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.

Dysplastic naevus vs. in situ melanoma: digital dermoscopy analysis.

BACKGROUND: To date, much confusion exists about the biological significance of dysplastic naevi and about the relationship between melanocytic dysplasia and clinical atypia. OBJECTIVES: To use a digital dermoscopy analyser with a series of 'borderline' pigmented skin lesions (i.e. dysplastic naevi and in situ melanomas) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. METHODS: The pigmented skin lesions (n = 174) were histologically examined by three experienced dermatopathologists and identified as in situ melanomas (n = 38) and dysplastic naevi (n = 136). The system evaluated 48 parameters as possible discriminant variables, grouped into four categories: geometry, colours, textures and islands of colour. Once the lesions were analysed (stepwise discriminant analysis), sensitivity, specificity and accuracy were calculated. RESULTS: At the end of the stepwise procedure the percentage of cases classified correctly was 71.8%. Of 136 dysplastic naevi only 98 were classified correctly, while 27 of 38 in situ melanomas were recognized correctly. CONCLUSIONS: We conclude that there are so far no digital dermoscopic criteria that can clearly distinguish dysplastic naevi from in situ melanomas.

Detection of expiratory flow limitation during mechanical ventilation: a simulation study.

Expiratory flow limitation (EFL) is frequent in mechanically ventilated patients with obstructive pulmonary disease and its prompt detection is important to optimize respiratory assistance. The present study aims to compare by simulation two methods for the detection of flow limitation in intensive care unit: the negative expiratory pressure (NEP) method and the external resistance (DeltaR) method. To this purpose, a non linear dynamic morphometric model of breathing mechanics, derived from the Weibel symmetrical description of lungs, was used to simulate a normal and an obstructive respiratory condition during artificial ventilation. Both methods revealed the presence of EFL in the pathological case. The NEP method seems to promote the collapse of the upper and intermediate airways, so producing an overestimation of the pathology result. On the contrary, during the DeltaR maneuver the same airways increase their radius and, therefore, EFL appears underestimated. The DeltaR method appears less practical with respect to the NEP method, because of the procedure required to select the appropriate resistance degree. Moreover the flow limited portion of expiration estimated by the DeltaR technique sounds rather dependent on the choice of the external resistance level.

Role of the mechanical properties of tracheobronchial airways in determining the respiratory resistance time course.

A physiologically based simulation model of breathing mechanics was considered in an attempt to interpret and explain the time course of input respiratory resistance during the breathing cycle, observed in recent studies on ventilated patients. The model assumes a flow-dependent Rohrer resistance for the upper extrathoracic airways and volume-dependent resistance and elastance for the intermediate airways. A volume-dependent resistance describes the dissipative pressure loss in the lower airways, and two constant elastances represent lung and chest wall elasticity. Simulated mouth flow and pressure signals obtained in a variety of well-controlled conditions were used to analyze total respiratory resistance and elastance estimated by an on-line algorithm based on a time-varying parameter model. These estimates were compared with those provided by classical estimation algorithms based on time-invariant models with two, three, and four parameters. The results show that the four-parameter model is difficult to identify, while the three-parameter one offers no substantial advantage for estimating input resistance with respect to the more simple two-parameter model. In contrast, the time-varying approach provides good on-line estimates of the simulated end-expiration and end-inspiration resistances. These values provide further information of potential clinical utility, with respect to time-invariant models. For example, the results show that the difference between the end-expiration and end-inspiration resistance increases when obstructions shift from the upper to the lower airways. The similarity of the results obtained with measured and simulated data indicates that, in spite of its simplicity, the simulation model describes important physiological mechanisms underlying changes in respiratory input resistance, specifically the mechanical properties of intermediate airways.

Effect of compliant intermediate airways on total respiratory resistance and elastance in mechanical ventilation.

Total respiratory resistance and elastance were estimated off-line in a sample of 60 patients undergoing mechanical ventilation by means of two regression models in order to analyse and understand a possible physiological mechanism determining differences in inspiration and expiration. The first model considered a single value for resistance and elastance over a whole breathing cycle, whereas the second model considered separate values for inspiratory and expiratory resistance and a single value for elastance. Inspiratory resistance was found to be lower than expiratory resistance, and intermediate values were obtained for resistance estimated over the whole breathing cycle. Student's t-test showed a highly significant difference between these resistance estimates, and principal components analysis demonstrated a significant increase in information when both inspiratory and expiratory resistances were used. Minor differences were found between values of elastance calculated with the two approaches. In an attempt to interpret these experimental results, a lung model incorporating the non-linear viscoelastic properties of the intermediate airways was considered. This model suggested that changes in intermediate airway volume play a significant role in breathing mechanics during artificial ventilation and indicated that inspiratory and expiratory resistance could be useful parameters for locating airway obstruction.

