Dermatological conditions presenting at the Emergency Department in Siena University Hospital from 2006 to 2011.

BACKGROUND: Published studies on emergency dermatology consultations are few because there are few dermatology emergency units in the world. No study has yet described the Italian situation. OBJECTIVES: To quantify and characterize patients evaluated in our dermatology emergency unit from 2006 to 2011. METHODS: We studied personal details, diagnosis, annual trend of cases, emergency level and hospitalization of dermatology cases over the 6-year period. RESULTS: A total of 12,226 patients were evaluated. The most numerous diagnostic group was infections (27.1%), followed by non-specific and descriptive diagnosis (22.5%), skin conditions caused by mechanical or physical agents (13.1%), eczematous diseases (10.5%), insect bites (9.5%) and urticaria/angio-oedema (8.8%). The most common indications for admission to hospital were skin conditions caused by mechanical or physical agents (33.3%), infections (27.5%), drug eruption (15.9%) and autoimmune or inflammatory disorders (7.4%). Emergency dermatology cases followed a variable annual trend, with more consultations in the summer months. CONCLUSION: This is the first long-term retrospective analysis of a large series of dermatology emergency patients. It provides useful quantitative and qualitative information on cases for physicians and the national health system for the purposes of improving patient care and cost-effectiveness.

Dermoscopy and digital dermoscopy analysis of palmoplantar 'equivocal' pigmented skin lesions in Caucasians.

BACKGROUND/AIM: The diagnosis of palmoplantar melanoma is often delayed and misdiagnosis is common, due to frequently unusual clinical presentation. We used a digital dermoscopy analyzer with a series of palmoplantar pigmented skin lesions (PP-PSL), and we compared sensitivity, specificity and diagnostic accuracy obtained with digital dermoscopy analysis (DDA) and classical dermoscopy. METHODS: Digital dermoscopy images of 107 PP-PSL were retrospectively obtained from the database of images of 3 Italian centers. The lesions (25 melanomas and 82 nevi) were all removed because of the presence of clinical and/or dermoscopic suspicious features. All digital images were analyzed using appropriate algorithms, and the diagnostic accuracy of the model was calculated. For comparison, dermoscopic images were clinically evaluated by two dermatologists and the Cohen ĸ concordance with DDA was calculated. RESULTS: The stepwise logistic regression analysis selected only 5 parameters out of 49. The logistic model achieved a sensitivity of 96% and a specificity of 87.8%. The Cohen ĸ concordance, evaluated by the Landis and Koch scale, supplied a substantial agreement between dermoscopy and DDA. CONCLUSIONS: DDA might be a useful diagnostic instrument in the evaluation of preselected PP-PSL. However, these findings should be confirmed in a formal clinical trial.

An informative probability model enhancing real time echobiometry to improve fetal weight estimation accuracy.

A multinormal probability model is proposed to correct human errors in fetal echobiometry and improve the estimation of fetal weight (EFW). Model parameters were designed to depend on major pregnancy data and were estimated through feed-forward artificial neural networks (ANNs). Data from 4075 women in labour were used for training and testing ANNs. The model was implemented numerically to provide EFW together with probabilities of congruence among measured echobiometric parameters. It enabled ultrasound measurement errors to be real-time checked and corrected interactively. The software was useful for training medical staff and standardizing measurement procedures. It provided multiple statistical data on fetal morphometry and aid for clinical decisions. A clinical protocol for testing the system ability to detect measurement errors was conducted with 61 women in the last week of pregnancy. It led to decisive improvements in EFW accuracy.

Bronchiolo-alveolar carcinoma: an analysis of survival predictors.

