Patient Impression of Improvement 1 year After Sacrospinous Hysteropexy Versus Vaginal Hysterectomy in Women with Pelvic Organ Prolapse Stage 2 or Higher.

INTRODUCTION AND HYPOTHESIS: Patient-reported outcomes are relevant outcomes in studies on pelvic organ prolapse (POP) surgery, as anatomical recurrence alone does not have a significant correlation with perceived improvement. In the present study, the patient's impression of improvement after 1 year is studied after vaginal hysterectomy (VH) versus sacrospinous hysteropexy (SSH) in large cohorts from daily clinical practice. We hypothesize that there is no difference between the groups. METHODS: This is a secondary analysis on prospectively collected data in a multicenter cohort of patients who underwent VH or SSH for symptomatic POP. All patients had a POP-Q stage ≥ 2 in at least one compartment at baseline and were treated with VH or SSH between 2002 and 2019. The primary outcome was the patient-reported score on the patient global impression of improvement index (PGI-I) 1 year after surgery. The secondary outcome was a composite outcome of surgical success, defined as the absence of recurrent POP beyond the hymen with bothersome bulge symptoms and/or repeat surgery. RESULTS: A total of 378 women (196 VH and 182 SSH) were included. The median score on the PGI-I did not differ between VH and SSH. At 1 year post-operatively, 77 women after VH (73%) and 77 women after SSH (75%) considered their condition (very) much improved (p = 0.86). There was no difference in composite outcome of surgical success (126 out of 137 women [92%] after VH, 118 out of 125 women [94%] after SSH; p = 0.44). CONCLUSIONS: Our study shows that there was no difference in the type of surgery, VH or SSH, with regard to the patient's impression of improvement 1 year postoperatively in a large cohort from daily clinical practice.

Laparoscopic Davydov vs. laparoscopic Vecchietti neovaginoplasty in women with Mayer-Rokitansky-Küster-Hauser syndrome; a systematic review and meta-analysis.

OBJECTIVE: To summarize the available evidence on the laparoscopic Davydov and Vecchietti methods to create a neovagina and to compare these techniques with a focus on neovaginal length, sexual function, operative time, and complications. DESIGN: A systematic electronic search up to August 2022 using PubMed and Embase is performed. SETTING: Not applicable. PATIENTS: Women with Mayer-Rokistansky-Küster-Hauser syndrome. INTERVENTIONS: All published clinical studies concerning the laparoscopic Davydov and laparoscopic Vecchietti procedures as a surgical technique to create a neovagina in women with Mayer-Rokistansky-Küster-Hauser syndrome were obtained. The guidelines for the preferred reporting items for systematic reviews and meta-analysis were followed. The following data were extracted: operative time, hospital stay, major early complications (within 3 months postsurgery), dilation therapy, neovaginal length, vaginal discharge, vaginal stenosis, time to sexual activity, sexual satisfaction, penetrative sexual activity, dyspareunia, score on the Female Sexual Function Index (FSFI), and duration of follow-up. The Newcastle Ottawa Scale was used to assess the quality of articles. MAIN OUTCOME MEASURES: Neovaginal length, FSFI scores, operative time, and complications. RESULTS: A total of 1,163 articles were identified, of which 33 studies were included in this systematic review. Of these, 12 studies (380 patients) are related to the Davydov method, 19 studies (1,126 patients) to the Vecchietti method, and 2 articles concern both. There is clinical heterogeneity and variety in the quality of the studies. Eighteen studies were included in the meta-analyses. The mean neovaginal length 12 months after the Davydov method is 8.3 cm (95% confidence interval [CI] 8.1-8.6), vs. 8.7 cm (95% CI 7.2-10.3) after the Vecchietti method. The mean FSFI score after the Davydov method is 28.9 (95% CI 26.8-31.1), compared with 27.5 (95% CI 25.0-30.1) after the Vecchietti method. The operative time of the Davydov method is 126 minutes (95% CI 109-143), compared with 40 minutes (95% CI 35-45) of the Vecchietti method. CONCLUSIONS: The operations yield comparable neovaginal length, sexual function, and complication rates. The mean FSFI scores indicate no sexual dysfunction in either group. The operative time of the Davydov method is significantly longer. There is no superiority shown for one of the surgical techniques in functional terms.

