa L; Carballedo, Angela; Fagan, Andrew J; Morris, Derek; Fahey, Ciara; Meaney, James; Frodl, Thomas

    2012-10-15

    Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene and its receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) have been implicated in mood disorders. The aim of this study was to examine whether the NTRK2 and BDNF polymorphisms impact brain white matter connections in major depressive disorder and whether they may also have an interactive effect with environmental stress in the form of early life adversity. The study group comprised 45 depressed patients and 45 age- and gender-matched control subjects. High angular resolution diffusion images were obtained and analyzed using tract-based spatial statistics. Analysis of a single nucleotide polymorphism in the BDNF (rs6265/Valine66Methionine) and NTRK2 (rs11140714) genes was performed. An interactive effect was found between NTRK2 and depression diagnosis maximally affecting the cingulum. Depressed patients homozygous for the A allele of NTRK2 showed significantly reduced fractional anisotropy compared with depressed patients with at least one copy of the G allele or control subjects with either the A/A or G carrier genotypes in the left and right corona radiata, left uncinate fasciculus, left inferior fronto-occipital fasciculus, left cerebral peduncle, posterior thalamic radiation, and middle cerebral peduncle. Significantly smaller gray matter volume was seen in frontal lobe regions in patients homozygous for the A allele. Polymorphisms in NTRK2 gene increase risk of architectural changes in several brain regions involved in emotional regulation. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. The radiative impact of major volcanic eruptions on stratospheric water vapour

    NASA Astrophysics Data System (ADS)

    Löffler, Michael; Brinkop, Sabine; Jöckel, Patrick

    2016-04-01

    Volcanic eruptions can have significant impact on the earth's weather and climate system. Besides the subsequent tropospheric changes also the stratosphere is influenced by large eruptions. Here changes in stratospheric water vapour after the two major volcanic eruptions of El Chichón in Mexico in 1982 and Mount Pinatubo on the Philippines in 1991 are investigated with chemistry-climate model simulations. This study is based on two simulations with specified dynamics of the EMAC model, performed within the Earth System Chemistry integrated Modelling (ESCiMo) project, of which only one includes the volcanic forcing through prescribed aerosol optical properties. The results show a significant increase in stratospheric water vapour after the eruptions, resulting from increased heating rates and the subsequent changes in stratospheric and tropopause temperatures in the tropics. The tropical vertical advection and the South Asian summer monsoon are identified as important sources for the additional water vapour in the stratosphere. Additionally, volcanic influences on the tropospheric water vapour and ENSO are evident.

  1. [Prognostic factors in head and neck mucoepidermoid carcinoma].

    PubMed

    Villavicencio-Ayala, Beatriz; Reséndiz-Colosia, Jaime Alonso; Labastida-Almendaro, Sonia; Torres-Núñe, María Guadalupe; Peña-Torres, Leandro Miguel; Gallegos-Hernández, José Francisco

    2008-01-01

    In patients with mucoepidermoid carcinoma (MEC) originating in salivary glands, because of the relative rarity of these tumors and the remarkable variability in their biological behavior, opinions differ about appropriate classification, grading, and treatment. We undertook this study to analyze clinical and histological prognostic factors in a series of patients with MEC using univariate and multivariate survival analyses. We reviewed 47 patients with MEC treated at our institution from 1985 to 2000. Clinical, epidemiological, treatment and follow-up data were obtained from medical records. All cases were histologically reviewed. The influence of prognostic factors on 5- and 10-year disease-specific survival was analyzed using Kaplan-Meier actuarial method and log-rank test. Cox regression tests were used to analyze the impact of the prognostic factors on survival. Females represented 59.6% of the patients. The major salivary glands were affected in 74.5%. Overall survival at 5 and 10 years was 78.3% and 69.3%, respectively. Disease-free survival at 5 years was 73.9% and at 10 years was 67.5%. Multivariate survival analysis revealed that tumor size (T4) (p = 0.0008), regional metastasis (p = 0.000), high histological grade (p = 0.0002), perineural invasion (p = 0.000), positive margin (p = 0.000), necrosis (p = 0.005), and intracystic component <20% (p = 0.0002) were all correlated with a poor prognosis. Clinical stage and histological grade are the main prognostic factors in mucoepidermoid carcinoma. Nevertheless, our univariate and multivariate analyses showed that other clinical and histological prognostic factors are independent significant indicators.

  2. Prognostic impact of viral reactivations in acute myeloid leukemia patients undergoing allogeneic stem cell transplantation in first complete response

    PubMed Central

    Guenounou, Sarah; Borel, Cécile; Bérard, Emilie; Yon, Edwige; Fort, Marylise; Mengelle, Catherine; Bertoli, Sarah; Sarry, Audrey; Tavitian, Suzanne; Huguet, Françoise; Attal, Michel; Récher, Christian; Huynh, Anne

    2016-01-01

    Abstract Cytomegalovirus (CMV) serological status of donor and recipient as well as CMV reactivation have been associated with a lower risk of relapse in acute myeloid leukemia (AML) patients after allogeneic stem cell transplantation (alloSCT). Since immunosuppression following transplant allows resurgence of many other viruses, we retrospectively evaluated the impact of viral reactivations on relapse and survival in a cohort of 136 AML patients undergoing alloSCT in first remission from sibling (68%) or unrelated (32%) donors. Myeloablative and reduced-intensity conditioning regimen were given to 71 and 65 patients, respectively. Including CMV reactivations, at least 1 viral reactivation was recorded in 76 patients. Viral reactivations were associated with a lower risk of relapse (adjusted HR 0.14; 95% CI 0.07–0.30; P < 0.01), better disease-free survival (aHR 0.29; 95% CI 0.16–0.54; P < 0.01) but higher non relapse mortality. This translated into a better overall survival (aHR 0.44; 95%CI 0.25–0.77; P < 0.01) in patients who experienced viral reactivation. Thus, viral reactivations, including but not limited to CMV reactivation, are associated with a better outcome particularly with regard to the risk of relapse in AML patients undergoing alloSCT. New guidelines regarding the choice of donor according to the CMV serostatus are needed. PMID:27902595

  3. Socio-economic impacts of major floods in Italy from 1951 to 2003

    NASA Astrophysics Data System (ADS)

    Lastoria, B.; Simonetti, M. R.; Casaioli, M.; Mariani, S.; Monacelli, G.

    2006-03-01

    Meteorological and hydrological monitoring and modeling, with particular regard for extreme hydrological events, represent important activities carried out by the Hydrological and Inland Waters Service of the Italian Agency for Environmental Protection and Technical Services (APAT). Recently, a study on the socio-economic effects of floods was published in the Italian Environmental Data Yearbook by APAT. It is based on processed data related to the major floods (i.e., events with at least a casualty or that have generated economic damages higher than 0.001% of the Gross Domestic Product) striking Italy between 1951 and 2003. Information was gathered from technical reports and/or databases belonging to APAT, Italian Regional Environmental Agencies (ARPAs), central and local authorities, research institutions and newspaper reports. These data are collected in tables reporting the number of flood events and of casualties and the amount of financial resources required for environmental restoration and/or for risk mitigation purposes. For year 2003, when APAT has begun a systematic monitoring of flood events in Italy, data concerning rainfall, number of persons involved, evacuation and urgent measures introduced to face the event (laws and acts) are also included. In this way, it was possible to realize a new database, in which flood events that caused the declaration of the state of emergency have been collected. Because of the difficulties in finding sufficiently reliable data for the period before the II World War, the collection of historical data started from 1951. During this period, about 50% of the flood events examined have caused at least 5 victims each, and about 10% more than 100; these data highlight the considerable social impact of flood events and suggest the importance of creating an integrated database to collect information about flood events involving all Europe. These two databases (the historical and updating archives) could be useful for taking

  4. Validation of the sleep impact scale in patients with major depressive disorder and insomnia.

    PubMed

    Lasch, Kathryn; Joish, Vijay N; Zhu, Yueping; Rosa, Kathleen; Qiu, Chunfu; Crawford, Bruce

    2009-07-01

    Chronic insomnia and depression are often associated. Measuring the impact on quality of life associated with changes in sleep in co-treatment of insomnia and depression requires a valid and reliable patient reported outcome (PRO) instrument. This study aimed to assess the validity of the Sleep Impact Scale (SIS), a sleep-specific PRO instrument, in a population comorbid with Major Depressive Disorder (MDD) and insomnia to support its use in clinical or clinical trial applications. Data from 379 subjects enrolled in a 27 week US, multi-center, phase IV, randomized, double-blind, parallel group, placebo-controlled trial of zolpidem tartrate extended-release taken in combination with escitalopram vs. placebo combined with escitalopram were pooled across treatment groups. Results from multi-trait analyses, tests of internal consistency and test-retest reliability, concurrent validity, known-groups validity, responsiveness, and thresholds for minimal important difference (MID) were examined. Mean baseline scores on the SIS ranged from 22.85 (+/-13.41) on Satisfaction with Sleep to 43.49 (+/-21.12) on Mental Fatigue, reflecting impairments due to sleep problems. The SIS was found to be internally consistent (alpha > or = 0.70 for all domains) and have good construct validity. The item-domain correlations were > or = 0.52 with no instance of an item correlating more highly with a domain other than its own. There were some floor and no ceiling effects. The test-retest reliability of the SIS domains ranged between 0.68 and 0.83. Clinical validity assessed through known groups methods was supported. The SIS was responsive to changes on all domains. Preliminary estimates of minimum important difference (MID) were obtained to interpret changes in SIS domains. Limitations include the need for further qualitative research on content validity and the lack of a patient global assessment of change. This study yielded adequate evidence of the validity of the SIS for use in clinical

  5. The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small cell lung cancer patients treated with definitive concurrent chemo-radiotherapy

    PubMed Central

    Oh, Dongryul; Ahn, Yong Chan; Park, Hee Chul; Lim, Do Hoon; Noh, Jae Myoung; Cho, Won Kyung; Pyo, Hongryull

    2017-01-01

    Background This study aimed to investigate the prognostic impact of supraclavicular lymph node (SCN) metastasis in patients who were treated with definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer (NSCLC). Results The 2- and 5-year overall survival (OS) rates were 57.3% and 35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN metastasis, respectively. The median OS was 34 months in both groups. There was no significant difference in OS between the two groups (p = 0.679). The 2- and 5-year progression-free survival (PFS) rates were 24.1% and 12.6% in patients without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis, respectively. Patients without SCN metastasis had slightly longer median PFS (10 months vs. 8 months), but the difference was not statistically significant (p = 0.223). In multivariate analysis, SCN metastasis was not a significant factor for OS (p = 0.391) and PFS (p = 0.149). Materials and Methods This retrospective analysis included 204 consecutive patients who were treated with chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients (58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease: mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one (1.2%). The patients were divided into two groups according to SCN metastasis. Conclusions SCN metastasis does not compromise treatment outcomes compared to other mediastinal metastasis in the setting of definitive chemoradiotherapy. PMID:28415687

  6. The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small cell lung cancer patients treated with definitive concurrent chemo-radiotherapy.

    PubMed

    Oh, Dongryul; Ahn, Yong Chan; Park, Hee Chul; Lim, Do Hoon; Noh, Jae Myoung; Cho, Won Kyung; Pyo, Hongryull

    2017-05-30

    This study aimed to investigate the prognostic impact of supraclavicular lymph node (SCN) metastasis in patients who were treated with definitive chemoradiotherapy for N3-IIIB stage non-small cell lung cancer (NSCLC). The 2- and 5-year overall survival (OS) rates were 57.3% and 35.7% in patients without SCN metastasis and 56.4% and 26.7% in patients with SCN metastasis, respectively. The median OS was 34 months in both groups. There was no significant difference in OS between the two groups (p = 0.679). The 2- and 5-year progression-free survival (PFS) rates were 24.1% and 12.6% in patients without SCN metastasis and 18.0% and 16.0% in patients with SCN metastasis, respectively. Patients without SCN metastasis had slightly longer median PFS (10 months vs. 8 months), but the difference was not statistically significant (p = 0.223). In multivariate analysis, SCN metastasis was not a significant factor for OS (p = 0.391) and PFS (p = 0.149). This retrospective analysis included 204 consecutive patients who were treated with chemoradiotherapy for N3-IIIB stage NSCLC between May 2003 and December 2012. A median RT dose of 66 Gy was administered over 6.5 weeks. Of these, 119 patients (58.3%) had SCN metastasis and 85 (41.7%) had another type of N3 disease: mediastinal N3 nodes in 84 patients (98.8%) and contralateral hilar node in one (1.2%). The patients were divided into two groups according to SCN metastasis. SCN metastasis does not compromise treatment outcomes compared to other mediastinal metastasis in the setting of definitive chemoradiotherapy.

  7. Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure - Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers.

    PubMed

    Miura, Masanobu; Sugimura, Koichiro; Sakata, Yasuhiko; Miyata, Satoshi; Tadaki, Soichiro; Yamauchi, Takeshi; Onose, Takeo; Tsuji, Kanako; Abe, Ruri; Oikawa, Takuya; Kasahara, Shintaro; Nochioka, Kotaro; Takahashi, Jun; Shimokawa, Hiroaki

    2016-05-25

    It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics. Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

  8. Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

    PubMed Central

    2013-01-01

    Introduction Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. Methods Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up. Results Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. Conclusions A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases. PMID:23302110

  9. Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy

    PubMed Central

    Aoki, Masahiko; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Fujioka, Ichitaro; Tanaka, Mitsuki; Ono, Shuichi; Takai, Yoshihiro

    2016-01-01

    The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45–60 Gy in 5–10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5–54.5 months). The median value of the average iodine density was 1.86 mg/cm3 (range, 0.40–9.27 mg/cm3). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors. PMID:26826198

  10. Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy.

    PubMed

    Aoki, Masahiko; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Fujioka, Ichitaro; Tanaka, Mitsuki; Ono, Shuichi; Takai, Yoshihiro

    2016-07-01

    The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5-10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.

  11. Oncologic outcomes and prognostic impact of urothelial recurrences in patients undergoing segmental and total ureterectomy for upper tract urothelial carcinoma

    PubMed Central

    Pedrosa, Jose A.; Masterson, Timothy A.; Rice, Kevin R.; Kaimakliotis, Hristos Z.; Monn, M. Francesca; Bihrle, Richard; Koch, Michael O.; Boris, Ronald S.

    2015-01-01

    Introduction: We evaluated the impact of urothelial recurrences in a cohort of patients undergoing segmental (SU) and total ureterectomy (TU) as an alternative to nephroureterectomy (NU) for upper tract urothelial carcinoma. Methods: Between 1999 and 2012, patients who underwent SU, TU and NU for treatment of upper tract urothelial carcinoma were evaluated. Demographic, surgical, pathologic and oncologic data were collected. Recurrence-free (RFS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier and multivariable Cox methods. Results: A total 141 patients were evaluated, 35 underwent SU, 10 TU and 96 NU. Patients who underwent TU were more likely to have bilateral disease (p < 0.01), solitary kidney (p < 0.01), and multifocal disease (p = 0.01). Organ-confined (p < 0.01) and low-grade disease (p < 0.01) were more common in the TU and SU groups compared with NU. At a median follow-up of 56.9 months (range: 0.2–181.1) disease relapse occurred in 88 (55.3%) patients. Localized recurrence occurred in 31.1% of SU/TU group compared to 27.1% (p = 0.62) of the NU group. Neither total nor segmental ureterectomy demonstrated significantly worse RFS (p = 0.26 and p = 0.81), CSS (p = 0.96 and p = 0.52) or overall survival (p = 0.59 and p = 0.55) compared with complete NU. Localized urothelial recurrence did not confer increased risk of cancer-specific (p = 0.73) or overall mortality (p = 0.39). The paper’s most important limitations include its retrospective nature and its relatively small number of patients. Conclusion: No significant survival differences were demonstrated between surgical approaches for upper tract urothelial cancer. Localized urothelial recurrence after surgical treatment for upper tract urothelial cancer does not affect mortality in this population. TU with ileal-substitution may provide an alternative option for patients with extensive ureteral disease and poor renal function. PMID:26085878

  12. Prognostic impact of human leukocyte antigen class I expression and association of platinum resistance with immunologic profiles in epithelial ovarian cancer.

