Surgical and functional outcomes of Dorsal Inlay Graft urethroplasty in revision vs primary hypospadias repair in the pediatric age.

INTRODUCTION: Over the years, Dorsal Inlay Graft (DIG) urethroplasty has gained worldwide acceptance for primary hypospadias repair. However, its safety and effectiveness for revision surgery are yet to be proven. OBJECTIVE: The aim of the study is to assess and compare complication rates and functional outcomes of DIG surgery in revision versus primary hypospadias repair. MATERIAL AND METHODS: We carried out a retrospective analysis of data collected from 53 consecutive DIG urethroplasties performed by a single surgeon at our institution. Patients were stratified in two groups - primary repair and redo-urethroplasty. For each group, we recorded standard pre-operative characteristics, surgical technicalities, complication rates and uroflowmetry parameters. RESULTS: Out of 53 DIG urethroplasties, 21 (39.6 %) where primary and 32 (60.4 %) were re-do. As expected, the two groups differed for median age at surgery: 20 months for primary and 68.5 months for revision surgery (p < 0.001). Additionally, all 21 (100 %) primary interventions were performed with a preputial graft, whereas among revision DIG urethroplasties only 2 (6.3 %) where preputial and 30 (93.8 %) were buccal (p < 0.001). Catheterization time (7 vs 8 days, p = 0.155) and postoperative complication rates (14.3 % vs 9.4 %, p = 0.581) were comparable between the primary and revision surgery group, respectively (all p > .05). Forty-two of the 53 patients underwent uroflowmetry during follow-up. Of these, 19 (63 %) patients presented with abnormal uroflowmetry and 11 (37 %) had equivocal parameters with no difference between the two groups. DISCUSSION: Dorsal Inlay Graft urethroplasty has long been known to be safe and effective for primary hypospadias repair. On the other hand, data on dorsal inlay graft urethroplasty as a salvage surgery after primary hypospadias repair failure is scarce. Surprisingly, according to our findings, surgical outcomes and complication rates are comparable between primary and revision hypospadias cases. Additionally, our results in the redo group are absolutely encouraging if compared to those reported in the literature for the same subset of patients. CONCLUSIONS: According to our findings, DIG urethroplasty is a safe and effective option to treat revision hypospadias repair.

Relation between adenomyosis and elastographic characteristics of the cervix.

STUDY QUESTION: Is there a possible etiologic link between cervical stiffness and adenomyosis? SUMMARY ANSWER: Women with adenomyosis have a stiffer internal cervical os than those without adenomyosis. WHAT IS KNOWN ALREADY: An increased myometrial contractility during menses, leading to breaches in the endometrial basal lamina and subsequent infiltration of endometrial cells into the myometrium, has been proposed as a possible pathogenic mechanism for adenomyosis. Intense menstrual pain has already been shown to be associated with an increased stiffness, at elastography, of the internal cervical os. STUDY DESIGN, SIZE, DURATION: A cross-sectional study on 275 women was performed between 1 February and 31 July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the participants, 103 were and 172 women were not affected by adenomyosis as evaluated by ultrasonography. General and clinical characteristics of the patients were collected. Strain elastography was used to document tissue stiffness at different regions of interest of the cervix, i.e. the internal cervical os, the middle cervical canal, the anterior and the posterior cervical compartment. Tissue stiffness was expressed as a colour score from 0.1 = blue/violet (high stiffness) to 3.0 = red (low stiffness). Simple and multiple logistic regression analyses were used to evaluate the relation between the presence of adenomyosis, as the dependent variable, and independent factors. MAIN RESULTS AND THE ROLE OF CHANCE: Women with adenomyosis had a higher prevalence (P = 0.0001) and intensity (P = 0.0001) of pain during menses, between menses and at intercourse compared to control. The internal cervical os colour score was lower (higher stiffness) in women with adenomyosis (0.55 ± 0.29 versus 0.67 ± 0.26; P = 0.001) and the middle cervical canal/internal cervical os colour score ratio was greater (3.32 ± 4.36 versus 2.59 ± 4.99; P = 0.008), compared to controls. Upon logistic regression modelling (R2 = 0.077), the internal cervical os stiffness was an independent factor related to adenomyosis (odds ratio (OR) 0.220, 95% CI 0.077, 0.627; P = 0.005) along with age (P = 0.005) and the use of gonadal steroid therapies (P = 0.002). We obtained the same results using a different logistic regression model (R2 = 0.069), by substituting the internal cervical os stiffness with the ratio of the middle cervical canal/internal cervical os stiffness (OR 1.157, 95% CI 1.024, 1.309; P = 0.019). LIMITATIONS, REASONS FOR CAUTION: Women did not undergo surgery therefore we have no histological confirmation of the adenomyosis diagnosis. Strain elastography is a semiquantitative analysis and can be conditioned by the force applied by the operator during the analysis. The data were obtained mainly in White women in a single centre. WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first study indicating that women with adenomyosis have an increased stiffness of the internal cervical os. The results indicate that a stiff internal cervical os, as determined by elastography, is a possible contributor to the development of adenomyosis. These findings may have clinical significance and should prompt further investigation. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Bioactive injectable hydrogels for on demand molecule/cell delivery and for tissue regeneration in the central nervous system.

