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STUDY QUESTION Does a logistic regression model and scoring system to predict viability of an intrauterine pregnancy of uncertain viability (PUV) perform as well in an independent patient group as the original patient group? SUMMARY ANSWER The model and scoring system showed good performance on external validation confirming their value for the prediction of miscarriage/viability in PUV patients up to 11–14 weeks of gestation. WHAT IS KNOWN ALREADY Several individual ultrasound and demographic factors have been described as predictors for miscarriage. A logistic regression model and simple scoring system using basic clinical and ultrasound features, such as maternal age, bleeding score, mean gestational sac diameter (MSD) and presence or absence of yolk sac, have been developed to allow patient-specific prediction of viability of PUV beyond the first trimester. STUDY DESIGN, SIZE, DURATION Prospective observational external validation cohort study in two inner city early pregnancy assessment units over a period of 18 months. PARTICIPANTS/MATERIALS, SETTING, METHODS All consecutive women with a PUV were recruited. Ultrasound (mean sac diameter and presence of yolk sac) and demographic variables (maternal age, bleeding score and gestational age) were noted. The outcome measure was first trimester (11–14 week) viability. Women with unknown first trimester outcome were excluded. Receiver operating characteristic (ROC) curves and calibration plots were constructed. Test performance was compared with the original development data set. A new model and scoring system, which did not include gestational age, was built and evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Of the 575 women who were recruited, first trimester outcome was known for 89.2% (n = 513). The model could only be validated in 400 patients, due to missing values in model variables and outcome. The model predicted viability with an area under the ROC curve (AUC) of 0.845 [95% confidence interval (CI), 0.806–0.884] compared with 0.774 (95% CI, 0.701–0.848) in the original study. The AUC for the scoring system was 0.832 (95% CI, 0.792–0.872) compared with 0.771 (95% CI, 0.698–0.844) from the original study data set. The new model and the scoring system, excluding gestational age, could be evaluated on 503 patients and resulted in an AUC of 0.801 (95% CI, 0.765–0.841) for the model and 0.773 (95% CI, 0.733–0.812) for the scoring system. LIMITATIONS, REASONS FOR CAUTION Approximately 22% of patients could not be validated due to missing variables and for 11% of patients the first trimester outcome was unknown. WIDER IMPLICATIONS OF THE FINDINGS Both the model and the scoring system showed excellent performance on external validation confirming their generalizability and utility in prediction of viability beyond the first trimester in clinical practice. An advantage of the mathematical models original Mo and new Mn and scoring systems original SSo and new SSn is that they can provide women with an individualized probability of the viability of their pregnancy using only demographic information, symptoms and TVS findings. Furthermore, the risk of miscarriage can be given immediately following examination. STUDY FUNDING/COMPETING INTEREST(S) T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. This research is supported by Research Council KUL GOA MaNet, iMinds 2012, Belgian Federal Science Policy Office IUAP P719. VVB is a postdoctoral fellow of the Research Foundation – Flanders (FWO). There are no conflicts of interest. [ABSTRACT FROM PUBLISHER]

Objectives To define the incidence and outcome of intrauterine pregnancy of uncertain viability (PUV) and to develop and assess the performance of a model and a scoring system to predict ongoing viability. Methods Of 1881 consecutive women undergoing transvaginal ultrasonography, a cohort of 493 women with an empty gestational sac <20 mm in mean diameter, gestational sac <25 mm in mean diameter and containing yolk sac only or an embryonic pole <6 mmin maximum length and without visible heart activity were followed until the end of the first trimester. Women with multiple pregnancies or who underwent termination of pregnancy were excluded. Outcome measures were pregnancy viability at initial 7-14-day follow-up and first-trimester viability at 11-14 weeks. The data were split randomly into two sets (two-thirds and one-third, respectively) in order to first develop and then test a mathematical model and a 'simple' model in the prediction of viability at each outcome point, based on maternal demographics, ultrasound features and symptoms. The performance of each system was assessed by receiver-operating characteristics (ROC) curve analysis and calibration plots on a test dataset. Results The incidence of PUV in this population was 29.2% (549/1881). Of the 493 pregnancies with initial (7-14 days) follow-up available, 307 (62.3%) were viable at this time and of the 444 pregnancies with follow-up at the end of the first trimester, 225 (50.7%) were still viable. Initial (7-14-day) viability was predicted by the model with an area under the ROC curve (AUC) of 0.837 (95% CI, 0.791-0.884) in the training dataset and 0.821 (95% CI, 0.756-0.885) in the test dataset. First-trimester (11-14-week) viability was predicted by the model with an AUC of 0.788 (95% CI, 0.734-0.842) in the training dataset and 0.774 (95% CI, 0.701-0.848) in the test dataset. The scoring system performed slightly worse than did the model, but had the advantage of being easily applicable. Conclusions When early pregnancy viability cannot be established immediately with ultrasound, use of either a logistic regression model or a scoring system allows an individualized prediction of first-trimester outcome. [ABSTRACT FROM AUTHOR]

