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

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

Zoologia medicinalis hibernica or, A treatise of birds, beasts, fishes, reptiles, or insects in this kingdom : giving an account of their medicinal virtues, and their names in English, Irish, and Latin : to which is added, a short treatise of the diagnostic and prognostic parts of medicine .../

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The adoption and use of diagnostic and prognostic technology within UK-based manufacturers

Manufacturers are seeking increasingly innovative ways to achieve competitive advantage. An emerging trend is to exploit diagnostic and prognostic technology to support service-led competitive strategies where the emphasis is put on the 'sale of use' rather than the 'sale of product'. However, little is known about the extent to which this technology is being exploited, the drivers and inhibitors, and the sectors where adoption is most prolific. This paper introduces the results of a survey conducted across the UK manufacturing sector to explore the extent, motivations, benefits, and challenges of deploying diagnostic and prognostic technology as an element of competitive strategy.

Cytoplasmic accumulation of NCoR in malignant melanoma: Consequences of altered gene repression and prognostic significance

Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function has been found deregulated in different types of cancer. In colorectal cancer cells, loss of nuclear NCoR is induced by Inhibitor of kappa B kinase (IKK) through the phosphorylation of specific serine residues. We here investigate whether NCoR function impacts in MM, which might have important diagnostic and prognostic significance. By IHC, we here determined the subcellular distribution of NCoR in a cohort of 63 primary invasive MM samples, and analyzed its possible correlation with specific clinical parameters. We therefore used a microarray-based strategy to determine global gene expression differences in samples with similar tumor stage, which differ in the presence of cytoplasmic or nuclear NCoR. We found that loss of nuclear NCoR results in upregulation of a specific cancer-related genetic signature, and is significantly associated with MM progression. Inhibition of IKK activity in melanoma cells reverts NCoR nuclear distribution and specific NCoR-regulated gene transcription. Analysis of public database demonstrated that inactivating NCoR mutations are highly prevalent in MM, showing features of driver oncogene.

Clinical and molecular characterization of feline mammary carcinomas overexpressing HER2 proto-oncogene (FMC-HER2+) : new strategies for effective diagnostic and cancer therapy

Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas

Primary spinal epidural lymphoma: patients' profile, outcome, and prognostic factors: a multicenter Rare Cancer Network study

RESUME Objectif : Les lymphomes épiduraux primaires représentent moins de 10% des tumeurs épidurales et de 0,1 à 3,3% de tous les lymphomes. Le but de cette étude a été d'évaluer le profil clinique de cette maladie rare, son traitement, ses résultats ainsi que ses facteurs de pronostic. Matériel et méthode : Entre 1982 et 2002, 52 patients présentant un lymphome épidural primaire ont été traités dans neuf institutions membres du Rare Cancer Network. Les critères d'inclusion comprenaient : une biopsie confirmant le lymphome non-hodgkinien, un stade IE et IIE selon la classification de Ann Arbor, un traitement à visée curative de radiothérapie combinée ou non à une chimiothérapie et un suivi d'au moins six mois. Selon la Working Formulation, 12 patients (23%) présentaient un lymphome de bas grade, 28 (54%) un grade intermédiaire et 12 (23%) un haut grade. Les hommes étaient atteints 1.9 fois plus fréquemment que les femmes. L'âge moyen était de 61 ans (intervalle : 21 à 96). Le bilan incluait un Ct-scan spinal (98%), une IRM (52%), un CT-scan thoraco-abdominal (77%) et une aspiration ou biopsie de moelle osseuse (96%). Les symptômes les plus fréquents comprenaient des douleurs dorsales (79% des patients), une faiblesse musculaire (92%) et des déficits sensoriels (71 %). Quarante-huit patients ont subi une laminectomie de décompression avec résection partielle ou complète (42% et 13% des cas respectivement), tous ont reçu une radiothérapie seule (20 patients) ou en combinaison avec une chimiothérapie (32 patients). La dose médiane totale était de 36 Gy (intervalle 6-50 Gy) avec une moyenne de 20 Gy par fraction (intervalle : 1-25). Le suivi moyen était de 71 mois (intervalle : 22-165 mois). Résultats : Suite au traitement, une progression locale a été observée chez 6 patients après un temps de latence moyen de 6 mois. Le taux de rechute systémique a été de 42% (22 patients) le plus souvent dans les ganglions lymphatiques (n=9) après un intervalle de temps moyen de 20 mois. Lors du dernier contrôle, 28 patients étaient vivants et 24 patients étaient décédés. Le taux de survie à 5 ans, le taux de survie sans maladie et le contrôle local étaient de 69%, 57% et 88% respectivement. En analyse univariée, les facteurs pronostics favorables statistiquement significatifs concernant la survie sans maladie étaient un âge inférieur à 63 ans, ainsi qu'une réponse neurologique complète. Pour la survie à 5 ans, les facteurs favorables étaient un âge inférieur à 63 ans. En analyse multivariée, les facteurs pronostics favorables pour la survie globale à 5 ans étaient une réponse neurologique complète, un traitement combiné, un volume de radiothérapie plus que focal, une dose totale de radiothérapie supérieure à 36 Gy et une résection partielle ou complète de la tumeur. En ce qui concerne la survie sans maladie, les facteurs pronostics favorables étáient un âge inférieur à 63 ans et un traitement combiné. Conclusion : Ce qui ressort de cette analyse est que le bilan diagnostic devrait inclure une IRM ou un CT-scan, un échantillon de tissu pour poser le diagnostic pathologique définitif de la lésion, une histoire médicale et un examen physique complet, une chimie sanguine, un CTscan thoraco-abdominal et une biopsie de la moelle osseuse, un PET-scan devrait également faire partie du bilan. Le traitement devrait consister, dans la phase aiguë, en une chirurgie de décompression avec ou sans résection, suivie d'une radiothérapie d'au moins 36Gy en 2 Gy par fraction et d'une chimiothérapie. Tous les patients présentant un lymphome de haut grade ou de grade intermédiaire devraient pouvoir bénéficier d'un traitement combiné.