    PubMed

    Mariya, Tasuku; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Asano, Takuya; Kuroda, Takafumi; Yasuda, Kazuyo; Mizuuchi, Masahito; Sonoda, Tomoko; Saito, Tsuyoshi; Sato, Noriyuki

    2014-12-01

    Epithelial ovarian cancer (EOC) is one of the most deadly carcinomas in females. Immune systems can recognize EOCs; however, a defect of human leukocyte antigen (HLA) class I expression is known to be a major mechanism for escape from immune systems, resulting in poor prognosis. The purpose of this study is to identify novel correlations between immunologic responses and other clinical factors. We investigated the expression of immunologic components in 122 cases of EOCs for which surgical operations were performed between 2001 and 2011. We immunohistochemically stained EOC specimens using an anti-pan HLA class I monoclonal antibody (EMR8-5) and anti-CD3, -CD4, and -CD8 antibodies, and we analyzed correlations between immunologic parameters and clinical factors. In multivariate analysis that used the Cox proportional hazards model, independent prognostic factors for overall survival in advanced EOCs included low expression level of HLA class I [risk ratio (RR), 1.97; 95% confidence interval (CI), 1.01-3.83; P = 0.046] and loss of intraepithelial cytotoxic T lymphocyte (CTL) infiltration (RR, 2.11; 95% CI, 1.06-4.20; P = 0.033). Interestingly, almost all platinum-resistant cases showed a significantly low rate of intraepithelial CTL infiltration in the χ(2) test (positive vs. negative: 9.0% vs. 97.7%; P < 0.001). Results from a logistic regression model revealed that low CTL infiltration rate was an independent factor of platinum resistance in multivariate analysis (OR, 3.77; 95% CI, 1.08-13.12; P = 0.037). Platinum-resistant EOCs show poor immunologic responses. The immune escape system of EOCs may be one of the mechanisms of platinum resistance. ©2014 American Association for Cancer Research.

  13. Impact of Climate Change on Five Major Crop Fungal Diseases: Building Climatic Indicators of Infection Risk

    NASA Astrophysics Data System (ADS)

    Launay, M.; Caubel, J.; Bourgeois, G.; Huard, F.; Garcia de Cortazar-Atauri, I.

    2013-12-01

    The climate change will modify the severity and occurrence of fungal crop diseases, as the bioclimatic niches of pathogens will shift according to temperature and rainfall patterns evolution. Therefore it becomes necessary to integrate fungal disease pressure assessment into evaluation tools of crop suitability at the regional level. The aim of this study was to build two climatic indicators, the Average Infection Efficiency (AIE) and the Number of Infection Days (NID), quantifying the potential effect of climate on infection intensity and occurrence. A simple and continuous function was developed to calculate them, which is easy to parameterize from experimental measurements, usable on large spatial scales and adaptable to various pathogens. The evolution of those climatic indicators was then studied for five major fungal crop diseases in Northern France, the phoma of oilseed rape, the potato late blight, the downy mildew of grape, the leaf rust of wheat and the net blotch of barley. These indicators were applied on a multisite analysis in Northern France. They were calculated during the crop cycle when the host plant is able to be infected, over the period between 1970 and 2100 for the balanced scenario of climate change A1B. In late spring and summer, higher temperatures combined with lower humidity reduced the risk of infection of potato late blight and downy mildew of grape. In autumn and spring the balance between warmer temperatures and lower humidity determined the risk of infection on oilseed rape and cereals: increased risk in late autumn and early spring, and decreased risk in early autumn and mid-spring when low humidity becomes limiting. This statement highlighted the need for using between year scale for a relevant analysis of climate change impact on infection risk. The indicators we developed are thus useful for land management at regional scale and medium term, in particular for stakeholders who need decision support tools through which they could

  14. Epidemiology and Impact of Knee Injuries in Major and Minor League Baseball Players.

    PubMed

    Dahm, Diane L; Curriero, Frank C; Camp, Christopher L; Brophy, Robert H; Leo, Tony; Meister, Keith; Paletta, George A; Steubs, John A; Mandelbaum, Bert R; Pollack, Keshia M

    2016-01-01

    Few studies have explored the frequency and impact of lower extremity injuries, such as those to the knee, among professional baseball players. The purpose of this study was to detail the epidemiology of knee injuries in Major League Baseball (MLB) and Minor League Baseball (MiLB) players during the 2011-2014 seasons. It was hypothesized that knee injuries are a common occurrence in these athletes, and represent a significant source of time away from play. The MLB Health and Injury Tracking System database was searched to identify all patients diagnosed with knee injuries during the 2011-2014 seasons. All injuries that occurred during the preseason, regular season, and postseason that resulted in time away from play were included. Injury data analyzed included total number of knee injuries, specific diagnoses, injury mechanisms, locations, player positions, and time lost. Descriptive statistics were conducted and injury rates per athlete-exposures were calculated. During the 2011-2014 seasons, a total of 2171 knee injuries occurred in MLB and MiLB players, representing 6.5% of all injuries in professional baseball. The knee injury rate across both the MLB and MiLB was 1.2 per 1000 athlete-exposures. The mean number of days missed per injury across both leagues was 16.2 with a total of 30,449 days of missed play amongst all athletes over the 4 seasons. Injuries to the knee were the fifth most common cause of missed time in all of baseball, and the fourth most common reason for missed games in the MLB alone. Approximately 12% of all injuries required surgical intervention. The most common mechanism of injury was noncontact (44%), and base runners were injured more frequently than any other position (24%). The infield (30%) and home plate (23%) were the most common locations in which injuries occurred. These data can be utilized for targeted injury prevention initiatives.

  15. Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

    PubMed Central

    Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C.; Sun, Ruifan; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Wang, Jinfeng; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Pham, Lan V.; Medeiros, L. Jeffrey; Young, Ken H.

    2015-01-01

    Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications. PMID:26324762

  16. Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma.

    PubMed

    Li, Ling; Xu-Monette, Zijun Y; Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C; Sun, Ruifang; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Møller, Michael B; Wang, Jinfen; Parsons, Ben M; Winter, Jane N; Piris, Miguel A; Pham, Lan V; Medeiros, L Jeffrey; Young, Ken H

    2015-09-15

    Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2- activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications.

  17. Distributed Prognostic Health Management with Gaussian Process Regression

    NASA Technical Reports Server (NTRS)

    Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

    2010-01-01

    Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

  18. Failure event types and prognostic factors after node-positive breast cancer in patients treated by adjuvant chemotherapy: impact on follow-up.

    PubMed

    Filleron, Thomas; Kramar, Andrew; Dalenc, Florence; Spielmann, Marc; Fumoleau, Pierre; Kerbrat, Pierre; Martin, Anne-Laure; Roché, Henri

    2012-06-01

    The role of post-therapeutic follow-up for breast cancer patients (pts) is open to debate. The aim of this study was to identify prognostic factors associated with the type of first event. Data of 2,820 pts included in three adjuvant trials for node-positive breast cancer were used. Competing risk methodology was used to identify prognostic factors associated with time to first failure according to type of event. After a median follow-up of 53 months, 732 pts had disease-related events (114 locoregional, 58 contralateral, and 560 distant metastasis). The prognostic factors associated with high locoregional recurrence were young age, number of positive lymph nodes and grade III. In multivariate analysis, the type of first event influenced post-relapse survival. Nottingham Prognostic Index identified three groups of pts at different risk of relapse. Early relapse is rare in the first year after surgery and is associated with more aggressive disease. Using the Nottingham Prognostic Index, it is possible to identify pts at lower risks of relapse for whom it seems reasonable to limit the frequency of routine follow-up during the first years. For pts at higher risk of locoregional recurrence, regular follow-up should be maintained in order to detect potential curative events.

  19. Analysis of the impacts of the President's tax proposal on major sectors of the energy industry

    SciTech Connect

    Not Available

    1985-08-01

    Purpose of this study is to assess the impact of the President's tax proposal on the energy sector. The study consists of two parts. The first part reported in this document, specifically addresses the impacts of the President's tax proposal on the oil and gas, coal, and electric utility sectors of the energy industry. Impacts were examined at both the project and corporate levels. The study focuses on proposed changes in corporate income taxation.

  20. Prognostics for Microgrid Components

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  1. Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D.

    PubMed

    Simbolo, Michele; Mafficini, Andrea; Sikora, Katarzyna O; Fassan, Matteo; Barbi, Stefano; Corbo, Vincenzo; Mastracci, Luca; Rusev, Borislav; Grillo, Federica; Vicentini, Caterina; Ferrara, Roberto; Pilotto, Sara; Davini, Federico; Pelosi, Giuseppe; Lawlor, Rita T; Chilosi, Marco; Tortora, Giampaolo; Bria, Emilio; Fontanini, Gabriella; Volante, Marco; Scarpa, Aldo

    2017-03-01

    Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours (LNETs) comprising the four World Health Organization classification categories: 53 typical carcinoid (TCs), 35 atypical carcinoid (ACs), 27 large-cell neuroendocrine carcinomas, and 33 small-cell lung carcinomas. A discovery screen was conducted on 46 samples by the use of whole-exome sequencing and high-coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes from both the discovery screen and current literature were verified in the 46 cases of the discovery screen, and validated on additional 102 LNETs by targeted NGS; their prevalence was then evaluated on the whole series. Thirteen of these 88 genes were also evaluated for copy number alterations (CNAs). Carcinoids and carcinomas shared most of the altered genes but with different prevalence rates. When mutations and copy number changes were combined, MEN1 alterations were almost exclusive to carcinoids, whereas alterations of TP53 and RB1 cell cycle regulation genes and PI3K/AKT/mTOR pathway genes were significantly enriched in carcinomas. Conversely, mutations in chromatin-remodelling genes, including those encoding histone modifiers and members of SWI-SNF complexes, were found at similar rates in carcinoids (45.5%) and carcinomas (55.0%), suggesting a major role in LNET pathogenesis. One AC and one TC showed a hypermutated profile associated with a POLQ damaging mutation. There were fewer CNAs in carcinoids than in carcinomas; however ACs showed a hybrid pattern, whereby gains of TERT, SDHA, RICTOR, PIK3CA, MYCL and SRC were found at rates similar to those in carcinomas, whereas the MEN1 loss rate mirrored that of TCs. Multivariate survival analysis revealed RB1 mutation (p = 0.0005) and TERT copy gain (p = 0.016) as independent predictors of poorer prognosis. MEN1 mutation was associated with poor prognosis in AC (p = 0.0045), whereas KMT2D mutation correlated with longer survival in SCLC

  2. Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

    PubMed

    Chen, Marcus Y; Rochitte, Carlos E; Arbab-Zadeh, Armin; Dewey, Marc; George, Richard T; Miller, Julie M; Niinuma, Hiroyuki; Yoshioka, Kunihiro; Kitagawa, Kakuya; Sakuma, Hajime; Laham, Roger; Vavere, Andrea L; Cerci, Rodrigo J; Mehra, Vishal C; Nomura, Cesar; Kofoed, Klaus F; Jinzaki, Masahiro; Kuribayashi, Sachio; Scholte, Arthur J; Laule, Michael; Tan, Swee Yaw; Hoe, John; Paul, Narinder; Rybicki, Frank J; Brinker, Jeffrey A; Arai, Andrew E; Matheson, Matthew B; Cox, Christopher; Clouse, Melvin E; Di Carli, Marcelo F; Lima, João A C

    2017-07-01

    Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not

  3. Valuing mortality impacts of smoke exposure from major southern California wildfires

    Treesearch

    Ikuho Kochi; Patricia A. Champ; John B. Loomis; Geoffrey H. Donovan

    2012-01-01

    While the mortality impacts of urban air pollution have been well addressed in the literature, very little is known about the mortality impacts and associated social cost from wildfire-smoke exposure (Kochi et al., 2010; U.S. Environmental Protection Agency, 2004). In an attempt to address this knowledge gap, we estimate the social cost associated with excess mortality...

  4. The Impact of Employing Brainstorming Strategy on Improving Writing Performance of English Major Students at Balqa Applied University in Jordan

    ERIC Educational Resources Information Center

    Amoush, Kholoud Hussein

    2015-01-01

    The study aimed at identifying the impact of employing brainstorming strategy on improving writing performance of English Major Students at Balqa Applied University in Jordan. The sample of the study which consisted of 80 male and female university students was distributed into two groups; experimental (taught by brainstorming strategy) and…

  5. A review of major factors influencing plant responses to recreation impacts

    NASA Astrophysics Data System (ADS)

    Kuss, Fred R.

    1986-09-01

    This article reviews some of the more important factors found to influence the susceptibility of plants to trampling impacts associated with recreational use of natural areas. A three-way interaction mediates plant responses to impacts: plant x environment x stress level(s). Plant responses vary in part according to the genetic constitution of the plant, life and growth form, the adaptive flexibility of the plant, and anatomical differences inherent to growth habit and morphology. Other factors that influence plant sensitivities to impacts are the habitat environments in which plants grow, since a number of conditions such as moisture excesses or deficiencies, nitrogen or oxygen starvation, late frosts, etc., cause physiological injury and may increase plant sensitivity to impacts. Among the environmental factors that may increase or lessen plant sensitivities to impacts are soil moisture levels, canopy density, elevation, aspect, microclimate, soil drainage, texture, fertility and productivity. Seasonal influences also bear consideration since environmental changes and phonological and physiological events are mediated by time of year. Stresses are caused by both direct and indirect forms of impact and vary according to season of use, frequency and amount of use, and the type of activity. These interactions are further complicated by evidence that inter- and intraspecific competition, antagonism, and commensalism may influence differences in the sensitivity of plant communities to impacts.

  6. To Stay or Leave: Factors That Impact Undergraduate Women's Persistence in Science Majors

    ERIC Educational Resources Information Center

    Gayles, Joy Gaston; Ampaw, Frim

    2016-01-01

    This study examined factors that influenced undergraduates' decision to enter, leave, or stay within science majors. In addition, we sought to understand if such decisions differed by gender and type of science major. Using Beginning Postsecondary Students (BPS) longitudinal survey data, we found that women were less likely to select a science…

  7. To Stay or Leave: Factors That Impact Undergraduate Women's Persistence in Science Majors

    ERIC Educational Resources Information Center

    Gayles, Joy Gaston; Ampaw, Frim

    2016-01-01

    This study examined factors that influenced undergraduates' decision to enter, leave, or stay within science majors. In addition, we sought to understand if such decisions differed by gender and type of science major. Using Beginning Postsecondary Students (BPS) longitudinal survey data, we found that women were less likely to select a science…

  8. When Music Goes up in Flames: The Impact of Advising on Music Major Burnout

    ERIC Educational Resources Information Center

    Teasley, Marilee L.; Buchanan, Erin M.

    2016-01-01

    Bringing their personalities and experiences to their relationships with students, academic advisors engage with a diverse population of students every semester. However, they meet with many students who display cynicism and exhaustion, known as burnout, toward their major. Over 300 music majors across the country were surveyed on their perceived…

  9. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204

  10. Prognostic impact of 18F-FDG PET/CT staging and of pathological response to neoadjuvant chemotherapy in triple-negative breast cancer.

    PubMed

    Groheux, D; Giacchetti, S; Delord, M; de Roquancourt, A; Merlet, P; Hamy, A S; Espié, M; Hindié, E

    2015-03-01

    Mortality is high in patients with locally advanced triple-negative breast cancer (TNBC), especially in those with residual tumour after neoadjuvant chemotherapy (NAC). The aim of this study was to determine if pretreatment (18)F-FDG PET/CT staging and pathological findings after NAC could together allow stratification of patients into prognostic groups. Initial staging with (18)F-FDG PET/CT was performed prospectively in 85 consecutive patients with stage II/III TNBC. Correlations between PET findings and disease-specific survival (DSS) were examined. In patients without distant metastases on PET staging, the impact of pathological response to NAC on DSS was examined. Patterns of recurrence were also analysed. (18)F-DG PET/CT revealed distant metastases in 11 of 85 patients (12.9 %). Among 74 M0 patients, 23 (31.1 %) showed a pathological complete response (pCR) at surgery, while 51 had residual invasive disease (no pCR). DSS differed considerably among the three groups of patients (log-rank P < .001): among patients with occult metastases on baseline PET/CT, 2-year DSS was 18.2 %, and among patients without initial metastases on PET/CT, 5-year DSS was 61.3 % in patients without pCR after NAC and 95.2 % in those with pCR. Of the 51 patients who did not achieve pCR, 21 relapsed (17 developed distant metastases). The sites of distant recurrence were: lung/pleura (nine patients), brain (eight patients), liver (six patients), distant lymph nodes (six patients) and bone (five patients). In patients with clinical stage II/III TNBC, (18)F-FDG PET/CT findings at initial staging and pathological response at the end of NAC allow three groups of patients with quite different prognoses to be defined. Extraskeletal recurrences predominated. Specific follow-up strategies in patients with TNBC who do not achieve pCR deserve investigation.

  11. Incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with neuromuscular scoliosis: A STROBE-compliant retrospective observational analysis.