Macroscopic and microscopic features of tumours have been analysed in 37 bronchiolo-alveolar carcinomas. Lymphocytes, Langerhans cells, collagen (mature and/or myofibroblastic), were quantitatively or semiquantitatively evaluated. Histology, stage, type of fibrosis, nuclear profile features (area and shape factors), amount and type of mucin secreted, number of mitoses, Langerhans cells, myofibroblasts and LeuM1+ cells were not related to survival. Gross morphology of the tumour and, to a lesser extent, lymphoid infiltrates (in particular UCHL1+ and L26+ peritumoral lymphoid cells) were the only variables significantly related to survival. Estimated survival functions were computed according to Cox's model: well demarcated tumours behaved significantly better than poorly demarcated tumours and even more so than diffuse or multiple mass. Lymphoid infiltrates were significantly more represented in and around well demarcated tumours: however, their survival predicting value was less than that of the gross type.

Morphometric distinction of low- and high-grade dysplasias in gastric biopsies.

Substantial agreement has previously been demonstrated between qualitative and morphometric grading of gastric dysplasia. In the present study, a further attempt is made to quantitatively define the dysplastic changes in relation to associated benign or malignant changes of gastric mucosa. In total, 232 cases were studied and were associated with benign peptic ulcer (89 cases), histologically proven gastric cancer (88 cases), and gastritis-associated mild, moderate, and severe dysplasias (55 cases). The analysis showed that one discriminant function consisting of seven morphometric features is sufficient to separate the regenerative and cancer-associated cases. The classification results obtained on the basis of this discriminant function in both training and testing sets are encouragingly similar, indicating that the classification is reliable. This was further confirmed by the results of the application of this rule in the mild, moderate, and severe dysplasia biopsies (the above-mentioned gastritis-associated cases) used in a previous study. The quantitative analysis permits two grades, instead of three, to be distinguished: low-grade and high-grade dysplasia.

Mantle zone lymphoma: a morphometric comparison with centrocytic and immunocytic lymphomas and reactive secondary follicles.

Nuclear size and shape of lymphoid cells were evaluated morphometrically in the mantle zone lymphoma, immunocytic lymphoma, and centrocytic lymphoma, and were compared with those of reactive secondary follicles. Shape factors (forms Ar, Ell, Pe, and Dia) have been used to quantitatively define the most frequent nuclear profiles. One of the testing sets consisted of the nuclei of the light, dark, and mantle regions of reactive nodes, as well as those of the centrocytic lymphoma, immunocytic lymphoma, and the mantle-fashion growth lymphoma. Another testing set was made up of only the three types of lymphoma and was used for evaluating the variability of shapes within these groups by means of a pattern recognition algorithm. The content of reactive T lymphocytes was assessed in all cases by immunohistochemistry. The results of transforming centroid values into geometric shapes by computer modelling indicated that only minor geometric differences existed between the a priori qualitatively chosen nuclear types and those modeled a posteriori by computer. All the nuclear types were found in each of the reactive regions and in each of the lymphomas. However, highly significant differences of distribution were detected among the three categories of lymphoma and between each reactive region and each lymphoma. The cases of centrocytic lymphoma showed constant findings in terms of nuclear composition, while lymphomas with mantle-fashion growth and the examples of immunocytic lymphoma showed significant variability. These observations confirm that the centrocytic lymphoma represents a distinct entity, although its normal counterpart is still unknown, and question the view that the immunocytoma and the mantle zone lymphoma correspond to homogenous categories of non-Hodgkin's lymphomas. In addition, since all the qualitatively and quantitatively detected nuclear types were found in all the reactive regions and in all the lymphomas, albeit with different distributions, it has to be assumed that only numerical differences exist among the various lymphomas and the reactive regions.

Low-frequency respiratory mechanics using ventilator-driven forced oscillations.

