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ABSTRACT: Subjective measurement of physical activity using questionnaires has prognostic value in COPD. However, their lack of accuracy and large individual variability limit their use for evaluation on an individual basis. We evaluated the capacity of the objective measurement of daily physical activity in patients with COPD using accelerometers to estimate their prognostic value.
In 173 consecutive subjects with moderate to very severe COPD, daily physical activity was measured using a triaxial accelerometer providing a mean of 1-min movement epochs as vector magnitude units (VMUs). Patients were evaluated by lung function testing and 6-min walk, incremental exercise, and constant work rate tests. Patients were followed for 5 to 8 years, and the end points were all-cause mortality, hospitalization for COPD exacerbation, and annual declining FEV(1).
After adjusting for relevant confounders, a high VMU decreased the mortality risk (adjusted hazard ratio [HR], 0.986; 95% CI, 0.981-0.992), and in a multivariate model, comorbidity, endurance time, and VMU were retained as independent predictors of mortality. The time until first admission due to COPD exacerbation was shorter for the patients with lower levels of VMU (adjusted HR, 0.989; 95% CI, 0.983-0.995). Moreover, patients with higher VMU had a lower hospitalization risk than those with a low VMU (adjusted incidence rate ratio, 0.099; 95% CI, 0.033-0.293). In contrast, VMU was not identified as an independent predictor of the annual FEV(1) decline.
The objective measurement of the daily physical activity in patients with COPD using an accelerometer constitutes an independent prognostic factor for mortality and hospitalization due to severe exacerbation.
Chest 01/2012; 142(2):338-46. · 5.25 Impact Factor
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Angelo Gámez-Pozo,
Iker Sánchez-Navarro,
Enrique Calvo,
María Teresa Agulló-Ortuño,
Rocío López-Vacas,
Esther Díaz,
Emilio Camafeita,
Manuel Nistal, Rosario Madero,
Enrique Espinosa,
Juan Antonio López,
Juan Ángel Fresno Vara
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ABSTRACT: With the completion of the human genome sequence, biomedical sciences have entered in the "omics" era, mainly due to high-throughput genomics techniques and the recent application of mass spectrometry to proteomics analyses. However, there is still a time lag between these technological advances and their application in the clinical setting. Our work is designed to build bridges between high-performance proteomics and clinical routine. Protein extracts were obtained from fresh frozen normal lung and non-small cell lung cancer samples. We applied a phosphopeptide enrichment followed by LC-MS/MS. Subsequent label-free quantification and bioinformatics analyses were performed. We assessed protein patterns on these samples, showing dozens of differential markers between normal and tumor tissue. Gene ontology and interactome analyses identified signaling pathways altered on tumor tissue. We have identified two proteins, PTRF/cavin-1 and MIF, which are differentially expressed between normal lung and non-small cell lung cancer. These potential biomarkers were validated using western blot and immunohistochemistry. The application of discovery-based proteomics analyses in clinical samples allowed us to identify new potential biomarkers and therapeutic targets in non-small cell lung cancer.
PLoS ONE 01/2012; 7(3):e33752. · 4.09 Impact Factor
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Jaime Feliu,
Ana María Jiménez-Gordo, Rosario Madero,
José Ramón Rodríguez-Aizcorbe,
Enrique Espinosa,
Javier Castro,
Jesús Domingo Acedo,
Beatriz Martínez,
Alberto Alonso-Babarro,
Raquel Molina,
Juan Carlos Cámara,
María Luisa García-Paredes,
Manuel González-Barón
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ABSTRACT: Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease.
From February 1, 2003, to December 31, 2005, 406 consecutive terminally ill patients were entered into the study. We analyzed 38 features prognostic of life expectancy among terminally ill patients by multivariable Cox regression and identified the most accurate and parsimonious model by backward variable elimination according to the Akaike information criterion. Five clinical and laboratory variables were built into a nomogram to estimate the probability of patient survival at 15, 30, and 60 days. We validated and calibrated the nomogram with an external validation cohort of 474 patients who were treated from June 1, 2006, through December 31, 2007.