    PubMed

    Jia, Rui; Li, Na; Xu, Bi-Yun; Zhang, Wei; Gu, Xiao-Ping; Ma, Zheng-Liang

    2017-03-01

    Factors influencing massive blood loss for neuromuscular scoliosis (NMS) patients.Despite advances in surgical and anesthetic techniques, scoliosis surgery is still associated with intraoperative massive blood loss, which can result in postoperative mortality and morbidity. The aim of this study was to assess the incidence, influencing factors, and prognostic impact of intraoperative massive blood loss in adolescents with NMS.A retrospective review of adolescents who underwent posterior spinal instrumentation and fusion for NMS was performed. Perioperative variables and data were recorded. Massive blood loss was defined as an estimated blood loss that exceeds 30% of total blood volume.We obtained data for 114 patients, of whom 63 (55%) had intraoperative massive blood loss. Compared with those without, patients with massive blood loss were more likely to be older, have lower body mass indexes (BMIs), larger Cobb angles, more fused levels, more osteotomy procedures, and prolonged duration of operation. Logistic regression analysis identified the number of fused levels to be more than 12 (P = 0.003, odds ratio = 6.614, 95% confidence interval [CI]: 1.891-23.131), BMI lower than 16.8 kg/m (P = 0.025, odds ratio = 3.293, 95% CI: 1.159-9.357), age greater than 15 years (P = 0.014, odds ratio = 3.505, 95% CI: 1.259-9.761), and duration of operation longer than 4.4 hours (P = 0.016, odds ratio = 3.746, 95% CI: 1.428-9.822) as influencing factors. Patients with massive blood loss are associated with more intraoperative colloids infusion and blood transfusions (red blood cell and fresh frozen plasma), as well as postoperative drainage volume.In adolescents with NMS who underwent posterior spinal instrumentation and fusion operations, intraoperative massive blood loss is common. The number of fused levels, BMI, age, and duration of operation are factors influencing intraoperative massive blood loss.

  12. Renal dysfunction in STEMI-patients undergoing primary angioplasty: higher prevalence but equal prognostic impact in female patients; an observational cohort study from the Belgian STEMI registry.

    PubMed

    Gevaert, Sofie A; De Bacquer, Dirk; Evrard, Patrick; Renard, Marc; Beauloye, Christophe; Coussement, Patrick; De Raedt, Herbert; Sinnaeve, Peter R; Claeys, Marc J

    2013-03-18

    Mortality in female patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty (pPCI) is higher than in men. We examined gender differences in the prevalence and prognostic performance of renal dysfunction at admission in this setting. A multicenter retrospective sub-analysis of the Belgian STEMI-registry identified 1,638 patients (20.6% women, 79.4% men) treated with pPCI in 8 tertiary care hospitals (January 2007-February 2011). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. Main outcome measure was in-hospital mortality. More women than men suffered from renal dysfunction at admission (42.3% vs. 25.3%, p < 0.001). Mortality in women was doubled as compared to men (9.5 vs. 4.7%, OR (95% CI) = 2.12 (1.36-3.32), p<0.001). In-hospital mortality for men and women with vs. without renal dysfunction was much higher (10.7 and 15.3 vs. 2.3 and 2.4%, p < 0.001). In a multivariable regression analysis, adjusting for age, gender, peripheral artery disease (PAD), coronary artery disease (CAD), hypertension, diabetes and low body weight (<67 kg), female gender was associated with renal dysfunction at admission (OR (95% CI) 1.65 (1.20-2.25), p = 0.002). In a multivariable model including TIMI risk score and renal dysfunction, renal dysfunction was an independent predictor of in-hospital mortality in both men (OR (95% CI) = 2.39 (1.27-4.51), p = 0.007) and women (OR (95% CI) = 4.03 (1.26-12.92), p = 0.02), with a comparable impact for men and women (p for interaction = 0.69). Female gender was independently associated with renal dysfunction at admission in pPCI treated patients. Renal dysfunction was equally associated with higher in-hospital mortality in both men and women.

  13. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

    PubMed

    Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

    2017-04-01

    The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

  14. The influence of recent major crater impacts on the surrounding surfaces of (21) Lutetia

    NASA Astrophysics Data System (ADS)

    Jutzi, M.; Thomas, N.; Benz, W.; El Maarry, M. R.; Jorda, L.; Kührt, E.; Preusker, F.

    2013-09-01

    We present 3-D simulations of impacts into Asteroid 21 Lutetia, the subject of a fly-by by the European Space Agency’s Rosetta mission to Comet 67P/Churyumov-Gerasimenko. Using a 3-D shape model of the asteroid, impacts of sizes sufficient to reproduce the observed craters in Lutetia’s North Polar Crater Cluster (NPCC) as observed by the OSIRIS experiment have been simulated using the Smoothed Particle Hydrodynamics technique. The asteroid itself has been modelled both as a homogeneous body and as a body with an iron core. Crater erasure in the vicinity of the NPCC has been observed by OSIRIS. The results show that this erasure has most probably been caused by ejecta deposition following the impact of a 2.3 km diameter projectile impacting at a velocity of 5 km s-1 (or an impact with similar energy). This would produce a crater of roughly 34 km in diameter comparable to the largest (and oldest) member of the NPCC. Erasure of craters via the shock associated with such an impact is shown to be less significant and does not reproduce the observed spatial distribution of erased craters or “ghost” craters. Time series of the surface velocity fields resulting from the simulated impacts are also presented. It is suggested that the surface velocity field and velocity shear may play a role in the generation of lineaments. Our model calculations show that the velocity field lines around 50 s after impact exhibit a reasonable qualitative correlation with the orientation of lineaments observed on the entire visible surface of Lutetia. It is also shown that incorporation of a core of 25-30 km in diameter does not modify the velocity field evolution with time and, as such, the presence or otherwise of such a core cannot be inferred from lineament observations if this concept for their formation is valid.

  15. Analysis of Chinese emissions trends of major halocarbons in monitoring the impacts of the Montreal Protocol

    NASA Astrophysics Data System (ADS)

    Li, S.; Park, S.; Park, M.; Kim, J.; Muhle, J.; Fang, X.; Stohl, A.; Weiss, R. F.; Kim, K.

    2013-12-01

    In this study we estimate the emission rates of anthropogenic halocarbons, which include CFC-11, CFC-12, HCFC-22, HCFC-141b, HCFC-142b, HFC-23, HFC-134a, HFC-32, HFC-125 and HFC-152a for China during the period of 2008 and 2012 using an interspecies correlation method (Kim et al., 2010; Li et al., 2011), which is a unique 'top-down' approach using in situ high-precision measurements at Gosan, a remote station on Jeju Island, Korea. Mixing ratios of ambient halocarbons have been measured every two hours using a cryogenic pre-concentration system coupled with gas chromatograph and mass selective detector (GC-MSD) as part of the Advanced Global Atmospheric Gases Experiment network. We first separated air-mass segments originating from China using a back-trajectory analysis to identify Chinese emission from the observations, and found that the mixing ratios of most of compounds presented significant correlations against those of HCFC-22. Based on the correlations, we analyzed emission strengths of individual compounds, which correspond to their slopes against HCFC-22 since the slope can be a useful proxy to demonstrate their emission trends with an assumption of relatively constant emission of HCFC-22 during the analysis period. The analysis showed about 14% increase in the emissions strengths of CFCs (mainly due to CFC-12) between 2008 and 2012 in China. Interestingly, HCFC-141b and HCFC-142b that are commonly known to be used for foam blowing agents revealed opposite trends in their emission strengths: ca. 48% increase of HCFC-141b versus ca. 22% decrease of HCFC-142b, suggesting the possibility of other major sources in case of China. The emission strengths of HFCs have been increasing due to significant emissions of HFC-32, HFC-125 and HFC-134a during the analysis period. However, HFC-23 which is a well-known byproduct of HCFC-22 production processes, showed decrease by about 22% in the emission strength. Reduction in HFC-23 emissions is most likely due to the

  16. Toward IVHM Prognostics

    NASA Technical Reports Server (NTRS)

    Walsh, Kevin; Venti, Mike

    2007-01-01

    This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

  17. Prognostic impact of history of follicular lymphoma, induction regimen and stem cell transplant in patients with MYC/BCL2 double hit lymphoma.

    PubMed

    Li, Shaoying; Saksena, Annapurna; Desai, Parth; Xu, Jie; Zuo, Zhuang; Lin, Pei; Tang, Guilin; Yin, C Cameron; Seegmiller, Adam; Jorgensen, Jeffrey L; Miranda, Roberto N; Reddy, Nishitha M; Bueso-Ramos, Carlos; Medeiros, L Jeffrey

    2016-06-21

    MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma. Patients received induction chemotherapy regimens including 61 R-CHOP, 31 R-EPOCH, 29 R-Hyper-CVAD, and 23 other regimens. Thirty-nine patients received a stem cell transplant (SCT) including 31 autologous and 8 allogeneic. Sixty-two patients achieved complete remission (CR) after induction chemotherapy. Median overall survival (OS) was 19 months. Clinicopathologic features were similar between patients with de novo tumors versus those with a history of FL (P > 0.05). Using multivariate analysis, achieving CR, undergoing SCT, stage and the International Prognostic Index were independent prognostic factors for OS. Stem cell transplantion was associated with improved OS in patients who failed to achieve CR, but not in patients who achieved CR after induction chemotherapy. In conclusion, patients with MYC/BCL2 DHL who present with de novo disease and patients with a history of FL have a similarly poor prognosis. Achievement of CR, regardless of the induction chemotherapy regimen used, is the most important independent prognostic factor. Patients who do not achieve CR after induction chemotherapy may benefit from SCT.

  18. Prognostic impact of history of follicular lymphoma, induction regimen and stem cell transplant in patients with MYC/BCL2 double hit lymphoma

    PubMed Central

    Li, Shaoying; Saksena, Annapurna; Desai, Parth; Xu, Jie; Zuo, Zhuang; Lin, Pei; Tang, Guilin; Yin, C. Cameron; Seegmiller, Adam; Jorgensen, Jeffrey L.; Miranda, Roberto N.; Reddy, Nishitha M; Bueso-Ramos, Carlos; Medeiros, L. Jeffrey

    2016-01-01

    MYC/BCL2 double hit lymphoma (DHL) has been the subject of many studies; however, no study has systemically compared the clinicopathologic features and prognostic factors between patients with de novo disease versus those with a history of follicular lymphoma (FL). In addition, the prognostic importance of several other issues remains controversial in these patients. In this retrospective study, we assess 157 patients with MYC/BCL2 DHL including 108 patients with de novo disease and 49 patients with a history of FL or rarely other types of low-grade B-cell lymphoma. Patients received induction chemotherapy regimens including 61 R-CHOP, 31 R-EPOCH, 29 R-Hyper-CVAD, and 23 other regimens. Thirty-nine patients received a stem cell transplant (SCT) including 31 autologous and 8 allogeneic. Sixty-two patients achieved complete remission (CR) after induction chemotherapy. Median overall survival (OS) was 19 months. Clinicopathologic features were similar between patients with de novo tumors versus those with a history of FL (P > 0.05). Using multivariate analysis, achieving CR, undergoing SCT, stage and the International Prognostic Index were independent prognostic factors for OS. Stem cell transplantion was associated with improved OS in patients who failed to achieve CR, but not in patients who achieved CR after induction chemotherapy. In conclusion, patients with MYC/BCL2 DHL who present with de novo disease and patients with a history of FL have a similarly poor prognosis. Achievement of CR, regardless of the induction chemotherapy regimen used, is the most important independent prognostic factor. Patients who do not achieve CR after induction chemotherapy may benefit from SCT. PMID:27203548

  19. Towards standardised evaluative measurement of nature impacts: two spatial planning case studies for major Dutch lakes.

    PubMed

    van Puijenbroek, P J T M; Sijtsma, F J; Wortelboer, F G; Ligtvoet, W; Maarse, M

    2015-02-01

    In the assessment of complex spatial planning projects, the ecological impacts and socio-economic impacts are fundamental to the evaluation. The measurements of ecological impacts of spatial plans have to be integrated in a standardised way. In the present paper, we analyse two Dutch case studies and apply the standardised Threat-Weighted Ecological Quality Area measurement. This measurement is developed to evaluate projects with terrestrial impacts but has not yet been applied for water evaluations. We aim to show how the use of a common measurement tool incorporates both ecological quality and degree of threat on criteria in the EU Water Framework Directive and Nature 2000. The measurements discussed here derive from two cases of cost-benefit analysis: The first case is the Markermeer, the second largest lake of The Netherlands, and a study on water quality improvement and nature restoration; an artificial island will also be the setting for a new residential area. The second case study is on water level management carried out on the IJsselmeer, the largest lake in the country. Results of our analysis show the potential impacts with a standardised method to the spatial distribution and quality of the ecosystems.

  20. Prognostic factors in soft tissue sarcoma.

    PubMed

    Maretty-Nielsen, Katja

    2014-11-01

    Despite major advances in the knowledge of soft tissue sarcoma (STS) during the last decades, no significant improvement in survival has been observed. Detailed data on the prognosis of STS are crucial in order to identify patients who might benefit from more aggressive treatment. Such data can be obtained from properly designed databases; however, the validation of data is crucial in order to obtain valid, reliable results. Furthermore, the majority of prognostic studies in STS have been limited by potential selection bias, low power, and biased estimates due to the statistical methods used, e.g., dichotomizing continuous variables, censoring competing events, as well as not adjusting for important confounders. The overall aim of this thesis was to investigate the prognosis of STS patients using data from the Aarhus Sarcoma Registry (ASR), covering western Denmark in the period from 1979 to 2008. In study I, we systematically validated data in the ASR and evaluated the validity, including completeness of patient registration and accuracy of data. In study II, we investigated the prognostic impact of patient-, tumor-, and treatment-related factors on local recurrence and disease-specific mortality. These were analyzed in a competing risk model in which continuous variables were included as cubic splines and possible confounders were selected based on directed acyclic graphs. In study III, we examined the impact of comorbidity on overall and disease-specific mortality. In study IV, we compared mortality in patients with abnormal biomarkers to those with normal values, assessed the significance of adjusting for comorbidity, as well as constructed a prognostic biomarker score. In study V, we described the relative mortality, i.e., the mortality in STS patients compared with the mortality in a general population, and compared relative and disease-specific estimates. The mortality in the general population was determined using an individually age- and sex

  1. Comparison of prognostic and predictive impact of genomic or central grade and immunohistochemical subtypes or IHC4 in HR+/HER2- early breast cancer: WSG-AGO EC-Doc Trial.

    PubMed

    Gluz, O; Liedtke, C; Huober, J; Peyro-Saint-Paul, H; Kates, R E; Kreipe, H H; Hartmann, A; Pelz, E; Erber, R; Mohrmann, S; Möbus, V; Augustin, D; Hoffmann, G; Thomssen, C; Jänicke, F; Kiechle, M; Wallwiener, D; Kuhn, W; Nitz, U; Harbeck, N

    2016-06-01

    Potential prognostic and predictive markers in early, intermediate-risk breast cancer (BC) include histological grade, Ki-67, genomic signatures, e.g. genomic grade index (GGI), and intrinsic subtypes. Their prognostic/predictive impact in hormone receptor (HR: ER and/or PR) positive/HER2- BC is controversial. WSG-AGO EC-Doc demonstrated superior event-free survival (EFS) in patients with 1-3 positive lymph node receiving epirubicin/cyclophosphamide-docetaxel (EC-Doc) versus 5-fluoruracil/epirubicin/cyclophosphamide (FEC). In a representative trial subset, we quantify concordance among factors used for clinical chemotherapy indication. We investigate the impact of central histology (n = 772), immunohistochemistry for intrinsic subtyping and IHC4, and dichotomous (GG) or continuous (GGI) genomic grade (n = 472) on patient outcome and benefit from taxane chemotherapy, focusing on HR+/HER2- patients (n = 459). Concordance of local grade (LG) with central (CG) or genomic grade was modest. In HR+/HER2- patients, low (GG-1: 16%), equivocal (GG-EQ: 17%), and high (GG-3: 67%) GG were associated with respective 5-year EFS of 100%, 93%, and 85%. GGI was prognostic for EFS within all LG subgroups and within CG3, whereas IHC4 was prognostic only in CG3 tumors.In unselected and HR+/HER2- patients, CG3 and luminal-A-like subtype entered the multivariate EFS model, but not IHC4 or GG. In the whole population, continuous GGI entered the model [hazard ratio (H.R.) of 75th versus 25th = 2.79; P = 0.01], displacing luminal-A-like subtype; within HR+/HER2- (H.R. = 5.36; P < 0.001), GGI was the only remaining prognostic factor.In multivariate interaction analysis (including central and genomic grade), luminal-B-like subtype [HR+ and (Ki-67 ≥20% or HER2+)] was predictive for benefit of EC-Doc versus FEC in unselected but not in HR+/HER2- patients. In the WSG-AGO EC-Doc trial for intermediate-risk BC, CG, intrinsic subtype (by IHC), and GG provide prognostic information. Continuous GGI

  2. Prognosis Research Strategy (PROGRESS) 3: prognostic model research.

    PubMed

    Steyerberg, Ewout W; Moons, Karel G M; van der Windt, Danielle A; Hayden, Jill A; Perel, Pablo; Schroter, Sara; Riley, Richard D; Hemingway, Harry; Altman, Douglas G

    2013-01-01

    Prognostic models are abundant in the medical literature yet their use in practice seems limited. In this article, the third in the PROGRESS series, the authors review how such models are developed and validated, and then address how prognostic models are assessed for their impact on practice and patient outcomes, illustrating these ideas with examples.