Currently there are no potential curative therapies that can improve the central nervous system (CNS) regeneration after traumatic injuries or diseases. Indeed, the regeneration of CNS is greatly impaired by limited drug penetration across the blood brain barrier (BBB), poor drug targeting, deficient progenitor neural cells and limited proliferation of mature neural cells. To overcome these limitations, bioengineered injectable hydrogels in combination with drug and cell therapy have been proposed to mimic the complexity of the CNS microenvironment and architecture. Additionally, to enhance relevant CNS regeneration, proper biophysical and biochemical cues are needed. Recently, great efforts have been devoted to tailor stimuli-responsive hydrogels as novel carrier systems which are able to guide neural tissue regeneration. This review provides an extensive overview on the most promising injectable hydrogels for neural tissue engineering. A special emphasis is made to highlight the ability of these hydrogels to deliver bioactive compounds/cells upon the exposure to internal and external stimuli. Bioactive injectable hydrogels have a broad application in central nervous system's (CNS) regeneration. This review gives an overview of the latest pioneering approaches in CNS recovery using stimuli-responsive hydrogels for several neurodegenerative disorders. STATEMENT OF SIGNIFICANCE: This review summarizes the latest innovations on bioactive injectable hydrogels, focusing on tailoring internal/external stimuli-responsive hydrogels for the new injectable systems design, able to guide neural tissue response. The purpose is to highlight the advantages and the limitations of thermo-responsive, photo responsive, magnetic responsive, electric responsive, ultrasound responsive and enzymes-triggered injectable hydrogels in developing customizable neurotherapies. We believe that this comprehensive review will help in identifying the strengths and gaps in the existing literature and to further support the use of injectable hydrogels in stimulating CNS regeneration.

Comparison of Histogram-based Textural Features between Cancerous and Normal Prostatic Tissue in Multiparametric Magnetic Resonance Images.

In the last decade, multiparametric magnetic resonance imaging (mpMRI) has been expanding its role in prostate cancer detection and characterization. In this work, 19 patients with clinically significant peripheral zone (PZ) tumours were studied. Tumour masks annotated on the whole-mount histology sections were mapped on T2-weighted (T2w) and diffusion-weighted (DW) sequences. Gray-level histograms of tumoral and normal tissue were compared using six first-order texture features. Multivariate analysis of variance (MANOVA) was used to compare group means. Mean intensity signal of ADC showed the highest showed the highest area under the receiver operator characteristics curve (AUC) equal to 0.85. MANOVA analysis revealed that ADC features allows a better separation between normal and cancerous tissue with respect to T2w features (ADC: P = 0.0003, AUC = 0.86; T2w: P = 0.03, AUC = 0.74). MANOVA proved that the combination of T2-weighted and apparent diffusion coefficient (ADC) map features increased the AUC to 0.88. Histogram-based features extracted from invivo mpMRI can help discriminating significant PZ PCa.

Ultrasound-based detection of glucocorticoid-induced impairments of muscle mass and structure in Cushing's disease.