Dosimetric aspects of a national survey of diagnostic and interventional radiology in Switzerland.

The effective dose delivered to the patient was determined, by modeling, for 257 types of examinations covering the different modalities of diagnostic and interventional radiology. The basic operational dosimetric quantities considered were obtained from the parameters of the examinations on the basis of dosimetric models. These models required a precise characterization of each examination. The operational dosimetric quantities were converted into doses to organs and effective doses using appropriate conversion factors. The determination of the collective effective dose to the Swiss population requires a number of corrections to account for the variability of several parameters: sensitivity of the detection system, age, gender, and build of the patient. The use of various dosimetric models is illustrated in this paper for a limited number of examination types covering the different radiological modalities, for which the established typical effective doses are given. With regard to individual doses, the study indicated that the average effective doses per type of examination can be classified into three levels: (a) the weakly irradiating examinations (less than 0.1 mSv), which represent 78% of the examinations and 4% of the collective dose, (b) the moderately irradiating examinations (between 0.1 mSv and 10 mSv), which represent 21% of the examinations and 72% of the collective dose, (c) the strongly irradiating examinations (more than 10 mSv), which represent 1% of the examinations and 24% of the collective dose.

Endoleak and in-stent thrombus detection with CT angiography in a thoracic aortic aneurysm phantom at different tube energies using filtered back projection and iterative algorithms.

PURPOSE: To determine the lower limit of dose reduction with hybrid and fully iterative reconstruction algorithms in detection of endoleaks and in-stent thrombus of thoracic aorta with computed tomographic (CT) angiography by applying protocols with different tube energies and automated tube current modulation. MATERIALS AND METHODS: The calcification insert of an anthropomorphic cardiac phantom was replaced with an aortic aneurysm model containing a stent, simulated endoleaks, and an intraluminal thrombus. CT was performed at tube energies of 120, 100, and 80 kVp with incrementally increasing noise indexes (NIs) of 16, 25, 34, 43, 52, 61, and 70 and a 2.5-mm section thickness. NI directly controls radiation exposure; a higher NI allows for greater image noise and decreases radiation. Images were reconstructed with filtered back projection (FBP) and hybrid and fully iterative algorithms. Five radiologists independently analyzed lesion conspicuity to assess sensitivity and specificity. Mean attenuation (in Hounsfield units) and standard deviation were measured in the aorta to calculate signal-to-noise ratio (SNR). Attenuation and SNR of different protocols and algorithms were analyzed with analysis of variance or Welch test depending on data distribution. RESULTS: Both sensitivity and specificity were 100% for simulated lesions on images with 2.5-mm section thickness and an NI of 25 (3.45 mGy), 34 (1.83 mGy), or 43 (1.16 mGy) at 120 kVp; an NI of 34 (1.98 mGy), 43 (1.23 mGy), or 61 (0.61 mGy) at 100 kVp; and an NI of 43 (1.46 mGy) or 70 (0.54 mGy) at 80 kVp. SNR values showed similar results. With the fully iterative algorithm, mean attenuation of the aorta decreased significantly in reduced-dose protocols in comparison with control protocols at 100 kVp (311 HU at 16 NI vs 290 HU at 70 NI, P ≤ .0011) and 80 kVp (400 HU at 16 NI vs 369 HU at 70 NI, P ≤ .0007). CONCLUSION: Endoleaks and in-stent thrombus of thoracic aorta were detectable to 1.46 mGy (80 kVp) with FBP, 1.23 mGy (100 kVp) with the hybrid algorithm, and 0.54 mGy (80 kVp) with the fully iterative algorithm.

