SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

Involvement of abscisic acid in the response of Medicago sativa plants in symbiosis with Sinorhizobium meliloti to salinity.

Legumes are classified as salt-sensitive crops with their productivity particularly affected by salinity. Abcisic acid (ABA) plays an important role in the response to environmental stresses as signal molecule which led us to study its role in the response of nitrogen fixation and antioxidant metabolism in root nodules of Medicago sativa under salt stress conditions. Adult plants inoculated with Sinorhizobium meliloti were treated with 1 µM and 10 µM ABA two days before 200 mM salt addition. Exogenous ABA together with the salt treatment provoked a strong induction of the ABA content in the nodular tissue which alleviated the inhibition induced by salinity in the plant growth and nitrogen fixation. Antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were induced by ABA pre-treatments under salt stress conditions which together with the reduction of the lipid peroxidation, suggest a role for ABA as signal molecule in the activation of the nodular antioxidant metabolism. Interaction between ABA and polyamines (PAs), described as anti-stress molecules, was studied being detected an induction of the common polyamines spermidine (Spd) and spermine (Spm) levels by ABA under salt stress conditions. In conclusion, ABA pre-treatment improved the nitrogen fixation capacity under salt stress conditions by the induction of the nodular antioxidant defenses which may be mediated by the common PAs Spd and Spm that seems to be involved in the anti-stress response induced by ABA.

MYH polyposis syndrome: clinical findings, genetics issues and management.

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.

Salicylic acid improves the salinity tolerance of Medicago sativa in symbiosis with Sinorhizobium meliloti by preventing nitrogen fixation inhibition.

In this work we have investigated the contribution of pretreatment with 0.1 and 0.5mM salicylic acid (SA) to the protection against salt stress in root nodules of Medicago sativa in symbiosis with Sinorhizobium meliloti. SA alleviated the inhibition induced by salinity in the plant growth and photosynthetic capacity of M. sativa-S. meliloti symbiosis. In addition, SA prevented the inhibition of the nitrogen fixation capacity under salt stress since nodule biomass was not affected by salinity in SA pretreated plants. Antioxidant enzymes peroxidase (POX), superoxide dismutase (SOD), ascorbate peroxidase (APX), dehidroascorbate reductase (DHAR) and glutathione reductase (GR), key in the main pathway that scavenges H2O2 in plants, were induced by SA pretreatments which suggest that SA may participate in the redox balance in root nodules under salt stress. Catalase activity (CAT) was inhibited around 40% by SA which could be behind the increase of H2O2 detected in nodules of plants pretreated with SA. The accumulation of polyamines (PAs) synthesized in response to salinity was prevented by SA which together with the induction of 1-aminocyclopropane-l-carboxylic acid (ACC) content suggest the prevalence of the ethylene signaling pathway induced by SA in detriment of the synthesis of PAs. In conclusion, SA alleviated the negative effect of salt stress in the M. sativa-S. meliloti symbiosis through the increased level of nodule biomass and the induction of the nodular antioxidant metabolism under salt stress. The H2O2 accumulation and the PAs inhibition induced by SA in nodules of M. sativa suggest that SA activates a hypersensitive response dependent on ethylene.

Analysis of the concordance in the EGFR pathway status between primary tumors and related metastases of colorectal cancer patients:implications for cancer therapy.

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.

Internet use by cancer patients: should oncologists 'prescribe' accurate web sites in combination with chemotherapy? A survey in a Spanish cohort.