PURPOSE: To investigate the glucocorticoid-induced impairments of muscle mass and structure in patients presenting different stages of steroid myopathy progression. METHODS: Thirty-three patients (28 women) affected by active (N = 20) and remitted (N = 13) Cushing's disease were recruited and the following variables were assessed: walking speed, handgrip strength, total body and appendicular muscle mass by bioelectrical impedance analysis (BIA), thickness and echo intensity of lower limb muscles by ultrasonography. RESULTS: The two groups of patients showed comparable values of both handgrip strength [median (interquartile range) values: active disease: 27.4 (7.5) kg vs. remitted disease: 26.4 (9.4) kg; P = 0.58] and walking speed [active disease: 1.0 (0.2) m/s vs. remitted disease: 1.1 (0.3) m/s; P = 0.43]. Also, the thickness of the four muscles and all BIA-derived sarcopenic indices were comparable (P > 0.05 for all comparisons) between the two groups. On the contrary, the echo intensity of vastus lateralis, tibialis anterior (lower portion), and medial gastrocnemius was significantly (P < 0.05 for all comparisons) higher in patients with active disease compared to patients with remitted disease. Finally, significant negative correlations were found in the whole group of patients between muscle echo intensity and muscle function assessments. CONCLUSIONS: We provided preliminary evidence that the ultrasound-derived measurements of muscle thickness and echo intensity can be useful to detect and track the changes of muscle mass and structure in patients with steroid myopathy and we suggest that the combined assessment of muscle mass, strength, and performance should be systematically applied in the routine examination of steroid myopathy patients.

Skeletonization algorithm-based blood vessel quantification using in vivo 3D photoacoustic imaging.

Blood vessels are the only system to provide nutrients and oxygen to every part of the body. Many diseases can have significant effects on blood vessel formation, so that the vascular network can be a cue to assess malicious tumor and ischemic tissues. Various imaging techniques can visualize blood vessel structure, but their applications are often constrained by either expensive costs, contrast agents, ionizing radiations, or a combination of the above. Photoacoustic imaging combines the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging, and image contrast depends on optical absorption. This enables the detection of light absorbing chromophores such as hemoglobin with a greater penetration depth compared to purely optical techniques. We present here a skeletonization algorithm for vessel architectural analysis using non-invasive photoacoustic 3D images acquired without the administration of any exogenous contrast agents. 3D photoacoustic images were acquired on rats (n = 4) in two different time points: before and after a burn surgery. A skeletonization technique based on the application of a vesselness filter and medial axis extraction is proposed to extract the vessel structure from the image data and six vascular parameters (number of vascular trees (NT), vascular density (VD), number of branches (NB), 2D distance metric (DM), inflection count metric (ICM), and sum of angles metric (SOAM)) were calculated from the skeleton. The parameters were compared (1) in locations with and without the burn wound on the same day and (2) in the same anatomic location before (control) and after the burn surgery. Four out of the six descriptors were statistically different (VD, NB, DM, ICM, p < 0.05) when comparing two anatomic locations on the same day and when considering the same anatomic location at two separate times (i.e. before and after burn surgery). The study demonstrates an approach to obtain quantitative characterization of the vascular network from 3D photoacoustic images without any exogenous contrast agent which can assess microenvironmental changes related to disease progression.

Sonosensitive theranostic liposomes for preclinical in vivo MRI-guided visualization of doxorubicin release stimulated by pulsed low intensity non-focused ultrasound.

The main goal of this study was to assess the theranostic performance of a nanomedicine able to generate MRI contrast as a response to the release from liposomes of the antitumor drug Doxorubicin triggered by the local exposure to pulsed low intensity non focused ultrasounds (pLINFU). In vitro experiments showed that Gadoteridol was an excellent imaging agent for probing the release of Doxorubicin following pLINFU stimulation. On this basis, the theranostic system was investigated in vivo on a syngeneic murine model of TS/A breast cancer. MRI offered an excellent guidance for monitoring the pLINFU-stimulated release of the drug. Moreover, it provided: i) an in vivo proof of the effective release of the liposomal content, and ii) a confirmation of the therapeutic benefits of the overall protocol. Ex vivo fluorescence microscopy indicated that the good therapeutic outcome was originated from a better diffusion of the drug in the tumor following the pLINFU stimulus. Very interestingly, the broad diffusion of the drug in the tumor stroma appeared to be mediated by the presence of the liposomes themselves. The results of this study highlighted either the great potential of US-based stimuli to safely trigger the release of a drug from its nanocarrier or the associated significant therapeutic improvement. Finally, MRI demonstrated to be a valuable technique to support chemotherapy and monitoring the outcome. Furthermore, in this specific case, the theranostic agent developed has a high clinical translatability because the MRI agent utilized is already approved for human use.

