Breast Imaging Reporting and Data System - BI-RADS®: valor preditivo positivo das categorias 3, 4 e 5. revisão sistemática da literatura

OBJETIVO: Avaliar artigos, na literatura, que verificam o valor preditivo positivo das categorias 3, 4 e 5 do Breast Imaging Reporting and Data System (BI-RADS®). MATERIAIS E MÉTODOS: Foi realizada pesquisa na base de dados Medline utilizando os termos "predictive value" e "BI-RADS". Foram incluídos 11 artigos nesta revisão. RESULTADOS: O valor preditivo positivo das categorias 3, 4 e 5 variou entre 0% e 8%, 4% e 62%, 54% e 100%, respectivamente. Três artigos avaliaram, concomitantemente, os critérios morfológicos das lesões que apresentaram maior valor preditivo positivo na mamografia, sendo nódulo espiculado o critério com maior valor preditivo positivo. CONCLUSÃO: Houve grande variabilidade do valor preditivo positivo das categorias 3, 4 e 5 do BI-RADS® em todos os estudos, porém foram identificadas diferenças metodológicas que limitaram a comparação desses estudos.

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Coma post-anoxique après arrêt cardiaque et hypothermie, peut-on encore prédire le pronostic en 2014 ?

L'encéphalopathie post-anoxique après arrêt cardiaque (AC) est une cause féquente d'admission pour coma en réanimation. Depuis les recommandations de 2003, l'hypothermie thérapeutique (HT) est devenue un standard de traitement après AC et est à l'origine de l'amélioration du pronostic au cours de cette derniere décennie. Les élements prédicteurs de pronostic validés par l'Académie Américaine de Neurologie avant l'ère de l'HT sont devenus moins précis. En effet, l'HT et la sédation retardent la reprise de la réponse motrice et peuvent altérer la valeur prédictive des réflexes du tronc cérébral. Une nouvelle approche est nécessaire pour établir un pronostic après AC et HT. L'enregistrement (pendant l'HTou peu après) d'une activité électroencéphalographique réactive et/ou continue est un bon prédicteur de récupération neurologique favorable après AC. Au contraire, la présence d'un tracé non réactif ou discontinu de type burst-suppression, avec une réponse N20 absente bilatérale aux potentiels évoqués somatosensoriels, sont presqu'à 100 % prédictifs d'un coma irréversible déjà à 48 heures après AC. L'HT modifie aussi la valeur prédictive de l'énolase neuronale spécifique (NSE), principal biomarqueur sérique de la lésion cérébrale post-anoxique. Un réveil avec bonne récupération neurologique a été récemment observé par plusieurs groupes chez des patients présentant des valeurs de NSE>33 μg/L à 48-72 heures : ce seuil ne doit pas être utilisé seul pour guider le traitement. L'imagerie par résonance magnétique de diffusion peut aider à prédire les séquelles neurologiques à long terme. Un réveil chez les patients en coma post-anoxique est de plus en plus observé, malgré l'absence précoce de signes moteurs et une élévation franche des biomarqueurs neuronaux. En 2014, une nouvelle approche multimodale du pronostic est donc nécessaire, pour optimiser la prédiction d'une évolution clinique favorable après AC. Hypoxic-ischemic encephalopathy after cardiac arrest (CA) is a frequent cause of intensive care unit (ICU) admission. Incorporated in all recent guidelines, therapeutic hypothermia (TH) has become a standard of care and has contributed to improve prognosis after CA during the past decade. The accuracy of prognostic predictors validated in 2006 by the American Academy of Neurology before the era of TH is less accurate. Indeed, TH and sedation may delay the recovery of motor response and alter the predictive value of brainstem reflexes. A new approach is needed to accurately establish prognosis after CA and TH. A reactive and/or continuous electroencephalogram background (during TH or shortly thereafter) strongly predicts good outcome. On the contrary, unreactive/spontaneous burst-suppression electroencephalogram pattern, together with absent N20 on somatosensory evoked potentials, is almost 100% predictive of irreversible coma. TH also affects the predictive value of neuronspecific enolase (NSE), the main serum biomarker of postanoxic injury. A good outcome can occur despite NSE levels >33 μg/L, so this cutoff value should not be used alone to guide treatment. Diffusion magnetic resonance imagery may help predict long-term neurological sequelae. Awakening from postanoxic coma is increasingly observed, despite the absence of early motor signs and pathological elevation of NSE. In 2014, a multimodal approach to prognosis is recommended to optimize the prediction of outcome after CA.

