Imaging techniques in the management of abnormal vaginal bleeding in non-pregnant women before and after menopause.

Transvaginal ultrasound plays a pivotal role in the management of non-pregnant women with abnormal vaginal bleeding. No other imaging technique has a role in the triage of these women. In women with postmenopausal bleeding, ultrasound is used to categorise women as at low or high risk of endometrial cancer, and the result of the ultrasound examination is the basis for further management. In women with abnormal vaginal bleeding before the menopause, the role of ultrasound is less clear. This is because some common causes of abnormal vaginal bleeding before the menopause cannot be diagnosed with ultrasound, such as infection, dysfunctional bleeding, or problems with intrauterine contraceptive devices or contraceptive pills. Nonetheless, transvaginal ultrasound may also sometimes be helpful in women with abnormal vaginal bleeding before the menopause. In this chapter, I present ultrasound findings in women with endometrial cancer, endometrial polyps, endometrial hyperplasia, adenomyosis, uterine myomas, including submucous myomas and leiomyosarcoma, and describe ultrasound-based triage of women with postmenopausal bleeding

Prediction of scar integrity and vaginal birth after caesarean delivery.

A statistically significant association with uterine rupture during a trial of labour after caesarean delivery was found in at least two studies for the following variables: inter-delivery interval (higher risk with short interval), birth weight (higher risk if 4000 g or over), induction of labour (higher risk), oxytocin dose (higher risk with higher doses), and previous vaginal delivery (lower risk). However, no clinically useful risk estimation model that includes clinical variables has been published. A thin lower uterine segment at 35-40 weeks, as measured by ultrasound in women with a caesarean hysterotomy scar, increases the risk of uterine rupture or dehiscence. No cut-off for lower uterine segment thickness, however, can be suggested because of study heterogeneity, and because prospective validation is lacking. Large caesarean hysterotomy scar defects in non-pregnant women seen at ultrasound examination increase the risk of uterine rupture or dehiscence in subsequent pregnancy, but the strength of the association is unknown. To sum up, we currently lack a method that can provide a reliable estimate of the risk of uterine rupture or dehiscence during a trial of labour in women with caesarean hysterotomy scar(s)

Normal cervical changes in parous women during the second half of pregnancy--a prospective, longitudinal ultrasound study.

OBJECTIVE: To determine what constitutes normal cervical changes during the second half of pregnancy in parous women delivering at term. DESIGN: The study comprises 21 healthy, pregnant parous women who all gave birth at term. They were examined with transvaginal ultrasound every two weeks from 24 gestational weeks until delivery. Cervical length and width were measured. The inner cervical os was assessed as being closed or open, the length and width of any opening were measured, and dynamic cervical changes (i.e. opening and closing of the inner cervical os during examination) were noted. RESULTS: Median cervical length was 41 mm (range 26-55) at the first examination and 29 mm (range 8-56) at the last examination. The corresponding figures for cervical width were 38 mm (range 29-47) and 46 mm (range 38-64). Cervical length decreased in 18 women but remained unchanged in three. Three patterns of change in cervical length were observed: in 12 women there was a steady, continuous decrease in cervical length (median decrease rate 1.1 mm/week, range 0.6-2.4); in four women the decrease rate accelerated towards the end of pregnancy, the median decrease rate after the change being 3.0 mm/week (range 1.5-4.8); and in two women there was a sudden drop in cervical length at term. Cervical width increased in 16 women but remained unchanged in five. Two patterns of change in cervical width were seen: 14 women manifested a steady continuous increase in cervical width (median 0.8 mm/week, range 0.4-1.8); in two women the increase rate accelerated from around 34 gestational weeks, the increase rate after the change being 4.1 and 5.9 mm/week, respectively. Opening of the internal cervical os was observed at least once in 11 (52%) women and was seen as early as at 24 and 25 gestational weeks in two women. The opening was always V-shaped (median length 6 mm, range 4-17; median width 7 mm, range 3-20). Dynamic changes of the internal cervical os were seen in three women (14%) at 25, 30 and 41 gestational weeks, respectively. CONCLUSION: The cervix of parous women decreases in length and increases in width from midpregnancy to term, but the pattern of change varies between individuals. Knowledge of the different patterns of normal change forms the basis of transvaginal ultrasound studies of pathological cervical changes during pregnancy

The sensitivity and specificity of transvaginal ultrasound with regard to acute pelvic inflammatory disease: a review of the literature.

This review aims to sum up current knowledge on the sensitivity and specificity of ultrasound features suggestive of acute pelvic inflammatory disease (PID)

Ultrasound for diagnosing acute salpingitis: a prospective observational diagnostic study.