The median overall survival was 29.1 days for the training set and 18.3 days for the validation set. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, lymphocyte levels, albumin levels, and time from initial diagnosis to diagnosis of terminal disease were retained in the multivariable Cox proportional hazards model as independent prognostic factors of survival and formed the basis of the nomogram. The nomogram had high predictive performance, with a bootstrapped corrected concordance index of 0.70, and it showed good calibration. External independent validation revealed 68% predictive accuracy.
We developed a highly accurate tool that uses basic clinical and analytical information to predict the probability of survival at 15, 30, and 60 days in terminally ill cancer patients. This tool can help physicians making decisions on clinical care at the end of life.
CancerSpectrum Knowledge Environment 11/2011; 103(21):1613-20. · 14.07 Impact Factor
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ABSTRACT: To examine perinatal morbidity and rate of hypoxic-ischemic encephalopathy in infants exposed to intrapartum sentinel events.
Retrospective cohort study from 2000-2005. Perinatal mortality, perinatal morbidity and rate of hypoxic-ischemic encephalopathy were compared in 3 groups of infants exposed to different risk factors for perinatal asphyxia (sentinel events, nonreassuring fetal status, elective cesarean section).
Five hundred eighty-six infants were studied. Perinatal mortality was 6% in the sentinel event group and 0.3% in the nonreassuring fetal status group (relative risk, 2.4; 95% confidence interval, 1.95-2.94). Perinatal morbidity was 2-6 times more frequent in infants exposed to sentinel events; the incidence of hypoxic-ischemic encephalopathy was 10%, compared with 2.5% in the nonreassuring fetal status group (relative risk, 1.93; 95% confidence interval, 1.49-2.52). No infant in the elective cesarean section group died, had perinatal morbidity, or developed encephalopathy.
Intrapartum sentinel events are associated with a high incidence of perinatal morbidity and hypoxic-ischemic encephalopathy.
American journal of obstetrics and gynecology 10/2011; 206(2):148.e1-7. · 3.28 Impact Factor
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ABSTRACT: Patients with advanced cancer often experience multiple concurrent symptoms. Few studies have explored symptom clusters (SCs) in this population.
The aim of the present study was to explore SCs in advanced cancer, evaluate the characteristics associated with various clusters, and determine their relationship to survival.
This study included patients in the palliative care program of the Hospital Universitario La Paz from 2003 to 2005. The Edmonton Symptom Assessment System and a supplement including 13 other symptoms were used to detect symptoms. Principal component analysis was performed to determine symptom relationships and compare SCs with associated parameters.
In total, 406 patients were included, 61% men and 39% women. The median age was 66.4 (range 18-95). The most common primaries were gastrointestinal (35%), lung (25%), genitourinary (8%), breast (5%), and head and neck (5%) carcinomas. The following clusters were identified: confusion (cognitive impairment, agitation, urinary incontinence), neuropsychological (anxiety, depression, and insomnia), anorexia-cachexia (anorexia, weight loss, and tiredness), and gastrointestinal (nausea and vomiting). The presence of these SCs was influenced by primary cancer site, gender, age, and performance status. Survival was related to the number of SCs present in a given patient: zero SC, 52 days; one SC, 38 days; two SCs, 23 days; and three to four SCs, 19 days; P < 0.001.
Different SCs can be identified in patients with advanced cancer. These SCs are influenced by primary cancer site, gender, age, and Eastern Cooperative Oncology Group performance status, and they can have prognostic value.
Journal of pain and symptom management 03/2011; 42(1):24-31. · 2.42 Impact Factor
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ABSTRACT: The purpose of this study was to identify factors associated with at-home death among patients with advanced cancer and create a decision-making model for discharging patients from an acute-care hospital.
We conducted an observational cohort study to identify the association between place of death and the clinical and demographic characteristics of patients with advanced cancer who received care from a palliative home care team (PHCT) and of their primary caregivers. We used logistic regression analysis to identify the predictors of at-home death.
