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 We also included two unpublished cohort studies.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.

Podocyte GSK3 is an evolutionarily conserved critical regulator of kidney function.

Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and ß) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-ß-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.

A review of the open laparoscopic Hasson technique and retrieval of adnexal specimen via umbilicus.

Laparoscopic entry techniques vary amongst surgeons and gynaecologists, with gynaecologists favouring Veress needle entry. Recent RCOG/BSGE recommendations have recommended retrieval of ovarian masses via the umbilical port with resultant less postoperative pain and a faster retrieval time than with retrieval through lateral ports of the same size. This is a prospective observational study reviewing the Hasson entry technique and the introduction of retrieval of specimens via the umbilicus in patients scheduled for a laparoscopy procedure at our day surgery unit. We found no immediate or major surgical complications and all specimens were successfully retrieved through the umbilicus. Pain scores were low. We recommend the technique for extirpative gynaecological surgery. Impact Statement This study confirms that conversion from the closed Veress to the open Hasson technique is achievable in a university hospital setting. Operator confidence during the learning phase is enhanced by the use of ultrasound to locate and measure the depth of the umbilical ligament. Retrieval of benign adnexal specimens through the umbilicus was very satisfactory.

Risk factors associated with preterm birth after a prior term delivery.

OBJECTIVE: The objective of this study was to assess the presence of newly acquired preterm birth (PTB) risk factors among primiparous women with no prior history of PTB. DESIGN: Case-control study. SETTING: Deliveries occurring within a large healthcare system from 2002 to 2012. POPULATION: Women with their first two consecutive pregnancies carried to ≥20(0/7)  weeks' gestation. METHODS: Those delivering the first pregnancy at term and the second preterm ≥20(0/7) and <37(0/7)  weeks (term-preterm cases) were compared with women with a term birth in their first two pregnancies (term-term controls). Social factors with the potential to change between the first and second pregnancies and intrapartum labour characteristics in the first pregnancy were compared between cases and controls. MAIN OUTCOME MEASURES: Risk factors for term-preterm sequence. RESULTS: About 38 215 women met inclusion criteria; 1353 (3.8%) were term-preterm cases. Cases and controls were similar with regard to race/ethnicity and maternal age at the time of the first and second deliveries. Cases delivered their second pregnancy approximately 3 weeks earlier (35.7 versus 39.1, P < 0.001). In multivariable models accounting for known PTB risk factors, women with a caesarean delivery in the first pregnancy [adjusted odds ratio (aOR) = 2.20; 95% confidence interval (CI) 1.57-3.08], new tobacco use (aOR = 2.33; 95% CI 1.61-3.38), and an interpregnancy interval <18 months (aOR = 1.37; 95% CI 1.21-1.55) were at increased risk of term-preterm sequence. CONCLUSION: Caesarean delivery in the first pregnancy, new tobacco use, and short interpregnancy interval <18 months are significant risk factors for term-preterm sequence. Women should receive postpartum counselling regarding appropriate interpregnancy interval and cessation of tobacco use. TWEETABLE ABSTRACT: Caesarean delivery in the 1st pregnancy is a significant risk factor for preterm birth following a term delivery.

Recurrent early pregnancy loss and antiphospholipid antibodies: where do we stand?

Evidence from basic science studies supports a causative relationship between antiphospholipid antibodies (aPL) and recurrent early miscarriage (REM) (prior to 10 weeks of gestation). However, human studies have not consistently found a relationship between aPL and REM. Members of the Obstetric Task Force of the 14th International Congress on Antiphospholipid Antibodies performed a literature review of the association of aPL and REM and searched for clinical trials in women with REM who tested positive for aPL. Of the 46 studies that investigated the relationship between aPL and REM, 27 found a positive association, seven found no association, and the remaining 12 papers could not report an association (lack of control group). The main identified problems for such conflicting results were varying definitions of REM (two or three abortions, not necessarily consecutive; different gestational age at which pregnancy losses occurred); analysis of patients with previous fetal death (>10 weeks) in the same group of REM; and different definitions of "positive aPL" (cutoffs not following international recommendations; small number of studies confirmed persistence of positive aPL after six to 12 weeks). The 10 identified randomized trials with proposed treatments for women with REM who test positive for aPL also had heterogeneous inclusion criteria, with only one trial limited to subjects who would meet the current criteria for antiphospholipid syndrome (APS) by both clinical and laboratory criteria. Against this background, we conclude that the association between REM and aPL remains inconclusive and that the findings of treatment trials are at best inconsistent and at worst misleading. More convincing data are critically needed. Studies that identify, or at least stratify, according to international consensus criteria and include standardized core laboratory testing results are crucial if we are to establish an evidence-based association between aPL and REM and treatment recommendations.

Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.

UNLABELLED: There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery. MATERIALS AND METHODS: This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period. RESULTS: Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group. DISCUSSION: Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

Listeria awareness among recently delivered mothers.

The level of knowledge of Listeria among mothers in Ireland is unknown. This prospective questionnaire study aims to evaluate the level of knowledge of recently delivered mothers regarding Listeria infection and its potential prevention. A response rate of 98% was achieved. A total of 271 (43.9%) mothers had heard about Listeria infection but only 187 (30.3%) knew that it was a food-borne pathogen. In total, 83 (13.5%) mothers recalled being told about Listeria infection by a midwife or doctor and 33 (5.3%) recalled receiving written information. A total of 224 (36.3%) of mothers were aware of the increased risk of listeriosis during pregnancy, while 250 (40.5%) knew the potential complications to the unborn fetus. A grand total of 505 (81.8%) mothers knew that they should avoid certain high-risk foods during pregnancy but 342 (55.4%) admitted to having consumed high-risk foods during their pregnancy. In conclusion, mothers' knowledge about listeriosis and its prevention was limited. Many mothers ate high-risk food during pregnancy. Antenatal advice regarding Listeria prevention needs to be improved.

Myomectomy: a suturing technique for the open procedure.

Uterine fibroids are common among women of reproductive age. In women who have not completed their family, a myomectomy is often suggested to preserve and improve fertility. Here, we would like to describe our technique of myomectomy in an open laparotomy procedure.

Pre-operative testing for pregnancy in Dublin day surgery units.

BACKGROUND: The safety of anaesthetic agents in early pregnancy cannot be guaranteed. Certain types of surgery, particularly gynaecological, may also be dangerous. It is therefore important to ensure that, female patients are not inadvertently pregnant when undergoing elective surgery. Different hospitals have different policies and guidelines in place to determine female patients' pregnancy status prior to elective surgery. AIMS: This study aims to evaluate practices in Ireland with regard to methods used to exclude pregnancy in premenopausal women attending for day surgery. METHODS: Postal questionnaires were sent to all consultants in Gynaecology and General Surgery. E-mail questionnaires were sent to all registrar trainees in both specialties. Letters were sent to nine Dublin teaching hospital day surgery units and followed up by telephone consultations. RESULTS: The overall response rate was poor at 34.3 %. Eighty per cent of respondents in the gynaecology specialty have encountered a preoperative patient with a positive pregnancy test at least once during their career versus 28.6 % in the surgical specialty. Only 35 % of gynaecology respondents would routinely inform female reproductive age patients of the need to avoid pregnancy prior to surgery versus 14.3 % in the surgical specialty. On the day of elective surgery, 90 % of gynaecologists would determine the LMP (last menstrual period) versus 35.7 % of surgeons. The policy at all nine Dublin teaching hospitals is to perform a urinary HCG preoperatively but, their policies vary as to whether the patient's LMP, age and medical history are considered when performing a urinary HCG test. CONCLUSION: It is important that, female patients are counselled appropriately regarding the importance of using adequate contraception or, abstinence in order to avoid pregnancy prior to elective surgical procedures. Our survey shows that, gynaecologists are more likely to give this advice compared to our surgical colleagues. Nevertheless, the number of gynaecologists who do this is surprisingly low (35 %). Urinary HCG is still the standard test used in most units to exclude pregnancy.

Accuracy of minimal-preparation computerized tomography in the investigation of suspected colorectal cancer in frail patients: the experience of Western General Hospital, Edinburgh.