Laser capture microdissection is a valuable tool in the preoperative molecular screening of follicular lesions of the thyroid: an institutional experience.

OBJECTIVES: The application of molecular tests to thyroid fine needle aspiration (FNA) has been shown to be a valuable tool to better refine the pre-operative malignant risk of patients with indeterminate cytology results. In this study, we investigated the feasibility of using the laser capture microdissection (LCM) technique to obtain DNA and RNA for molecular tests in routine thyroid FNA smears. METHODS: Nine coupled FNA and histological retrospective cases and 31 prospective FNA cases with a follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) diagnosis were included in this study. Both cytological and histological specimens were investigated by direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) for BRAF and RAS mutations and for PAX8/PPARG and RET/PTC rearrangements, respectively. RESULTS: LCM yielded good DNA and RNA quality in all cases (100%) in both series, irrespective of the staining used (Giemsa, Papanicolaou, immunostain for thyroglobulin) and the cytology technique (conventional or liquid-based preparations). Total mutations found in the FNA and in the corresponding histological specimen in both series were: one PAX8/PPARG rearrangement in a follicular carcinoma (FC), four NRAS mutations [in two FCs, one papillary carcinoma and one follicular adenoma (FA)] and one HRAS mutation in one FA. The sensitivity was 67% and the specificity was 91%. CONCLUSIONS: LCM is a valuable tool to obtain good quality DNA and RNA for molecular tests in cytological material from thyroid FNA, and can be a useful option in the management of patients with an FN/SFN FNA diagnosis.

Similar worldwide patterns in the sex pheromone signal and response in the oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae).

The response of Grapholita molesta (Busck) males to three-component sex pheromone blends containing a 100% ratio of the major sex pheromone component, (Z)-8-dodecenyl acetate and a 10% ratio of (Z)-8-dodecenol, but with varying ratios of (E)-8-dodecenyl acetate (0.4, 5.4, 10.4, 30.4, and 100.1% E-blends) was tested with populations in eight stone and pome fruit orchards in Europe, Asia, and North and South America. Traps baited with the 5.4% E-blend caught significantly more males than traps with any other blend with all populations. Significantly more males were caught in traps baited with the 10.4% E-blend than in traps with the remaining blends, except with the 0.4% E-blend in Turkey. Significant differences in male moth catches occurred between the other blends with the 0.4>30.4% E-blend, and the 30.4>100.1% E-blend. Male moth catches with the 100.1% E-blend only differed from the hexane control in Chile. No apparent differences were noted to these blends in populations collected from pome or stone fruits. Flight tunnel assays to synthetic blends with a subset of populations were similar to the field results, but the breadth of the most attractive E-blends was wider. Flight tunnel assays also demonstrated a high level of male-female cross-attraction among field-collected populations. Female gland extracts from field-collected populations did not show any significant variation in their three-component blends. The only exceptions in these assays were that long-term laboratory populations were less responsive and attractive, and produced different blend ratios of the two minor components than recently collected field populations.

Ozone autohemotherapy induces long-term cerebral metabolic changes in multiple sclerosis patients.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated haemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

Link between automated coronary calcium volumes from intravascular ultrasound to automated carotid IMT from B-mode ultrasound in coronary artery disease population.