We identified 380 patients who met the study inclusion criteria; of these, 245 patients (64%) died at home, 72 (19%) died in an acute-care hospital, 60 (16%) died in a palliative care unit, and three (1%) died in a nursing home. Median follow-up was 48 days. We included the 16 variables that were significant in univariate analysis in our decision-making model. Five variables predictive of at-home death were retained in the multivariate analysis: caregiver's preferred place of death, patients' preferred place of death, caregiver's perceived social support, number of hospital admission days, and number of PHCT visits. A subsequent reduced model including only those variables that were known at the time of discharge (caregivers' preferred place of death, patients' preferred place of death, and caregivers' perceived social support) had a sensitivity of 96% and a specificity of 81% in predicting place of death.
Asking a few simple patient- and family-centered questions may help to inform the decision regarding the best place for end-of-life care and death.
Journal of Clinical Oncology 02/2011; 29(9):1159-67. · 18.37 Impact Factor
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P Cejas,
M López-Gómez,
C Aguayo, R Madero,
J Moreno-Rubio,
J de Castro Carpeño,
C Belda-Iniesta,
J Barriuso,
V Moreno García,
E Díaz,
E Burgos,
M Gonzalez-Barón,
J Feliu
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ABSTRACT: Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91% between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100%), 66 (94%), 43 (61%), 46 (66%) and 36 (54%), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.
Current cancer drug targets 01/2011; 12(2):124-31. · 5.13 Impact Factor
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ABSTRACT: The proto-oncogen cyclin D1 has been implicated in the development and behavior of vestibular schwannoma. This study evaluates the association between cyclin D1 expression and other known prognostic factors in facial function outcome 1 year after vestibular schwannoma surgery.
Sixty-four patients undergoing surgery for vestibular schwannoma were studied. Immunohistochemistry analysis was performed with anticyclin D1 in all cases. Cyclin D1 expression, as well as other demographic, clinical, radiologic, and intraoperative data, was correlated with 1-year postoperative facial function.
Good 1-year facial function (Grades 1-2) was achieved in 73% of cases. Cyclin D1 expression was found in 67% of the tumors. Positive cyclin D1 staining was more frequent in patients with Grades 1 to 2 (75%) than in those with Grades 3 to 6 (25%). Other significant variables were tumor volume and facial nerve stimulation after tumor resection. The area under the receiver operating characteristics curve increased when adding cyclin D1 expression to the multivariate model.
Cyclin D1 expression is associated to facial outcome after vestibular schwannoma surgery. The prognostic value of cyclin D1 expression is independent of tumor size and facial nerve stimulation at the end of surgery.
Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 01/2011; 32(1):136-40. · 1.44 Impact Factor
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Iker Sánchez-Navarro,
Angelo Gámez-Pozo,
Manuel González-Barón,
Alvaro Pinto-Marín,
David Hardisson,
Rocío López, Rosario Madero,
Paloma Cejas,
Marta Mendiola,
Enrique Espinosa,
Juan Angel Fresno Vara
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ABSTRACT: Recent reports demonstrate the feasibility of quantifying gene expression by using RNA isolated from blocks of formalin-fixed, paraffin-embedded (FFPE) tumor tissue. The development of molecular tests for clinical use based on archival materials would be of great utility in the search for and validation of important genes or gene expression profiles. In this study, we compared the performance of different normalization strategies in the correlation of quantitative data between fresh frozen (FF) and FFPE samples and analyzed the parameters that characterize such correlation for each gene. Total RNA extracted from FFPE samples presented a shift in raw cycle threshold (Cq) values that can be explained by its extensive degradation. Proper normalization can compensate for the effects of RNA degradation in gene expression measurements. We show that correlation between normalized expression values is better for moderately to highly expressed genes whose expression varies significantly between samples. Nevertheless, some genes had no correlation. These genes should not be included in molecular tests for clinical use based on FFPE samples. Our results could serve as a guide when developing clinical diagnostic tests based on RT-qPCR analyses of FFPE tissues in the coming era of treatment decision-making based on gene expression profiling.