Patient's preference for sacrospinous hysteropexy or modified Manchester operation: A discrete choice experiment.

OBJECTIVE: To investigate women's preference for modified Manchester (MM) or sacrospinous hysteropexy (SH) as surgery for uterine prolapse. DESIGN: Labelled discrete choice experiment (DCE). SETTING: Eight Dutch hospitals. POPULATION: Women with uterine prolapse, eligible for primary surgery and preference for uterus preservation. METHODS: DCEs are attribute-based surveys. The two treatment options were labelled as MM and SH. Attributes in this survey were treatment success ( levels SH: 84%, 89%, 94%; levels MM: 89%, 93%, 96%), dyspareunia (levels: 0%, 5%, 10%), cervical stenosis (levels: 1%, 6%, 11%) and severe buttock pain (levels: 0%, 1%). A different combination of attribute levels was used in each choice set. Women completed nine choice sets, making a choice based on attribute levels. Data were analysed in multinomial logit models. MAIN OUTCOME MEASURES: Women's preference for MM or SH. RESULTS: 137 DCEs were completed (1233 choice sets). SH was chosen in 49% of the choice sets, MM in 51%. Of all women, 39 (28%) always chose the same surgery. After exclusion of this group, 882 choice sets were analysed, in which women preferred MM, likely associated with a labelling effect, i.e. description of the procedure, rather than the tested attributes. In that group, MM was chosen in 53% of the choice sets and SH in 47%. When choosing MM, next to the label, dyspareunia was relevant for decision-making. For SH, all attributes were relevant for decision-making. CONCLUSIONS: The preference of women for MM or SH seems almost equally divided. The variety in preference supports the importance of individualised healthcare.

What do we need to know about anatomy in gynaecology: A Delphi consensus study.

OBJECTIVE: Determination of the anatomical structures that should be taught to ensure safe and competent practice among general gynaecologists. STUDY DESIGN: A two-round Delphi survey, face-to-face meeting in focus groups and an individual interview. Participants were medical doctors and trainees from gynaecology, surgery, urology and radiology from academic, non-academic teaching and non-academic, non-teaching hospitals in the Netherlands. Relevant structures were collected from gynaecology surgery atlas based on most common gynaecological surgeries and diseases. These structures were supplemented and critically viewed in focus groups followed by a Delphi survey. In the Delphi survey gynaecologist and trainee's gynaecology from all over the Netherlands scored the items on a Likert scale between 1 (not relevant) and 5 (highly relevant). Consensus was defined when ≥ 70 % of the panellist scored the item as relevant or very relevant and the average rating was ≥ 4. Main outcome was clinically relevant anatomical structures. RESULTS: Consensus on 86 clinically relevant anatomical structures divided by nine categories. CONCLUSIONS: This study identified a core list of anatomical structures that are relevant to the safe and competent practice of general gynaecologists and that can be used to guide gynaecology postgraduate education. This is the first step in a much wider and complex process of becoming a competent gynaecologist.

Diagnostic Accuracy and Clinical Implications of Translabial Ultrasound for the Assessment of Levator Ani Defects and Levator Ani Biometry in Women With Pelvic Organ Prolapse: A Systematic Review.