  3. Separating the Air Quality Impact of a Major Highway and Nearby Sources by Nonparametric Trajectory Analysis

    EPA Science Inventory

    Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur di...

  4. The Pervasiveness and Impact of Corporate Quality Circles: A Survey of Major American Corporations.

    ERIC Educational Resources Information Center

    Hellweg, Susan A.; And Others

    To assess the pervasiveness of quality circles in American corporations, as well as to ascertain perceptions of their impact in terms of various organizational outcomes, a 45-item questionnaire was mailed to personnel directors of the Fortune 500 corporations. Some time after the initial mailing, a follow-up mailing was executed to maximize the…

  5. Analysis of the impacts of the President's tax proposal on major sectors of the energy industry

    SciTech Connect

    Not Available

    1985-08-01

    The purpose of this study is to assess the impact of the President's tax proposal on the energy sector. The study consists of two parts. The first part specifically addresses the impacts of the President's tax proposal on the oil and gas, coal, and electric utility sectors of the energy industry. Impacts were examined at both the project and corporate levels. The study focuses on proposed changes in corporate income taxation. Results show that the impacts of the President's tax proposal vary across the energy sector. Taxes levied on coal operations would rise. Those levied on oil and gas remain about the same if measured at the overall corporate level. Looking at oil and gas production operations separately from other lines of business (downstream, foreign, and subsidiary operations), taxes would tend to fall, except in the case of the small independents. Taxes paid by electric utilities would tend to fall. Within each sector, however, substantial variation among firms would be evident due to differing circumstances of corporate diversity and rate of growth. 11 figs., 38 tabs.

  6. Separating the Air Quality Impact of a Major Highway and Nearby Sources by Nonparametric Trajectory Analysis

    EPA Science Inventory

    Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur di...

  7. The Impact of Extensive Reading on College Business Majors in Taiwan

    ERIC Educational Resources Information Center

    Shih, Ying-Chun

    2015-01-01

    The effects of extensive reading on EFL context have been examined with a variety of studies. This study examined the impact of extensive reading on reading proficiency while the participants were taught reading strategies. Furthermore, this study explored whether there were any differences between intervention and control groups on the reading…

  8. The Impact of Cooperative Quizzes in a Large Introductory Astronomy Course for Non-Science Majors

    ERIC Educational Resources Information Center

    Zeilik, Michael; Morris, Vicky J.

    2004-01-01

    In Astronomy 101 at the University of New Mexico, we carried out a repeated-items experiment on quizzes and tests to investigate the impact of cooperative testing. This trial was the only change in a reformed course format that had been refined over previous semesters. Our research questions were: (1) Did cooperative quizzes result in gains for…

  9. The Pervasiveness and Impact of Electronic Communication Technologies in Organizations: A Survey of Major American Corporations.

    ERIC Educational Resources Information Center

    Hellweg, Susan A.; And Others

    A survey of the Fortune 500 corporations was conducted to ascertain the pervasiveness and perceived impact of five electronic communication technologies (electronic mail, videotex, interactive computers, video teleconferencing, and word processing). Ninety-four corporations responded to a 53-item questionnaire and follow-up survey. Analysis of the…

  10. The Impact of Cooperative Quizzes in a Large Introductory Astronomy Course for Non-Science Majors

    ERIC Educational Resources Information Center

    Zeilik, Michael; Morris, Vicky J.

    2004-01-01

    In Astronomy 101 at the University of New Mexico, we carried out a repeated-items experiment on quizzes and tests to investigate the impact of cooperative testing. This trial was the only change in a reformed course format that had been refined over previous semesters. Our research questions were: (1) Did cooperative quizzes result in gains for…

  11. Palliating the impact of fixation of a major gene on the genetic variation of artificially selected polygenes.

    PubMed

    Sánchez, Leopoldo; Caballero, Armando; Santiago, Enrique

    2006-10-01

    Selective sweeps of variation caused by fixation of major genes may have a dramatic impact on the genetic gain from background polygenic variation, particularly in the genome regions closely linked to the major gene. The response to selection can be restrained because of the reduced selection intensity and the reduced effective population size caused by the increase in frequency of the major gene. In the context of a selected population where fixation of a known major gene is desired, the question arises as to which is the optimal path of increase in frequency of the gene so that the selective sweep of variation resulting from its fixation is minimized. Using basic theoretical arguments we propose a frequency path that maximizes simultaneously the effective population size applicable to the selected background and the selection intensity on the polygenic variation by minimizing the average squared selection intensity on the major gene over generations up to a given fixation time. We also propose the use of mating between carriers and non-carriers of the major gene, in order to promote the effective recombination between the major gene and its linked polygenic background. Using a locus-based computer simulation assuming different degrees of linkage, we show that the path proposed is more effective than a similar path recently published, and that the combination of the selection and mating methods provides an efficient way to palliate the negative effects of a selective sweep.

  12. Prognostic Impact of Primary Tumor Location on Clinical Outcomes of Metastatic Colorectal Cancer Treated With Cetuximab Plus Oxaliplatin-Based Chemotherapy: A Subgroup Analysis of the JACCRO CC-05/06 Trials.

    PubMed

    Sunakawa, Yu; Ichikawa, Wataru; Tsuji, Akihito; Denda, Tadamichi; Segawa, Yoshihiko; Negoro, Yuji; Shimada, Ken; Kochi, Mitsugu; Nakamura, Masato; Kotaka, Masahito; Tanioka, Hiroaki; Takagane, Akinori; Tani, Satoshi; Yamaguchi, Tatsuro; Watanabe, Takanori; Takeuchi, Masahiro; Fujii, Masashi; Nakajima, Toshifusa

    2017-09-01

    Primary tumor location is a critical prognostic factor in metastatic colorectal cancer (mCRC); however, it remains unclear whether tumor location is a predictor of the response to cetuximab treatment. It is also uncertain if BRAF mutation contributes to the impact of tumor location on survival. We assessed the prognostic impact of tumor location on clinical outcomes in mCRC patients treated with first-line cetuximab chemotherapy. The associations of tumor location with overall survival and progression-free survival were evaluated in mCRC patients with KRAS exon 2 wild-type tumors who were enrolled onto 2 clinical trials: JACCRO CC-05 of cetuximab plus FOLFOX (n = 57, UMIN000004197) and CC-06 of cetuximab plus SOX (n = 61, UMIN000007022). Tumors proximal or from splenic flexure to rectum were defined as right-sided or left-sided, respectively. In addition, exploratory RAS and BRAF mutation analyses were performed. A total of 110 patients were assessable for tumor location; 90 had left-sided tumors. Left-sided tumors were significantly associated with longer overall survival (36.2 vs. 12.6 months, hazard ratio = 0.28, P < .0001) and progression-free survival (11.1 vs. 5.6 months, hazard ratio = 0.47, P = .0041) than right-sided tumors; similar results were obtained in multivariate analysis. A subanalysis showed that the association was evident in the FOLFOX group and that tumor location was an independent prognostic factor irrespective of BRAF status in RAS wild-type patients. Primary tumor location might be a predictor of survival independent of BRAF status in mCRC patients who receive first-line cetuximab combined with oxaliplatin-based chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Comorbidities of COPD Have a Major Impact on Clinical Outcomes, Particularly in African Americans

    PubMed Central

    Putcha, Nirupama; Han, Meilan K.; Martinez, Carlos H.; Foreman, Marilyn G.; Anzueto, Antonio R.; Casaburi, Richard; Cho, Michael H.; Hanania, Nicola A.; Hersh, Craig P.; Kinney, Gregory L.; Make, Barry J.; Steiner, Robert M.; Lutz, Sharon M.; Thomashow, Byron M.; Williams, Andre A.; Bhatt, Surya P.; Beaty, Terri H.; Bowler, Russell P.; Ramsdell, Joe W.; Curtis, Jeffrey L.; Everett, Douglas; Hokanson, John E.; Lynch, David A.; Sutherland, E. Rand; Silverman, Edwin K.; Crapo, James D.; Wise, Robert A.; Regan, Elizabeth A.; Hansel, Nadia N.

    2014-01-01

    Background: COPD patients have a great burden of comorbidity. However, it is not well established whether this is due to shared risk factors such as smoking, if the comorbidities impact patients’ exercise capacity and quality of life, or whether there are racial disparities in their impact on COPD. Methods: We analyzed data from 10,192 current and ex-smokers with (cases) and without COPD (controls) from the Genetic Epidemiology of COPD (COPDGene®) study cohort to establish risk for COPD comorbidities adjusted for pertinent covariates. In adjusted models, we examined comorbidity prevalence and impact in African-Americans (AA) and non-Hispanic whites (NHW). Results: Comorbidities are more common in individuals with COPD compared to those with normal spirometry (controls), and the risk persists after adjustments for covariates including pack-years smoked. After adjustment for confounders, 8 conditions were independently associated with worse exercise capacity, quality of life and dyspnea. There were racial disparities in the impact of comorbidities on exercise capacity, dyspnea and quality of life, with the presence of osteoarthritis and gastroesophageal reflux disease having a greater negative impact on all three outcomes in AAs than NHWs (p<0.05 for all interaction terms). Conclusions: Individuals with COPD have a higher risk for comorbidities than controls, an important finding shown for the first time comprehensively after accounting for confounders. Individual comorbidities are associated with worse exercise capacity, quality of life, and dyspnea, in AAs compared with NHWs. Note: The abstract of a previous version of this work was presented at the American Thoracic Society Conference in Philadelphia, PA on May 21, 2013. PMID:25695106

  14. Student Input, Student Involvement, and College Environment Factors Impacting the Choice of Academic Major.

    ERIC Educational Resources Information Center

    Coperthwaite, Corby A.; Knight, William E.

    This study investigated the ability of student inputs, student involvements, and college environments to predict seven groups of academic majors. The research was conducted using a sample of college sophomores extracted from High School and Beyond 1982 follow-up cohort, N=43,614 (weighted). Among the findings of the hierarchical discriminant…

  15. An Analysis of Five Major Public Laws and Their Impact on the Handicapped.

    ERIC Educational Resources Information Center

    King, John D.; Humphrey, Jackie Hance

    The study developed and tested a systematic format for discovering and displaying relationships among five major federal laws concerning the handicapped: P.L. 93-112 (Rehabilitation Act of 1973), P.L. 93-380 (Education Amendments of 1974), P.L. 94-63 (Special Health Revenue Sharing Act of 1974), P.L. 94-103 (Developmentally Disabled Assistance and…

  16. IMPACTS OF TRAFFIC ON AIR QUALITY AND HEALTH EFFECTS NEAR MAJOR ROADWAYS

    EPA Science Inventory

    A growing number of epidemiological studies conducted in Europe, Asia, and North America have identified an increase in occurrence of adverse health effects for populations living near major roads. However, the biological mechanism(s) leading to the adverse effects have not been...

  17. IMPACTS OF TRAFFIC ON AIR QUALITY AND HEALTH EFFECTS NEAR MAJOR ROADWAYS

    EPA Science Inventory

    A growing number of epidemiological studies conducted in Europe, Asia, and North America have identified an increase in occurrence of adverse health effects for populations living near major roads. However, the biological mechanism(s) leading to the adverse effects have not been...

  18. The Impact of Leadership Roles and Internships on Undergraduate Business Major Field Test (MFT) Scores

    ERIC Educational Resources Information Center

    Ward, Chris; Yates, Dan; Song, Joon Young

    2014-01-01

    It is often the goal or mission of higher education to prepare graduates for leadership roles in organizations and the community. Even if we are to assume that leadership skills can be developed, determining the appropriate ways to teach and measure leadership is often debated. Our study used quantitative data from the ETS Business Major Field…

  19. Natural Science Majors and Liberal Education: The Impact of a Living-Learning Community

    ERIC Educational Resources Information Center

    Hutt, Chris D.

    2012-01-01

    The purpose of this study was to explore the articulated experiences of natural science majors who were participating in a liberal arts living-learning community. Using the American Association of College and University's (2002) report, "Greater Expectations" as an organizing framework, this study sought to determine how--if at…

  20. Water quality of four major lakes in Mississippi, USA: Impacts on human and aquatic ecosystem health

    USDA-ARS?s Scientific Manuscript database

    Harmful algal blooms (HABs), harmful microorganisms (pathogens) and toxic metals represent three major agents of water quality deterioration. Better water quality is of utmost importance to water bodies that provide recreational opportunities, even better quality is expected in the water bodies that...

  1. Natural Science Majors and Liberal Education: The Impact of a Living-Learning Community

    ERIC Educational Resources Information Center

    Hutt, Chris D.

    2012-01-01

    The purpose of this study was to explore the articulated experiences of natural science majors who were participating in a liberal arts living-learning community. Using the American Association of College and University's (2002) report, "Greater Expectations" as an organizing framework, this study sought to determine how--if at…

  2. The Expression and Prognostic Impact of CD95 Death Receptor and CD20, CD34 and CD44 Differentiation Markers in Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    M. Kamazani, Fatemeh; Bahoush-Mehdiabadi, Gholamreza; Aghaeipour, Mahnaz; Vaeli, Shahram; Amirghofran, Zahra

    2014-01-01

    Objective: This study investigated the expression and prognostic significance of the CD95 death receptor and CD20, a B cell-lineage associated marker, along with CD34 and CD44 non-lineage associated molecules in Iranian children with acute lymphoblastic leukemia (ALL). Methods: We performed immunophenotyping for expressions of the molecules in blood samples from children diagnosed with ALL by using a panel of monoclonal antibodies for flow cytometry analysis. The expression of markers was evaluated in relation to clinical and paraclinical features as well as response to treatment in the patients. Findings : CD95 showed a higher expression in T-ALL compared to B-ALL (P<0.001). Analysis of the clinical and laboratory findings at diagnosis in the group of B-ALL patients revealed an association between CD95 expression with lower white blood cell (WBC) numbers and bone marrow blasts (P<0.05). We detected a positive correlation between the expressions of CD95 and CD44 (r=0.445, P<0.01) in B-ALL patients. There was an association between CD20 expression and several poor prognostic factors that included increased extramedullary involvement (EMI) and decreased platelet numbers (P<0.008). The mean expression of CD34 in B-ALL was higher than T-ALL (P=0.004). At follow-up, complete remission duration (CRD) and survival duration did not significantly differ between patients who were positive or negative for each marker. Conclusion: Association of the studied molecules with several prognostic factors implies the significance of CD95 molecule as favorable and CD20 as unfavorable prognostic markers for childhood ALL. PMID:25755857

  3. Separating the air quality impact of a major highway and nearby sources by nonparametric trajectory analysis.

    PubMed

    Henry, Ronald C; Vette, Alan; Norris, Gary; Vedantham, Ram; Kimbrough, Sue; Shores, Richard C

    2011-12-15

    Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur dioxide concentrations were collected from December 2008 to December 2009. The purpose of the study was to determine the impact of the highway at three downwind monitoring stations using an upwind station to measure background concentrations. NTA was used to precisely determine the contribution of the highway to the average concentrations measured at the monitoring stations accounting for the spatially heterogeneous contributions of other local urban sources. NTA uses short time average concentrations, 5 min in this case, and constructed local back-trajectories from similarly short time average wind speed and direction to locate and quantify contributions from local source regions. Averaged over an entire year, the decrease of concentrations with distance from the highway was found to be consistent with previous studies. For this study, the NTA model is shown to be a reliable approach to quantify the impact of the highway on local air quality in an urban area with other local sources.

  4. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    PubMed

    Pinheiro, Dammy; Chang, Yu-Mei; Bryant, Hannah; Szladovits, Balazs; Dalessandri, Tim; Davison, Lucy J; Yallop, Elizabeth; Mills, Emily; Leo, Chiara; Lara, Ana; Stell, Anneliese; Polton, Gerry; Garden, Oliver A

    2014-01-01

    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  5. Dissecting the Regulatory Microenvironment of a Large Animal Model of Non-Hodgkin Lymphoma: Evidence of a Negative Prognostic Impact of FOXP3+ T Cells in Canine B Cell Lymphoma

    PubMed Central

    Pinheiro, Dammy; Chang, Yu-Mei; Bryant, Hannah; Szladovits, Balazs; Dalessandri, Tim; Davison, Lucy J.; Yallop, Elizabeth; Mills, Emily; Leo, Chiara; Lara, Ana; Stell, Anneliese; Polton, Gerry; Garden, Oliver A.

    2014-01-01

    The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms. PMID:25119018

  6. Prognostic impact of RUNX1 and ETV6 gene copy number on pediatric B-cell precursor acute lymphoblastic leukemia with or without hyperdiploidy.

