Clinical prognostic indicators of dysphagia following prolonged orotracheal intubation in ICU patients

Introduction The development of postextubation wallowing dysfunction is well documented in the literature with high prevalence in most studies. However, there are relatively few studies with specific outcomes that focus on the follow-up of these patients until hospital discharge. The purpose of our study was to determine prognostic indicators of dysphagia in ICU patients submitted to prolonged orotracheal intubation (OTI). Methods We conducted a retrospective, observational cohort study from 2010 to 2012 of all patients over 18 years of age admitted to a university hospital ICU who were submitted to prolonged OTI and subsequently received a bedside swallow evaluation (BSE) by a speech pathologist. The prognostic factors analyzed included dysphagia severity rate at the initial swallowing assessment and at hospital discharge, age, time to initiate oral feeding, amount of individual treatment, number of orotracheal intubations, intubation time and length of hospital stay. Results After we excluded patients with neurologic diseases, tracheostomy, esophageal dysphagia and those who were submitted to surgical procedures involving the head and neck, our study sample size was 148 patients. The logistic regression model was used to examine the relationships between independent variables. In the univariate analyses, we found that statistically significant prognostic indicators of dysphagia included dysphagia severity rate at the initial swallowing assessment, time to initiate oral feeding and amount of individual treatment. In the multivariate analysis, we found that dysphagia severity rate at the initial swallowing assessment remained associated with good treatment outcomes. Conclusions Studies of prognostic indicators in different populations with dysphagia can contribute to the design of more effective procedures when evaluating, treating, and monitoring individuals with this type of disorder. Additionally, this study stresses the importance of the initial assessment ratings.

Changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization at admission to ICU and the relation to outcome

Objective To evaluate the changes in tissue perfusion parameters in dogs with severe sepsis/septic shock in response to goal-directed hemodynamic optimization in the ICU and their relation to outcome. Design Prospective observational study. Setting ICU of a veterinary university medical center. Animals Thirty dogs with severe sepsis or septic shock caused by pyometra who underwent surgery and were admitted to the ICU. Measurements and Main Results Severe sepsis was defined as the presence of sepsis and sepsis-induced dysfunction of one or more organs. Septic shock was defined as the presence of severe sepsis plus hypotension not reversed with fluid resuscitation. After the presumptive diagnosis of sepsis secondary to pyometra, blood samples were collected and clinical findings were recorded. Volume resuscitation with 0.9% saline solution and antimicrobial therapy were initiated. Following abdominal ultrasonography and confirmation of increased uterine volume, dogs underwent corrective surgery. After surgery, the animals were admitted to the ICU, where resuscitation was guided by the clinical parameters, central venous oxygen saturation (ScvO2), lactate, and base deficit. Between survivors and nonsurvivors it was observed that the ScvO2, lactate, and base deficit on ICU admission were each related independently to death (P = 0.001, P = 0.030, and P < 0.001, respectively). ScvO2 and base deficit were found to be the best discriminators between survivors and nonsurvivors as assessed via receiver operator characteristic curve analysis. Conclusion Our study suggests that ScvO2 and base deficit are useful in predicting the prognosis of dogs with severe sepsis and septic shock; animals with a higher ScvO2 and lower base deficit at admission to the ICU have a lower probability of death.

PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes

Abstract Background Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis.

Distribution of sewage input in marine sediments around a maritime Antarctic research station indicated by molecular geochemical indicators

Sediments from Admiralty Bay, Antarctica were collected during the austral summers of 2002/2003 and 2003/2004 in order to assess the distribution and concentration of sewage indicators originating from Comandante Ferraz Brazilian Antarctic Station. Fecal sterols (coprostanol + epicoprostanol) and linear alkylbenzenes (LABs) ranged from <0.01 to 0.95 mu g g(-1) and <1.0 to 23 ng g(-1) dry weight, respectively. In general, the higher concentrations were found only locally in the vicinity of Ferraz station at Martel Inlet. Baseline values for fecal sterols and coprostanone were calculated as 0.19 and 0.40 mu g g(-1), respectively. According to fecal sterols concentrations, sewage contribution to Martel Inlet has increased more than twice since 1997, as result of the increase in the number of researchers at the station especially during the last decade. A low correlation was found between total LABs and fecal steroids, which could be attributed to the contribution of the natural sources of steroids. (C) 2010 Elsevier B.V. All rights reserved.

Do established prognostic factors explain the different mortality rates in ICU septic patients around the world?