OBJECTIVE: The aim of this study was to assess the diagnostic accuracy and clinical implications of translabial 3-dimensional (3D) ultrasound for the assessment of levator ani defects and biometry in women with pelvic organ prolapse (POP). METHODS: We performed a systematic literature search through computerized databases including MEDLINE (via PubMed), EMBASE (via OvidSP), and the Cochrane Library using both medical subject headings and text terms from January 1, 2003, to December 25, 2015.We included articles that reported on POP status and diagnostic accuracy measurements with translabial 3D ultrasound or transperineal ultrasound for the detection of levator ani defects or for measuring pelvic floor biometry, that is, levator ani hiatus, or reported on the clinical relevance of using translabial 3D ultrasound for levator ani defects or measuring pelvic floor biometry in women with POP. RESULTS: Thirty-one articles were selected in accordance with parts of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that can be applied to studies of diagnostic accuracy. Twenty-two articles (71%) are coauthored by 1 expert in this field. Detecting levator ani defects with translabial 3D ultrasound compared with magnetic resonance imaging showed a moderate to good agreement, whereas measuring hiatal biometry on translabial 3D ultrasound compared with magnetic resonance imaging showed a moderate to very good agreement.The interobserver agreement for diagnosing levator ani defects and measuring the levator hiatal area showed a moderate to very good agreement. Furthermore, levator ani defects increase the risk of cystocele and uterine prolapse, and levator ani defects are associated with recurrent POP.Finally, a larger hiatus was associated with POP and recurrent POP. CONCLUSIONS: Translabial 3D ultrasound is reproducible for diagnosing levator ani defects and ballooning hiatus. Both levator ani defects and a larger hiatal area are, in a selected population of patients with pelvic floor dysfunction, associated with POP and recurrent POP. More research is needed concerning external validation because most data in this article are coauthored by 1 expert in this field.

Recurrence risk is associated with preoperatively advanced prolapse stage: Is there a difference between women with stage 2 and those with stage 3 or 4 cystocele?

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) recurrence after surgery is a major problem. POP that is more advanced preoperatively is associated with a higher risk of recurrence postoperatively. We hypothesized that women with a stage 2 cystocele differ from those with a stage 3 or 4 cystocele. The aim of this study was to compare the baseline characteristics of women with mild and those with more advanced cystocele. METHODS: Patients had participated in one of two multicenter prospective cohort studies on women undergoing conventional anterior colporrhaphy without previous POP surgery. This was a secondary analysis of these data. Women with a preoperative cystocele stage 2 were compared with women with a stage 3 or 4 cystocele. Logistic regression models were employed to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Two hundred and sixty-nine women were assessed, of whom 132 (49.1%) had an advanced cystocele. Only older age was significantly associated with advanced cystocele preoperatively, with an OR of 1.07 (95% CI 1.04-1.10). There were no significant differences between women with advanced or stage 2 cystocele in body mass index, vaginal deliveries, assisted delivery, positive family history of POP, concurrent rectocele, concurrent uterine of vaginal vault prolapse, major levator ani muscle defects, or levator hiatal area. CONCLUSIONS: Women with advanced cystocele were significantly older than women with stage 2 cystocele. This raises the question whether it would be favorable to perform POP surgery in an earlier stage, i.e., at a younger age, in order to prevent POP recurrence.

Genome-wide expression analysis of a rice mutant line under salt stress.

Salinity is a major environmental stress to plants. In this study, the ability of plants to tolerate salt was investigated by studying growth, physiological characteristics, and expression levels of genes related to the salt-stress response in the salt-tolerant rice mutant (Till-II-877), which was derived from γ-ray irradiation. Compared to plants grown under normal conditions, the height and root length of wild type (WT) were reduced by approximately 40 and 29% following exposure to salt stress for 3 weeks, whereas Till-II-877 line showed 29 and 23% reductions in plant height and root length, respectively. No significant changes were observed in total chlorophyll content, and the malondialdehyde content of the mutant increased less than that of the WT under salt treatment. Gene expression was compared between the WT and mutant lines using microarray analysis. An unbiased analysis of the gene expression datasets allowed us to identify the pathways involved in salt-stress responses. Among the most significantly affected pathways, changes in gene expression were observed in α-linolenic acid and linoleic acid metabolism (in lipid metabolism), fructose and mannose metabolism and glycolysis-gluconeogenesis (in carbohydrate metabolism), cysteine and methionine metabolism (in amino acid metabolism), and carbon fixation (in the energy metabolism of photosynthetic organisms) under salt stress. These results show that the differential response of plants subjected to salt stress was due to changes in multiple metabolic pathways. These findings increase our understanding of the effects of salt stress in rice and may aid in the development of salt-tolerant rice cultivars.