Expression of the ALK protein by anaplastic large-cell lymphomas correlates with high proliferative activity.

A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80). Tumor cells expressing NPM-ALK exhibit markedly enhanced proliferative activity, but comparative cellular kinetic studies on ALK(+) (ALK lymphomas) and ALK(-) lymphomas are lacking. The present study showed that ALK(+) lymphomas, detected with the monoclonal antibody ALKc (n = 17), had significantly higher average values for the proliferation-associated parameters mitotic index, ana/telophase index, growth index (x x mitotic index - apoptotic index, assuming x = 3), percentages of Ki-67(+) cells and fraction of cells expressing cyclin A or B or the cell cycle-regulatory protein p34(cdc2) than did ALK(-) ALCLs (n = 15). Whether this intense proliferative activity contributes to the good response to chemotherapy and favorable outcome of ALK(+) ALCLs remains to be assessed in a larger series of patients. Our findings support the notion that ALK(+) and ALK(-) ALCLs are 2 distinct disease entities.

Modified Karhunen-Loéve expansion for evaluating skin-colour-associated melanoma risk factors.

An approach based on the modified Karhunen-Loéve expansion (MKLE) of constitutive and facultative skin colour data acquired by colorimeters in melanoma patients and healthy control subjects, was used to identify two colour features defining skin-colour-associated risk of melanoma. None of four common statistical classifiers trained on colour features were sufficiently accurate for allowing skin colour alone to be used for classification purposes, though a Bayesian quadratic classifier matched the transformed data well. This study supersedes the indeterminate character of most common clinical criteria based on qualitative factors and, irrespective of the results of classification, provides objective skin colour information for the prevention of melanoma.

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.

Expression of p34(cdc2) and cyclins A and B compared to other proliferative features of non-Hodgkin's lymphomas: a multivariate cluster analysis.

In view of recent knowledge on proteins regulating the cell cycle, we re-evaluated proliferative features of 98 diffusely growing non-Hodgkin's lymphomas. The combined use of 5 proliferation-associated variables (mitotic indices and percentages of Ki-67(+), p34(cdc2+), cyclin A(+) and cyclin B(+) cells) and their entry into a multivariate cluster analysis separated, without overlaps, the entire cohort into 3 groups (clusters) with (1) low, (2) intermediate and (3) high proliferative activity. Conversely, bivariate plots exposed considerable cluster overlaps. Multivariate stepwise discriminant analysis of all cases revealed a decreasing order of discriminant power for % Ki-67(+) cells > % p34(cdc2+) cells > mitotic index > % cyclin A(+) cells > % cyclin B(+) cells. The combined use of 2 variables only, mitotic index and % p34(cdc2+) cells, allowed a clear-cut separation of clusters 2 and 3. In bivariate plots, correlations were best between % Ki-67(+) cells and % cyclin A(+) cells and between mitotic indices and % cyclin B(+) cells. Except for chronic lymphocytic leukemias, immunocytomas and marginal zone lymphomas (all in cluster 1), individual lymphoma entities were distributed among at least 2 clusters. There was, however, a marked preponderance of mantle cell lymphomas and diffuse follicular center lymphomas in cluster 1 and of diffuse large B-cell lymphomas and peripheral T-cell lymphomas in cluster 2. Anaplastic large-cell lymphomas predominated in cluster 3 and responded best to therapy.

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.

Cellular kinetic differences between Hodgkin's and anaplastic large cell lymphomas: relation to the expression of p34cdc2 and cyclin B-1.

Our study was designed to compare cellular kinetic parameters of classical Hodgkin's disease (HD) with those of anaplastic large cell lymphomas (ALCL-C, common type; and ALCL-HL, Hodgkin's like), with a particular focus on the G2/M transition. These disorders share some phenotypic properties, e.g., CD30 positivity of putative neoplastic cells. The percentages of cells expressing p34cdc2 (p34) and cyclin B-1 (cyclin-B), which form a complex (maturation/mitosis promoting factor, MPF) regulating the G2-M phases of the cell cycle, were also registered. Highly significant differences between HD and ALCL-C were recognized: a) in HD, evidence for abortive mitosis (i.e., difficulty to proceed beyond the metaphase stage) and consequent multinucleation and/or deletion of CD30+ cells was prominent, in contrast to ALCL-C. This was associated with a markedly lower fraction of large atypical cells (LAC) expressing cyclin-B in the cytoplasm and the nucleus (C + N) in HD than in ALCL-C; b) the extent of multinucleation of CD30+ cells in HD, but not in ALCL-C, was correlated with the %p34+ LAC; c) the proportions of LAC expressing p34 and/or cyclin-B (C) were positively related to the percentages of cyclin-B (C + N)+ LAC in ALCL-C but not in HD; d) in HD, in contrast to ALCL-C, the size of the fraction of cyclin-B (C + N)+ LAC did not correlate with the ana/telophase indices (ATI, reflecting successful completion of mitosis) and the magnitude of cell loss; e) in ALCL-C, the percentages of p34+ LAC were positively correlated with ATI or the degree of CD30+ cell deletion, but inversely in HD. With regard to all parameters mentioned above, ALCL-HL tended to take an intermediate position between HD and ALCL-C, but sided more with the latter. In conclusion, our present results suggest a derangement of MPF kinetics and functions that is more profound in HD than in ALCL-C.