BioTechniques 05/2010; 48(5):389-97. · 2.67 Impact Factor
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Iker Sánchez-Navarro,
Angelo Gámez-Pozo,
Alvaro Pinto,
David Hardisson, Rosario Madero,
Rocío López,
Belén San José,
Pilar Zamora,
Andrés Redondo,
Jaime Feliu,
Paloma Cejas,
Manuel González Barón,
Juan Angel Fresno Vara,
Enrique Espinosa
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ABSTRACT: Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.
We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.
An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.
This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.
BMC Cancer 01/2010; 10:336. · 3.01 Impact Factor
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ABSTRACT: The duration and severity of systemic hypotension have been related with altered neurodevelopment. Cerebral circulation is pressure-passive in low birth weight infants with early systemic hypotension who receive cardiovascular support. The treatment of early systemic hypotension is controversial, because it has been associated with short-term and long-term morbidity in retrospective studies. However, there has been no prospective information on cardiovascular support for hypotension and morbidity.
Our goal for this prospective study was to evaluate the effect on neurodevelopment resulting from the use of vasopressors/inotropes for early systemic hypotension.
Low birth weight infants with early systemic hypotension (<24 hours of life; study group) were assigned randomly to receive dopamine (2.5-10 microg/kg per minute) or epinephrine (0.125-0.5 microg/kg per minute) in progressively larger doses until target blood pressure was attained (treatment-success subgroup). Hemodynamically stable patients who did not receive cardiovascular support were the control group. Outcome measures were serial cranial ultrasound up to 40 weeks, structured neurologic evaluation (every 3 months), and neurodevelopmental test at 2 to 3 years of age.
One hundred thirty patients were included (study = 60; treatment success = 38; controls = 70). Study-group patients had lower birth weight, gestational age, and 5-minute Apgar score, higher rates of premature rupture of membranes, need for cardiorespiratory resuscitation at birth, and sickness shortly after birth than the control group. The patients in the study group also had significantly higher serum troponin I levels at birth. Initial cranial ultrasound findings did not differ between groups, but the final cranial ultrasounds revealed higher rates of severe periventricular hemorrhage in the study group and higher rates of normal cranial ultrasounds in the control group. Only the latter remained when the treatment-success subgroup and control group were compared. Multivariate analysis did not detect any association between final cranial ultrasounds and the use of vasopressors/inotropes. Sixteen infants died and 103 were followed up (90% survival rate). No differences between groups were found in the rates of abnormal neurologic status, developmental delay, or combined adverse outcome (death or cerebral palsy or severe neurodevelopmental delay).
Cautious use of cardiovascular support to treat early systemic hypotension in low birth weight infants seems to be safe. The question of whether raising systemic blood pressure to within a normal range will improve outcome should be examined by using appropriate study designs.
PEDIATRICS 05/2009; 123(5):1369-76. · 4.47 Impact Factor
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Enrique Espinosa,
Iker Sánchez-Navarro,
Angelo Gámez-Pozo,
Alvaro Pinto Marin,
David Hardisson, Rosario Madero,
Andrés Redondo,
Pilar Zamora,
Belén San José Valiente,
Marta Mendiola,
Manuel González Barón,
Juan Angel Fresno Vara
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ABSTRACT: Gene profiling may improve prognostic accuracy in patients with early breast cancer, but this technology is not widely available. We used commercial assays for qRT-PCR to assess the performance of the gene profiles included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Ratio.
153 patients with early breast cancer and a minimum follow-up of 5 years were included. All tumours were positive for hormonal receptors and 38% had positive lymph nodes; 64% of patients received adjuvant chemotherapy. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) specimens using a specific kit. qRT-PCR amplifications were performed with TaqMan Gene Expression Assays products. We applied the three gene-expression-based models to our patient cohort to compare the predictions derived from these gene sets.