Anatomical Cystocele Recurrence: Development and Internal Validation of a Prediction Model.

OBJECTIVE: To develop a prediction model that estimates the risk of anatomical cystocele recurrence after surgery. METHODS: The databases of two multicenter prospective cohort studies were combined, and we performed a retrospective secondary analysis of these data. Women undergoing an anterior colporrhaphy without mesh materials and without previous pelvic organ prolapse (POP) surgery filled in a questionnaire, underwent translabial three-dimensional ultrasonography, and underwent staging of POP preoperatively and postoperatively. We developed a prediction model using multivariable logistic regression and internally validated it using standard bootstrapping techniques. The performance of the prediction model was assessed by computing indices of overall performance, discriminative ability, calibration, and its clinical utility by computing test characteristics. RESULTS: Of 287 included women, 149 (51.9%) had anatomical cystocele recurrence. Factors included in the prediction model were assisted delivery, preoperative cystocele stage, number of compartments involved, major levator ani muscle defects, and levator hiatal area during Valsalva. Potential predictors that were excluded after backward elimination because of high P values were age, body mass index, number of vaginal deliveries, and family history of POP. The shrinkage factor resulting from the bootstrap procedure was 0.91. After correction for optimism, Nagelkerke's R and the Brier score were 0.15 and 0.22, respectively. This indicates satisfactory model fit. The area under the receiver operating characteristic curve of the prediction model was 71.6% (95% confidence interval 65.7-77.5). After correction for optimism, the area under the receiver operating characteristic curve was 69.7%. CONCLUSION: This prediction model, including history of assisted delivery, preoperative stage, number of compartments, levator defects, and levator hiatus, estimates the risk of anatomical cystocele recurrence.

PPARγ neddylation essential for adipogenesis is a potential target for treating obesity.

The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

Factors related to number of present teeth in Korean elderly adults aged 55-84 years.

OBJECTIVES: The aim of this study was to determine the associations between the number of present teeth (NT) and socio-economic, demographic and oral health behavioural factors among Korean adults aged 55-84 years. METHODS: The total subjects comprised 3767 individuals who were examined and who answered the questions on socio-economic status and oral health behaviour from the fourth Korean National Health and Nutrition Examination Survey conducted from 2007 to 2009. The dependent variable was NT, with binary status divided by the median. Socio-economic and demographic factors included gender, educational level, parent's educational levels, region of residence, household income, type of health insurance and mother's economic activity. Oral health behaviours were as follows: daily toothbrushing frequency, smoking status, recent dental visit and illegal dental treatment. Multivariate logistic regression models were applied to explain the associations between NT and other variables. RESULTS: In a model adjusted by socio-economic, demographic and oral health behavioural variables, subjects who lived in urban areas were more likely to have larger NT compared to those in suburban areas (OR: 1.22, P = 0.025). Males were more likely to have larger NT (OR: 1.90, P < 0.001), and daily toothbrushing frequency was associated with NT (OR = 1.25, P = 0.023). Non-smokers (OR: 2.44, P < 0.001) and past smokers (OR: 1.70, P < 0.001) were more likely to have lager NT compared to current smokers. Subjects without illegal dental treatments were more likely to have lager NT compared to those with illegal dental treatments (OR = 2.21, P < 0.001). CONCLUSIONS: Interventions aiming to preserve present teeth in elderly adults should consider socio-economic, demographic and oral health behavioural factors.