    PubMed

    Kutlay, Nuket Yurur; Pekpak, Esra; Altıner, Sule; Ileri, Talia; Vicdan, Arzu Nedime; Dinçaslan, Handan; Ince, Elif Unal; Tukun, Fatma Ajlan

    2016-09-01

    The ETV6/RUNX1 fusion gene is a valuable prognostic marker that is frequently observed in B-cell precursor acute lymphoblastic leukemia (B-cell ALL). However, the clinical significance of copy number aberrations in these genes remains unclear. In this study, the effects of various aberrations inETV6 and RUNX1 gene copy number on disease prognosis were evaluated in 21 pediatric patients diagnosed with B-cell ALL with/without t(12;21). The prognostic significance of changes in gene copy number of ETV6 or RUNX1 in the presence or absence of hyperdiploidy, trisomy 21, and t(12;21) translocation were also evaluated. RUNX1 gene copy number amplifications were detected in 83 % of the patients who lacked t(12;21) and in all of the patients with hyperdiploidy. Trisomy 21 was detected in 78 % of the patients with hyperdiploidy. Changes in ETV6 gene copy number were detected in patients who lacked both the t(12;21) translocation and RUNX1 gene copy number amplifications. However, RUNX1 gene copy number amplification and ETV6 deletion were observed in all of the patients with t(12;21). RUNX1 gene copy number amplification was associated with hyperdiploidy, but not with t(12;21). Thus, the evaluation of distinct FISH and cytogenetic patterns in patients with B-cell ALL may strengthen the prognostic significance of changes in gene copy number.

  7. Impact of video-assisted thoracoscopic major lung resection on immune function.

    PubMed

    Ng, Calvin S H; Wan, Innes Y P; Yim, Anthony P C

    2009-08-01

    Video-assisted thoracoscopic major lung resection for early stage non-small-cell lung carcinoma has been associated with less postoperative pain, better preserved pulmonary function, shorter hospital stay, and enhanced tolerance of adjuvant chemotherapy compared to thoracotomy. Initial concerns regarding safety, oncological clearance, and cost effectiveness were unfounded. Several recent trials have reported improved long-term survival in patients with early stage non-small-cell lung carcinoma undergoing video-assisted thoracoscopic major lung resection, compared to the open technique, although there are inconsistencies. Interestingly, the immune status and autologous tumor killing ability of lung cancer patients have previously been associated with long-term survival. Video-assisted thoracoscopic lung resection results in an attenuated postoperative inflammatory response, but more importantly, it better preserves postoperative immune function. Circulating natural killer and T-cell numbers, T-cell oxidative activity, and levels of immunochemokines such as insulin growth factor binding protein-3 are higher after video-assisted thoracoscopic surgery than after thoracotomy. Recently, interest has developed in the role of the angiogenesis factor, vascular endothelial growth factor, after cancer surgery. Whether differences in immunological and biochemical mediators contribute towards improved long-term survival following video-assisted thoracoscopic major lung resection for cancer remains to be confirmed.

  8. A Comprehensive Prognostics Approach for Predicting Gas Turbine Engine Bearing Life

    DTIC Science & Technology

    2004-06-01

    PROGNOSTICS APPROACH FOR PREDICTING GAS TURBINE ENGINE BEARING LIFE Rolf Orsagh, Michael Roemer, Jeremy Sheldon Impact Technologies, LLC 125...Wright-Patterson AFB, OH 45433 ABSTRACT Development of practical and verifiable prognostic approaches for gas turbine engine bearings will play...unnecessary maintenance on engines that operate under unusually mild conditions. A comprehensive engine bearing prognostic approach is presented

  9. Impact of a major disaster on the mental health of a well-studied cohort.

    PubMed

    Fergusson, David M; Horwood, L John; Boden, Joseph M; Mulder, Roger T

    2014-09-01

    There has been growing research into the mental health consequences of major disasters. Few studies have controlled for prospectively assessed mental health. This article describes a natural experiment in which 57% of a well-studied birth cohort was exposed to a major natural disaster (the Canterbury, New Zealand, earthquakes in 2010-2011), with the remainder living outside of the earthquake area. To examine the relationships between the extent of earthquake exposure and mental health outcomes following the earthquakes-net of adjustment for potentially confounding factors related to personal circumstances, prior mental health, and childhood family background. Data were gathered from the Christchurch Health and Development Study, a 35-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). This general community sample included 952 participants with available data on earthquake exposure and mental health outcomes at age 35 years. A composite measure of exposure to the events during and subsequent to the 4 major (Richter Scale >6.0) Canterbury earthquakes during the years 2010-2011. DSM-IV symptom criteria for major depression; posttraumatic stress disorder; anxiety disorder; suicidal ideation/attempt; nicotine dependence; alcohol abuse/dependence; and illicit drug abuse/dependence. Outcomes were measured approximately 20 to 24 months after the onset of exposure to the earthquakes and were assessed using DSM-IV diagnostic criteria and measures of subclinical symptoms. After covariate adjustment, cohort members with high levels of exposure to the earthquakes had rates of mental disorder that were 1.4 (95% CI, 1.1-1.7) times higher than those of cohort members not exposed. This increase was due to increases in the rates of major depression; posttraumatic stress disorder; other anxiety disorders; and nicotine dependence. Similar results were found using a measure of subclinical symptoms (incidence rate ratio, 1.4; 95% CI, 1

  10. Prognostic Impact of Combined Contrast-Induced Acute Kidney Injury and Hypoxic Liver Injury in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Results from INTERSTELLAR Registry

    PubMed Central

    Suh, Young Ju; Kim, Tae-Hoon; Jang, Ho-Jun; Suh, Jon; Park, Hyun Woo; Oh, Pyung Chun; Shin, Sung-Hee; Woo, Seong-Il; Kim, Dae-Hyeok; Kwan, Jun; Kang, WoongChol

    2016-01-01

    Background Besides contrast-induced acute kidney injury(CI-AKI), adscititious vital organ damage such as hypoxic liver injury(HLI) may affect the survival in patients with ST-elevation myocardial infarction (STEMI). We sought to evaluate the prognostic impact of CI-AKI and HLI in STEMI patients who underwent primary percutaneous coronary intervention (PCI). Methods A total of 668 consecutive patients (77.2% male, mean age 61.3±13.3 years) from the INTERSTELLAR STEMI registry who underwent primary PCI were analyzed. CI-AKI was defined as an increase of ≥0.5 mg/dL in serum creatinine level or 25% relative increase, within 48h after the index procedure. HLI was defined as ≥2-fold increase in serum aspartate transaminase above the upper normal limit on admission. Patients were divided into four groups according to their CI-AKI and HLI states. Major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of all-cause mortality, non-fatal MI, non-fatal stroke, ischemia-driven target lesion revascularization and target vessel revascularization were recorded. Results Over a mean follow-up period of 2.2±1.6 years, 94 MACCEs occurred with an event rate of 14.1%. The rates of MACCE and all-cause mortality were 9.7% and 5.2%, respectively, in the no organ damage group; 21.3% and 21.3% in CI-AKI group; 18.5% and 14.6% in HLI group; and 57.7% and 50.0% in combined CI-AKI and HLI group. Survival probability plots of composite MACCE and all-cause mortality revealed that the combined CI-AKI and HLI group was associated with the worst prognosis (p<0.0001 for both). Conclusion Combined CI-AKI after index procedure and HLI on admission is associated with poor clinical outcomes in patients with STEMI who underwent primary PCI. (INTERSTELLAR ClinicalTrials.gov number, NCT02800421.) PMID:27415006

  11. Assessing Resiliency in a Large Lake Receiving Mine Tailings Waste: Impacts of Major Environmental Disturbance.

    NASA Astrophysics Data System (ADS)

    Petticrew, Ellen; Owens, Philip; Albers, Sam

    2016-04-01

    On 4th August 2014, the tailings impoundment of the Mount Polley copper and gold mine in British Columbia failed. Material from the impoundment (surface area = 2.7 km2) flowed into nearby Polley Lake and Hazeltine Creek, before discharging into Quesnel Lake, a large (ca. 100 km long, >500 m deep), relatively pristine lake. Initial estimates suggest that approximately 25 Mm3 of tailings (water and solids) and eroded soils and surficial materials from Hazeltine Creek were delivered to Quesnel Lake, raising the lake by 7.7 cm. Much of this material was deposited at the bottom of Quesnel Lake but a plume of fine-grained sediment (D50 of ca. 1 μm) remained suspended in the water column. The impact of the distribution of this sediment was monitored over the next 15 months using water column profiling for temperature, conductivity, fluorescence and turbidity with depth. The plume movement was regulated by natural processes associated with the physical limnology of this large fjord lake, specifically, seiche events which transferred suspended particles both up-lake, against the flow regime, and down-lake into the Quesnel River. Samples of lake water and bottom sediment taken from the impacted area show elevated levels of total metals and other elements, which may have important ecosystem implications in this watershed. Indeed, the breach occurred at a time when a peak run of sockeye salmon were returning to their natal streams in the Quesnel basin. Zooplankton sampling for metals was initiated in fall 2014 to determine up take of metals into the food web. This poster describes the failure of the impoundment dam and presents results of sampling the aquatic environment over the first fifteen months of impact.

  12. Antibiotic resistance as a major public health concern: epidemiology and economic impact.

    PubMed

    Ciorba, Veronica; Odone, Anna; Veronesi, Licia; Pasquarella, Cesira; Signorelli, Carlo

    2015-01-01

    Antimicrobial resistance (AMR) is mainly sustained by the improper use of antibiotics and has become a global public health concern both in the field of human and animal health. Italy has the highest prevalence of AMR among European countries, in particular carbapenem-resistant Klebsiella pneumoniae, which reached 34.3% in 2013. Multidrug-resistant microorganisms' infections are associated with increased risk of complications, higher hospitalization rates, increased healthcare costs, loss of productivity and increased mortality. This paper summarizes the most recent epidemiological data regarding the spread of antibiotic resistance in Italy, consumption and economic impact, outlining the need for timely action and integrated approaches in all countries.

  13. Analysis of the Impact of Major Dust Events on the Aerosols Characteristics over Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Farahat, Ashraf; El-Askary, Hesham; Al-Shaibani, Abdulaziz; Hariri, Mustafa M.

    2015-04-01

    The Kingdom of Saudi Arabia is a major source of atmospheric dust. Frequent dust storms blow up and significantly affect human activities, airports and citizens' health. Aerosols optical and physical characteristics are influenced by major dust storms outbreaks. In this, paper, ground based AERONET measurements are integrated with space-borne sensors, namely MODIS and CALIPSO to analyze aerosols' characteristics during March - May of 2009 where a massive dust storm blew up and caused a widespread heavy atmospheric dust load over Saudi Arabia and the same period during 2010, where less dust activities were reported. The MODIS Deep Blue AOD analysis showed similar aerosols pattern over the land, however a substantial variance in aerosol loading during March - May 2009 compared with the same period in 2010 was observed. The angstrom exponent analysis showed that the majority of aerosol measurements in 2009 and 2010 are dominated by coarse-mode particles with angstrom exponent < 0.5. Detailed analysis of aerosol optical properties shows significant influence of coarse mode particles in the enhanced aerosol loading in 2009. The volume depolarization rations (VDR) derived from CALIPSO backscattering measurements is used to find latitudinal profile of mean aerosol optical depth to indicate the type of particles and to discriminate spherical aerosols with non-spherical particles. Acknowledgement The authors would like to acknowledge the support provided by the King Abdel Aziz City for Science & Technology (KACST) for funding this work under grant No. (MT-32-76). The support provided by the Deanship of Research at King Fahd University of Petroleum & Minerals (KFUPM) is gratefully acknowledged.

  14. Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Hanusa, Barbara H.; Moses-Kolko, Eydie L.; Bogen, Debra L.; Hunker, Diane F.; Perel, James M.; Jones-Ivy, Sonya; Bodnar, Lisa M.; Singer, Lynn T.

    2015-01-01

    Objective Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. Method This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. Results Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. Conclusions For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%. PMID:19289451

  15. Minimizing environmental impacts of a major construction: the Øresund link.

    PubMed

    Gray, John S

    2006-04-01

    The Øresund Link is a 4-lane motorway with a 2-line rail link between Copenhagen, Denmark, and Malmö, Sweden, built across the Øresund Sound between the 2 countries. The environmental concerns associated with construction of the Link were that that it might affect the water and salt flow through the Sound and into and out of the Baltic Sea, lead to destruction of the cod fishery, and affect other biological systems. An International Expert Panel was formed to design mitigation strategies to avoid negative environmental impacts. The Panel designed stringent environmental controls for the construction, of which the most significant was to limit sediment discharges to 5% of the dredged material. This was one-fifth of the discharge limit construction companies usually accept as normal for such a large-scale project. An environmental monitoring program was instituted to monitor compliance with the environmental control measures. As a result of the imposition of tough environmental requirements, the Link was built with little environmental impact and 3 y after it was completed, environmental conditions have returned to normal.

  16. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    PubMed

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  17. Pomalidomide Shows Significant Therapeutic Activity against CNS Lymphoma with a Major Impact on the Tumor Microenvironment in Murine Models

    PubMed Central

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A.; Moghaddam, Mehran F.; Copland, John A.; Tun, Han W.

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  18. The Impact of Panic-Agoraphobic Comorbidity on Suicidality in Hospitalized Patients with Major Depression

    PubMed Central

    Brown, Lily A.; Gaudiano, Brandon A.; Miller, Ivan W.

    2013-01-01

    Background Previous research in outpatient samples suggests that panic and agoraphobic comorbidity is related to suicidality in outpatients with major depression. The purpose of the study was to further investigate this relationship specifically in a hospitalized sample. Method The current study examined the severity of current suicidal ideation and behaviors in a psychiatric hospital sample diagnosed with major depressive disorder alone (MDD; n = 28) versus MDD plus panic-agoraphobic spectrum disorders (MDD+PAS; n = 69). Results Members of the MDD+PAS group were significantly more likely to have had a suicide attempt history, higher current depression severity, and higher current suicidal severity compared with individuals in the MDD alone group. The relationship between current suicidality and comorbid PAS remained significant after controlling for overall depression severity and other clinical factors. Conclusions These findings suggest that panic-agoraphobic comorbidity is associated with a greater risk for suicidality in hospitalized patients which cannot be adequately explained by the level of current depression alone. The clinical and research implications for these findings are discussed. PMID:20099269

  19. Re-plumbing the Terrestrial Hydrosphere: Scope and Impact of Major Inter-basin Water Transfers

    NASA Astrophysics Data System (ADS)

    Shikhmacheva, K. V.; Vorosmarty, C. J.; Fekete, B. M.; Afshari, S.; Aside, B.; Chibisova, Y.; Dopson, I.; Link, H.; Mouden, A.

    2013-12-01

    The availability of water has become one of the main concerns in modern history and it is an important policymaking strategy. Increasing population, agricultural intensification, rapid urbanization, industrial expansion and environmental changes increase water demand on region and global scales. Inter-Basin Water Transfer (IBWT) is an important element of satisfying immediate water requirements. The complex engineering structures divert water flow between watersheds, thus ';re-plumbing' terrestrial hydrosphere. We report here an analysis of inter-basin water transfer for the Northeast region, which is a part of an NSF funded project entitled 'The NorthEast Regional Earth System Model (NE-RESM).' In addition, this work is also a part of a global IBWT study. First, we present the IBWT geo-referenced assembled data set, derived from from maps, published documents and online resources. The information in the data base was classified by project name, diverted volume, source location, usage, status of construction, transport distance and purpose. The key feature of the dataset is geo-location of the projects, that allows further analysis of the hydrologic impact of each of the projects as well as their collective significance. Upon completion of the data-collection phase, the inputs were verified using RiverGIS and ArcGIS software. In addition, we investigated some key measures of IBWT distortion of regional-scale hydrology as well as their socio-economic impacts across the Northeast region. We calculated several indicators to assess these impacts, for example the donor-to-recipient basin flow ratio, which represents the 'gain' and 'loss' of water relative to the natural flow on a basin scale. Elements of the regional IBWT data base will be incorporated into the regional-scale Water Balance Model (WBM), and linked to the operation of reservoirs and dams. While focused on the Northeastern U.S., we believe that this data, its testing and applications will yield broad use

  20. Climate Change and Its Impact on the Yield of Major Food Crops: Evidence from Pakistan

    PubMed Central

    Ali, Sajjad; Liu, Ying; Ishaq, Muhammad; Shah, Tariq; Abdullah; Ilyas, Aasir; Din, Izhar Ud

    2017-01-01

    Pakistan is vulnerable to climate change, and extreme climatic conditions are threatening food security. This study examines the effects of climate change (e.g., maximum temperature, minimum temperature, rainfall, relative humidity, and the sunshine) on the major crops of Pakistan (e.g., wheat, rice, maize, and sugarcane). The methods of feasible generalized least square (FGLS) and heteroscedasticity and autocorrelation (HAC) consistent standard error were employed using time series data for the period 1989 to 2015. The results of the study reveal that maximum temperature adversely affects wheat production, while the effect of minimum temperature is positive and significant for all crops. Rainfall effect towards the yield of a selected crop is negative, except for wheat. To cope with and mitigate the adverse effects of climate change, there is a need for the development of heat- and drought-resistant high-yielding varieties to ensure food security in the country. PMID:28538704

  1. Climate Change and Its Impact on the Yield of Major Food Crops: Evidence from Pakistan.

    PubMed

    Ali, Sajjad; Liu, Ying; Ishaq, Muhammad; Shah, Tariq; Abdullah; Ilyas, Aasir; Din, Izhar Ud

    2017-05-24

    Pakistan is vulnerable to climate change, and extreme climatic conditions are threatening food security. This study examines the effects of climate change (e.g., maximum temperature, minimum temperature, rainfall, relative humidity, and the sunshine) on the major crops of Pakistan (e.g., wheat, rice, maize, and sugarcane). The methods of feasible generalized least square (FGLS) and heteroscedasticity and autocorrelation (HAC) consistent standard error were employed using time series data for the period 1989 to 2015. The results of the study reveal that maximum temperature adversely affects wheat production, while the effect of minimum temperature is positive and significant for all crops. Rainfall effect towards the yield of a selected crop is negative, except for wheat. To cope with and mitigate the adverse effects of climate change, there is a need for the development of heat- and drought-resistant high-yielding varieties to ensure food security in the country.