Background. The aim of this paper was to clarify if previously established prognostic factors explain the different mortality, rates observed in ICU septic patients around the world. Methods. This is a sub-study from the PROGRESS study, which was an international, prospective, observational registry of ICU patients with severe sepsis. For this study we included 10930 patients from 24 countries that enrolled more than 100 patients in the PROGRESS. The effect of potential prognostic factors on in-hospital mortality was examined using univariate and multivariate logistic regression. The complete set of data was available for 7022 patients, who were considered in the multivariate analysis. Countries were classified according to country, income, development status, and in-hospital mortality terciles. The relationship between countries' characteristics and hospital mortality mortality was evaluated using linear regression. Results. Mean in-hospital mortality was 49.2%. Severe sepsis in-hospital mortality varied widely in different countries, ranging from 30.6% in New Zealand to 80.4% in Algeria. Classification as developed or developing country was not associated with in-hospital mortality (P=0.16), nor were levels of gross national product per capita (P=0.15). Patients in the group of countries with higher in-hospital mortality, had a crude OR for in-hospital death of 2.8 (95% CI 2.5-3.1) in comparison to those in the lower risk group. After adjustments were made for all other independent variables, the OR changed to 2.9 (95% CI 2.5-3.3). Conclusion. Severe sepsis mortality varies widely, in different countries. All known markers of disease severity and prognosis do not fully, explain the international differences in mortality,. Country, income does not explain this disparity, either. Further studies should be developed to verify if other organizational or structural factors account for disparities in patient care and outcomes. (Minerva Anestesiol 2012;78:1215-25)

FGFR4 Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Mouth and Oropharynx

Background: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. Patients and Methods: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. Results: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. Conclusion: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.

Efficient Placement of Fault Indicators in an Actual Distribution System Using Evolutionary Computing

This paper proposes an evolutionary computing strategy to solve the problem of fault indicator (FI) placement in primary distribution feeders. More specifically, a genetic algorithm (GA) is employed to search for an efficient configuration of FIs, located at the best positions on the main feeder of a real-life distribution system. Thus, the problem is modeled as one of optimization, aimed at improving the distribution reliability indices, while, at the same time, finding the least expensive solution. Based on actual data, the results confirm the efficiency of the GA approach to the FI placement problem.

Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC.

The density of metastatic lymph node as prognostic factor in squamous cell carcinoma of the tongue and floor of the mouth

The presence of metastatic lymph nodes is a relevant prognostic factor in oral cancer. Objective: This paper aims to assess metastatic lymph node density (pN+) in patients with tongue and floor-of-mouth squamous cell carcinoma (SCC) and the association of this parameter with disease-free survival (DFS). Materials and Methods: A group of 182 patients seen between 1985 and 2007 was included, 169 of which were males. Five were on stage I, 35 on stage II, 56 on stage III, and 85 on stage IV. Median values were considered in lymph node density assessment, and the Kaplan-Meier curve was used to evaluate DFS; survival differences within the group were elicited through the log-rank test. Results: An average 3.2 metastatic lymph nodes were excised from the patients in the group. Density ranged from 0.009 to 0.4, with a mean value of 0.09. Five-year DFS rates were of 44% and 28% for the groups with lymph node densities below and above the median respectively (p = 0.006). Two-year local/regional control was achieved for 71% and 49% for the patients below and above the median density respectively (p = 0.01). In terms of pN staging, local/regional control was achieved in 70% and 54% of pN1 and pN2 patients respectively, albeit without statistical significance (0.20%). Conclusion: Lymph node density may be used as a prognostic indicator for tongue and floor-ofmouth SCC.

Foraminifera as indicators of marine pollutant contamination on the inner continental shelf of southern Brazil

Analyses of living foraminiferal and environmental parameters near an outfall at Mar Grosso Beach (Laguna, SC, Brazil) demonstrate its usefulness as indicators of domestic sewage pollution. The low species diversity may be due to sand accumulation in the central part. Higher diversity was noted closer to the mouth of Laguna estuarine system where reduced salinity and higher temperatures indicate freshwater influence, suggesting a relationship between increased diversity and greater availability of terrestrial food. On the basis of foraminiferal diversity and average coliform count the higher values are closer to the mouth of the estuarine system and under the influence of the outfall. Due to the effect of local hydrodynamics, the particulate organic waste derived from the outfall does not settle down locally, and thus, do not accumulate nearby. Our hypothesis is that the fine material derived from the outfall is accumulating on the southwestern and northwestern parts of the beach.