STUDY QUESTION: What are the diagnostic benefits of using ultrasound in patients with a clinical suspicion of acute salpingitis and signs of pelvic inflammatory disease (PID)? SUMMARY ANSWER: In patients with a clinical suspicion of acute salpingitis, the absence of bilateral adnexal masses at ultrasound decreases the odds of mild-to-severe acute salpingitis about five times, while the presence of bilateral adnexal masses increases the odds about five times. WHAT IS KNOWN ALREADY: PID is difficult to diagnose because the symptoms are often subtle and mild. The diagnosis is usually based on clinical findings, and these are unspecific. The sensitivity and specificity of ultrasound with regard to salpingitis have been reported in one study (n = 30) of appropriate design, where most patients had severe salpingitis (i.e. pyosalpinx) or tubo-ovarian abscess. STUDY DESIGN, SIZE, DURATION: This diagnostic test study included 52 patients fulfilling the clinical criteria of PID. Patients were recruited between October 1999 and August 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients underwent a standardized transvaginal gray scale and Doppler ultrasound examination by one experienced sonologist (index test) before diagnostic laparoscopy by a laparoscopist blinded to the ultrasound results. The final diagnosis was determined by laparoscopy, histology of the endometrium and other histology where relevant (reference standard). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 52 patients, 23 (44%) had a final diagnosis unrelated to genital infection, while the other 29 had cervicitis (n = 3), endometritis (n = 9) or salpingitis (n = 17; mild n = 4, moderate n = 8, severe, i.e. pyosalpinx n = 5). Bilateral adnexal masses and bilateral masses lying adjacent to the ovary were seen more often on ultrasound in patients with salpingitis than with other diagnoses (bilateral adnexal masses: 82 versus 17%, i.e. 14/17 versus 6/35, P = 0.000, positive likelihood ratio 4.8, negative likelihood ratio 0.22; bilateral masses adjacent to ovary: 65 versus 17%, i.e.11/17 versus 6/35, P = 0.001, positive likelihood ratio 3.8, negative likelihood ratio 0.42). In cases of salpingitis, the masses lying adjacent to the ovaries were on average 2-3 cm in diameter, solid (n = 14), unilocular cystic (n = 4), multilocular cystic (n = 3) or multilocular solid (n = 1), with thick walls and well vascularized at colour Doppler. In no case were the cogwheel sign or incomplete septae seen. All 13 cases of moderate or severe salpingitis were diagnosed with ultrasound (detection rate 100%, 95% confidence interval 78-100%) compared with 1 of 4 cases of mild salpingitis. Three of six cases of appendicitis, and two of two ovarian cysts were correctly diagnosed with ultrasound, and one case of adnexal torsion was suspected and then verified at laparoscopy. LIMITATIONS, REASONS FOR CAUTION: The sample size is small. This is explained by difficulties with patient recruitment. There are few cases of mild salpingitis, which means that we cannot estimate with any precision the ability of ultrasound to detect very early salpingitis. The proportion of cases with salpingitis of different grade affects the sensitivity and specificity of ultrasound, and the sensitivity and specificity that we report here are applicable only to patient populations similar to ours. WIDER IMPLICATIONS OF THE FINDINGS: The information provided by transvaginal ultrasound is likely to be of help when deciding whether or not to proceed with diagnostic laparoscopy in patients with symptoms and signs suggesting PID and, if laparoscopy is not performed, to select treatment and plan follow-up. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by funds administered by Malmö University Hospital and two Swedish governmental grants (ALF-medel and Landstingsfinansierad Regional Forskning). The authors have no conflict of interest

Improved modeling of clinical data with kernel methods

Objective: Despite the rise of high-throughput technologies, clinical data such as age, gender and medical history guide clinical management for most diseases and examinations. To improve clinical management, available patient information should be fully exploited. This requires appropriate modeling of relevant parameters. Methods: When kernel methods are used, traditional kernel functions such as the linear kernel are often applied to the set of clinical parameters. These kernel functions, however, have their disadvantages due to the specific characteristics of clinical data, being a mix of variable types with each variable its own range. We propose a new kernel function specifically adapted to the characteristics of clinical data. Results: The clinical kernel function provides a better representation of patients' similarity by equalizing the influence of all variables and taking into account the range r of the variables. Moreover, it is robust with respect to changes in r. Incorporated in a least squares support vector machine, the new kernel function results in significantly improved diagnosis, prognosis and prediction of therapy response. This is illustrated on four clinical data sets within gynecology, with an average increase in test area under the ROC curve (AUC) of 0.023, 0.021, 0.122 and 0.019, respectively. Moreover, when combining clinical parameters and expression data in three case studies on breast cancer, results improved overall with use of the new kernel function and when considering both data types in a weighted fashion, with a larger weight assigned to the clinical parameters. The increase in AUC with respect to a standard kernel function and/or unweighted data combination was maximum 0.127, 0.042 and 0.118 for the three case studies. Conclusion: For clinical data consisting of variables of different types, the proposed kernel function which takes into account the type and range of each variable - has shown to be a better alternative for linear and non-linear classification problems. (C) 2011 Elsevier B.V. All rights reserved

Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery

Background Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term. Methods Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses. Results We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups. Conclusions In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD

Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group

Objectives To prospectively assess the diagnostic performance of simple ultrasound rules to predict benignity/malignancy in an adnexal mass and to test the performance of the risk of malignancy index, two logistic regression models, and subjective assessment of ultrasonic findings by an experienced ultrasound examiner in adnexal masses for which the simple rules yield an inconclusive result

Normal cervical changes in parous women during the second half of pregnancy - a prospective, longitudinal ultrasound study

OBJECTIVE: To determine what constitutes normal cervical changes during the second half of pregnancy in parous women delivering at term. DESIGN: The study comprises 21 healthy, pregnant parous women who all gave birth at term. They were examined with transvaginal ultrasound every two weeks from 24 gestational weeks until delivery. Cervical length and width were measured. The inner cervical os was assessed as being closed or open, the length and width of any opening were measured, and dynamic cervical changes (i.e. opening and closing of the inner cervical os during examination) were noted. RESULTS: Median cervical length was 41 mm (range 26-55) at the first examination and 29 mm (range 8-56) at the last examination. The corresponding figures for cervical width were 38 mm (range 29-47) and 46 mm (range 38-64). Cervical length decreased in 18 women but remained unchanged in three. Three patterns of change in cervical length were observed: in 12 women there was a steady, continuous decrease in cervical length (median decrease rate 1.1 mm/week, range 0.6-2.4); in four women the decrease rate accelerated towards the end of pregnancy, the median decrease rate after the change being 3.0 mm/week (range 1.5-4.8); and in two women there was a sudden drop in cervical length at term. Cervical width increased in 16 women but remained unchanged in five. Two patterns of change in cervical width were seen: 14 women manifested a steady continuous increase in cervical width (median 0.8 mm/week, range 0.4-1.8); in two women the increase rate accelerated from around 34 gestational weeks, the increase rate after the change being 4.1 and 5.9 mm/week, respectively. Opening of the internal cervical os was observed at least once in 11 (52%) women and was seen as early as at 24 and 25 gestational weeks in two women. The opening was always V-shaped (median length 6 mm, range 4-17; median width 7 mm, range 3-20). Dynamic changes of the internal cervical os were seen in three women (14%) at 25, 30 and 41 gestational weeks, respectively. CONCLUSION: The cervix of parous women decreases in length and increases in width from midpregnancy to term, but the pattern of change varies between individuals. Knowledge of the different patterns of normal change forms the basis of transvaginal ultrasound studies of pathological cervical changes during pregnancy

A Mathematical Model for Interpretable Clinical Decision Support with Applications in Gynecology

Over time, methods for the development of clinical decision support (CDS) systems have evolved from interpretable and easy-to-use scoring systems to very complex and non-interpretable mathematical models. In order to accomplish effective decision support, CDS systems should provide information on how the model arrives at a certain decision. To address the issue of incompatibility between performance, interpretability and applicability of CDS systems, this paper proposes an innovative model structure, automatically leading to interpretable and easily applicable models. The resulting models can be used to guide clinicians when deciding upon the appropriate treatment, estimating patient-specific risks and to improve communication with patients.We propose the interval coded scoring (ICS) system, which imposes that the effect of each variable on the estimated risk is constant within consecutive intervals. The number and position of the intervals are automatically obtained by solving an optimization problem, which additionally performs variable selection. The resulting model can be visualised by means of appealing scoring tables and color bars. ICS models can be used within software packages, in smartphone applications, or on paper, which is particularly useful for bedside medicine and home-monitoring. The ICS approach is illustrated on two gynecological problems: diagnosis of malignancy of ovarian tumors using a dataset containing 3,511 patients, and prediction of first trimester viability of pregnancies using a dataset of 1,435 women. Comparison of the performance of the ICS approach with a range of prediction models proposed in the literature illustrates the ability of ICS to combine optimal performance with the interpretability of simple scoring systems.The ICS approach can improve patient-clinician communication and will provide additional insights in the importance and influence of available variables. Future challenges include extensions of the proposed methodology towards automated detection of interaction effects, multi-class decision support systems, prognosis and high-dimensional data