BACKGROUND: Cancer patients search for information about prognosis and treatment. Internet has become a major source of medical information. Its impact on oncology patients is not well known. PATIENTS AND METHODS: Three hundred and eighty questionnaires were distributed to cancer patients and companions and 293 were returned. The type of information they obtained online, its usefulness, and its impact on the patient-physician relationship as well as other sources of searching were demanded. Student t-tests, chi-square tests, and multivariate regression logistic analysis were carried out. RESULTS: Internet use was low (27% patients, 58% relatives). Cancer-specific information was the principal research (41% and 70%). For 61% patients, the information had been useful. Information provided by clinicians was the primary reason to not use Internet (37% and 67%). Twenty-two percent patients discussed it with clinicians. Among other sources, health professional (62% and 51%) and printed materials (18% and 25%) were the most demanded. CONCLUSIONS: Cancer patients and carers reported a low use of the Internet for searching medical information, although it helps patients to better cope with cancer. To discuss this information may strengthen the patient-physician relationship. Physicians should ensure that their patients receive reliable online information.

Complete response with pegylated liposomal doxorubicin as a second-line therapy in metastatic ovarian carcinosarcoma: Significance of assessment of the response by FDG-PET.

► We present a case report of a patient with an ovarian carcinosarcoma who achieve a complete response with PLD as a second-line therapy. ► There is little evidence regarding the effectiveness of second-line therapies in ovarian carcinosarcoma. ► Our case illustrates that the RECIST criteria is unreliable in predicting the histopathological treatment response in carcinosarcomas. ► FDG-PET was significantly more accurate than size-based criteria.

Clinical presentation of anxiety among patients with epilepsy.

Different factors have been related with interictal anxiety, reported in 10%-25% of patients with epilepsy. We determined the frequency of interictal anxiety in 196 patients with active epilepsy in a cross-sectional survey to know which symptoms of anxiety were most frequently reported in patients with epilepsy and to analyze the factors associated with their presence. Patients were assessed with the Beck Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS), and the Hamilton Anxiety Scale (HAMA). Data were analyzed with a logistic regression model. The HAMA ratings revealed that 38.8% experienced significant anxiety symptoms, as defined by a rating above 18 points. Use of primidone, depression, cryptogenic, and posttraumatic etiologies significantly predicted anxiety after logistic regression. Symptoms related to higher scores on HAMA were anxious mood, tension, insomnia, intellectual function, depressed mood, cardiovascular and genitourinary symptoms. Further studies should be performed to define the role of psychosocial factors in the development and evolution of anxiety among these patients.

[Evaluation of the care of the elderly program in frail elderly individuals with COPD in primary care centers in Sabadell (Spain)]. / Evaluación del programa de atención a personas mayores frágiles diagnosticadas de EPOC en los centros de atención primaria de Sabadell.

OBJECTIVE: To evaluate the effectiveness of the "Care of the Elderly" program developed by primary care teams in improving the quality of life of frail elderly individuals with a diagnosis of chronic obstructive pulmonary disease (COPD) living in Sabadell (Spain) compared with that of patients receiving routine care. METHOD: A quasi-experimental study with an experimental and a control group was performed in the nursing consultation service of 6 randomly selected primary care centers in Sabadell. The variables studied were quality of life measured by the EuroQuol (EQ-5D), the impact of COPD on health status measured by the St. George's respiratory questionnaire (SGRQ), the number of visits to the center and the emergency department, and hospital admissions. The study was performed over a 2-year period. RESULTS: The mean age of the 203 patients studied was 74.94 years (standard deviation [SD] = 6.11). The intervention was not effective in improving quality of life as measured by the EQ-5D, or in reducing the impact of COPD on health status measured by the SGRQ, or the number of visits to the center and hospital admissions. A statistically significant impact was found on the number of visits to the emergency department (p = 0.03). CONCLUSIONS: The "Care of the Elderly" program in frail elderly individuals with COPD was not effective. The present study is of use in identifying aspects that are ineffective so that nurses designing future programs and studies can include new aspects such as treatment adherence, smoking cessation, and patient satisfaction.

Sleep disturbances, socioeconomic status, and seizure control as main predictors of quality of life in epilepsy.