Salivary gland cancer in Finland: Incidence, histological distribution, outcome and prognostic factors

Salivary gland cancer (SGC) is a rare cancer. The histological classification of SGC is complex and its biological behavior highly variable: it may vary from a low-grade tumor to a high-grade and often fatal malignancy. These circumstances make this cancer a diagnostic and therapeutic challenge. Older age and exposure to ionizing radiation are known risk factors. The mainstay of treatment is surgery combined with adjuvant radiation therapy, when appropriate. In addition to the histological type, the only well known prognostic factor is the TNM classification, which describes the tumor size and the amount of metastases. This study was performed using a full population-based nationwide cohort of SGC patients and tumors diagnosed in Finland in 1991-1996. The annual incidence of SGC in the entire population was, on average, 47.7 per year. By histological re-evaluation of 237 specimens the most frequent histological types were the adenoid cystic carcinoma (n=65; 27%), the mucoepidermoid carcinoma (n=45; 19%) and the acinic cell carcinoma (n=41; 17%). The highest 10-year disease-specific survival rate occurred among patients with acinic cell carcinoma (90%), followed by mucoepidermoid carcinoma (81%) and adenoid cystic carcinoma (60%). A high volume-corrected index (VCI) of Ki-67 correlated with worse survival of patients with SGC. Computer-assisted morphometric analyses of CD34-positive vessels indicated an unfavorable prognosis for patients with mucoepidermoid carcinoma and an association with poor survival among patients with acinic cell carcinoma. A high level of expression of matrix metalloproteinase-9 (MMP-9) showed a trend for a poorer prognosis in salivary duct carcinoma, and a high level of MMP-13 and a low level of MMP-1 had a trend for a poorer prognosis of patients with SGC. A low level of MMP-7 was associated with a poor prognosis of patients with acinic cell and mucoepidermoid carcinoma.

Chronic subdural hematoma: epidemiological and prognostic analysis of 176 cases

Objective : To characterize patients with chronic subdural hematoma undergoing surgery and to identify prognostic indicators. Methods : We conducted a retrospective analysis of patients diagnosed with chronic subdural hematoma (CSDH) undergoing surgical treatment. We analyzed: age, period from trauma to diagnostic imaging, pre and postoperative Glasgow coma scale, type of surgery, associated comorbidities, use of postoperative drainage and outpatient treatment. Results : The sample consisted of 176 patients, 126 male and 50 female patients (ratio 2.5 : 1), ages ranged from six months to 97 years, with an average of 59.3 years. CSDH was caused by trauma in 52% of patients, with the time from trauma to imaging averaging 25.05 days; 37.7% were hypertensive patients and 20% had a neurological disease. Eighty-five (48.3%) patients were elderly and altered consciousness was present in 63% of cases. Of the 91 (51.7%) non-elderly patients, 44% presented with headache, altered consciousness occurred in 40% and motor abnormalities in 27.5%. The CSDH was located on the right in 41%, left in 43% and bilaterally in 16% of patients. Conclusion : the change of consciousness was the most common clinical alteration in the elderly and headache in non-elderly. The most associated comorbidity was the arterial hypertension and the most frequent cause, head trauma. The trepanation with two oriffices associated with a closed drainage system was the most used operating, with high efficacy and low complication rate.

Human papillomavirus (HPV) and associated diseases: between applied diagnostic and basic research

Human Papillomavirus (HPV) is the cause of cervical cancers (among these, adenocarcinoma, AdCa) and is associated to a subgroup of oropharyngeal carcinomas (OPSCCs). Even if the risk for cancer development is linked to the infection by some viral genotypes, mainly HPV16 and 18, viral DNA alone seems not to be sufficient for diagnosis. Moreover, the role of the virus in OPSCCs has not been totally clarified yet. In the first part of the thesis, the performances concerning viral genotyping in clinical cervical samples of a new pyrosequencing-based test and a well-known hybridization-based assay have been compared. Similar results between the methods have been obtained. However, the former showed advantages in detecting intratype variants, higher specificity and a broader spectrum of detectable HPV types. The second part deals with the evaluation of virological markers (genotyping, viral oncoproteins expression, viral load, physical state and CpG methylation of HPV16 genome) in the diagnosis/prognosis of cervical AdCa and HPV-associated OPSCCs. HPV16 has been confirmed the most prevalent genotype in both the populations. Interestingly, the mean methylation frequency of viral DNA at the early promoter showed the tendency to be associated to invasion for cervical AdCa and to a worse prognosis for OPSCCs, suggesting a promising role as diagnostic/prognostic biomarker. The experiments of the third part were performed at the DKFZ in Heidelberg (Germany) and dealt with the analysis of the response to IFN-k transfection in HPV16-positive cervical cancer and head&neck carcinoma cell lines to evaluate its potential role as new treatment. After 24h, we observed increased IFN-b expression which lead to the up-regulation of genes involved in the antigens presentation pathway (MHC class I and immunoproteasome) and antiviral response as well, in particular in cervical cancer cell lines. This fact suggested also the presence of different HPV-mediated carcinogenic pathways between the two anatomical districts.