We evaluated the potential for using a fast Fourier transform (FFT) analysis applied to a standard ventilator waveform to estimate (< 2 Hz) frequency dependence of respiratory or lung resistance (R) and elastance (E). In four healthy humans we measured pressure and flow at the airway opening while applying sine wave forcing from 0.2 to 0.6 Hz at two tidal volumes (VT; 250 and 500 ml). We then applied a step inspiratory ventilator flow wave with relaxed expiration at the same VT and only 0.2 Hz. Step waveform data were also acquired from nine mechanically ventilated patients under intensive care unit conditions. Finally, we simultaneously measured total respiratory (rs), lung (L), and chest wall (cw) impedance data from two dogs (0.156-2 Hz) before and after severe pulmonary edema. Rrs and Ers were estimated by the FFT approach. Humans displayed a small frequency dependence in Rrs and Ers from 0.2 to 0.6 Hz, and both Rrs and Ers decreased at the higher VT. The spectral estimates of Rrs and Ers with the step ventilator wave were often qualitatively comparable to sine wave results below 0.6 Hz but became extremely erratic above the third harmonic. Conversely, in dogs the step wave produced reliable and stable estimates up to 2 Hz in all conditions. Nevertheless, Ecw and Ers still displayed clear and correlated oscillations with increasing frequency, whereas EL showed none. This suggests that nonlinear processes, most likely at the chest wall, contribute to periodic-like fluctuations in respiratory mechanical properties when estimated by applying FFT to a step ventilator wave. Moreover, in humans, but not dogs, a ventilator flow cycle contains insufficient signal energy beyond the third harmonic. We show that the amount of energy available at higher frequencies is largely governed by the mechanical time constant contributing to passive expiratory flow. In dogs the shorter time constant contributes to increased energy. In essence, the frequency content of the flow is subject dependent, and this is not a desirable situation for controlling the quality of the impedance spectra available from a standard ventilator wave.

Digital dermoscopy analysis for the differentiation of atypical nevi and early melanoma: a new quantitative semiology.

OBJECTIVES: To use a digital dermoscopy analyzer with a series of "borderline" pigmentary skin lesions (ie, clinically atypical nevi and early melanoma) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. DESIGN: A total of 147 pigmentary skin lesions were histologically examined by 3 experienced dermatopathologists and identified as nevi (n = 90) and melanomas (n = 57). The system evaluated 36 variables to be studied as possible discriminant variables, grouped into 4 categories: geometries, colors, textures, and islands of color. SETTING: University medical department. PATIENTS: A sample of patients with excised pigmentary skin lesions (nevi and melanomas). MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the model for evaluating "borderline" pigmentary skin lesions. RESULTS: After multivariate stepwise discriminant analysis, only 13 variables were selected to compute the canonical discriminant function. CONCLUSION: The present method made it possible to determine which objective variables are important for distinguishing atypical benign pigmentary skin lesions and early melanoma.

Quantitative characterization and study of the relationship between constitutive-facultative skin color and phototype in Caucasians.

In this study constitutive and facultative colorimetric values were quantified to determine the physiologic changes in Caucasian skin color and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Our population consisted of 401 subjects ranging in age from 24 to 28 years with similar life styles. Skin color was measured with a Minolta CR-200 colorimeter on the upper medial quarter of the buttock (constitutive color) and on the cheek (facultative color). Advanced multivariate statistical analysis allowed differentiation between constitutive and facultative skin color in relation to the phototype to be quantified. Moreover, Kullback divergence showed that the probability of correctly determining a subject's phototype is high when the variables of constitutive and facultative skin color are considered together. This interesting result makes it possible, in the future, to use colorimetric values of exposed and nonexposed skin, together with determination of Fitzpatrick phototype and of other phenotypic characters, to better predict cutaneous sun reactivity.

Relationship between skin color and sun exposure history: a statistical classification approach.

In this study our aim was to determine the biophysical values of constitutive skin color in Caucasians and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Constitutive skin color was measured on the buttock, with a Minolta CR-200 colorimeter, in a population-of 557 consecutive subjects belonging to phototype categories I, II, III and IV. The colorimeter expresses the results in five different color systems. We used the "Yxy" and L*a*b* systems, which are the most widespread in dermatology. Statistical analysis of the data showed that the "Yxy" system is even more discriminant than the L*a*b* system when the Fitzpatrick classification scheme is adopted as the reference and shows a poor ability to correctly classify the intermediate phototypes (II and III). On the contrary the "Yxy" system performs well in distinguishing phototypes I and IV. To establish whether this low discriminating capacity for phototypes II and III is related to a low discriminating capacity of the method suggested by Fitzpatrick or by our procedure, an objective technique (minimal erythemal dose) should be used to evaluate the percentage errors of classification of both the Fitzpatrick method and instrumental measurement of skin color. The results of such a study are extremely important because the evaluation of skin color is objective, simple and has potential applications in dermatology and cosmetology.