Improving quality of life is the most important goal for patients with epilepsy. To recognize the factors associated with quality of life in patients with epilepsy in Mexico, we performed a cross-sectional survey using the Quality of Life in Epilepsy 31 (QOLIE-31) inventory to assess the quality of life of 401 adult patients with epilepsy at the National Institute of Neurology and Neurosurgery of Mexico. Clinical and demographical data were collected. Multiple regression was used to determine which factors affected quality of life in our patients. The variables that most strongly predicted a lower QOLIE-31 total score after multiple regression were sleep disorders (P<0.001), socioeconomic status (P<0.001), female gender (P=0.002), and high seizure frequency (P=0.001). In our study, neither depression nor time of evolution of epilepsy had significant influence on QOLIE-31 scores.

Is dementia reversible in patients with neurocysticercosis?

OBJECTIVE: To determine the correlates and outcome of dementia in patients with neurocysticercosis (NCC). METHODS: Ninety consecutive patients with untreated NCC underwent a cognitive assessment (Mini-mental State Examination, Neurobehavioral Cognitive Status Examination, and IQCODE) and were classified as having or not having dementia according to DSM-IV criteria. Imaging and cerebrospinal fluid examination data were recorded. The cognitive measures were repeated six months after treatment with albendazole and steroids. RESULTS: At the initial evaluation 15.5% (n = 14) of the patients were classified as having dementia. Dementia was associated with older age, lower education level, increased number of parasitic lesions in the brain (mostly in the frontal, temporal, and parietal lobes). After six months, 21.5% of the patients from the dementia group continued to have a full dementia disorder and 78.5% no longer fulfilled the DSM-IV criteria for dementia, although some of these patients still showed mild cognitive decline. CONCLUSIONS: The results of this study suggest that dementia occurs frequently in patients with untreated NCC, and it is reversible in most cases.

[Frequency of neuropsychiatric signs and symptoms in patients with viral encephalitis]. / Frecuencia de signos y síntomas neuropsiquiátricos en pacientes con encefalitis viral.

INTRODUCTION: Acute viral encephalitis (AVE) is a frequent condition that usually courses with psychiatric alterations but few systematic studies have been conducted to investigate it. AIMS: To determine the frequency and the progression of the neuropsychiatric symptoms in patients with AVE. PATIENTS AND METHODS: A retrospective study was carried out. AVE was defined as an acute and progressively coursing condition in previously healthy subjects, with clinical signs of diffuse alteration of the central nervous system, abnormal electroencephalogram and/or inflammatory cerebrospinal fluid (CSF). We excluded patients who previously had epilepsy, a positive serodiagnosis for human immunodeficiency virus (HIV), and cases compatible with herpes simplex encephalitis from electroencephalographic or imaging data with focalisation towards temporal, frontal, regions or a positive DNA test for herpes in CSF. Finally, 83 patients were included. The psychiatric signs and symptoms that were produced were recorded during the acute phase and one year after discharge from hospital (sequelae). RESULTS: The psychiatric disorders in the acute phase were psychomotor agitation (67%), drowsiness (55%), disorientation (47%), visual hallucinations (43%) and aggressiveness (34%). One year after hospitalisation, in a sample of 70 patients in a clinical control, we found memory disorders (16%), aggressiveness (9%), aphasia (8%), visual hallucinations (8%), and auditory hallucinations (7%). The mortality rate was 6%. CONCLUSIONS: Neuropsychiatric disorders are very frequent during the acute phase of viral encephalitis, which is relevant for the differential diagnosis in patients who visit emergency departments with behavioural disorders. One year after hospital discharge, the main sequelae are of a neuropsychiatric nature and cognitive impairment is predominant.

Health-related quality of life of patients with HIV: impact of sociodemographic, clinical and psychosocial factors.