After a median follow-up of 91 months, 22% of patients relapsed. The distant metastasis-free survival (DMFS) at 5 years was calculated for each profile. For the 70-Gene Signature, DMFS was 95% -good prognosis- versus 66% -poor prognosis. In the case of the Recurrence Score, DMFS was 98%, 81% and 69% for low, intermediate and high-risk groups, respectively. Finally, for the Two-Gene Ratio, DMFS was 86% versus 70%. The 70-Gene Signature and the Recurrence Score were highly informative in identifying patients with distant metastasis, even in multivariate analysis.
Commercially available assays for qRT-PCR can be used to assess the prognostic utility of previously published gene expression profiles in FFPE material from patients with early breast cancer. Our results, with the use of a different platform and with different material, confirm the robustness of the 70-Gene Signature and represent an independent test for the Recurrence Score, using different primer/probe sets.
PLoS ONE 02/2009; 4(6):e5911. · 4.09 Impact Factor
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Angelo Gámez-Pozo,
Iker Sánchez-Navarro,
Manuel Nistal,
Enrique Calvo, Rosario Madero,
Esther Díaz,
Emilio Camafeita,
Javier de Castro,
Juan Antonio López,
Manuel González-Barón,
Enrique Espinosa,
Juan Angel Fresno Vara
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ABSTRACT: Proteomics is expected to play a key role in cancer biomarker discovery. Although it has become feasible to rapidly analyze proteins from crude cell extracts using mass spectrometry, complex sample composition hampers this type of measurement. Therefore, for effective proteome analysis, it becomes critical to enrich samples for the analytes of interest. Despite that one-third of the proteins in eukaryotic cells are thought to be phosphorylated at some point in their life cycle, only a low percentage of intracellular proteins is phosphorylated at a given time.
In this work, we have applied chromatographic phosphopeptide enrichment techniques to reduce the complexity of human clinical samples. A novel method for high-throughput peptide profiling of human tumor samples, using Parallel IMAC and MALDI-TOF MS, is described. We have applied this methodology to analyze human normal and cancer lung samples in the search for new biomarkers. Using a highly reproducible spectral processing algorithm to produce peptide mass profiles with minimal variability across the samples, lineal discriminant-based and decision tree-based classification models were generated. These models can distinguish normal from tumor samples, as well as differentiate the various non-small cell lung cancer histological subtypes.
A novel, optimized sample preparation method and a careful data acquisition strategy is described for high-throughput peptide profiling of small amounts of human normal lung and lung cancer samples. We show that the appropriate combination of peptide expression values is able to discriminate normal lung from non-small cell lung cancer samples and among different histological subtypes. Our study does emphasize the great potential of proteomics in the molecular characterization of cancer.
PLoS ONE 01/2009; 4(11):e7731. · 4.09 Impact Factor
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Paloma Cejas,
Miriam López-Gómez,
Cristina Aguayo, Rosario Madero,
Javier de Castro Carpeño,
Cristóbal Belda-Iniesta,
Jorge Barriuso,
Víctor Moreno García,
Javier Larrauri,
Rocío López,
Enrique Casado,
Manuel Gonzalez-Barón,
Jaime Feliu
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ABSTRACT: KRAS mutations in colorectal cancer primary tumors predict resistance to anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy in patients with metastatic colorectal cancer, and thus represent a true indicator of EGFR pathway activation status.
KRAS mutations were retrospectively studied using polymerase chain reactions and subsequent sequencing of codons 12 and 13 (exon 2) in 110 patients with metastatic colorectal tumors. These studies were performed using tissue samples from both the primary tumor and their related metastases (93 liver, 84%; 17 lung, 16%). All patients received adjuvant 5-Fluorouracil-based polychemotherapy after resection of metastases. None received anti-EGFR therapy. Mutations in KRAS were observed in 37 (34%) of primary tumors and in 40 (36%) of related metastases, yielding a 94% level of concordance (kappa index 0.86). Patients with primary tumors possessing KRAS mutations had a shorter disease-free survival period after metastasis resection (12.0 vs 18.0 months; P = 0.035) than those who did not. A higher percentage of KRAS mutations was detected in primary tumors of patiens with lung metastases than in patients with liver metastases (59% vs 32%; p = 0.054). To further evaluate this finding we analyzed 120 additional patients with unresectable metastatic colorectal cancer who previously had their primary tumors evaluated for KRAS mutational status for clinical purposes. Separately, the analysis of these 120 patients showed a tendency towards a higher degree of KRAS mutations in primary tumors of patients with lung metastases, although it did not reach statistical significance. Taken together the group of 230 patients showed that KRAS was mutated significantly more often in the primary tumors of patients with lung metastases (57% vs 35%; P = 0.006).
Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.
PLoS ONE 01/2009; 4(12):e8199. · 4.09 Impact Factor
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Marta Mendiola,
Jorge Barriuso,
Andrés Redondo,
Adrián Mariño-Enríquez, Rosario Madero,
Enrique Espinosa,
Juan Angel Fresno Vara,
Iker Sánchez-Navarro,
Ginés Hernández-Cortes,
Pilar Zamora,
Elia Pérez-Fernández,
María Miguel-Martín,
Asunción Suárez,
José Palacios,
Manuel González-Barón,
David Hardisson
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ABSTRACT: Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients.
RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001).
It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.
PLoS ONE 01/2008; 3(12):e4051. · 4.09 Impact Factor
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Cristóbal Belda-Iniesta,
Rosario Perona,
Javier de Castro Carpeño,
Paloma Cejas,
Enrique Casado,
Cristina Manguan-García,
Inmaculada Ibanez de Caceres,
Isabel Sanchez-Perez,
Francisco Bernabeu Andreu,
Javier Alves Ferreira,
Alfredo Aguilera,
Javier de la Peña,
Elia Perez-Sánchez, Rosario Madero,
Jaime Feliu,
María Sereno,
Manuel González-Barón
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ABSTRACT: Human recombinant erythropoietin (hrEPO) therapy might be associated with tumor progression and death. This effect has been suggested to be secondary to rhEPO binding to its receptor (EPOR) expressed on cancer cells. However, there are several concerns about EPOR functionality when expressed on cancer cells. In this paper we have provided evidence that EPOR expressed in cancer cells could be implicated in proliferation events because a transfection of EPOR siRNA to EPOR-expressing bladder cancer cells resulted in a marked reduction in cell growth. However, these cell lines do not grow in the presence of hrEPO. Furthermore, bladder cancer patients that expressed EPOR in tumor samples had a reduced survival in absence of rhEPO treatment. Therefore, EPOR is implicated in bladder cancer growth but this effect appears to be independent from rhEPO supplementation. Reports which suggest that rhEPO promotes cancer growth due to the expression of EPOR in cancer cells must be observed with caution since in the presence of functional EPOR rhEPO does not promote growth.
Cancer biology & therapy 11/2007; 6(10):1600-5. · 2.64 Impact Factor
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ABSTRACT: Despite the decrease in listening habits, about half of the patients still enjoy music post implantation. Better quality of sound through the implant improves music enjoyment and contributes to achievement of better postoperative quality of life (QOL).
To evaluate music perception and enjoyment in cochlear implant (CI) users, and to assess their influence on QOL.
Sixty-five post-lingually deaf CI recipients were enrolled in this study. A musical questionnaire evaluated musical background, listening habits, and quality of musical sound through the CI. The validated Glasgow Benefit Inventory (GBI) was used to quantify changes in QOL.
Fifty-two patients answered the questionnaires. Listening habits (music enjoyment and hours spent listening to music per week) significantly decreased following implantation when compared with the same parameters before deafness. Nevertheless, 52% of the patients enjoyed music post implantation. The quality of musical sound was rated >50 (0-100 scale) for the adjective pairs 'like-dislike', 'sounds like music-doesn't sound like music' and 'natural-mechanical' by most users. Med-el device users obtained better scores in the adjective pair 'sounds like music-doesn't sound like music' than Cochlear device users. Recipients rating higher scores for quality of sound enjoyed music post implantation and had higher total GBI scores than those rating lower scores.