Translabial three-dimensional ultrasonography compared with magnetic resonance imaging in detecting levator ani defects.

OBJECTIVE: To assess the diagnostic performance of translabial three-dimensional ultrasonography in detecting major levator ani defects in women with pelvic organ prolapse compared with magnetic resonance imaging (MRI) and to assess the interobserver agreement in detecting levator ani defects with translabial three-dimensional ultrasonography. METHODS: In a multicenter cohort study, 140 women indicated for primary surgery of pelvic organ prolapse quantification stage II or more cystocele were included. Patients undergoing mesh surgery or concomitant stress incontinence surgery were excluded. All consenting patients underwent translabial three-dimensional ultrasonography and MRI of the pelvic floor before surgery. Two observers (out of a pool of four observers) assessed translabial three-dimensional ultrasound images; two other observers (out a pool of five observers) assessed MRIs for levator ani muscle damage. In case of disagreement, the images were discussed in a consensus meeting. RESULTS: Of the 135 scans, 45 major levator ani defects were detected on ultrasonogram (33.3%) and 32 were confirmed at MRI (23.7%). Of the 41 major levator ani defects detected on MRI, nine were missed at translabial three-dimensional ultrasonogram. Sensitivity was 0.78 (32 of 41) (95% confidence interval [CI] 0.65-0.91) and specificity was 0.86 (81 of 94) (95% CI 0.79-0.93) in detecting major levator ani defects with translabial three-dimensional ultrasonography compared with MRI. There was good agreement scoring levator ani defects on translabial three-dimensional ultrasonography, with a κ of 0.67 (95% CI 0.58-0.76); agreement in recognizing major levator ani defects was moderate, with a κ of 0.53 (95% CI 0.37-0.69). CONCLUSION: Translabial three-dimensional ultrasonography shows reasonable agreement with MRI in detecting major levator defects. Because of the moderate interobserver agreement, it will be difficult to implement ultrasonography in daily practice. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, www.trialregister.nl, NTR2220.

Effects of in ovo injection with selenium on immune and antioxidant responses during experimental necrotic enteritis in broiler chickens.

This study was conducted to investigate the effects of in ovo injection of Se on modulating the immune system and antioxidant responses in broiler chickens with experimental necrotic enteritis. Broiler eggs were injected at 18 d of embryo age with either 100 µL of PBS alone or sodium selenite (Na2SeO3) in PBS, providing 0 (SS0), 10 (SS10), or 20 (SS20) µg of Se/egg. At 14 d posthatch, PBS-treated and uninfected chickens were kept as the control group, whereas the remaining chickens were orally infected with 1.0 × 10(4) sporulated oocysts of Eimeria maxima (SS0, SS10, SS20). At 18 d posthatch, E. maxima-infected chickens were orally infected with 1.0 × 10(9) cfu of Clostridium perfringens. Infected control SS0 group showed significantly decreased BW compared with the uninfected control. However, SS20 group showed significantly increased BW compared with the infected control SS0 group, whereas the BW were similar among uninfected control and infected SS10 and SS20 groups. The SS10 group showed significantly lower intestinal lesions compared with the SS0 group, and oocyst production was decreased in both SS10 and SS20 groups. Serum malondialdehyde level and catalase activity were also decreased in both SS10 and SS20 groups, whereas the superoxide dismutase level was significantly lower in the SS10 group compared with the SS0 group. The SS20 group showed significantly higher levels of transcripts for IL-1ß and IL-6 in intestine, and SS10 and SS20 groups had higher levels of transcripts for IL-8 and inducible nitric oxide synthase expression and decreased glutathione peroxidase 7 mRNA levels compared with the SS0 group. The SS10 and SS20 groups also showed increased serum antibody levels to C. perfringens α-toxin and NetB toxin compared with the SS0 group. These collective results suggest that the injection of Se into the amniotic cavity of developing eggs may be beneficial for enhancing immune and antioxidant responses in the hatched chickens exposed to the necrotic enteritis-causing pathogens.

Comparison of RECIST 1.0 and RECIST 1.1 on computed tomography in patients with metastatic colorectal cancer.

OBJECTIVE: We conducted this study to compare tumor measurement by computed tomography (CT) and tumor response assessment between Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and RECIST 1.1 in patients with metastatic colorectal cancer (CRC). METHODS: We reviewed the medical records of patients with metastatic CRC who received first-line chemotherapy between January 2004 and December 2012 and compared CT tumor measurement using two RECIST versions. RESULTS: A total of 58 patients who had target lesions according to RECIST 1.0 were included in the study. The number of target lesions recorded by RECIST 1.1 was significantly lower than that by RECIST 1.0, with a decrease experienced in 48 patients (82.7%). Six patients had no target lesions because of the new criteria of RECIST 1.1 for lymph node size. Out of 95 lymph nodes from 58 patients, only 40% were defined as target lesions according to RECIST 1.1. The overall response rate of first-line chemotherapy according to RECIST 1.0 and 1.1 was 41.5 and 40.4%, respectively. The best tumor responses showed almost perfect agreement between RECIST 1.1 and RECIST 1.0 (ĸ = 0.913). Three patients showed disagreement of the best responses between the two RECIST versions. CONCLUSION: RECIST 1.1 showed a highly concordant response assessment with RECIST 1.0 in metastatic CRC and its clinical impact on therapeutic decisions was minimal.

Xanthohumol inhibits cellular proliferation in a breast cancer cell line (MDA-MB231) through an intrinsic mitochondrial-dependent pathway.

AIMS: Xanthohumol isolated from hops has been reported to exhibit anticancer effects in diverse human cancers. However, its effect on breast cancer has not yet been clearly defined. The purpose of this study was to investigate the effects of xanthohumol on breast cancer cell proliferation. MATERIALS AND METHODS: After treatment with 5 µM, 10 µM, and 20 µM xanthohumol for 48 h, cells from the human breast cancer cell line MDA-MB-231 were studied using colony assay, flow cytometry, and western blotting. RESULTS: The survival rate of the MDA-MB231 cells treated with 10 µM and 20 µM xanthohumol for 48 h decreased significantly by 64.7 ± 1.8% and 40.1 ± 1.8%, respectively. The numbers of SubG0/G1 cells in the group treated with 10 µM and 20 µM xanthohumol increased significantly to 11.3 ± 0.2 and 18.4 ± 0.1, respectively. A ladder pattern of DNA fragmentation was also observed. Xanthohumol increased the expression of Bax in the mitochondria, which correspondingly decreased in the cytoplasm. The activity of caspase-3 and caspase-9 was shown to increase significantly in the treated groups but not in the control group. CONCLUSIONS: Xanthohumol inhibited the proliferation of MDA-MB-231 cells through a mitochondria- and caspase-dependent apoptotic pathway. This result suggests that xanthohumol might serve as a novel therapeutic drug for breast cancer.

Differences in the risk factors of reflux esophagitis according to age in Korea.

The prevalence of gastroesophageal reflux disease in Korea has been believed to be low, but the incidence of gastroesophageal reflux disease in Korea is expected to increase because of the longer life expectancy and more ingestion of westernized food. The aim of this study was to report differences in the risk factors of reflux esophagitis (RE) according to age in Korea. We prospectively recruited the subjects who had RE among those who visited a health promotion center for upper gastrointestinal cancer surveillance at Hallym Medical Center (five institutions) between January 2008 and February 2009. The enrolled study participants comprised 742 subjects with RE and 1484 healthy controls. The independent risk factors of RE in young and adult group were male sex, smoking, coffee, body mass index ≥ 25, hiatal hernia, and Helicobacter pylori negativity. The risk factors of RE in elderly group were smoking, coffee, and hiatal hernia. The risk factors for RE according to age group were found to differ. In elderly group, Helicobacter pylori infection was not a significant protective factor contrary to young and adult groups.

Right insular atrophy in neurocardiogenic syncope: a volumetric MRI study.

BACKGROUND AND PURPOSE: Alterations in the central autonomic network are hypothesized to play a role in the pathophysiologic mechanism underlying neurocardiogenic syncope; however, few data are available regarding the structural changes of the brain in this condition. We used voxel-based morphometry and regional volumetry to identify possible neuroanatomic correlates. MATERIALS AND METHODS: We prospectively studied 32 patients with neurocardiogenic syncope with a positive response to the head-up tilt test and 32 controls who had no history of syncope. We used voxel-based morphometry to compare GM volumes between patients and controls. In addition, regional volumes of structures known to be included in the central autonomic network were measured and compared between the groups. Correlation analyses were also performed between clinical variables and anatomic data. RESULTS: Voxel-based morphometry showed a significant GM volume reduction in the right insular cortex in patients with neurocardiogenic syncope compared with controls (corrected P = .033). Regional volumetry showed a significant reduction of right insular volumes in patients compared with controls (P = .002, MANCOVA). Smaller right insular volumes in patients with neurocardiogenic syncope were related to larger drops in systolic (P = .020) and diastolic (P = .003) blood pressures during the head-up tilt test. CONCLUSIONS: We observed a novel finding of right insular atrophy in patients with neurocardiogenic syncope with a positive response to the head-up tilt test, implicating the role of right insular dysfunction in the pathophysiologic mechanism underlying neurocardiogenic syncope. Our findings further support the hypothesis that right insular dysfunction may cause a decrease in sympathetic activity and a reciprocal increase in parasympathetic activity, leading to syncope.

Protocol for translabial 3D-ultrasonography for diagnosing levator defects (TRUDIL): a multicentre cohort study for estimating the diagnostic accuracy of translabial 3D-ultrasonography of the pelvic floor as compared to MR imaging.

BACKGROUND: Pelvic organ prolapse (POP) is a condition affecting more than half of the women above age 40. The estimated lifetime risk of needing surgical management for POP is 11%. In patients undergoing POP surgery of the anterior vaginal wall, the re-operation rate is 30%. The recurrence risk is especially high in women with a levator ani defect. Such defect is present if there is a partially or completely detachment of the levator ani from the inferior ramus of the symphysis. Detecting levator ani defects is relevant for counseling, and probably also for treatment. Levator ani defects can be imaged with MRI and also with Translabial 3D ultrasonography of the pelvic floor. The primary aim of this study is to assess the diagnostic accuracy of translabial 3D ultrasonography for diagnosing levator defects in women with POP with Magnetic Resonance Imaging as the reference standard. Secondary goals of this study include quantification of the inter-observer agreement about levator ani defects and determining the association between levator defects and recurrent POP after anterior repair. In addition, the cost-effectiveness of adding translabial ultrasonography to the diagnostic work-up in patients with POP will be estimated in a decision analytic model. METHODS/DESIGN: A multicentre cohort study will be performed in nine Dutch hospitals. 140 consecutive women with a POPQ stage 2 or more anterior vaginal wall prolapse, who are indicated for anterior colporapphy will be included. Patients undergoing additional prolapse procedures will also be included. Prior to surgery, patients will undergo MR imaging and translabial 3D ultrasound examination of the pelvic floor. Patients will be asked to complete validated disease specific quality of life questionnaires before surgery and at six and twelve months after surgery. Pelvic examination will be performed at the same time points. Assuming a sensitivity and specificity of 90% of 3D ultrasound for diagnosing levator defects in a population of 120 women with POP, with a prior probability of levator ani defects of 40%, we will be able to estimate predictive values with good accuracy (i.e. confidence limits of at most 10% below or above the point estimates of positive and negative predictive values).Anticipating 3% unclassifiable diagnostic images because of technical reasons, and a further safety margin of 10% we plan to recruit 140 patients. TRIAL REGISTRATION: Nederlands trial register NTR2220.

Fracture in long bones stabilised by telescopic intramedullary rods in patients with osteogenesis imperfecta.

We investigated the fracture-free survival of long bones stabilised by a telescopic intramedullary rod (TIMR) in patients with osteogenesis imperfecta with respect to the remodelling status of fracture or osteotomy sites and TIMR regions, in order to identify risk factors for fracture. A total of 44 femora and 28 tibiae in 25 patients with a mean age of 5.0 years (1.9 to 10.5) at presentation were studied. There were six patients with Sillence type I, five with type III, 13 with type IV and one with type V osteogenesis imperfecta. All received bisphosphonate treatment at the same stage during the mean follow-up of 7.3 years (0.5 to 18.1). The fracture-free survival was estimated at 6.2 years (95% confidence interval 5.1 to 7.3) by Kaplan-Meier analysis. More than half the fracture or osteotomy sites remained in a less-remodelled state at the latest follow-up or time of fracture. Of the 33 fractures, 29 (87.9%) occurred in long bones containing a less-remodelled site, and these fractures were located at this site. The relative fracture risk at the rod tip was significantly greater than in any other TIMR region (p < 0.001), and this was higher in bone segments having a less-remodelled site. This study shows a persistent fracture risk in TIMR-stabilised long bones, especially at less-remodelled fracture or osteotomy sites and at the rod tip.

A simple assessment method for auditing multi-centre unilateral cleft lip repairs.

The aim of a cleft lip repair is to achieve a functional and aesthetically acceptable upper lip and nose appearance. However, the methods of assessing severity and outcome are still very subjective. Fortunately, it is recognised that human judgement can act as a very reliable tool in assessing facial attractiveness. Therefore, using a simple subjective assessment method, a multi-centre comparison study was performed. Following the Clinical Standards Advisory Group review (1998) and subsequent reconfiguration of the cleft services in the UK a tri-centre comparative audit, involving three out of the nine designated UK cleft centres, was set up. Photographs of 37 patients (consecutive where possible), with complete unilateral cleft lip defects from six regional cleft units (seven surgeons), taken preoperatively and then taken 5 years postoperatively were examined by 10 medical and 10 laypersons to rate the severity and perceived difficulty of repair preoperatively and aesthetic outcome postoperatively. This was repeated after 2 weeks. A five-point scale was used for the assessment. Weighted kappa scores were used to assess agreements within and between rater reliability. Results showed high levels of intra- and inter-rater reproducibility in both groups of raters. This technique was used as a ranking tool to assess the aesthetic outcomes of surgical repair and thereby rank surgeons within our supra-regional audit. This technique can be employed to aid education, stimulate research and also coordinate national inter-centre comparisons following cleft lip repairs.

Effects of a priming dose of fentanyl during anaesthesia on the incidence and severity of fentanyl-induced cough in current, former and non-smokers.

Fentanyl is commonly used during anaesthesia and can cause fentanyl-induced cough (FIC). This study investigated whether a priming dose of fentanyl reduced FIC, and determined the factors associated with increased risk of FIC. Subjects undergoing elective surgery under general anaesthesia (n = 800) were randomized into four groups: group 1 received 2 µg/kg fentanyl bolus; groups 2, 3 and 4 received a priming dose of fentanyl 0.5 µg/kg followed by 1.5 µg/kg after 1, 2 or 3 min, respectively. The incidence of FIC was 17.0%, 10.0%, 12.5% and 11.5% for groups 1, 2, 3 and 4, respectively, with no significant between-group differences in FIC incidence or severity. The mean FIC onset time was 22 s. Former smokers were 2.91 times more likely than current smokers to experience cough. A fentanyl priming dose did not reduce the incidence and severity of FIC. Former smokers were hyper-reactive to fentanyl compared with current smokers.