OBJECTIVES: This study aims to analyse how a wide group of clinical, social, demographic and psychological factors are related to both physical and mental quality of life in HIV + patients. DESIGN: A cross-sectional study was carried out of 320 HIV + patients in antiretroviral treatment who attended infectious diseases units in four hospitals in the region of Andalusia (Spain). METHODS: Health-Related Quality of Life was measured by the MOS-HIV. Included as independent variables were: sociodemographic variables, variables related to antiretroviral therapy, psychosocial variables like social support (Duke-UNC-11) and psychological morbidity (GHQ-28), variables related to main risk behaviours and clinical variables. RESULTS: In the multiple linear regression analysis, a better PHS quality of life was found to be associated with the absence of mental illness, social support, not being an intravenous drug user and using more than one type of non-injectable drug. A better quality of life, in mental terms, was found to be associated with fewer years as a non-intravenous drug user, having social support, absence of mental illness, not being an intravenous drug user taking only one additional pill, not having any difficulty in taking the medication, and being female. CONCLUSIONS: The study of other non-biological factors that may be related to quality of life has been limited practically to social support and the emotional state. This study highlights the importance of these factors independently from the clinical state, as well as the existence of other psychological and behavioural factors that are also related.

Primidone is associated with interictal depression in patients with epilepsy.

Depressive symptoms are common in epilepsy. To determine associations between depression and demographic, clinical, and pharmacological factors among epileptic patients, we conducted a cross-sectional survey. We evaluated 241 epileptic outpatients at a neurological center in a 6-month period. Depressive syndrome was diagnosed when both the Montgomery-Asberg Scale and the Beck Depression Inventory were rated above the standard cutoff points. Bivariate and multivariate analyses were performed to assess the differences between depressed and nondepressed patients with respect to demographic, clinical, and pharmacological features. Depressive syndrome was diagnosed in 42.7% of patients (n=103). Factors associated in the bivariate analysis were: cryptogenic etiology, posttraumatic epilepsy, use of primidone, and inadequate seizure control. After logistic regression, inadequate seizure control (OR 3.08, 95% CI 1.40-6.77, P=0.005) and use of primidone (OR 4.08, 95% CI 2.09-7.98; P<0.001) remained significantly associated. Depression was common and associated with inadequate seizure control and use of primidone.

[Non-valvular atrial fibrillation and completed stroke: factors determining mortality, recurrence and prognosis after a first event in the Mexican population]. / Fibrilación auricular no valvular e infarto cerebral: determinantes de mortalidad, recurrencia y pronóstico después de un primer evento en población mexicana.

AIMS: Non-valvular atrial fibrillation (NVAF) accounts for 25% of completed strokes (CS) of a cardioembolic origin in patients over 60 years old. Our aim was to define the predictors of a good and poor prognosis after a CS secondary to an NVAF in our milieu. PATIENTS AND METHODS: We evaluated the risk factors (RF) and severity of CS in relation to death, functionality and recurrence at 5 years. 81 patients between the ages of 49 and 88 were followed up consecutively for 1 to 90 months; 38 (46.9%) of them were males. Multivariate analysis was performed with the following independent variables: age, gender, smoking, hypertension, heart disease, diabetes mellitus and characteristics of the stroke. The severity of the CS was assessed by means of the modified Rankin scale, which was dichotomised into a good prognosis (0-2) and a poor prognosis (> or = 3), both basal and at the end of the clinical control. We also evaluated the secondary preventive treatment used and its relation with recurrence, prognosis, death and complications. RESULTS: No RF was linked to a poor prognosis or recurrence; 88% had a poor prognosis. Antiplatelet drugs were used in 42% of cases and 39% received anticoagulants. A good final progression was observed in 9.5% of the patients treated with antiplatelet drugs versus 35% of those receiving anticoagulation therapy (p = 0.004). Severity of the CS on admission was worse in the aspirin group, with no differences in recurrence and mortality. A better prognosis was observed in patients from urban areas. CONCLUSIONS: Use of antiplatelet drugs, living in a rural area and a Rankin score of > or = 3 on admission are factors suggesting a poor prognosis in the clinical control at 5 years.