Motivation: New application areas of survival analysis as for example based on micro-array expression data call for novel tools able to handle high-dimensional data. While classical (semi-) parametric techniques as based on likelihood or partial likelihood functions are omnipresent in clinical studies, they are often inadequate for modelling in case when there are less observations than features in the data. Support vector machines (svms) and extensions are in general found particularly useful for such cases, both conceptually (non-parametric approach), computationally (boiling down to a convex program which can be solved efficiently), theoretically (for its intrinsic relation with learning theory) as well as empirically. This article discusses such an extension of svms which is tuned towards survival data. A particularly useful feature is that this method can incorporate such additional structure as additive models, positivity constraints of the parameters or regression constraints.Results: Besides discussion of the proposed methods, an empirical case study is conducted on both clinical as well as micro-array gene expression data in the context of cancer studies. Results are expressed based on the logrank statistic, concordance index and the hazard ratio. The reported performances indicate that the present method yields better models for high-dimensional data, while it gives results which are comparable to what classical techniques based on a proportional hazard model give for clinical data.Contact: vanya.vanbelle@esat.kuleuven.beSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM PUBLISHER]

The article presents a prospective study on the association of ovarian crescent sign (OCS) in benign and malignant adnexal pathology. The study covers 1,938 patients with an adnexal mass who underwent the International Ovarian Tumor Analysis (IOTA) Phase 2 study on various centers globally. The patients, some were evaluated of OCS, were scanned using ultrasound based on the same IOTA protocol. Moreover, it shows that the presence of the OCS is not associated with malignant adnexal masses.

This work studies a new survival modeling technique based on least-squares support vector machines. We propose the use of a least-squares support vector machine combining ranking and regression. The advantage of this kernel-based model is threefold: (i) the problem formulation is convex and can be solved conveniently by a linear system; (ii) non-linearity is introduced by using kernels, componentwise kernels in particular are useful to obtain interpretable results; and (iii) introduction of ranking constraints makes it possible to handle censored data. In an experimental setup, the model is used as a preprocessing step for the standard Cox proportional hazard regression by estimating the functional forms of the covariates. The proposed model was compared with different survival models from the literature on the clinical German Breast Cancer Study Group data and on the high-dimensional Norway/Stanford Breast Cancer Data set. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine the optimal gestational age at which to establish the location and viability of an early pregnancy using transvaginal ultrasonography (TVS). Methods: This was a prospective study of 1442 women undergoing initial TVS at no more than 84 days gestation. Logistic regression analysis was performed to determine the relationship between gestational age and the ability to confirm viability or non-viability, in women with and without symptoms of pain and bleeding. Results: The commonest TVS finding prior to 35 days was a pregnancy of unknown location, from 35 to 41 days an early intrauterine pregnancy of uncertain viability and from 42 days a viable intrauterine pregnancy. Miscarriage could only be diagnosed on initial TVS after 35 days. There was no difference between the ability to make a diagnosis for women with certain or uncertain dates (P = 0.719). The chance of confirming viability increased rapidly per day of gestation until 49 days and thereafter plateaued. Of the 29 ectopic pregnancies diagnosed, 72% presented prior to 49 days gestation and all of these women presented with pain, bleeding or a previous ectopic pregnancy history. Conclusions: The ability to confirm viability or non-viability is significantly related to gestational age. In asymptomatic women with no previous ectopic pregnancy TVS should be delayed until 49 days. Our data suggest that this would reduce the number of inconclusive scans, without an associated increase in morbidity from missed ectopic pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To determine whether intravenous contrast ultrasound examination is superior to gray-scale or power Doppler ultrasound for discrimination between benign and malignant adnexal masses with complex ultrasound morphology. Methods: In an international multicenter study, 134 patients with an ovarian mass with solid components or a multilocular cyst with more than 10 cyst locules, underwent a standardized transvaginal ultrasound examination followed by contrast examination using the contrast-tuned imaging technique and intravenous injection of the contrast medium SonoVue(R). Time intensity curves were constructed, and peak intensity, area under the intensity curve, time to peak, sharpness and half wash-out time were calculated. The sensitivity and specificity with regard to malignancy were calculated and receiver-operating characteristics (ROC) curves were drawn for gray-scale, power Doppler and contrast variables and for pattern recognition (subjective assignment of a certainly benign, probably benign, uncertain or malignant diagnosis, using gray-scale and power Doppler ultrasound findings). The gold standard was the histological diagnosis of the surgically removed tumors. Results: After exclusions (surgical removal of the mass > 3 months after the ultrasound examination, technical problems), 72 adnexal masses with solid components were used in our statistical analyses. The values for peak contrast signal intensity and area under the contrast signal intensity curve in malignant tumors were significantly higher than those in borderline tumors and benign tumors, while those for the benign and borderline tumors were similar. The area under the ROC curve of the best contrast variable with regard to diagnosing borderline or invasive malignancy (0.84) was larger than that of the best gray-scale (0.75) and power Doppler ultrasound variable (0.79) but smaller than that of pattern recognition (0.93). Conclusion: Findings on ultrasound contrast examination differed between benign and malignant tumors but there was a substantial overlap in contrast findings between benign and borderline tumors. It appears that ultrasound contrast examination is not superior to conventional ultrasound techniques, which also have difficulty in distinguishing between benign and borderline tumors, but can easily differentiate invasive malignancies from other tumors. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "The value of assessment of patient history and pain and bleeding scores prior to early pregnancy transvaginal ultrasound assessment," by C. Bottomley, and colleagues is presented.