Clinical and videofluoroscopic diagnosis of dysphagia in chronic encephalopathy of childhood

Objective To evaluate the contribution of deglutition videofluoroscopy in the clinical diagnosis of dysphagia in chronic encephalopathy of childhood. Materials and Methods The study sample consisted of 93 children diagnosed with chronic encephalopathy, in the age range between two and five years, selected by convenience among patients referred to the authors' institution by speech therapists, neurologists and gastroenterologists in the period from March 2010 to September 2011. The data collection was made at two different moments, by different investigators who were blind to each other. Results The method presented low sensitivity for detecting aspiration with puree consistency (p = 0.04). Specificity and negative predictive value were high for clinical diagnosis of dysphagia with puree consistency. Conclusion In the present study, the value for sensitivity in the clinical diagnosis of dysphagia demonstrates that this diagnostic procedure may not detect any change in the swallowing process regardless of the food consistency used during the investigation. Thus, the addition of the videofluoroscopic method can significantly contribute to the diagnosis of dysphagia.

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Role of ErbB2 and ErbB4 in Cancer Growth, Prognosis and as Targets for Immunotherapy

ErbB receptors (EGFR, ErbB2, ErbB3 and ErbB4) are growth factor receptors that regulate signals of cell differentiation, proliferation, migration and survival. Inappropriate activation of these receptors is associated with the development and severity of many cancers and has prognostic and predictive value in cancer therapy. Drugs, such as therapeutic antibodies, targeted against EGFR and ErbB2, are currently used in therapy of breast, colorectal and head and neck cancers. The role of ErbB4 in tumorigenesis has remained relatively poorly understood. Alternative splicing produces four different isoforms of one ErbB4 gene. These isoforms (JM-a, JM-b, CYT-1 and CYT-2) are functionally dissimilar and proposed to have different roles in carcinogenesis. The juxtamembrane form JM-a undergoes regulated intramembrane proteolysis producing a soluble receptor ectodomain and an intracellular domain that translocates into the nucleus and regulates transcription. Nuclear signaling via JM-a isoform stimulates cancer cell proliferation. This study aimed to develop antibodies targeting the proposed oncogenic ErbB4 JM-a isoform that show potential in inhibiting ErbB4 dependent tumorigenesis. Also, the clinical relevance of ErbB4 shedding in cancer was studied. The currently used monoclonal antibody trastuzumab, targeting ErbB2, has shown efficacy in breast cancer therapy. In this study novel tissues with ErbB2 amplification and trastuzumab sensitivity were analyzed. The results of this study indicated that a subpopulation of breast cancer patients demonstrate increased shedding and cleavage of ErbB4. A JM-a isoform-specific antibody that inhibited ErbB4 shedding and consequent activation of ErbB4 had anti-tumor activity both in vitro and in vivo. Thus, ErbB4 shedding associates with tumor growth and specific targeting of the cleavable JM-a isoform could be considered as a strategy for developing novel ErbB-based cancer drugs. In addition, it was demonstrated that ErbB2 amplification is common in intestinal type gastric cancers with poor clinical outcome. Trastuzumab inhibited growth of gastric and breast cancer cells with equal efficacy. Thus, ErbB2 may be a useful target in gastric cancer.

The application of cDNA and tissue microarray methods in the study of human carcinomas

Currently, numerous high-throughput technologies are available for the study of human carcinomas. In literature, many variations of these techniques have been described. The common denominator for these methodologies is the high amount of data obtained in a single experiment, in a short time period, and at a fairly low cost. However, these methods have also been described with several problems and limitations. The purpose of this study was to test the applicability of two selected high-throughput methods, cDNA and tissue microarrays (TMA), in cancer research. Two common human malignancies, breast and colorectal cancer, were used as examples. This thesis aims to present some practical considerations that need to be addressed when applying these techniques. cDNA microarrays were applied to screen aberrant gene expression in breast and colon cancers. Immunohistochemistry was used to validate the results and to evaluate the association of selected novel tumour markers with the outcome of the patients. The type of histological material used in immunohistochemistry was evaluated especially considering the applicability of whole tissue sections and different types of TMAs. Special attention was put on the methodological details in the cDNA microarray and TMA experiments. In conclusion, many potential tumour markers were identified in the cDNA microarray analyses. Immunohistochemistry could be applied to validate the observed gene expression changes of selected markers and to associate their expression change with patient outcome. In the current experiments, both TMAs and whole tissue sections could be used for this purpose. This study showed for the first time that securin and p120 catenin protein expression predict breast cancer outcome and the immunopositivity of carbonic anhydrase IX associates with the outcome of rectal cancer. The predictive value of these proteins was statistically evident also in multivariate analyses with up to a 13.1- fold risk for cancer specific death in a specific subgroup of patients.