  2. The impact of major surgery on blood coagulation factors and thrombin generation.

    PubMed

    Horne, McDonald K; Merryman, Paula K; Cullinane, Ann M; Nghiem, Khanh; Alexander, H Richard

    2007-09-01

    We studied the blood coagulation system of 14 patients with metastatic malignancies before and after they had undergone major surgery. In addition to measuring a battery of coagulation factors, we assessed the function of the system with assays of whole blood thrombin generation. With the exceptions of factor VIII (fVIII), which increased, and fibrinogen and fIX, which did not change, the activities of all the pro- and anticoagulant proteins were significantly lower postoperatively. However, the thrombin generating capacity of the system was relatively preserved. Although the integral of thrombin activity over time was lower after surgery, the mean peak thrombin concentration was unchanged and the time to clot formation was shortened. Similar changes could be reproduced by lowering the concentrations of pro- and anticoagulant factors together in control blood samples. Therefore, simultaneous reductions in pro- and anticoagulant proteins postoperatively worked to maintain the functional integrity of the blood coagulation system. 2007 Wiley-Liss, Inc

  3. Impact of a major cyclone on a southeast African estuarine lake system

    NASA Astrophysics Data System (ADS)

    Forbes, A. T.; Cyrus, D. P.

    The St Lucia lake and estuarine system in northern Natal, South Africa was struck by Cyclone Domoina on 31 January 1984. This is the only cyclone known to have traversed part of South Africa. The ensuing flood levels in the St Lucia system (which have been exceeded perhaps only one other time in recorded history) provided an opportunity to assess the effect of a major disturbance on a subtropical estuarine system. Major geomorphological changes occurred in the mouth area where all man-made structures were obliterated. The two river channels were scoured from 2-3 m to 10-14 m in depth and widened by up to 300 m, while the shoreline between the two channels retreated in places up to 100 m. An estimated 16∗10 6 m 3 of sediment were removed from the lower reaches of the system including areas of mangrove and Phragmites australis swamp. One-metre tall mangrove saplings died following inundation lasting days to weeks. Effects on the fauna included redistribution of the tanaid Apseudes digitalis, the mysid Mesopodopsis africana, the copepod Pseudodiaptomus stuhlmanni, the polychaete Scololepis squamata and the bivalve Solen cylindraceus, all typical lake species which appeared in the tidal channel linking the lake with the sea. Responses of other species such as the penaeid prawns, the crab Scylla serrata and the sole Solea bleekeri suggested that physiological tolerance, extended larval or juvenile recruitment periods and prey switching minimized long-term flood effects. No large-scale mortalities were noted, and the absence of a temperature shock is considered to be a significant feature.

  4. Long-term prognostic impact of CT-Leaman score in patients with non-obstructive CAD: Results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.

    PubMed

    Andreini, Daniele; Pontone, Gianluca; Mushtaq, Saima; Gransar, Heidi; Conte, Edoardo; Bartorelli, Antonio L; Pepi, Mauro; Opolski, Maksymilian P; Ó Hartaigh, Bríain; Berman, Daniel S; Budoff, Matthew J; Achenbach, Stephan; Al-Mallah, Mouaz; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; Cury, Ricardo; Delago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Feuchtner, Gudrun; Kim, Yong-Jin; Kaufmann, Philipp A; Leipsic, Jonathon; Lin, Fay Y; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J; Villines, Todd C; Dunning, Allison; Marques, Hugo; Rubinshtein, Ronen; Hindoyan, Niree; Gomez, Millie; Min, James K

    2017-03-15

    Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD). From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality. Patient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not. CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. A quantitative assessment of human impacts on decrease in sediment flux from major Chinese rivers entering the western Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Chu, Z. X.; Zhai, S. K.; Lu, X. X.; Liu, J. P.; Xu, J. X.; Xu, K. H.

    2009-10-01

    Major rivers with high sediment or water discharge act as natural integrators of surficial processes, including human activities within their drainage basins, and they are also the primary sources of terrestrial materials entering the ocean. The river-derived materials flux entering the coastal oceans, however, has been strongly affected by anthropogenic activities. Recent studies related to human impacts on river sediment flux have mainly focused on qualitative descriptions. Here we present a quantitative assessment of human impacts on decrease in sediment flux from nine major Chinese rivers entering the western Pacific Ocean, including Changjiang (Yangtze), Huanghe (Yellow), Zhujiang (Pearl), Songhuajiang, Liaohe, Haihe, Huaihe, Qiantangjiang, and Minjiang. During 1959-2007, dams and reservoirs, soil and water conservation programs, water consumption, as well as sand mining decreased the amount of sediment delivered to the ocean by 28, 11.5, 7.5 and 3 gigatons (Gt), respectively. If combined (50 Gt for the period 1959-2007), this reduction was close to the total decreased sediment flux (43 Gt) measured from these nine major rivers over the same period. Besides, the temporal variations in water and sediment fluxes into the ocean from these rivers generally during 1953-2007 were presented. These results are useful for further studies on Chinese and even global river-derived material flux to the ocean and associated ecological risks.

  6. Adverse prognostic impact of abnormal lesions detected by genome-wide single nucleotide polymorphism array-based karyotyping analysis in acute myeloid leukemia with normal karyotype.

    PubMed

    Yi, Jun Ho; Huh, Jungwon; Kim, Hee-Jin; Kim, Sun-Hee; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Sohn, Sang Kyun; Moon, Joon Ho; Kim, Sung Hyun; Kim, Kyoung Ha; Won, Jong Ho; Mun, Yeung Chul; Kim, Hawk; Park, Jinny; Jung, Chul Won; Kim, Dong Hwan

    2011-12-10

    This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) -based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses. A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis. Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020). Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.

  7. Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer

    PubMed Central

    Sperduti, Isabella; Iapicca, Pierluigi; Visca, Paolo; Alessandrini, Gabriele; Antoniani, Barbara; Pilotto, Sara; Ludovini, Vienna; Vannucci, Jacopo; Bellezza, Guido; Sidoni, Angelo; Tortora, Giampaolo; Radisky, Derek C.; Crinò, Lucio; Cognetti, Francesco; Facciolo, Francesco; Mottolese, Marcella

    2014-01-01

    Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk. PMID:25373410

  8. Circulating Tumor Cells Detected by RT-PCR for CK-20 before Surgery Indicate Worse Prognostic Impact in Triple-Negative and HER2 Subtype Breast Cancer

    PubMed Central

    Hwang, Seong Bae; Lee, Hye Yoon; Kim, Hoon Yub

    2012-01-01

    Purpose Circulating tumor cells (CTC) clearly correlate with unfavorable outcomes for patients with metastatic breast cancer, but the long-term prognostic implications of CTC for molecular subtypes of operable breast cancer are not yet known. We explored the relationships between previously established prognostic factors and CTC in operable breast cancer, and the significance of CTC by breast cancer molecular subtype. Methods We retrospectively evaluated 166 patients with operable breast cancer (stage I-IIIA) diagnosed from April 1997 to May 2003. CTC were detected using cytokeratin-20 (CK-20) mRNA expression in peripheral blood samples that were collected just prior to surgery under general anesthesia. Clinicopathological characteristics of the cancer were analyzed according to CTC status. Metastasis-free survival (MFS) and overall survival (OS) were analyzed according to CTC status and breast cancer molecular subtype. Results CK-20 mRNA-positive CTC was detected in 37 of 166 patients (22.3%) and was not correlated with any previous clinical factors in univariate analysis (p>0.05). After a median follow-up of 100 months, the patients with CK-20 mRNA-positive CTC had less favorable outcomes in terms of MFS and OS than those without detectable CTC (log-rank p<0.05). Among molecular subtypes of operable breast cancer, the patients with CK-20 mRNA-positive CTC had shorter MFS and OS in triple negative and human epidermal growth factor 2 (HER2) breast cancer subtype (log-rank, p<0.05). Conclusion CK-20 mRNA-positive CTC may lend insight into tumor progression as a prognostic indicator especially in the triple negative and HER2 subtypes of operable breast cancer. PMID:22493626

  9. Excellent Outcomes and Lack of Prognostic Impact of Cell of Origin for Localized Diffuse Large B-cell Lymphoma in the Rituximab Era

    PubMed Central

    Kumar, Anita; Lunning, Matthew A.; Zhang, Zhigang; Migliacci, Jocelyn C.; Moskowitz, Craig H.; Zelenetz, Andrew D.

    2015-01-01

    Summary Therapeutic options for limited-stage diffuse large B cell lymphoma (DLBCL) include short- or full-course R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) +/- radiotherapy. The optimal treatment remains unclear. The prognostic value of cell-of-origin (COO) in early stage DLBCL is unknown. Patients with limited-stage DLBCL (stage I or stage II, non-bulky) treated with R-CHOP +/- involved field radiotherapy (IFRT) from 1999 – 2012 were included. COO by the Hans algorithm was analysed in a subset of patients. Of 261 patients, 30% were stage I (N=82), 37% Stage IE (N=96), <1% stage IXEE (N=1), 18% stage II (N=46) and 14% Stage IIE (N=37). The stage-modified IPI stratified patients into prognostically relevant groups. There was no significant difference in progression-free survival (PFS) or overall survival (OS) for patients in the germinal centre B-cell-like (GCB; n=65) and non-GCB cohorts (n=22). Seventeen patients received R-CHOP x 3-4 cycles (Arm A), 147 received R-CHOP x 3-4 cycles + IFRT (Arm B), 48 received R-CHOP x6 cycles (Arm C), and 50 received R-CHOP x6 cycles +IFRT (Arm D). The outcomes were excellent, with 5-year PFS of 82% and 5-year OS of 93%, and were similar across the 4 treatment groups. In the rituximab era, outcomes for limited-stage DLBCL, regardless of treatment approach, were excellent. Baseline COO was not a significant prognostic factor in patients treated with short-course R-CHOP + IFRT. PMID:26456939

  10. Fire regimes in Russia and their impacts on major biogeochemical cycles

    NASA Astrophysics Data System (ADS)

    Shvidenko, A.; Shchepashchenko, D.; Kraxner, F.; Bartalev, S.

    2015-12-01

    The warming trend in Russia for period of 1976-2014 was more than two times higher than the global one. Change of precipitation was regionally diverse, but on average not enough to compensate the high warming rate. Variability of seasonal weather increased with long dry and warm periods. Severe heat waves are regularly observed in different regions of the country. Three available remote sensing products of spatially explicit distribution of burnt area in Russia (GFED4; Institute of Forest SB RAS, Krasnoyarsk; and Space Research Institute, RAS, Moscow) reported rather consistent average burnt areas for the period of 2000-2010 (from 8.3 to 9.4 x 106 ha year-1); however, the differences for individual years, particularly for 2011-2012 are large. Of the total fire area, about 2/3 were on forest land. A typical feature of fire regimes of recent decades is increasing frequency and severity of mega-fires, which envelope vast regions (up to millions of hectares) with numerous simultaneously burning areas, cause large ecological, economic and social losses and often provide irreversible impacts on forest ecosystems. Such fires occurred in different regions of Russia in 1998 (7.7 x 106 ha of burnt areas), 2002 (8.2), 2003 (16.6), 2005 (8.5), 2006 (12.4), 2007 (8.9), 2008 (16.8), 2009 (10.4), 2010 (7.9), 2011 (8.8 x 106 ha), 2012 (15.8 x 106 ha). We present a full fire carbon budget for 2000-2012 as a proxy of severity of fire regimes, based on 1) a country's Integrated Land Information System, which contains georeferenced land cover, amount of fuel by types and annual burnt areas at resolution of 1km; and 2) regionally distributed models of fire severity. The amount of fuel consumed by fire is estimated at 135 Tg C yr-1 with large interannual variation and uncertainties ~25%. We discuss ecological consequences of fire, its impact on successions, health and productivity of forest ecosystems as well as predicted dynamics of fire regimes over 21st century.

  11. Soil compartment is a major determinant of the impact of simulated rainfall on desert microbiota.

    PubMed

    Aslam, Shazia N; Dumbrell, Alex J; Sabir, Jamal S; Mutwakil, Mohammed H Z; Baeshen, Mohammed M N; Abo-Aba, Salah E M; Clark, Dave R; Yates, Steven A; Baeshen, Nabih A; Underwood, Graham J C; McGenity, Terry J

    2016-12-01

    Although desert soils support functionally important microbial communities that affect plant growth and influence many biogeochemical processes, the impact of future changes in precipitation patterns on the microbiota and their activities is largely unknown. We performed in-situ experiments to investigate the effect of simulated rainfall on bacterial communities associated with the widespread perennial shrub, Rhazya stricta in Arabian desert soils. The bacterial community composition was distinct between three different soil compartments: surface biological crust, root-attached, and the broader rhizosphere. Simulated rainfall had no significant effect on the overall bacterial community composition, but some population-level responses were observed, especially in soil crusts where Betaproteobacteria, Sphingobacteria, and Bacilli became more abundant. Bacterial biomass in the nutrient-rich crust increased three-fold one week after watering, whereas it did not change in the rhizosphere, despite its much higher water retention. These findings indicate that between rainfall events, desert-soil microbial communities enter into stasis, with limited species turnover, and reactivate rapidly and relatively uniformly when water becomes available. However, microbiota in the crust, which was relatively enriched in nutrients and organic matter, were primarily water-limited, compared with the rhizosphere microbiota that were co-limited by nutrients and water. © 2016 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  12. Economic impact of clinical variability in preoperative testing for major outpatient surgery.

    PubMed

    Gil-Borrelli, Christian Carlo; Agustí, Salomé; Pla, Rosa; Díaz-Redondo, Alicia; Zaballos, Matilde

    2016-05-01

    With the purpose of decreasing the existing variability in the criteria of preoperative evaluation and facilitating the clinical decision-making process, our hospital has a protocol of preoperative tests to use with ASA I and ASA II patients. The aim of the study was to calculate the economic impact caused by clinicians' non-adherence to the protocol for the anaesthesiological evaluation of ASA 1 and ASA II patients. A retrospective study of costs with a random sample of 353 patients that were seen in the consultation for Anesthesiology over a period of one year. Aspects related to the costs, patient's profiles and specialties were analysed, according to the degree of fulfillment of the protocol. The lack of adherence to the the protocol was 70%. 130 chest X-rays and 218 ECG were performed without indication. This generated an excess costs of 34 € per patient. Taking into account the expenses of both tests and the attended population undergoing ambulatory surgery during the one-year period, an excess spending for the hospital of between 69.164 € and 83.312 € was estimated. Clinical variability should be reduced and the creation of synergies between the different departments should be enhanced in order to adjust the request for unnecessary complementary tests to decrease health care and to improve the quality of patient care. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. The Impact of Cooperative Quizzes in a Large Introductory Astronomy Course for Non Science Majors

    NASA Astrophysics Data System (ADS)

    Zeilik, Michael; Morris, Vicky J.

    In Astronomy 101 at the University of New Mexico, we carried out a repeated-items experiment on quizzes and tests to investigate the impact of cooperative testing. This trial was the only change in a reformed course format that had been refined over previous semesters. Our research questions were: Did cooperative quizzes result in gains for the class overall? Did these gains "stick" within the semester? In the spring and fall semesters of 2000, students took quizzes individually and in cooperative learning teams, and tests individually. Normalized gain, , on the quizzes averaged about 0.4, and effect size about 0.8 (approximately a 10% increase in class mean score). Repeating selected quiz items on a subsequent test demonstrated that the gain was sustained over a month in both semesters. In addition, we compared demographics of UNM students with those of the National Astronomy Diagnostic Test project. We found that UNM students are similar to the national sample, except in ethnicity (more Hispanic American, fewer White). Based on these results, we judge that our cooperative quiz strategy will likely succeed in other "Astro 101" classes.