AIM: Establishing relationship between coronary calcium volumes from Intravascular Ultrasound (IVUS) and automated carotid intima-media thickness (cIMT) helps in understanding the genetic nature of atherosclerosis disease. In this research, we have quantified the detected calcium from IVUS video frames and associated a relationship between coronary calcium volumes computed and automated cIMT from B-mode ultrasound. METHODS: Coronary calcium volume is computed from IVUS and auto cIMTs are computed using B-mode ultrasound. An automated computer based application is developed and tested on 100 patient volumes (an average of 2549 frames per volume) to calculate lesion area and normalized coronary calcium volume. We use an integrated approach for volume computation which is based on lesion area per frame. We have measured the normalized volume from the calcium detected video frames using proposed integration method. The cIMT of 100 carotids were measured with novel and dedicated automated software analysis (AtheroEdge™ from AtheroPoint™ LLC, Roseville, CA, USA). RESULTS: The computer-based coronary calcium volume (from IVUS) showed a correlation coefficient with respect to cIMT for left and right carotids as 9.1% and 13.9%, respectively. CONCLUSION: Coronary calcium volume computed from IVUS and auto cIMT are moderately correlated. The association between auto cIMT (right side) vs. computer-based coronary calcium volume (IVUS) is stronger than the association between auto cIMT (left side) vs. computer-based coronary calcium volume.

MRI assessment of temporomandibular disorders: an approach to diagnostic and therapeutic setting.

AIMS: The aim of this study was to evaluate the relationship between the clinical and the radiological data obtained by magnetic resonance imaging (MRI) in patients with temporomandibular disorder (TMD). METHODOLOGY: The study group included 17 patients with symptoms of TMDs. The radiological assessments before and after therapy was evaluated by MRI; in the clinical analysis, signs and associated symptoms have been assessed. RESULTS: With MRI before therapy, we were able to distinguish the specific type of TMD that each patient had. At the end of the treatment, a general improvement of the clinical status was noticed; MRI, however, showed the permanence of several degrees of condyle-disc incoordination in some patients. CONCLUSIONS: Certainly TMDs can be diagnosed without MRI; nevertheless, MRI gives us the possibility to obtain objective data of the patients concerned. Symptoms recorded during a clinical evaluation cannot be the only terms of diagnosis; MRI provides objective data in the diagnostic and post-therapy phases.

A review on ultrasound-based thyroid cancer tissue characterization and automated classification.

In this paper, we review the different studies that developed Computer Aided Diagnostic (CAD) for automated classification of thyroid cancer into benign and malignant types. Specifically, we discuss the different types of features that are used to study and analyze the differences between benign and malignant thyroid nodules. These features can be broadly categorized into (a) the sonographic features from the ultrasound images, and (b) the non-clinical features extracted from the ultrasound images using statistical and data mining techniques. We also present a brief description of the commonly used classifiers in ultrasound based CAD systems. We then review the studies that used features based on the ultrasound images for thyroid nodule classification and highlight the limitations of such studies. We also discuss and review the techniques used in studies that used the non-clinical features for thyroid nodule classification and report the classification accuracies obtained in these studies.

Quantitative assessment of cancer vascular architecture by skeletonization of high-resolution 3-D contrast-enhanced ultrasound images: role of liposomes and microbubbles.

The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of microbubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient "theranostic" (i.e. therapeutic 1 diagnostic) ultrasound probes.

Evolutionary algorithm-based classifier parameter tuning for automatic ovarian cancer tissue characterization and classification.

PURPOSE: Ovarian cancer is one of the most common gynecological cancers in women. It is difficult to accurately and objectively diagnose benign and malignant ovarian tumors using ultrasound and other tests. Hence, there is an imperative need to develop a computer-aided diagnostic (CAD) system for ovarian tumor classification in order to reduce patient anxiety and the cost of unnecessary biopsies. In this paper, we present an automatic CAD system for the detection of benign and malignant ovarian tumors using advanced image processing and data mining techniques. MATERIALS AND METHODS: In the proposed system, Hu's invariant moments, Gabor transform parameters and entropies are first extracted from the acquired ultrasound images. Significant features are then used to train a probabilistic neural network (PNN) classifier for classifying the images into benign and malignant categories. The model parameter (σ) for which the PNN classifier performs the best is identified using a genetic algorithm (GA). RESULTS: The proposed system was validated using 1300 benign images and 1300 malignant images, obtained from 10 patients with a benign disease and 10 with a malignant disease. We used 23 statistically significant (p < 0.0001) features. By evaluating the classifier using a ten-fold cross-validation technique, we were able to achieve an average classification accuracy of 99.8 %, sensitivity of 99.2 % and specificity of 99.6 % with a σ of 0.264. CONCLUSION: The proposed system is automated and hence is more objective, can be easily deployed in any computer, is fast and accurate and can act as an adjunct tool in helping physicians make a confident call about the nature of the ovarian tumor under evaluation.