Personality and Depression

The aim of this study was to illustrate the associations of personality variables and depression. The first study population consisted of 50 patients with DSM-IV defined major depressive disorder. Subjects were randomized to receive either fluoxetine medication or short-term psychodynamic psychotherapy. The Hamilton Depression Rating Scale was completed at the baseline and in the follow-up at four months. Baseline mature defense style measured with the Defense Style Questionnaire predicted favourable outcome in the fluoxetine treatment group, whereas no associations were found in psychotherapy group. The Psychological Mindedness Scale scores were not predictive for recovery in patients receiving psychotherapy or medication. The Psychological Mindedness Scale seems not to be useful in selecting optimal treatment in major depressive disorder. Harm Avoidance measured with the Temperament and Character Inventory associated with the baseline severity of the depressive state. In the fluoxetine treatment group high Reward Dependence, high Self-Directedness and high Cooperativeness were predictive for more severe depression in the four months follow-up, whereas no associations were found in the psychotherapy treatment group. It is possible that the result reflects the differences in the placebo response. The second data were derived from the Finnish Public Sector Study. These prospective studies with four years follow-up focused on the predictive value of optimism and pessimism, first, to work disability with a diagnosis of depression lasting at least 90 days and returning to work (N= 38214) , and second, to the likelihood of initiating antidepressant medication treatment lasting at least 100 days and ending the treatment (N= 29930). Results show that low optimism associates with the elevated risk of work disability and higher likelihood of antidepressant use. High pessimism associated with higher likelihood starting at least 100 days antidepressant medication and not stopping medication during the follow up. High pessimism did not seem to predict the entering to depression related work disability, but in the case of disability period it associated with the lower likelihood of returning to work. The thesis shows that personality features play a role as a vulnerability factor, and influence the onset and course of depression. Taking these factors into account more than is currently done may increase the possibilities to enhance the treatment results in depression.

Socially Competent Leadership - predictors, impacts and skilling in engineering

Earlier management studies have found a relationship between managerial qualities and subordinate impacts, but the effect of managers‘ social competence on leader perceptions has not been solidly established. To fill the related research gap, the present work embarks on a quantitative empirical effort to identify predictors of successful leadership. In particular, this study investigates relationships between perceived leader behavior and three selfreport instruments used to measure managerial capability: 1) the WOPI Work Personality Inventory, 2) Raven‘s general intelligence scale, and 3) the Emotive Communication Scale (ECS). This work complements previous research by resorting to both self-reports and other-reports: the results acquired from the managerial sample are compared to subordinate perceptions as measured through the ECS other-report and the WOPI360 multi-source appraisal. The quantitative research is comprised of a sample of 8o superiors and 354 subordinates operating in eight Finnish organizations. The strongest predictive value emerged from the ECS self- and other-reports and certain personality dimensions. In contrast, supervisors‘ logical intelligence did not correlate with leadership perceived as socially competent by subordinates. 16 of the superiors rated as most socially competent by their subordinates were selected for case analysis. Their qualitative narratives evidence the role of life history and post-traumatic growth in developing managerial skills. The results contribute to leadership theory in four ways. First, the ECS self-report devised for this research offers a reliable scale for predicting socially competent leader ability. Second, the work identifies dimensions of personality and emotive skills that can be considered predictors of managerial ability and benefited from in leader recruitment and career planning. Third, the Emotive Communication Model delineated on the basis of the empirical data allows for a systematic design and planning of communication and leadership education. Fourth, this workfurthers understanding of personal growth strategies and the role of life history in leader development and training. Finally, this research advances educational leadership by conceptualizing and operationalizing effective managerial communications. The Emotive Communication Model devised directs the pedagogic attention in engineering to assertion, emotional availability and inspiration skills. The proposed methodology addresses classroom management strategies drawing from problem-based learning, student empowerment, collaborative learning, and so-called socially competent teachership founded on teacher immediacy and perceived caring, all constituting strategies moving away from student compliance and teacher modelling. The ultimate educational objective embraces the development of individual engineers and organizational leaders that not only possess traditional analytical and technical expertise and substantive knowledge but are intelligent also creatively, practically, and socially.

Early screening for preeclampsia

Preeclampsia, which affects about 3 to 5% of pregnant women, is the most frequent medical complication in pregnancy and the most important cause of maternal and perinatal morbidity and mortality. During the past three decades, numerous clinical, biophysical, and biochemical screening tests have been proposed for the early detection of preeclampsia. Literature shows large discrepancies in the sensitivity and predictive value of several of these tests. No single screening test used for preeclampsia prediction has gained widespread acceptance into clinical practice. Instead, its value seems to be in increasing the predictive value of panels of tests, which include other clinical measurements. The aim of this review was to examine the combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, together with biomarkers in the preeclampsia prediction.

Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms

Objective The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer. Methods The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin-eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases. Results The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of highgrade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68. Conclusion Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry.

Structural basis for the pathophysiology of lipoprotein(a) in the athero-thrombotic process

Lipoprotein Lp(a) is a major and independent genetic risk factor for atherosclerosis and cardiovascular disease. The essential difference between Lp(a) and low density lipoproteins (LDL) is apolipoprotein apo(a), a glycoprotein structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic enzyme. This structural homology endows Lp(a) with the capacity to bind to fibrin and to membrane proteins of endothelial cells and monocytes, and thereby to inhibit plasminogen binding and plasmin generation. The inhibition of plasmin generation and the accumulation of Lp(a) on the surface of fibrin and cell membranes favor fibrin and cholesterol deposition at sites of vascular injury. Moreover, insufficient activation of TGF-ß due to low plasmin activity may result in migration and proliferation of smooth muscle cells into the vascular intima. These mechanisms may constitute the basis of the athero-thrombogenic mode of action of Lp(a). It is currently accepted that this effect of Lp(a) is linked to its concentration in plasma. An inverse relationship between Lp(a) concentration and apo(a) isoform size, which is under genetic control, has been documented. Recently, it has been shown that inhibition of plasminogen binding to fibrin by apo(a) is also inversely associated with isoform size. Specific point mutations may also affect the lysine-binding function of apo(a). These results support the existence of functional heterogeneity in apolipoprotein(a) isoforms and suggest that the predictive value of Lp(a) as a risk factor for vascular occlusive disease would depend on the relative concentration of the isoform with the highest affinity for fibrin

Adrenocortical tumors in children

Childhood adrenocortical tumors (ACT) are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations) and selected genetic syndromes (Beckwith-Wiedemann syndrome) have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing). Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S), which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Expression of CD40 ligand, interferon-gamma and Fas ligand genes in endomyocardial biopsies of human cardiac allografts: correlation with acute rejection

The purpose of the present study was to investigate the expression (mRNA) of CD40 ligand (CD40L), interferon-gamma (IFN-gamma) and Fas ligand (FasL) genes in human cardiac allografts in relation to the occurrence of acute cardiac allograft rejection as well as its possible value in predicting acute rejection. The mRNA levels were determined by a semiquantitative reverse transcriptase-polymerase chain reaction method in 39 samples of endomyocardial biopsies obtained from 10 adult cardiac transplant recipients within the first six months after transplantation. Biopsies with ongoing acute rejection showed significantly higher CD40L, IFN-gamma and FasL mRNA expression than biopsies without rejection. The median values of mRNA expression in biopsies with and without rejection were 0.116 and zero for CD40L (P<0.003), 0.080 and zero for IFN-gamma (P<0.0009), and 0.156 and zero for FasL (P<0.002), respectively. In addition, the levels of IFN-gamma mRNA were significantly increased 7 to 15 days before the appearance of histological evidence of rejection (median of 0.086 in pre-rejection biopsies), i.e., they presented a predictive value. This study provides further evidence of heightened expression of immune activation genes during rejection and shows that some of these markers may present predictive value for the occurrence of acute rejection.

Reliability and validity of the interactive observation scale for psychiatric inpatients applied by nursing aides in daily ward practice

The main characteristic of the nursing Interactive Observation Scale for Psychiatric Inpatients (IOSPI) is the necessity of interaction between raters and patients during assessment. The aim of this study was to evaluate the reliability and validity of the scale in the "real" world of daily ward practice and to determine whether the IOSPI can increase the interaction time between raters and patients and influence the raters' opinion about mental illness. All inpatients of a general university hospital psychiatric ward were assessed daily over a period of two months by 9 nursing aides during the morning and afternoon shifts, with 273 pairs of daily observations. Once a week the patients were interviewed by a psychiatrist who filled in the Brief Psychiatric Rating Scale (BPRS). The IOSPI total score was found to show significant test-retest reliability (interclass correlation coefficient = 0.83) and significant correlation with the BPRS total score (r = 0.69), meeting the criteria of concurrent validity. The instrument can also discriminate between patients in need of further inpatient treatment from those about to be discharged (negative predictive value for discharge = 0.91). Using this scale, the interaction time between nursing aides and patients increased significantly (t = 2.93, P<0.05) and their opinion about the mental illness changed. The "social restrictiveness" factor of the opinion scale about mental illness showed a significant reduction (t = 4.27, P<0.01) and the "interpersonal etiology" factor tended to increase (t = 1.98, P = 0.08). The IOSPI was confirmed as a reliable and valid scale and as an efficient tool to stimulate the therapeutic attitudes of the nursing staff.