Relationship between minimal phototoxic dose and skin colour plus sun exposure history: a neural network approach.

Before beginning PUVA-therapy it is important to accurately gauge an individual's degree of psoralen photosensitivity. This determination is usually based on an individual's skin phototype or minimal phototoxic dose. Since minimal phototoxic dose is technically complex and time consuming to measure, sun reactivity skin phototype is often used instead; however, it has recently been shown that skin phototype lacks specificity as a predictor of an individual's minimal phototoxic dose. In this study, an artificial neural network was developed to attempt to predict the minimal phototoxic dose from skin colour measurements combined with skin phototype. Our results showed that minimal phototoxic dose was predicted with an error less than 1 J/cm2 in only about half the subjects. In conclusion, minimal phototoxic dose probably cannot be predicted with sufficient accuracy on the basis of skin colour and skin phototype alone.

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.

A new approach for tracking respiratory mechanical parameters in real-time.

A new recursive least-squares procedure for on-line tracking of changes in viscoelastic properties of respiratory mechanics is proposed and applied to artificially ventilated patients. Classical least-squares methods based on simple first-order linear models with time-constant parameters generally provide systematic residuals that hardly satisfy standard statistical tests for model validation in terms of residuals. On the other hand, high order and/or nonlinear models introduce parameters whose estimates are of difficult interpretation in a clinical context. The present procedure overcomes these limitations by using the well-known first-order model of respiratory mechanics, wherein variability of resistance and elastance during the breathing cycle is allowed to take into account nonlinear and high-order behavior. Mean and standard deviation of resistance and elastance estimates, relative to a respiratory cycle, are then determined recursively. Feasibility of the method is evaluated by applying it both to experimental and simulated pressure-airflow signals measured in an intensive care unit during mechanical ventilation of patients recovering from heart surgery. Results demonstrate that the proposed procedure provides data description satisfying statistical tests, such as residual whiteness, and reliable estimates of viscoelastic lung parameters even during substantial and fast variations in the respiratory status. In addition, unlike classical methods, the new technique provides the means for on-line evaluation of parameter variability during each respiratory cycle, by the estimate of their standard deviations. This is important in clinical practice, because only the knowledge of reliable parameter values and standard deviations enables significant changes in the respiratory viscoelastic characteristics, and thus in patient status, to be assessed.

Nearest-neighbor analysis of spatial point patterns: application to biomedical image interpretation.

Analysis of the spatial distributions of objects is fundamental to biomedical image interpretation. Nearest-neighbor (NN) methods are generally used to assess whether objects are arranged at random or in a deterministic manner. Simple standard NN techniques, however, may fail to identify complex spatial organizations. To overcome this problem the present study proposes a NN iterative algorithm that enables deterministic spatial patterns to be detected by identifying the distances between objects for which there is the greatest deviation from randomness and hence the amplitude of the areas of maximum reciprocal influence between objects. The performance of the algorithm is evaluated by applying it to both manufactured and experimental data. The manufactured date example showed that the proposed procedure produced neither false positives or negatives. The method proved to be extremely sensitive, detecting even small deviations from randomness. The experimental analysis was applied to the study of the spatial distribution of apopototic structures in malignant neoplastic tissue. It showed that the apopototic cells and bodies are characterized by a complex spatial pattern, and aggregate closely.

Presence of the bcl-2 protein and apoptosis in non-Hodgkin lymphomas with diffuse growth pattern.

In an attempt to further clarify the role of the apoptosis-counteracting protein bcl-2, non-Hodgkin lymphomas (NHL, n = 170) were examined immunohistochemically, across the boundaries of histologic classification, for the presence of this oncoprotein, in comparison with apoptotic indices (AI) and percentages of Ki-67+ cells (growth fraction). The results of this retrospective study revealed a highly significant inverse relationship ("mirror image") between the proportion of bcl-2+ cells and the AI per case. Both these parameters, although variable, clearly distinguished low- from high-grade-malignancy lymphomas according to the Kiel classification. Cluster analysis detected 2 separate groups of high-grade NHL, one with rather high AI and low percentages of bcl-2+ cells, comprising most anaplastic large-cell lymphomas, the other group with reverse characteristics. We found no correlation between the percentage of bcl-2+ cells per case and overall survival.