  14. Differential Transmembrane Domain GXXXG Motif Pairing Impacts Major Histocompatibility Complex (MHC) Class II Structure*

    PubMed Central

    Dixon, Ann M.; Drake, Lisa; Hughes, Kelly T.; Sargent, Elizabeth; Hunt, Danielle; Harton, Jonathan A.; Drake, James R.

    2014-01-01

    Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II αβ heterodimer in determining molecular structure and function. Our previous studies identified an MHC class II conformer that is marked by the Ia.2 epitope. These Ia.2+ class II conformers are lipid raft-associated and able to drive both tyrosine kinase signaling and efficient antigen presentation to CD4 T cells. Here, we establish that the Ia.2+ I-Ak conformer is formed early in the class II biosynthetic pathway and that differential pairing of highly conserved transmembrane domain GXXXG dimerization motifs is responsible for formation of Ia.2+ versus Ia.2− I-Ak class II conformers and controlling lipid raft partitioning. These findings provide a molecular explanation for the formation of two distinct MHC class II conformers that differ in their inherent ability to signal and drive robust T cell activation, providing new insight into the role of MHC class II in regulating antigen-presenting cell-T cell interactions critical to the initiation and control of multiple aspects of the immune response. PMID:24619409

  15. Impact of Major Coronal Mass Ejections on Geospace during 2005 September 7-13

    NASA Astrophysics Data System (ADS)

    Wang, Yuming; Xue, Xianghui; Shen, Chenglong; Ye, Pinzhong; Wang, S.; Zhang, Jie

    2006-07-01

    We have analyzed five major CMEs originating from NOAA active region (AR) 808 during the period of 2005 September 7-13, when the AR 808 rotated from the east limb to near solar meridian. Several factors that affect the probability of the CMEs' encounter with the Earth are demonstrated. The solar and interplanetary observations suggest that the second and third CMEs, originating from E67° and E47°, respectively, encountered the Earth, while the first CME originating from E77° missed the Earth, and the last two CMEs, although originating from E39° and E10°, respectively, probably only grazed the Earth. On the basis of our ice cream cone mode and CME deflection model, we find that the CME span angle and deflection are important for the probability of encountering Earth. The large span angles allowed the middle two CMEs to hit the Earth, even though their source locations were not close to the solar central meridian. The significant deflection made the first CME totally miss the Earth even though it also had wide span angle. The deflection may also have made the last CME nearly miss the Earth even though it originated close to the disk center. We suggest that, in order to effectively predict whether a CME will encounter the Earth, the factors of the CME source location, the span angle, and the interplanetary deflection should all be taken into account.

  16. Impact of major coronal mass ejections on geo-space during September 7 -- 13, 2005

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Xue, X.; Shen, C.; Ye, P.; Wang, S.; Zhang, J.

    2006-05-01

    We have analyzed five major CMEs originating from NOAA active region (AR) 808 during the period of September 7 to 13, 2005, when the AR 808 rotated from the east limb to near solar meridian. Several factors that affect the probability of the CMEs' encounter with the Earth are demonstrated. The solar and interplanetary observations suggest that the 2nd and 3rd CMEs, originating from E67 and E47 respectively, encountered the Earth, while the 1st CME originating from E77 missed the Earth, and the last two CMEs, originating from E39 and E10 respectively, probably only grazed the Earth. Based on our ice-cream cone model (Xue et al. 2005a) and CME deflection model (Wang et al. 2004b), we find that the CME span angle and deflection are important for the probability of encountering. The large span angles make middle two CMEs hit the Earth, though their source locations were not close to the solar central meridian. The significant deflection makes the first CME totally missed the Earth though it also had wide span angle. The deflection may also make the last CME nearly missed the Earth though it originated close to the disk center. We suggest that, in order to effectively predict whether a CME will encounter the Earth, the factors of the CME source location, the span angle, and the interplanetary deflection should all be taken into account.

  17. Does Comorbid Social Anxiety Disorder Impact the Clinical Presentation of Principal Major Depressive Disorder?

    PubMed Central

    Dalrymple, Kristy L.; Zimmerman, Mark

    2008-01-01

    Background Although previous research has examined comorbidity in principal Social Anxiety Disorder (SAD), few studies have examined the disorders for which those with comorbid SAD seek treatment. Further, studies have shown that depressive disorders often are associated with SAD, but few have examined the clinical characteristics of patients with this particular comorbidity. Method The current study examined the prevalence of various principal Axis I disorders in 577 individuals diagnosed with comorbid SAD. Results Consistent with previous research, Major Depressive Disorder (MDD) was the most frequent principal diagnosis in patients with comorbid SAD. Those with principal MDD and comorbid SAD (MDD-SAD) were compared to those with MDD without SAD (MDD) on demographic and clinical characteristics. Patients with MDD-SAD versus those with MDD were more severe in terms of social functioning, duration of depressive episode, suicidal ideation, time out of work, presence of current alcohol abuse/dependence, and age of onset of MDD. Social functioning, duration of episode, suicidal ideation, and age of onset of MDD remained significant even after controlling for additional comorbid disorders. Conclusions Findings suggest the need for future research to determine how treatments could be adapted for this commonly occurring comorbidity. PMID:17188365

  18. The Global Burden of Liver Disease: The Major Impact of China

    PubMed Central

    Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

    2016-01-01

    Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus, HBV), nonalcoholic fatty liver disease and alcoholic liver disease affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its “leader in liver diseases” title by investing large amounts of money in funding research, vaccines and drug development for liver diseases, and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China. PMID:25164003

  19. Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity

    PubMed Central

    Li, Li; Shelton, Richard Charles; Chassan, Rachel Ann; Hammond, John Charles; Gower, Barbara Ann; Garvey, Timothy W

    2016-01-01

    Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes. PMID:27274905

  20. The global burden of liver disease: the major impact of China.

    PubMed

    Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

    2014-12-01

    Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China.

  1. Negative impact of urban habitat on immunity in the great tit Parus major.

    PubMed

    Bailly, Juliette; Scheifler, Renaud; Belvalette, Marie; Garnier, Stéphane; Boissier, Elena; Clément-Demange, Valérie-Anne; Gète, Maud; Leblond, Matthieu; Pasteur, Baptiste; Piget, Quentin; Sage, Mickaël; Faivre, Bruno

    2016-12-01

    Urban habitats are described as having an overall negative influence on many fitness-related traits in several bird species, but a vital function such as immunity remains poorly studied. The immune response is strongly linked to individual condition, which partly depends on resource availability and the parasitic context that often differ between urban and natural habitats. A difference between the immunity of populations dwelling in urban areas and populations from more natural habitats can, therefore, be hypothesized. We conducted a 2-year experimental study on great tits (Parus major) in urban and forest areas. We stimulated the constitutive immunity of nestlings and assessed both the inflammatory response by measuring the plasma levels of haptoglobin, an inflammatory marker, and its activation cost through the loss of body mass. In addition, we checked the nestlings for ectoparasites and assessed haemosporidian prevalence in adults. Nestlings from urban sites produced relatively less haptoglobin and lost more body mass than those from forest sites, which suggests that the activation of constitutive immunity is more costly for birds living in urban sites than for those living in the forest. We detected no ectoparasite in birds in both habitats. However, urban adults showed lower haemosporidian prevalence than forest ones, suggesting a reduced exposure to these parasites and their vectors in towns. Overall, our study provides evidence for an immune difference between urban and forest populations. Because immunity is crucial for organism fitness, it is of prime interest to identify causes and processes at the origin of this difference.

  2. Impact of early-life stress and resilience on patients with major depressive disorder.

    PubMed

    Seok, Jeong-Ho; Lee, Kyoung-Uk; Kim, Won; Lee, Seung-Hwan; Kang, Eun-Ho; Ham, Byung-Joo; Yang, Jong-Chul; Chae, Jeong-Ho

    2012-11-01

    Early-life stress (ELS) has a long-lasting effect on affective function and may entail an increased risk for major depressive disorder (MDD). However, resilience can play a protective role against developing psychopathology. In this study, we investigated the relationships of depressive symptoms with ELS and resilience in MDD. Twenty-six patients with MDD as well as age- and gender-matched healthy controls were included in this study. Each subject was assessed concerning ELS, resilience, and depressive symptom severity with self-report questionnaires. Independent samples t-test and Mann-Whitney test were performed to compare ELS and resilience between the patient and control groups. Spearman correlation analyses and linear regression analysis were conducted to investigate significant ELS and resilience factors associated with depressive symptoms. In the MDD patient group, subjects reported greater exposure to inter- parental violence, and five factor scores on the resilience scale were significantly lower in comparison to the control group. In linear regression analysis, in regards to resilience, depressive symptom score was significantly associated with self-confidence and self-control factors; however, ELS demonstrated no significant association with depressive symptoms. Among resilience factors, self-confidence and self-control may ameliorate depressive symptoms in MDD. ELS, including inter-parental violence, physical abuse and emotional abuse, might be a risk factor for developing depression. Assessment of early-life stress and intervention programs for increasing resilience capacity would be helpful in treating MDD.

  3. Causes of different impact of Major Baltic Inflows on cod reproduction in the Gotland Basin of the Baltic Sea

    NASA Astrophysics Data System (ADS)

    Karaseva, E. M.; Zezera, A. S.

    2016-09-01

    The impact of the Major Baltic Inflows (MBIs) of 1976, 1993, and 2003 on cod reproduction in the Gotland Basin of the Baltic Sea is considered based on calculations of the eastern Baltic cod egg abundance and offspring survival indices. The reproductive success (1976-1977) was defined by the elevation of the 11 psu isohaline and deepening of the 2 mL/L isooxygene surface, which provided the formation of a water layer suitable for cod spawning at a depth of 90-130 m. Prerequisites of the appearance of the reproductive layer in 1976-1977 were a previously high salinity level and penetrating two successive MBIs in one year. The cause of the weak MBI impact in 1993 was the previous salinity minimum; in 2003 it was rapid oxygen depletion due to an increase in temperature. As a result of their weaker influence, small and fragmented cod spawning biotopes appeared in the Gotland Basin.

  4. Psoriasis has a major secondary impact on the lives of family members and partners.

    PubMed

    Eghlileb, A M; Davies, E E G; Finlay, A Y

    2007-06-01

    Psoriasis affects the quality of life (QoL) of relatives and partners of patients with psoriasis, but little is known about this secondary impact. To identify the different ways in which the lives of relatives and partners of people with psoriasis are affected by the disease. Relatives and partners of patients with psoriasis participated. Subjects were excluded if they had any skin disease. The severity of the psoriasis of the patients was measured using the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and Psoriasis Disability Index (PDI). Subjects either had intensive qualitative interviews with one researcher or responded to a postal questionnaire. Both methods identified ways in which their relative's or partner's psoriasis had affected their lives. Thirty-three subjects were interviewed and 30 replied by postal questionnaire. Twenty-eight of the 63 subjects were relatives (seven men and 21 women) and 35 were partners (16 men and 19 women). The median age was 51 years (range 20-80). The patients (n = 63) had a mean DLQI of 10, mean PDI of 13.8 and mean PASI of 5.2. Forty different aspects of QoL impairment of relatives and partners were identified. The percentage of subjects in whom any of these aspects were mentioned is illustrated in six different categories. Seventy per cent stated that the treatment of their relative or partner resulted in them having to spend extra time on housework; 57% described psychological pressures including anxiety, being upset and being worried about the patient's future; 55% described social disruption due to lack of social confidence either because of embarrassment or because of the time required for care duties; 44% described limitations to holiday plans, sport and leisure activities and evenings out; 37% described limitations on their daily activities such as shopping, work and time spent with other family members; 37% felt that their close relationships had deteriorated. Only 8% described no

  5. Impacts and mitigation of excess diesel-related NOx emissions in 11 major vehicle markets

    NASA Astrophysics Data System (ADS)

    Anenberg, Susan C.; Miller, Joshua; Minjares, Ray; Du, Li; Henze, Daven K.; Lacey, Forrest; Malley, Christopher S.; Emberson, Lisa; Franco, Vicente; Klimont, Zbigniew; Heyes, Chris

    2017-05-01

    Vehicle emissions contribute to fine particulate matter (PM2.5) and tropospheric ozone air pollution, affecting human health, crop yields and climate worldwide. On-road diesel vehicles produce approximately 20 per cent of global anthropogenic emissions of nitrogen oxides (NOx), which are key PM2.5 and ozone precursors. Regulated NOx emission limits in leading markets have been progressively tightened, but current diesel vehicles emit far more NOx under real-world operating conditions than during laboratory certification testing. Here we show that across 11 markets, representing approximately 80 per cent of global diesel vehicle sales, nearly one-third of on-road heavy-duty diesel vehicle emissions and over half of on-road light-duty diesel vehicle emissions are in excess of certification limits. These excess emissions (totalling 4.6 million tons) are associated with about 38,000 PM2.5- and ozone-related premature deaths globally in 2015, including about 10 per cent of all ozone-related premature deaths in the 28 European Union member states. Heavy-duty vehicles are the dominant contributor to excess diesel NOx emissions and associated health impacts in almost all regions. Adopting and enforcing next-generation standards (more stringent than Euro 6/VI) could nearly eliminate real-world diesel-related NOx emissions in these markets, avoiding approximately 174,000 global PM2.5- and ozone-related premature deaths in 2040. Most of these benefits can be achieved by implementing Euro VI standards where they have not yet been adopted for heavy-duty vehicles.

  6. Impacts and mitigation of excess diesel-related NOx emissions in 11 major vehicle markets.

    PubMed

    Anenberg, Susan C; Miller, Joshua; Minjares, Ray; Du, Li; Henze, Daven K; Lacey, Forrest; Malley, Christopher S; Emberson, Lisa; Franco, Vicente; Klimont, Zbigniew; Heyes, Chris

    2017-05-25

    Vehicle emissions contribute to fine particulate matter (PM2.5) and tropospheric ozone air pollution, affecting human health, crop yields and climate worldwide. On-road diesel vehicles produce approximately 20 per cent of global anthropogenic emissions of nitrogen oxides (NOx), which are key PM2.5 and ozone precursors. Regulated NOx emission limits in leading markets have been progressively tightened, but current diesel vehicles emit far more NOx under real-world operating conditions than during laboratory certification testing. Here we show that across 11 markets, representing approximately 80 per cent of global diesel vehicle sales, nearly one-third of on-road heavy-duty diesel vehicle emissions and over half of on-road light-duty diesel vehicle emissions are in excess of certification limits. These excess emissions (totalling 4.6 million tons) are associated with about 38,000 PM2.5- and ozone-related premature deaths globally in 2015, including about 10 per cent of all ozone-related premature deaths in the 28 European Union member states. Heavy-duty vehicles are the dominant contributor to excess diesel NOx emissions and associated health impacts in almost all regions. Adopting and enforcing next-generation standards (more stringent than Euro 6/VI) could nearly eliminate real-world diesel-related NOx emissions in these markets, avoiding approximately 174,000 global PM2.5- and ozone-related premature deaths in 2040. Most of these benefits can be achieved by implementing Euro VI standards where they have not yet been adopted for heavy-duty vehicles.

  7. Genetic background has a major impact on differences in sleep resulting from environmental influences in Drosophila.

    PubMed

    Zimmerman, John E; Chan, May T; Jackson, Nicholas; Maislin, Greg; Pack, Allan I

    2012-04-01

    To determine the effect of different genetic backgrounds on demographic and environmental interventions that affect sleep and evaluate variance of these measures; and to evaluate sleep and variance of sleep behaviors in 6 divergent laboratory strains of common origin. Assessment of the effects of age, sex, mating status, food sources, and social experience using video analysis of sleep behavior in 2 different strains of Drosophila, white(1118ex) (w(1118ex)) and white Canton-S (w(CS10)). Sleep was also determined for 6 laboratory strains of Canton-S and 3 inbred lines. The variance of total sleep was determined for all groups and conditions. The circadian periods and the effects of age upon sleep were the same between w(1118ex) and w(CS10) strains. However, the w(1118ex) and w(CS10) strains demonstrated genotype-dependent differences in the effects upon sleep of sex, mating status, social experience, and being on different foods. Variance of total sleep was found to differ in a genotype dependent manner for interventions between the w(1118ex) and w(CS10) strains. Six different laboratory Canton-S strains were found to have significantly different circadian periods (P < 0.001) and sleep phenotypes (P < 0.001). Three inbred lines showed reduced variance for sleep measurements. One must control environmental conditions in a rigorously consistent manner to ensure that sleep data may be compared between experiments. Genetic background has a significant impact upon changes in sleep behavior and variance of behavior due to demographic factors and environmental interventions. This represents an opportunity to discover new genes that modify sleep/wake behavior.

  8. Estimating System Impact of Earthquakes on a Major Metropolitan Roadway Network

    NASA Astrophysics Data System (ADS)

    Perkins, D. M.; Taylor, C. E.; Werner, S. D.