Prognostic significance of the number of lymph nodes in elective neck dissection for tongue and mouth floor cancers

The presence of metastatic lymph nodes is a relevant aspect in the treatment of head and neck cancer, bringing about a 50% reduction in survival. Objective: To assess the number of lymph nodes removed in the neck dissection and their relationship with the prognosis. Methods: A retrospective study involving 143 patients with tongue and mouth floor epidermoid carcinoma, which histological exam showed no lymph node metastases. Among those, 119 were males and 24 females, with mean age of 54 years. As to the primary tumor site, 65 were in the tongue and 78 in the mouth floor. T stage distribution was of four T1, 84 T2, 36 T3 and 19 T4. We carried out 176 neck dissections, unilateral in 110 cases and bilateral in 33. Of these, 78 were radical and 98 selective. The patients were broken down into three groups, according to the 33 and 66 percentiles of the number of lymph nodes resected. Results: The mean number of resected lymph nodes was 27; 24 in selective dissections and 31 in the complete ones. We did not have statistically significant differences when associated to the T and N stages. Conclusions: The larger number of lymph nodes dissected in the neck dissection identifies the group of better prognoses among pN0 cases.

Prognostic value of thumb pain sensation in birth brachial plexopathy

Objective: To evaluate the prognostic value of absent thumb pain sensation in newborns and young infants with birth brachial plexopathy. Methods: We evaluated 131 patients with birth brachial plexopathy with less than two months of age. Pain sensation was evoked by thumb nail bed compression to evaluate sensory fibers of the upper trunk (C6). The patients were followed-up monthly. Patients with less than antigravity elbow flexion at six months of age were considered to have a poor outcome. Results: Thirty patients had absent thumb pain sensation, from which 26 showed a poor outcome. Sensitivity of the test was 65% and specificity was 96%. Conclusion: Evaluation of thumb pain sensation should be included in the clinical assessment of infants with birth brachial plexopathy.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

Background: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

MicroRNAs miR-146-5p and let-7f as prognostic tools for aggressive papillary thyroid carcinoma: a case report

Papillary thyroid cancer (PTC) is the most incident histotype of thyroid cancer. A certain fraction of PTC cases (5%) are irresponsive to conventional treatment, and refractory to radioiodine therapy. The current prognostic factors for aggressiveness are mainly based on tumor size, the presence of lymph node metastasis, extrathyroidal invasion and, more recently, the presence of the BRAFT(1799A) mutation. MicroRNAs (miRNAs) have been described as promising molecular markers for cancer as their deregulation is observed in a wide range of tumors. Recent studies indicate that the over-expression of miR-146b-5p is associated with aggressiveness and BRAFT(1799A) mutation. Furthermore, down-regulation of let-7f is observed in several types of tumors, including PTC. In this study, we evaluated the miR146b-5p and let-7f status in a young male patient with aggressive, BRAFT(1799A)-positive papillary thyroid carcinoma, with extensive lymph node metastases and short-time recurrence. The analysis of miR-146b-5p and let-7f expression revealed a distinct pattern from a cohort of PTC patients, suggesting caution in evaluating miRNA expression data as molecular markers of PTC diagnosis and prognosis. Arq Bras Endocrinol Metab. 2012;56(8):552-7

Immunohistochemistry Analysis of Proteins Related with Apoptosis as Prognostic Factor in Epidermoid Carcinoma of Penis

The aim was to analyze the protein expression of apoptotic genes caspase-3, caspase-8 and bcl-2 with the immunohistochemistry technique, correlating with tumor grade (I, II and III) and with the patient survival in order to understand the basic mechanism of tumoral transformation. The immunohistochemistry reactions on 50 samples of squamous cell carcinoma were carried out with the avidin-biotin immunoperoxidase method and antigen recovery. The analyses were made using the graduation method "in crosses" (0 to 4 crosses - no stain to more than 75% of positives cells) and in categories (low, intermediate, high) of the cytoplasm immunoreactivity of the epidermoid penile carcinoma cells. It was observed a statistically significant difference when the expression of caspase-3 were compared with the grades land II of the tumor (p=0.0010) and when comparing the patient survival with the grades I and II of the tumor (p=0.0212). The protein bcl-2 was more expressed than caspase-3 and caspase-8 proteins, suggesting that the apoptotic rate in this carcinoma is low. The higher expression of the anti-apoptotic protein bcl-2 suggests a higher preservation of the tumoral cells.