An abstract of the article "Improved performance of a model and simple scoring system to predict outcome of intrauterine pregnancy of uncertain viability: an external validation study," by S. Guha, V. Van Belle, C. Bottomley, C. Stalder and T. Bourne is presented.

An abstract of the article "External validation of a simple ultrasound based scoring system to predict pregnancy viability beyond the first trimester," by S. Guha, V. Van Belle, C. Bottomley, C. Stalder and T. Bourne is presented.

An abstract of the conference paper "Prediction of pregnancy viability by means of scoring systems: towards a 'risk of miscarriage' index," by C. Bottomley and colleagues is presented.

An abstract of the conference paper "Optimal timing of transvaginal ultrasound to confirm early pregnancy viability," by C. Bottomley, and colleagues is presented.

An abstract of the research paper "Determination of Outcome in Very Early Intrauterine Pregnancies of Uncertain Viability," by C. Bottomley and colleagues is presented.

The article presents a study which examines whether intravenous contrast ultrasound is superior in determining the difference between benign and malignant adnexal masses with complex ultrasound morphology compared with gray-scale or power Doppler ultrasound. It assesses the intravenous contrast ultrasound characteristics obtained by contrast-tuned imaging (CnTI) and the contrast medium SonoVue. Results show that ultrasound contrast examination is not superior to conventional ultrasound.

An abstract of the conference paper "Presence of acoustic streaming in different types of adnexal masses," by C. Van Holsbeke, and colleagues is presented.

An abstract of the article "Ultrasound contrast examination to discriminate benign and malignant adnexal masses," by A. C. Testa and colleagues, is presented.

Background: Elevated levels of matrix metalloproteinases have been found to associate with poor prognosis in various carcinomas. This study aimed at evaluating plasma levels of MMP1, MMP8 and MMP13 as diagnostic and prognostic markers of breast cancer.Methods: A total of 208 breast cancer patients, of which 21 with inflammatory breast cancer, and 42 healthy controls were included. Plasma MMP1, MMP8 and MMP13 levels were measured using ELISA and correlated with clinicopathological characteristics.Results: Median plasma MMP1 levels were higher in controls than in breast cancer patients (3.45 vs. 2.01 ng/ml), while no difference was found for MMP8 (10.74 vs. 10.49 ng/ml). ROC analysis for MMP1 revealed an AUC of 0.67, sensitivity of 80% and specificity of 24% at a cut-off value of 4.24 ng/ml. Plasma MMP13 expression could not be detected. No correlation was found between MMP1 and MMP8 levels. We found a trend of lower MMP1 levels with increasing tumour size (p = 0.07); and higher MMP8 levels with premenopausal status (p = 0.06) and NPI (p = 0.04). The median plasma MMP1 (p = 0.02) and MMP8 (p = 0.007) levels in the non-inflammatory breast cancer patients were almost twice as high as those found in the inflammatory breast cancer patients. Intriguingly, plasma MMP8 levels were positively associated with lymph node involvement but showed a negative correlation with the risk of distant metastasis. Both controls and lymph node negative patients (pN0) had lower MMP8 levels than patients with moderate lymph node involvement (pN1, pN2) (p = 0.001); and showed a trend for higher MMP8 levels compared to patients with extensive lymph node involvement (pN3) and a strong predisposition to distant metastasis (p = 0.11). Based on the hypothesis that blood and tissue protein levels are in reverse association, these results suggest that MMP8 in the tumour may have a protective effect against lymph node metastasis.Conclusion: In summary, we observed differences in MMP1 and MMP8 plasma levels between healthy controls and breast cancer patients as well as between breast cancer patients. Interestingly, our results suggest that MMP8 may affect the metastatic behaviour of breast cancer cells through protection against lymph node metastasis, underlining the importance of anti-target identification in drug development. [ABSTRACT FROM AUTHOR]