    2003-12-01

    The impact of an earthquake on the Memphis, TN, roadway system has been estimated using a prototype computer program, REDARS (Risks from Earthquake DAmage to Roadway Systems). For scenario earthquakes, the program computes ground motions and ground deformations at bridges and other components throughout the system. Then, estimates of costs and times to repair this damage, together with the component's ability to accommodate traffic flows during repairs, are estimated, and these are used to establish modified post-earthquake system states at various times after the earthquake. Transportation network analysis procedures are then applied to each system state, in order to estimate how post-earthquake traffic flows and travel times are affected by these various roadway closures. Consequences of this damage to the roadway system, in terms of economic losses, reduced access to key locations in the regions (e.g., hospitals, airports, etc.) are then estimated. Uncertainties are incorporated throughout. Using Monte Carlo simulation in earthquake occurrence and modeled uncertainties, the program was used to produce a 50,000-year history of annual estimated drive-time loss in dollars, with nearly 800 non-zero loss years. The ordered list of annual losses makes up an empirical annual-rate loss distribution function. From this list, likelihood functions for the 500-yr and 2500-yr losses can be obtained, yielding most likely values of about 300 million dollars and 600 million, respectively, with ranges of uncertainty (10th to 90th percentile) of about 10 and 20 percent. The ordered list of non-zero losses is nearly exponentially distributed. This simple structure permits estimation, through the employment of bootstrapping with variance-reduction techniques, of the average conditional loss around several tens of times more precise than the average of the simulated losses. The model for earthquake magnitude, locations, and occurrence frequency has been taken from the US Geological

  9. Routine aspiration of subglottic secretions after major heart surgery: impact on the incidence of ventilator-associated pneumonia.

    PubMed

    Pérez Granda, M J; Barrio, J M; Hortal, J; Muñoz, P; Rincón, C; Bouza, E

    2013-12-01

    Aspiration of subglottic secretions (ASS) is recommended in patients requiring mechanical ventilation for ≥48h. We assessed the impact of the introduction of ASS routinely in all patients after major heart surgery in an ecological study comparing ventilator-acquired pneumonia (VAP) incidence, days of mechanical ventilation, and cost of antimicrobial agents before and after the implementation of ASS. Before and after the intervention the results (per 1000 days) were: VAP incidence, 23.92 vs 16.46 (P = 0.04); cost of antimicrobials, €71,384 vs €63,446 (P = 0.002); and days of mechanical ventilation, 507.5 vs 377.5 (P = 0.009). From the moment of induction of anaesthesia all patients undergoing major heart surgery should routinely receive ASS.

  10. A major impact of the influenza seasonal epidemic on intensive care units, Réunion, April to August 2016

    PubMed Central

    Filleul, Laurent; Ranoaritiana, Dany Bakoly; Balleydier, Elsa; Vandroux, David; Ferlay, Clémence; Jaffar-Bandjee, Marie-Christine; Jaubert, Julien; Roquebert, Bénédicte; Lina, Bruno; Valette, Martine; Hubert, Bruno; Larrieu, Sophie; Brottet, Elise

    2016-01-01

    The 2016 seasonal influenza in Réunion in the southern hemisphere, was dominated by influenza A(H1N1)pdm09 (possibly genogroup 6B.1). An estimated 100,500 patients with acute respiratory infection (ARI) consulted a physician (cumulative attack rate 11.9%). Sixty-six laboratory-confirmed cases (65.7/100,000 ARI consultations) were hospitalised in an intensive care unit, the highest number since 2009. Impact on intensive care units was major. Correlation between severe cases was 0.83 between Réunion and France and good for 2009 to 2015. PMID:27918264

  11. The impact of spirituality before and after treatment of major depressive disorder.

    PubMed

    Peselow, Eric; Pi, Sarah; Lopez, Enrique; Besada, André; Ishak, Waguih William

    2014-03-01

    The authors sought to assess spirituality in depressed patients and evaluate whether the degree of initial depressive symptoms and response to pharmacotherapy treatment has a correlation with degree of spirituality and belief in God. Our participants included 84 patients who presented to a depression/anxiety clinic for naturalistic treatment of their depressive illness over the course of two years. All patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for major depression, as confirmed by structured interviews using the Structured Clinical Interview for DSM-IV, and were treated with selective serotonin reuptake inhibitors for eight weeks. Patients were evaluated at baseline and after treatment using the Montgomery Asberg Depression Rating Scale, the Beck Hopelessness Scale, the Dysfunctional Attitude Scale, and the Spiritual Orientation to Life scale. At baseline, patients reporting greater spirituality had significantly lower measures of hopelessness, dysfunctional attitudes, and depressive symptoms. Those who believed in God had a greater mean change score than those who did not on the Montgomery Asberg Depression Rating Scale, the Beck Hopelessness Scale, and the Dysfunctional Attitude Scale, with the Montgomery Asberg Depression Rating Scale showing the greatest mean change score. Significant correlations were detected between the Spiritual Orientation to Life scale score and the Montgomery Asberg Depression Rating Scale, the Beck Hopelessness Scale, and the Dysfunctional Attitude Scale pre-scores, post-scores, and change scores. The findings suggest that greater spirituality is associated with less severe depression. Moreover, the degree to which the measures of depressive symptom severity, hopelessness, and cognitive distortions improved over the course of eight weeks was significantly greater for those patients who were more spiritual.

  12. Changing Impact of Modifiable Risk Factors on the Incidence of Major Outcomes of Type 1 Diabetes

    PubMed Central

    Miller, Rachel G.; Secrest, Aaron M.; Ellis, Demetrius; Becker, Dorothy J.; Orchard, Trevor J.

    2013-01-01

    OBJECTIVE The incidence of type 1 diabetes complications appears to be decreasing, but relative contributions of risk factors are unclear. We thus estimated the effect of modifiable risk factors on the incidence of a composite end point, major outcomes of diabetes (MOD). RESEARCH DESIGN AND METHODS The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study was used to derive two cohorts based on diabetes diagnosis year (1960–1969 and 1970–1980). Baseline exam data in the current analysis for the 1960s group were collected in 1986–1988 and for the 1970s in 1996–1998. Each group was followed for 8 years for MOD incidence (diabetes-related death, myocardial infarction, revascularization procedure/blockage ≥50%, stroke, end-stage renal disease, blindness, and amputation). Assessed risk factors include the following: HbA1c, hypertension, microalbuminuria, BMI, hypercholesterolemia, and smoking. Accelerated failure time models were used to estimate the acceleration factor. RESULTS MOD incidence decreased in the 1970s cohort (15.8% [95% CI 11.6–21.4]) compared with the 1960s (22.6% [17.0–29.1]) over the 8-year follow-up (P = 0.06). Hypertension and microalbuminuria were associated with significantly accelerated MOD incidence in both cohorts (P < 0.01 for both). High HbA1c (P = 0.0005), hypercholesterolemia (P = 0.01), and current smoking (P = 0.003) significantly accelerated the incidence of MOD in the 1960s but not 1970s cohort. BMI was not associated with MOD in either cohort. CONCLUSIONS These results suggest that hypertension and microalbuminuria remain important predictors of complications that are not being adequately addressed. PMID:24170748

  13. Alteration of T Cell Subtypes in Beta-Thalassaemia Major: Impact of Ferritin Level

    PubMed Central

    Karimi, Leila; Beshkar, Pezhman

    2016-01-01

    Introduction Oxidative damage and regular antigenic stimulation are main factors in accelerating immunosenescence. The present study was conducted to investigate new concepts of early immunosenescence in thalassaemia patients. Materials and Methods Twenty seven beta-thalassaemia major patients and a group of matched healthy volunteers aged 10-30 years in Shahrekord, Iran were recruited into the study. Ferritin level was determined and CD4 or CD8 T cells were analysed versus phenotyping markers, CD27, CD28, CD57 and CCR7, by flowcytometry. Data were analysed by Mann-Whitney and Spearman’s correlation coefficient test in SPSS 11.5. Results Absolute lymphocytosis and partial decrease in T cells were observed in the patients. CD4+CD57+ and CD4+CCR7- T cells were significantly higher, whereas CD8+CD27+ and CD8+CCR7+ T cells were partially higher in patients. A negative correlation was observed between ferritin level and number of CD8+CD27+ and CD8+CCR7+ T cells, whereas the correlation was positive between ferritin level and number of CD57+ T cells. Conclusion Moderate alteration of T cell repertoire and increase in CCR27-, CCR7-, and CD57+ T cells could reflect antigenic stimulation, decline in naïve T cells, and being closer to terminally differentiated cells. Effect of iron overload is potentially explained by positive correlation of blood transfusion and ferritin level with frequency of CD3+CD27- and that of ferritin with frequency of CD57+ T cells. PMID:27042462

  14. The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

    PubMed

    Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

    2015-08-01

    Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity.

  15. Impact of electroconvulsive therapy on magnetoencephalographic correlates of dysfunctional emotional processing in major depression.

    PubMed

    Zwanzger, Peter; Klahn, Anna Luisa; Arolt, Volker; Ruland, Tillmann; Zavorotnyy, Maxim; Sälzer, Johannes; Domschke, Katharina; Junghöfer, Markus

    2016-04-01

    In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  16. Prognostic factors and impact of adjuvant treatments on local and metastatic relapse of soft-tissue sarcoma patients in the competing risks setting.

    PubMed

    Italiano, Antoine; Le Cesne, Axel; Mendiboure, Jean; Blay, Jean-Yves; Piperno-Neumann, Sophie; Chevreau, Christine; Delcambre, Corinne; Penel, Nicolas; Terrier, Philippe; Ranchere-Vince, Dominique; Lae, Marick; Le Guellec, Sophie; Michels, Jean-Jacques; Robin, Yves Marie; Bellera, Carine; Bonvalot, Sylvie

    2014-11-01

    In the medical literature many analyses of outcomes of sarcoma patients were performed without regard to the problem of "competing risks." We analyzed local relapse-free and metastasis-free survival in a population of 3255 adult patients with a primary soft-tissue sarcoma (STS) included in the French Sarcoma Group database. Cumulative incidence of local and metastatic relapse was estimated by accounting for death as a competing event. On multivariate analysis, age, tumor site, histological subtype, and grade were independent adverse prognostic factors for local relapse, whereas tumor depth and size had no influence. Histological subtype, tumor depth, tumor size, and grade were independent adverse prognostic factors for metastatic relapse. Despite a higher incidence of competing deaths in patients managed with adjuvant radiotherapy than in patients not receiving radiotherapy, adjuvant radiotherapy was associated with a significant benefit in terms of local relapse-free survival. Despite a similar cumulative incidence of competing deaths in patients with grade 2 and grade 3 disease, we found that the benefit of adjuvant chemotherapy was present only in patients with grade 3 and not in patients with grade 2 disease. In the setting of competing risks, tumor biology reflected by histological grade is a crucial predictor of local relapse, whereas tumor depth and size have poor if any influence. Grade could also predict the benefit of adjuvant chemotherapy in patients with STS. © 2014 American Cancer Society.

  17. Ki-67 and PCNA Expression in Canine Mammary Tumors and Adjacent Nonneoplastic Mammary Glands: Prognostic Impact by a Multivariate Survival Analysis.

    PubMed

    Carvalho, M I; Pires, I; Prada, J; Lobo, L; Queiroga, F L

    2016-11-01

    The assessment of tumor proliferation has been considered a determining prognostic factor in canine mammary tumors (CMTs). However, no studies have assessed the prognostic importance of proliferation in adjacent nonneoplastic mammary glands. We included 64 CMTs (21 benign and 43 malignant) and studied the proliferation index (PI) of Ki-67 and proliferating cell nuclear antigen (PCNA) together with several clinicopathological characteristics. A positive and statistically significant correlation between the PI of Ki-67 and PCNA in tumors and adjacent nonneoplastic mammary glands was observed in benign and malignant tumors. Tumor size, skin ulceration, histological type, mitotic index, nuclear grade, differentiation grade, histological grade of malignancy, lymph node metastasis, Ki-67, and PCNA expression in tumors and adjacent nonneoplastic mammary glands were statistically associated with overall survival by univariate analysis in malignant cases (n = 43). Histological grade of malignancy and high intratumoral PCNA retained their significance by multivariate analysis arising as independent predictors of overall survival. Interestingly, the PI of Ki-67 and PCNA of adjacent nontumoral mammary glands were associated with clinicopathological features of tumor aggressiveness and shorter overall survival, demonstrating the need to better explore this adjacent non-neoplastic tissue. © The Author(s) 2016.

  18. Prognostic utility of coronary computed tomographic angiography

    PubMed Central

    Otaki, Yuka; Berman, Daniel S.; Min, James K.

    2013-01-01

    Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a noninvasive method that enables accurate detection and exclusion of anatomically obstructive coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. There are numerous potential advantages of CCTA beyond simply luminal stenosis assessment including quantification of atherosclerotic plaque volume as well as assessment of plaque composition, extent, location and distribution. In recent years, an array of studies has evaluated the prognostic utility of CCTA findings of CAD for the prediction of major adverse cardiac events, all-cause death and plaque instability. This prognostic information enhances risk stratification and, if properly acted upon, may improve medical therapy and/or behavioral changes that may enhance event-free survival. The goal of the present article is to summarize the current status of the prognostic utility of CCTA findings of CAD. PMID:23809386

  19. ATM has a major role in the double-strand break repair pathway dysregulation in sporadic breast carcinomas and is an independent prognostic marker at both mRNA and protein levels.

    PubMed

    Rondeau, S; Vacher, S; De Koning, L; Briaux, A; Schnitzler, A; Chemlali, W; Callens, C; Lidereau, R; Bièche, I

    2015-03-17

    Ataxia telangiectasia mutated (ATM) is a kinase that has a central role in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of DNA double-strand breaks (DSB). In breast cancer, a low level of ATM was correlated with poor outcome; however, the molecular mechanism of this downregulation is still unclear. We used qRT-PCR assay to quantify mRNA levels of ATM gene in 454 breast tumours from patients with known clinical/pathological status and outcome; reverse phase protein arrays (RPPA) were used to assess the levels of ATM and 14 proteins in 233 breast tumours. ATM mRNA was associated with poor metastasis-free survival (MFS) (P=0.00012) on univariate analysis. ATM mRNA and protein levels were positively correlated (P=0.00040). A low level of ATM protein was correlated with poorer MFS (P=0.000025). ATM expression at mRNA or protein levels are independent prognostic factors on multivariate analysis (P=0.00046 and P=0.00037, respectively). The ATM protein level was positively correlated with the levels of six proteins of the DSB repair pathway: H2AX (P<0.0000001), XRCC5 (P<0.0000001), NBN (P<0.0000001), Mre11 (P=0.0000029), Rad50 (P=0.0064), and TP53BP1 (P=0.026), but not with proteins involved in other pathways that are altered in cancer. Low expression of ATM protein was significantly associated with high miR-203 expression (P=0.011). We confirmed that ATM expression is an independent prognostic marker at both RNA and protein levels. We showed that alteration of ATM is involved in dysregulation of the DSB repair pathway. Finally, miR-203 may be responsible for downregulation of ATM in breast cancers.

  20. ATM has a major role in the double-strand break repair pathway dysregulation in sporadic breast carcinomas and is an independent prognostic marker at both mRNA and protein levels

    PubMed Central

    Rondeau, S; Vacher, S; De Koning, L; Briaux, A; Schnitzler, A; Chemlali, W; Callens, C; Lidereau, R; Bièche, I

    2015-01-01

    Background: Ataxia telangiectasia mutated (ATM) is a kinase that has a central role in the maintenance of genomic integrity by activating cell cycle checkpoints and promoting repair of DNA double-strand breaks (DSB). In breast cancer, a low level of ATM was correlated with poor outcome; however, the molecular mechanism of this downregulation is still unclear. Methods: We used qRT–PCR assay to quantify mRNA levels of ATM gene in 454 breast tumours from patients with known clinical/pathological status and outcome; reverse phase protein arrays (RPPA) were used to assess the levels of ATM and 14 proteins in 233 breast tumours. Results: ATM mRNA was associated with poor metastasis-free survival (MFS) (P=0.00012) on univariate analysis. ATM mRNA and protein levels were positively correlated (P=0.00040). A low level of ATM protein was correlated with poorer MFS (P=0.000025). ATM expression at mRNA or protein levels are independent prognostic factors on multivariate analysis (P=0.00046 and P=0.00037, respectively). The ATM protein level was positively correlated with the levels of six proteins of the DSB repair pathway: H2AX (P<0.0000001), XRCC5 (P<0.0000001), NBN (P<0.0000001), Mre11 (P=0.0000029), Rad50 (P=0.0064), and TP53BP1 (P=0.026), but not with proteins involved in other pathways that are altered in cancer. Low expression of ATM protein was significantly associated with high miR-203 expression (P=0.011). Conclusion: We confirmed that ATM expression is an independent prognostic marker at both RNA and protein levels. We showed that alteration of ATM is involved in dysregulation of the DSB repair pathway. Finally, miR-203 may be responsible for downregulation of ATM in breast cancers. PMID:25742469