Limitations of the Odds Ratio in Gauging the Performance of a Diagnostic or Prognostic Marker

A marker that is strongly associated with outcome (or disease) is often assumed to be effective for classifying individuals according to their current or future outcome. However, for this to be true, the associated odds ratio must be of a magnitude rarely seen in epidemiological studies. An illustration of the relationship between odds ratios and receiver operating characteristic (ROC) curves shows, for example, that a marker with an odds ratio as high as 3 is in fact a very poor classification tool. If a marker identifies 10 percent of controls as positive (false positives) and has an odds ratio of 3, then it will only correctly identify 25 percent of cases as positive (true positives). Moreover, the authors illustrate that a single measure of association such as an odds ratio does not meaningfully describe a marker’s ability to classify subjects. Appropriate statistical methods for assessing and reporting the classification power of a marker are described. The serious pitfalls of using more traditional methods based on parameters in logistic regression models are illustrated.

Statistical characterization and development of summary measures of non-normal distributions of nuclear morphometry data from prostate cancer cells for use as prognostic indicators

Nuclear morphometry (NM) uses image analysis to measure features of the cell nucleus which are classified as: bulk properties, shape or form, and DNA distribution. Studies have used these measurements as diagnostic and prognostic indicators of disease with inconclusive results. The distributional properties of these variables have not been systematically investigated although much of the medical data exhibit nonnormal distributions. Measurements are done on several hundred cells per patient so summary measurements reflecting the underlying distribution are needed.^ Distributional characteristics of 34 NM variables from prostate cancer cells were investigated using graphical and analytical techniques. Cells per sample ranged from 52 to 458. A small sample of patients with benign prostatic hyperplasia (BPH), representing non-cancer cells, was used for general comparison with the cancer cells.^ Data transformations such as log, square root and 1/x did not yield normality as measured by the Shapiro-Wilks test for normality. A modulus transformation, used for distributions having abnormal kurtosis values, also did not produce normality.^ Kernel density histograms of the 34 variables exhibited non-normality and 18 variables also exhibited bimodality. A bimodality coefficient was calculated and 3 variables: DNA concentration, shape and elongation, showed the strongest evidence of bimodality and were studied further.^ Two analytical approaches were used to obtain a summary measure for each variable for each patient: cluster analysis to determine significant clusters and a mixture model analysis using a two component model having a Gaussian distribution with equal variances. The mixture component parameters were used to bootstrap the log likelihood ratio to determine the significant number of components, 1 or 2. These summary measures were used as predictors of disease severity in several proportional odds logistic regression models. The disease severity scale had 5 levels and was constructed of 3 components: extracapsulary penetration (ECP), lymph node involvement (LN+) and seminal vesicle involvement (SV+) which represent surrogate measures of prognosis. The summary measures were not strong predictors of disease severity. There was some indication from the mixture model results that there were changes in mean levels and proportions of the components in the lower severity levels. ^

Diagnostic and clinical factors associated with pulpal and periapical pain

A retrospective survey was designed to identify diagnostic subgroups and clinical factors associated with odontogenic pain and discomfort in dental urgency patients. A consecutive sample of 1,765 patients seeking treatment for dental pain at the Urgency Service of the Dental School of the Federal University of Goiás, Brazil, was selected. Inclusion criteria were pulpal or periapical pain that occurred before dental treatment (minimum 6 months after the last dental appointment), and the exclusion criteria were teeth with odontogenic developmental anomalies and missing information or incomplete records. Clinical and radiographic examinations were performed to assess clinical presentation of pain complaints including origin, duration, frequency and location of pain, palpation, percussion and vitality tests, radiographic features, endodontic diagnosis and characteristics of teeth. Chi-square test and multiple logistic regression were used to analyze association between pulpal and periapical pain and independent variables. The most frequent endodontic diagnosis of pulpal pain were symptomatic pulpitis (28.3%) and hyperreactive pulpalgia (14.4%), and the most frequent periapical pain was symptomatic apical periodontitis of infectious origin (26.4%). Regression analysis revealed that closed pulp chamber and caries were highly associated with pulpal pain and, conversely, open pulp chamber was associated with periapical pain (p<0.001). Endodontic diagnosis and local factors associated with pulpal and periapical pain suggest that the important clinical factor of pulpal pain was closed pulp chamber and caries, and of periapical pain was open pulp chamber.