Acta Oto-Laryngologica 07/2007; 127(7):682-6. · 1.08 Impact Factor
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ABSTRACT: Vertical transmission (VT) is the main route of human immunodeficiency virus (HIV) infection in children. Since the publication of PACTG 076 study in 1994, several preventive methods against the vertical transmission of the HIV have been developed. In this study, we compare the clinical and epidemiological profile of HIV-infected pregnant women and the VT rate in the years 1994 and 2004.
We looked at maternal, obstetric and pediatric variables of HIV-infected women and their children, born in 1994 and 2004, who were followed in Hospital La Paz.
We included 40 mother-infant couples in 1994 and 35 couples in 2004. The HIV vertical transmission rate was 35% in 1994 and 0% in 2004. We did not find changes in Hepatitis C virus (HCV) vertical transmission. In 1994, HIV-infected mothers had a more advanced HIV-disease and the major route of HIV-transmission was the intravenous drug use. Vaginal delivery was more frequent and rupture of membranes was longer than in 2004. The main route of maternal HIV infection in 2004 was sexual contact. In this same year, the use of combination antiretroviral therapy, even during pregnancy, was generalized, the elective cesarean section was the most frequent form of delivery, and every newborn received zidovudine.
In the last decade, there have been important epidemiological changes in HIV-infected mothers in our society. The administration of antiretroviral therapy during pregnancy and to the newborn, as well as other obstetric strategies, can prevent HIV vertical transmission. Nevertheless, we did not find any change in the risk of HCV vertical transmission.
Medicina Clínica 04/2007; 128(9):321-4. · 1.38 Impact Factor
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ABSTRACT: The aims of this study were to determine the effect of a secondary prevention program on the treatment and control of coronary risk factors and to assess whether it improves functional capacity. The study involved 401 patients with coronary heart disease (mean age 57.1 years; 89% men). Clinical and anthropometric data, including blood pressure, were recorded, and electrocardiography, laboratory analysis and exercise testing were performed before and after the program, which lasted 2-3 months. The therapeutic intervention comprised pharmacological treatment of coronary risk factors and the encouragement of life-style changes, including a recommended medically supervised physical exercise regime. By the end of the program, lipid and lipoprotein levels had improved significantly (P< .001 for all). The proportion of smokers decreased from 37.4% to 3.6% (P< .001). Functional capacity increased by 26% (P< .001). In conclusion, patients who took part in the secondary prevention program experienced improvements in cardiovascular risk profile and functional capacity.
Revista Espa de Cardiologia 03/2007; 60(2):205-8. · 2.53 Impact Factor
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ABSTRACT: The unquestionable benefit of antiretroviral therapy in reducing the rate of mother-to-child transmission can be lessened by potential maternal or neonatal toxicity.
To analyze obstetric and perinatal complications in a cohort of HIV-infected pregnant women and their relationship with maternal antiretroviral therapy.
One hundred and sixty-seven HIV-infected pregnant women who delivered at Hospital Universitario La Paz, Madrid, Spain between January 1997 and December 2003.
Data on the clinical and epidemiological characteristics of HIV-infected patients, previous and current antiretroviral therapy, gestational diabetes mellitus, length of pregnancy, mode of delivery, and weight of the newborn were collected. Pregnancy outcomes were compared with those of all the pregnant women attended at our hospital.
Gestational diabetes mellitus, premature delivery, and low birth weight.
Gestational diabetes mellitus was diagnosed in 8.9% of patients. All the cases of gestational diabetes were in the combined antiretroviral therapy group, and the majority were receiving triple antiretroviral therapy with a protease inhibitor. The risk of developing this pathology was greater among women receiving antiretroviral therapy prior to pregnancy. The premature delivery rate was 29% and the low birth weight rate was 28%.
Gestational diabetes mellitus is more common in HIV-infected women than in the general population and is related to combined antiretroviral therapy, especially the use of protease inhibitors, which suggests the need for close follow-up during pregnancy in HIV-infected patients. Nevertheless, the adverse perinatal consequences observed were more related to maternal factors than to antiretroviral therapy.
Acta Obstetricia Et Gynecologica Scandinavica 02/2007; 86(4):409-15. · 1.77 Impact Factor