Traditional methods of investigating suspected colorectal carcinoma (CRC) such as barium enema, colonoscopy and computerized tomography (CT) pneumocolon are often poorly tolerated by frail or elderly patients. Comparatively, minimal-preparation CT (MPCT) is a non-invasive investigation that does not require bowel preparation. The aim of this study was to review MPCTs carried out at the Western General Hospital, Edinburgh, and compare findings with current published data. Retrospective analysis of 85 patients (age range 55-99 years) who underwent MPCTs at the Western General Hospital between May 2005 and June 2008 was undertaken. Results were followed up using clinical notes, pathological and surgical databases. Subsequent outcomes were analysed (average follow-up 22 months). The prevalence of CRC within the study cohort was 0.14. Sensitivity of MPCT was 1 (95% confidence interval [CI], 0.69-1) with a specificity of 0.93 (95% CI, 0.84-0.97). Thirty percent of patients were found to have extracolonic findings requiring further investigation or intervention. Of the patients, 4.7% had an extracolonic malignancy diagnosed on MPCT. MPCT is a sensitive and specific method of investigating CRC in the elderly, infirm or immobile. Our results were found to be comparable with that of current published data, validating the service provided at the Western General Hospital.

Thrombus load and acute right ventricular failure in pulmonary embolism: correlation and demonstration of a "tipping point" on CT pulmonary angiography.

OBJECTIVES: The aim of this study was to determine the correlation between increasing pulmonary embolism thrombus load and right ventricular (RV) dilatation as demonstrated by CT pulmonary angiography (CTPA) and to assess the thrombus load threshold which indicates impending RV decompensation. METHODS: 2425 consecutive CTPAs were retrospectively analysed. Thrombus load using a modified Miller score (MMS), RV to left ventricular (RV:LV) ratio, presence of septal shift, and pulmonary artery and aorta size were analysed in 504 positive CTPA scans and a representative cohort of 100 negative scans. Results were correlated using non-parametric analysis (two-tailed t-test or χ(2) test) and Pearson's rank correlation. RESULTS: Increasing thrombus load correlated with a higher RV:LV ratio, with a statistically significant difference in RV:LV ratios between the negative and positive pulmonary embolism (PE) cohorts. Larger thrombus loads (MMS ≥12 vs MMS <12) were strongly correlated with RV strain (mean RV:LV ratio, 1.323 vs 0.930; p<0.0001). Smaller thrombus loads had no significant influence on RV strain. Septal shift was also more likely with an MMS of ≥12, as was an increase in pulmonary artery diameter (r=0.221, p<0.001). CONCLUSION: With increasing thrombus load in PE, there is CTPA evidence of RV decompensation with an MMS threshold of 12. This suggests a "tipping point" beyond which RV decompensation is more likely to occur. This is the first study to describe this tipping point between a thrombus load of MMS >12 and an increase in RV:LV ratio. This finding may help to improve risk stratification in patients with acute PE diagnosed by CTPA.

Piriformis pyomyositis, an unusual presentation of leg pain post partum--case report and review of literature.

Piriformis pyomyositis is defined as a subacute infection of skeletal muscles associated with systemic infectious symptoms. In the literature it rarely occurs postpartum. We report a case of piriformis pyomyositis involving a parturient and review the published cases available in the literature.

Comparative study on the outcome of obstetric cholestasis.

OBJECTIVES: The aim of this study was to determine the characteristics and outcomes of obstetric cholestasis (OC) and the significance of measuring total bile acid (TBA) to aid diagnosis. METHODS: This study was conducted over a 27-month period at a tertiary referral maternity hospital (>8000 deliveries annually). In the study period, 753 women presented with pruritus of no specific origin. This group was divided into OC (TBA > or =6 micromol/L, N=151) and idiopathic pruritus of pregnancy (TBA <6 micromol/L, N=602). The latter group served as controls. Data were collected retrospectively and analyzed using SPSS 11.4 for Windows (SPSS Inc., Chicago, IL, USA). RESULTS: Patients were matched for age, ethnicity, parity, and smoking status, sex of baby, and Apgar scores at 1 and 5 minutes. OC was noted to be higher in twin pregnancies. Twice as many mothers in the OC group were induced compared to controls. Of the OC group, 18.0% delivered preterm versus 7.7% of controls. Of the mothers with OC, 48.3% had a TBA in the range of 11-39.9 micromol/L, 21.2% had a TBA >40 micromol/L, and the remaining 30.5% had a TBA between 6 and 10.9 micromol/L. Of the OC group with preterm delivery, all had a raised TBA >11 micromol/L. CONCLUSIONS: The presence of OC increases preterm delivery, both idiopathic and iatrogenic. Increasing induction, admission to the neonatal intensive care unit, and low birth weight were also noted. A TBA cut-off value of >11 micromol/L will more accurately aid the diagnosis of OC in the absence of raised liver function test results, reducing the over-diagnosis of this condition.

Predictors of malignant potential of cystic lesions of the pancreas.

BACKGROUND: Cystic lesions of the pancreas (CLP) are a diagnostic dilemma, the correct characterisation of which determines surgical management. METHODS: From 1995 to 2005, radiology and pathology records were reviewed for the presence of CLP. CLP were divided into three groups; Group 1: Benign, Group 2: Pre-malignant, and Group 3: Malignant. RESULTS: Seventy-nine of 121 patients were included [Group 1: n=46, Group 2: n=10, Group 3: n=23], with a median age at diagnosis of 68 (31-92) years. The median follow-up period was 24 (14-84) months. On univariate analysis, female gender (p=0.04), jaundice (p<0.01), raised serum ALT concentration (p=0.03), cyst size (> or = 2.5 cm) (p<0.01), and biliary duct dilatation (p<0.01) were associated with malignant potential. Benign cysts were more likely to present incidentally (p<0.01). On multi-variate analysis, cyst size (> or =2.5 cm) was an independent predictor of malignant potential. Sub-group analysis revealed that cysts <2.5 cm in the head of the pancreas with evidence of biliary obstruction (either abnormal liver function; raised ALT [p=0.01], ALP [p=0.01], total bilirubin [p=0.02], and/or biliary duct dilatation [p<0.01]) were associated with malignant potential. CONCLUSION: Cyst size > or =2.5 cm on computer tomography imaging was an independent predictor of pre-malignant and malignant pancreatic cysts. Cyst size and the presence of biliary obstruction predict potentially malignant cysts of the head of the pancreas, which require surgical management.

Complementary and alternative medicines versus prescription drugs: perceptions of emergency department patients.

BACKGROUND: The perceptions of emergency department (ED) patients towards complementary and alternative medicines (CAM) are poorly understood. We assessed these perceptions and compared CAM users with non-users, particularly regarding CAM safety and efficacy. METHODS: This was an analytical, cross sectional survey of ED patients undertaken in a tertiary referral ED. A five point Likert scale evaluated patients' level of agreement with statements relating to CAM and prescription drugs. RESULTS: Of 404 patients who were enrolled (participation rate 97.1%), 275 (68.1%; 95% confidence interval (CI) 63.2 to 72.5) were CAM users (had taken a CAM within the previous 12 months). There were 178 patients (44.1%, 95% CI 39.2 to 49.1) who agreed or strongly agreed that CAM are drug free, and there was no significant difference between CAM users and non-users (p = 0.77). There were 115 patients (28.5%, 95% CI 24.2 to 33.2) who agreed or strongly agreed that CAM are always safe to take with prescription drugs, and there were no significant difference between CAM users and non-users (p = 0.39). Significantly more CAM users agreed or strongly agreed that CAM are safe to take, can prevent people from becoming ill, allow people to be in charge of their own health, can treat the mind, body, and spirit, and are more effective than prescription drugs (p<0.01). Significantly fewer CAM users agreed or strongly agreed that prescription drugs are safe to take (p<0.001). CONCLUSION: Considerable proportions of ED patients are CAM users yet are ignorant of the nature and potential toxicities of CAM. In addition, CAM users have significantly different perceptions of CAM and prescription drugs from non-users. The impact of these perceptions on clinical practice needs evaluation.