Instrumental measurement of skin colour and skin type as risk factors for melanoma: a statistical classification procedure.

A statistical procedure to evaluate melanoma risk in Caucasian subjects on the basis of colorimetric measurement of skin colour and Fitzpatrick phototype is described. One hundred and sixty melanoma patients and 546 randomized healthy subjects of similar age, sex and place of origin were examined in the same period for skin colour using a tristimulus colorimeter and for Fitzpatrick phototype. A clinical score for classification purposes was obtained by statistical discriminant analysis with multivariate data transformation and dimension reduction techniques. A Fisher linear classifier was chosen for its simplicity and robustness in correctly predicting melanoma risk in new subjects. The classification rule was designed to avoid classifying subjects at high risk for melanoma as low risk, i.e. to give a negligible number of false negatives at the expense of more false positives. The procedure is objective and readily adapted to different clinical requirements. This is only a preliminary study but it is hoped that by performing more complex statistical analyses, e.g. neural networks, and adding other parameters (proven risk factors such as number of naevi) the performance will be further improved.

Comparison of algorithms for tracking short-term changes in arterial circulation parameters.

Three recursive methods especially suited for identification of systems with rapidly changing parameters are applied to tracking of the viscoelastic properties of the systemic arterial bed. These methods include two least squares (LS) algorithms with constant or variable forgetting factor (RLS and LSVF) and a LS algorithm incorporating both a constant forgetting factor and covariance modification (CFCM). The methods are presented in a unified framework and their sensitivity with respect to the design variables is investigated using noisy data from computer simulations. All analysed methods have shown themselves to be able to satisfactory track rapid changes in peripheral resistance. The LSVF method, which offers slightly better performances than the classical RLS, may be preferred when calculation efficiency is the prime requirement. The CFCM algorithm, although maintaining reasonable simplicity, shows the best tracking ability also on varying of the noise sequence.

Two new algorithms for tracking arterial parameters in nonstationary noise conditions.

Two new algorithms with reduced sensitivity to the changing environment are applied to tracking arterial circulation parameters. They are variants of the Least-Squares (LS) algorithm with Variable Forgetting factor (LSVF), and of the Constant Forgetting factor-Covariance Modification (CFCM) LS algorithm, devised to overcome their main practical deficiencies related to noise level sensitivity and the high number of design variables, respectively. To this end, adaptive mechanisms are incorporated to estimate observation noise variance in LSVF and the rate of change for the different parameters in CFCM. Specific computer simulation experiments are presented to compare their effectiveness with the original counterparts and to provide guidelines for their optimal tuning at different noise levels. Moreover, algorithm performance degradation, consequent on changes in the noise level compared to that assumed during the tuning phase, is analyzed. In particular, it is shown that, when the noise level changes with respect to the tuning value, the new LSVF algorithm is much more robust than the original one, whose performance degrades rapidly. The new CFCM algorithm is characterized by a reduced number of design variables with respect to its original counterpart. Nevertheless, it can be preferred only when low noise signals are used for estimation.

Influence of flow pattern on the parameter estimates of a simple breathing mechanics model.

The first-order model of breathing mechanics is widely used in clinical practice to assess the viscoelastic properties of the respiratory system. Although simple, this model takes the predominant features of the pressure-flow relationship into account but gives highly systematic residuals between measured and model-predicted variables. To achieve a better fit of the entire data set, an approach hypothesizing deterministic time-variations of model parameters, summarized by information-weighted histograms was recently proposed by Bates and Lauzon. The present study uses flow and pressure data measured in intensive care patients to evaluate the real potential of this approach in clinical practice. Information-weighted histograms of the model parameters, estimated by an on-line identification algorithm, were first constructed by taking into account the parameter percentage standard deviations. Then, the influence of the respiratory flow pattern on the calculated histograms was evaluated by the Kolmogorov-Smirnov statistical test. The results show that the method gives good reproducibility under stable experimental conditions. In addition, for a given airflow waveform, an increase in respiratory frequency shifts the histograms representing time-varying viscous properties strongly versus lower values, whereas it shifts the histograms representing time-varying elastic properties slightly versus higher values. On the other hand, the same histograms were highly dependent on the airflow waveform, especially for the viscous properties. Even in a limited experimental work, in all the conditions considered, the method provides results which agree well with the physiological knowledge of nonlinear and multicompartment behavior of respiratory mechanics.