Time and time-frequency analysis of near-infrared signals for the assessment of ozone autohemotherapy long-term effects in multiple sclerosis.

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy system (NIRS) to monitor the cerebral oxygenation of 9 subjects: 4 remitting-relapsing multiple sclerosis (MS) sufferers and 5 controls. Subjects were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). From the time and time-frequency analysis of the NIRS signals we extracted 128 variables, which were used to characterize the metabolic brain pattern during the therapy. We showed that by using only 7 NIRS variables out of 128 it is possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.

Diagnosis of Hashimoto's thyroiditis in ultrasound using tissue characterization and pixel classification.

Hashimoto's thyroiditis is the most common type of inflammation of the thyroid gland, and accurate diagnosis of Hashimoto's thyroiditis would be helpful to better manage the disease process and predict thyroid failure. Most of the published computer-based techniques that use ultrasound thyroid images for Hashimoto's thyroiditis diagnosis are limited by lack of procedure standardization because individual investigators use various initial ultrasound settings. This article presents a computer-aided diagnostic technique that uses grayscale features and classifiers to provide a more objective and reproducible classification of normal and Hashimoto's thyroiditis-affected cases. In this paradigm, we extracted grayscale features based on entropy, Gabor wavelet, moments, image texture, and higher order spectra from the 100 normal and 100 Hashimoto's thyroiditis-affected ultrasound thyroid images. Significant features were selected using t-test. The resulting feature vectors were used to build the following three classifiers using tenfold stratified cross validation technique: support vector machine, k-nearest neighbor, and radial basis probabilistic neural network. Our results show that a combination of 12 features coupled with support vector machine classifier with the polynomial kernel of order 1 and linear kernel gives the highest accuracy of 80%, sensitivity of 76%, specificity of 84%, and positive predictive value of 83.3% for the detection of Hashimoto's thyroiditis. The proposed computer-aided diagnostic system uses novel features that have not yet been explored for Hashimoto's thyroiditis diagnosis. Even though the accuracy is only 80%, the presented preliminary results are encouraging to warrant analysis of more such powerful features on larger databases.

Automated carotid intima-media thickness and its link for prediction of SYNTAX score in Japanese coronary artery disease patients.

AIM: The purpose of this study was to evaluate whether the automated carotid intima-media thickness (CIMT) identified by using automated software could predict the SYNTAX score for coronary artery disease (CAD) patients. METHODS: Three-hundred-seventy consecutive patients (males 218; median age 69±11 years) who underwent carotid-ultrasound and coronary angiography were analyzed. Two experienced interventional cardiologists calculated the SYNTAX score from the carotid angiograms. After ultrasonographic examinations were performed, the plaque score (PS) was calculated and automated carotid IMT analysis was obtained by a fully automated algorithm. Correlation and stepwise logistic regression analysis were calculated and also the receiver operating characteristics (ROC) curve analysis was computed. RESULTS: The mean SYNTAX score was 8.1±14.4; the PS was 7.1±14.4 and the mean CIMT was 0.86±0.23 mm (Normality rejected with a P-value of 0.001). A statistically significant correlation was found between the CIMT and SYNTAX score (r=0.323; P=0.0001) and between the PS and SYNTAX score (r=0.583; P=0.0001). The area under the ROC curve (Az) between CIMT and coronary artery disease was 0.648 (P=0.0001) and the CIMT of 1 mm or more was associated with the presence coronary artery disease with a specificity of 90.5%. Logistic regression analysis confirmed the association between CIMT and SYNTAX score (P=0.0002). CONCLUSIONS: Results of our study using an automated algorithm showed a statistical significant association between CIMT and SYNTAX score and indicated that CIMT may be considered a reliable parameter for prediction of SYNTAX score in coronary artery disease patient population from Japan.

Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma.

BACKGROUND: As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies. METHODS: After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing. RESULTS: Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552). CONCLUSIONS: Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials.