Applying graph theory to improve the quality of scientific evidence from textual information: Neural injuries after gynaecologic pelvic surgery for genital prolapse and urinary incontinence.

AIMS: To provide the overall rate for all types of neurologic iatrogenic injuries during urogynaecologic surgery from textual data. METHODS: Systematic research focused on complications of gynaecologic surgery and neurologic injuries in abstracts. Keywords concerning complications (cluster A), unspecific; neurologic issues (cluster B); surgery (generic words) (cluster C); specific gynaecologic operations (cluster D); and specific gynaecologic operations for pelvic organ prolapse and urinary incontinence (cluster E) were extracted. Associations among clusters of keywords were assessed by using multiple runs of text-mining software Semantic Brand Score (SBS, https://semanticbrandscore.com/#primary). Association scores were converted into probabilities. The rate of neurologic complications in urogynaecologic surgery was calculated ("a priori" probability) by applying Bayes' theorem. Textual estimates of neurological injuries in urogynaecologic surgery are 0.035554 (95% confidence intervals 0.019607-0.0515001; no quantitative data were found). To test if the probability calculated on textual information was the same as quantitative data reports ("a posteriori" probability), the rate of neurologic complication of all gynaecologic surgery was calculated using a meta-analytics approach and was compared with the textual analysis value. RESULTS: The rate of neurologic complications in gynaecologic surgery after meta-analytic data synthesis has been 0.016489 (95% confidence intervals 0.012163-0.022320), which is equal to the textual estimate (0.016889, 95% confidence intervals 0.019607-0.051501). Therefore, 0.035554 is a reliable likelihood to observe a neurologic complication in urogynaecologic surgery. CONCLUSION: Iatrogenic nerve injuries in urogynaecologic surgery are higher than whole gynaecologic surgery. Text-mining software SBS and probability conversion can provide reliable answers from overall scholars' opinions on unsolved clinical questions when better evidence is lacking.

Estimate of the proportion of uncertain diagnoses of pudendal neuralgia in women with chronic pelvic-perineal pain: A systematic review with a descriptive data synthesis.

BACKGROUND: There is a gap between pudendal neuralgia (PN) due to pudendal entrapment syndrome and PN without pudendal entrapment syndrome. The latter could have atypical symptoms. AIM: Defining a rate of atypical PN from a clinical series of female patients with chronic pelvic-perineal pain. METHODS: The atypical PN was defined as a pain not meeting clinical criteria for pudendal entrapment syndrome. The effect size was the rate of atypical PN. Such a rate was expected to be found among patients screened for enrollment in clinical series on pudendal neuropathic pain. A systematic search was performed looking for clinical series on PN. Studies must report information on female patients, pelvic-perineal pain, at least a clinical criterion for diagnosing the pudendal neurogenic origin of pain, the proportion of patients with pain not meeting the clinical criterion/a for diagnosing the pudendal entrapment pain. RESULTS: From 2637 references, nine studies were included for qualitative analysis. Three of them were not suitable for data synthesis: one assessed the rate of PN after hip arthroscopy; second enrolled miscellaneous patients, a third investigated patients with gynecological diseases. Six studies involved patients with suspicion of pudendal entrapment symptoms (205 patients observed), allowing data synthesis. One of these series was judged as being of good quality. The overall rate of atypical PN is 0.013 (95% confidence interval, 0.008-0.021), I2 0%. Further analysis suggests the risk of bias for all studies. CONCLUSIONS: Atypical PN in females is low when clinical criteria for pudendal entrapment syndrome are applied.

Serendipitous Signs, Symptoms, Laboratory Parameters, and Instrumental Patterns of Amniotic Fluid Embolism: Lessons from an Analysis of Case Reports.

Objective: Serendipitous Signs, Symptoms, Laboratory Parameters, and Instrumental Patterns of Amniotic Fluid Embolism: Lessons from an Analysis of Case Reports. Study Design: Wide analysis of the case reports on AFE published from 1990 to 2014. A scoring system for quantifying the relevance was attributed to each sign, symptom, laboratory parameter, and instrumental abnormal pattern in AFE cases. Principal component rotated factor analysis was used to reduce data. The residual signs, symptoms, and laboratory and instrumental parameters were introduced in a multivariable logistic regression model (dependent variable: survival). Results: AFE, clinically, has at least 2 serendipitous symptoms (restlessness and confusion, at rates between 10­15%) and a serendipitous laboratory parameter (rise in C-reactive protein blood levels, between 2­3%). Fatal AFE cases relate mostly to the severity of cardiac and pulmonary impairment, rather than with restlessness, confusion, and rise in C-reactive protein. Conclusion: The hypothesis that AFE has atypical behavior should be retained; the extent to which serendipitous findings of AFE relate to AFE outcomes is uncertain.

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy.

STUDY QUESTION: What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome? SUMMARY ANSWER: Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle. WHAT IS KNOWN ALREADY: We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE. STUDY DESIGN, SIZE, DURATION: A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively). LIMITATIONS, REASONS FOR CAUTION: Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases. WIDER IMPLICATIONS OF THE FINDINGS: A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.

Influence of hCG on inducible nitric oxide synthase gene expression in ram testicular arteries.

UNLABELLED: Background. Experimental evidence suggests a relationship between the vasodilatory effect of hCG and the NOS system in the testis. The influence of hCG administration on testicular vascular NOS gene expression has not been fully investigated. OBJECTIVE: This study aimed to evaluate the presence of the nitric oxide syntheses gene in ram testicular arteries and the influence of hCG administration on its expression. MATERIALS AND METHODS: Both testicular arteries of sixteen rams were extracted before and after i.v. administration of 5000 IU of hCG or placebo. The expression of the iNOS gene was investigated by real time PCR. Data were analyzed by means of Wilcoxon and Mann-Whitney tests. A p value of < 0.05 was considered statistically significant. RESULTS: PCR revealed the presence of iNOS mRNA in all basal samples but the expression of the iNOS gene was significantly reduced in all arteries obtained 24 h after the administration of either hCG or placebo. A significant reduction in the expression of iNOS gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups. On the other hand hCG stimulation did not significantly influence iNOS expression following its administration compared to a placebo. CONCLUSION: Ram testicular arteries express the iNOS gene but hCG stimulation did not significantly influence iNOS expression. A significant reduction in the expression of this gene was observed in the testicular arteries extracted after 24 h in both treated and placebo groups, suggesting that iNOS expression on the testicular artery could be influenced by the spermatic vessel ligation of the controlateral testis.

ACE inhibitors and angiotensin receptor blockers could promote the onset of endometrial polyps in hypertensive women.

OBJECTIVE: To investigate whether anti-hypertensive therapy is a risk factor for the onset of endometrial polyps in hypertensive women. METHODS: A sample of 305 hypertensive patients was analyzed. By applying multivariable logistic regression analysis, the odds of developing endometrial polyps relative to the known risk factors for endometrial polyps and to the class of anti-hypertensive drugs were calculated. RESULTS: The variables reaching significance after multivariable logistic regression analysis included the following: hypertension not-in-therapy (odds ratio 2.544; 95% confidence intervals 1.249 - 5.182; p = 0.010); ACE inhibitor therapy (odds ratio 2.400; 95% confidence intervals 1.248 - 4.614; p = 0.009); angiotensin receptor blockers (odds ratio 2.091; 95% confidence intervals 1.044 - 4.187; p = 0.037); and fasting glucose level (odds ratio 1.018; 95% confidence intervals 1.007 - 1.030; p = 0.001). CONCLUSIONS: Although the results should be interpreted carefully, it appears that ACE inhibitors and, to a lesser extent, angiotensin receptor blockers may promote the onset of endometrial polyps in hypertensive patients.

A simplified classification for describing colposcopic vaginal patterns.

OBJECTIVE: This study aimed to highlight that colposcopic vaginal patterns are not specific, unlike cervical colposcopic patterns, and to provide a simpler classification of vaginal colposcopic patterns. MATERIALS AND METHODS: A total of 223 patients who underwent colposcopy with Schiller test were assessed (hierarchical log-linear model) retrospectively. RESULTS: The greatest predictability for histologically confirmed warts and cancers is represented by colposcopic patterns of wart and cancer. Lugol-negative area is strongly predictive of koilocytosis, even if it is found in other vaginal lesions. Thickened epithelium seems to better predict a severe vaginal lesion, whereas thin white epithelium better suggests a mild vaginal lesion. Colposcopic patterns were simplified as follows: Lugol-negative area, white epithelia (thin white epithelium and white thickened epithelium), vascular lesions (regular and irregular mosaicisms and punctations), wart, and cancer. Thus, koilocytosis is predicted by the Lugol-negative area, whereas white epithelia patterns and vascular patterns are not specific, suggesting overall vaginal intraepithelial neoplasias. Wart and cancer patterns are pathognomonic for histologically confirmed warts and cancers. CONCLUSIONS: Vaginal colposcopy poorly predicts the severity of vaginal lesions. By including each type of white epithelium within a new category called "white epithelia patterns" and each type of vascular pattern within a new category called "vascular patterns," it is possible to simplify vaginal colposcopy without compromising its accuracy.

Ursodeoxycholic acid in the treatment of pregnancy cholestasis: a data-set available for Meta-analyses.

BACKGROUND: The recent literature on intrahepatic cholestasis of pregnancy raises questions on the best management of such a disease. Improved evidence might be achieved by meta-analyses. AIM: Providing data for allowing individual patients meta-analyses and aggregate data meta-analyses. METHODS: Data were collected retrospectively at the Fabia Mater Hospital of Rome (Italy), between 2013 and 2018. Several variables were collected and analyzed according to low-level bile acid (less than 40 µmol/L) and high-level bile acid (at least 40 µmol/L). Eighty-three cases of pregnancy cholestasis, diagnosed according to itching symptoms and excluding bile diseases, were collected and analyzed, both descriptively and inferentially. CONCLUSION: The analyzed data do not provide significant evidence supporting the use of ursodeoxycholic acid to prevent composite adverse fetal outcomes but they can be included in further meta-analyses.

Looking for Responders among Women with Chronic Pelvic Pain Treated with a Comicronized Formulation of Micronized Palmitoylethanolamide and Polydatin.

Background: Palmitoylethanolamide is reported to solve pain and neuroinflammation in different models of chronic and neurodegenerative diseases. Some concerns have been illustrated for cautiously interpreting the available literature on the topic. Specifically, there is a lack of evidence about palmitoylethanolamide and female chronic pelvic pain. Concerns will be best solved by randomized trials. The present study was aimed at finding the best responders to micronized palmitoylethanolamide in female patient with chronic pelvic pain, using the existing literature at individual patient level, to help further randomized trial planning. Methods: After a systematic research, eligible studies (the ones enrolled female patients treated for chronic pelvic pain or for dyspareunia, dysuria, dyschezia, and dysmenorrhea with or without chronic pelvic pain) were assessed at individual patient data level. Conditional probabilities were calculated to assess variables conditioning the rates of good responders (pain score points more or equal to 3 reduction), poor responders (2 pain score reduction), and nonresponders at a three-month follow-up. Results: Only cases treated with palmitoylethanolamide comicronized with polydatin for a short period can be assessed. Good responders are more than 50%. In chronic pelvic pain, there is a 19.0% conditional probability to find good responders among patients with pain score at enrolment of 6 to 8 and of 6.8% to find poor responders among patients with a pain score at enrolment of 6 to 8. Painful disease does not matter on responders' rates. Conclusion: Best responders to comicronized palmitoylethanolamide/polydatin are patients with pain score higher than 6 at enrolment, irrespective of other variables.

Assessing the ratio between new Covid-19 cases and new tests for Sars-Cov-2 in Italy by fractal investigation.

AIM: processing the heterogeneous data on the Italian Covid-19 epidemic by fractal investigation on the trend curve of the ratio between new Covid19 cases/new Sars-Cov-2 tests. METHODS: New cases of Covid-19 disease and new tests were calculated from raw data freely available on the Italian governing website. The effectiveness of Italian government Decrees aiming to obtain lock-down was assessed by fractal investigation. Self-similarity parameters of presumed fractal shapes obtained 6 days after each Decree were estimated, when possible. Self-organized criticality was also assessed to check for chaos involvement in disturbing the fractal shapes. Shapes were then compared and were used to estimate the number of new tests for Sars-Cov-2 that Italy would be able to perform. RESULTS: The full lock-down changed the biocomplexity of the Covid-19 epidemic in Italy. If the biocomplexity of Covid-19 did not change after the lock-down, Italy should have been able to perform at least 25490 tests daily (±8940) on average, while real data show that a larger number of tests were done (p<0.001) (thereby obtaining the lowering of contagions). If the same biocomplexity was observed before full lock down, Italy would be able to perform 7088 tests daily (±5163) on average, while real data show that a lower number of tests were done (p=0.029) (thereby observing the worsening of contagions). CONCLUSION: in case of heterogeneous data, fractal investigation would be prove useful for assessing and estimating trends.

Updated fractal assessment of Italian Covid-19 disease.

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Assessing the regional policies of Italian regions in managing the Cesarean delivery phenomenon: a fractal analysis.

OBJECTIVES: Assessing the 2017 administrative data on Cesareans delivery in Italy by using fractal statistic. METHODS: 2017 administrative data on Italian Cesarean deliveries are freely available as crude numbers and rates according to each Italian region, according to Italian health institute type and according to first or repeated Cesarean. As already reported, the Italian Cesarean delivery phenomenon is in relationship with hospital, regional, cultural perspectives in caring pregnancy and delivery. Fractal statistics can best assess the biocomplexity underlying the Italian Cesarean section phenomenon. Fractal shapes and self-organized criticality of the Cesarean section phenomenon for each Italian region were done. Fractal shapes were compared to find similarities by using global test of coincidence among regression lines. RESULTS: In the regions where the health care institutes are more than a type, there are evanescent similar fractal shapes. Self-organized criticality assessment demonstrates that chaos is largely involved in Cesarean delivery phenomenon in all Italian regions and in Italy. The fractal images for each region are able to highlight the item causing the deviation from fractal shapes in each region. CONCLUSION: Fractal statistics could be used to compare regional or hospital policies in performing Cesareans, starting from Cesareans rates extracted from administrative data.

Conservative methotrexate treatment of a scar pregnancy case: adding evidence to the evidence.

A single case of ultrasonographic-guided local injection of methotrexate for managing scar pregnancy is reported. The outcome was successful and had no side effects. The case was reported to increase the evidence supporting this type of management.

Perspectives of Italian pregnant women on pregnancy examinations and pregnancy care: is the caregiver more important than the care?

AIM: Assessing awareness of Italian low-risk pregnant patients on low-risk pregnancy care and what do they feel about their own pregnancy. METHODS: A questionnaire was administered to 382 low-risk pregnant women. This questionnaire assessed general knowledge of low-risk pregnancy, low-risk pregnancy care, and how much patients rated ten topics of low-risk pregnancy care. It would be expected that the knowledge of each topic would associates with the patient's perceived importance of that topic. RESULTS: Poor knowledge of pregnancy care was proven. Patients seem to incorrectly overrate vaginal examinations and obstetric and gynecologist-led care, while they attribute appropriate importance to midwife-led care. The more examinations performed (vaginal examinations, sonographic checks, cardiotocographies), the higher their rating. CONCLUSIONS: In Italy, expectations of pregnant women about their own pregnancy are incorrectly trusted in the obstetrics and gynecologists. Both poor knowledge of pregnancy care and cultural perspectives on the birth process amongst Italian people explain the finding. Referring low-risk pregnant women to midwives would help them to rate more the care than the caregiver.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis.

BACKGROUND: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. METHODS: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 µmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. FINDINGS: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35-3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04-2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86-1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39-0·91; p=0·016). INTERPRETATION: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. FUNDING: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.

Cecal endometriosis as a cause of ileocolic intussusception.

Endometriosis is a disease that can affect various organs, has an unclear symptomatology, and in extreme cases, can result in intestinal obstruction. This particular case illustrates the synchronous localization of endometriosis, both genital and intestinal, resulting in ileo-colic and colonic intussusception. The relative diagnostic and therapeutic approach for such a rare occurrence is discussed.

A pregnant woman and the SARS-CoV-2 infection: how are barriers easily crossed?

A case of SARS-CoV-2 in a pregnant woman is described. How the case has crossed the barriers is highlighted, hoping this will be useful in planning appropriate intervention in cases of infected pregnant women.

Likelihood of Accomplishing an In-Patient Hysteroscopic Myomectomy in a One-Step Procedure: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the feasibility rate of one-step hysteroscopic myomectomy according to the technique adopted. METHODS: In July 2016, PubMed, ClinicalTrials.gov, SCOPUS, Scielo, and AJOL databases were used for searching references. Series of in-patient hysteroscopic myomectomies reporting success rate in only one-step procedure, categorization of submucous fibroids, explanation of the surgical technique, and description of patients were considered eligible for meta-analysis (retrospective, prospective randomized studies). Two authors extracted the data. Rate of myomectomies accomplished in only a surgical step and rate of intraoperative complications were extracted per protocol. A modified GRADE score was used for quality assessment. Random-effect models were already assumed. Mean rates were compared among subgroups. RESULTS: One thousand two hundred and fifty-seven studies were screened and 241 of these were read for eligibility. Seventy-eight series were included in qualitative synthesis and 24 series were included in quantitative synthesis. Wide heterogeneity was found. In series with <50% of G2 myomas treated, the slicing technique feasibility rate was 86.5% while techniques for enucleating the deep portion of the myomas showed a feasibility rate of 92.3% (p < 0.001). In series with ≥50% of G2 myomas treated, the slicing technique feasibility rate was 70.6% while techniques for enucleating the deep portion of myomas showed a feasibility rate of 88.4% (p < 0.001). In series with ≥50% of G2 myomas treated, the slicing technique feasibility rate was 70.6% while techniques for enucleating the deep portion of myomas showed a feasibility rate of 88.4% (. CONCLUSION: In case of submucous myomas with intramural development, the slicing technique was correlated with a lower rate of in-patient hysteroscopic myomectomies accomplished in a one-step procedure and a higher complications rate.

Correlations between the proportion of type III female genital mutilations in the series and adverse obstetric outcomes: a short meta-analysis.

Background: Authors have reported that evidence on health harms of female genital mutilation is poor.Aim: Meta-analyzing prospective studies on adverse obstetric outcomes according to the severity of female genital mutilation.Method: Prospective studies were already acknowledged in previous meta-analyses and used for calculations. The proportions of type III female genital mutilation were extracted by full-texts, along with the proportions of adverse obstetric outcomes. Assuming random models, the proportions were encoded for meta-analysis and weighted for the inverse of the variance. Nonparametric correlations among weighted proportions of type III female genital mutilation and weighted proportions of obstetric outcomes were built. Analyzable obstetric outcome were: cesarean section, instrumental delivery, episiotomy, post-partum hemorrhage, low Apgar score - need of resuscitation.Results: Meta-analyzable series are few and heterogeneous. There is a trend of direct correlation among the proportion of type III female genital mutilations in the series and the proportion of cesarean section, instrumental deliveries, post-partum hemorrhage and low Apgar scores at birth or need of neonatal resuscitation. The significance was reached for the post-partum hemorrhage and for the fetal adverse outcome.Conclusion: It should be retained that type III female genital mutilation is likely to be a serious concern for birth.