Tracking time-varying properties of the systemic vascular bed.

The problem of tracking changes in viscoelastic properties of the systemic arterial bed is considered and a recursive estimation procedure, belonging to the class of output-error algorithms with adjustable compensator, is developed and discussed. By means of computer simulations, suitable values are determined for the key design variable which controls the tradeoff between tracking ability and noise sensitivity of the algorithm. In this way, the algorithm allows on-line estimation of arterial compliance, peripheral resistance, and characteristic impedance on the basis of aortic pressure and flow signals. Furthermore, the results obtained from data numerically simulated, as well as measured on a mock circulatory system, demonstrate that the dominant arterial time-constant can be tracked by the algorithm using only measurements of the aortic pressure during diastole.

Electrical analogs for monitoring vascular properties in artificial heart studies.

The problem of choosing parametric descriptions of the systemic vascular bed suitable for monitoring beat-to-beat changes in peripheral vascular properties is considered. Three simple models with two, three, and five elements are compared, essentially exploiting the Akaike information criterion combined with reasonable requirements for estimate accuracy. Analysis of pressure data, which are either simulated by the five-element model or measured on a mock circulatory system during abrupt changes in peripheral resistance, suggests guidelines for model selection. In particular, the five-element model exhibits very close adherence to physical reality by allowing for reflection, while the classical windkessel model provides the most reproducible estimates.

Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression.

As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

The nuclei in cutaneous malignant melanoma, stage I, are smaller in survivors than in non-survivors.

Cutaneous melanoma, stage I, from 35 survivors at 5 year follow-up and 16 non-survivors were studied. Mean nuclear area in the superficial layer was significantly larger than in the deep layer both in survivors and non-survivors, but the ratio between nuclear area in superficial and deep layers (so-called maturation index) did not differ between survivors and non-survivors. In comparison with the survivors, the mean nuclear area of non-survivors was significantly larger both in the superficial (51.1 microns2 vs 43.7 microns2, p less than 0.01) and deep (42.9 microns2 vs 36.4 microns2, p less than 0.05) layer. This points to a general increase in nuclear areas in metastasizing tumors. Furthermore, the coefficient of variation of nuclear area [(standard deviation/mean) x 100] was not different between survivors and non-survivors, either in the superficial or in the deep layer. Inspection of histograms of areas of 1000-2000 nuclei per case in 20 random cases (10 survivors and 10 non-survivors) showed a homogeneous increase in nuclear area in non-survivors. None of the histograms revealed a cell clone with especially large nuclei. These data show that the increased mean nuclear area in non-survivors is due to a homogeneous increase of all nuclei throughout the tumor and not to a special cell clone with large nuclei within nuclei of otherwise normal size. The difference in mean nuclear area in superficial and deep layers indicates that careful selection of nuclei in either of these layers is essential to obtain reproducible and comparable results with interactive morphometry.

A simple computational approach to model parameter estimation.

The desire to describe biological data using mathematical models has led to the rapid development of various analytical techniques for model identification and parameter estimation. The procedures used may be non-linear and complex, and require long calculation periods. Thus, the aid of a personal computer renders efficient the application of these rather complicated procedures. In this study we developed a simple identification programme for heparan sulfate pharmacodynamics which can be easily and rapidly implemented on a personal computer. The programme is based on an iterative algorithm performing a non-linear regression analysis by the least-square method. This programme was applied to a clinical measured variables with which it was possible to quantify the pharmacodynamic effect of heparan sulfate.