Evidence-based surgical procedures to optimize caesarean outcomes: an overview of systematic reviews.

Background: Caesarean section (CS) is the most performed major surgery worldwide. Surgical techniques used for CS vary widely and there is no internationally accepted standardization. We conducted an overview of systematic reviews (SR) of randomized controlled trials (RCT) to summarize the evidence on surgical techniques or procedures related to CS. Methods: Searches were conducted from database inception to 31 January 2024 in Cochrane Database of Systematic Reviews, PubMed, EMBASE, Lilacs and CINAHL without date or language restrictions. AMSTAR 2 and GRADE were used to assess the methodological quality of the SRs and the certainty of evidence at outcome level, respectively. We classified each procedure-outcome pair into one of eight categories according to effect estimates and certainty of evidence. The overview was registered at PROSPERO (CRD 42023208306). Findings: The analysis included 38 SRs (16 Cochrane and 22 non-Cochrane) published between 2004-2024 involving 628 RCT with a total of 190,349 participants. Most reviews were of low or critically low quality (AMSTAR 2). The SRs presented 345 procedure-outcome comparisons (237 procedure versus procedure, 108 procedure versus no treatment/placebo). There was insufficient or inconclusive evidence for 256 comparisons, clear evidence of benefit for 40, possible benefit for 17, no difference of effect for 13, clear evidence of harm for 14, and possible harm for 5. We found no SRs for 7 pre-defined procedures. Skin cleansing with chlorhexidine, Joel-Cohen-based abdominal incision, uterine incision with blunt dissection and cephalad-caudal expansion, cord traction for placental extraction, manual cervical dilatation in pre-labour CS, changing gloves, chromic catgut suture for uterine closure, non-closure of the peritoneum, closure of subcutaneous tissue, and negative pressure wound therapy are procedures associated with benefits for relevant outcomes. Interpretation: Current evidence suggests that several CS surgical procedures improve outcomes but also reveals a lack of or inconclusive evidence for many commonly used procedures. There is an urgent need for evidence-based guidelines standardizing techniques for CS, and trials to fill existing knowledge gaps. Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO).

Co-designing a web-based education platform for patients with early pregnancy loss.

Canadian emergency departments (EDs) frequently provide care to patients undergoing early pregnancy loss. Unfortunately, in this setting, patients commonly have negative experiences, in part due to lack of appropriate follow-up and education on symptoms that may arise after discharge. In response to this gap, our team created a free, web-based, patient-informed educational platform for women to access accurate information on early pregnancy loss. This free and publicly accessible resource was launched in May 2022 at Mount Sinai Hospital in Toronto and was shared with EDs across Canada.

RéSUMé: Les services d'urgence (SU) canadiens fournissent fréquemment des soins aux patientes qui subissent une perte de grossesse précoce. Malheureusement, dans ce contexte, les patientes ont souvent des expériences négatives, en partie à cause du manque de suivi approprié et d'éducation sur les symptômes qui peuvent apparaître après la sortie de l'hôpital. Pour combler cette lacune, notre équipe a créé une plate-forme éducative gratuite, basée sur le Web et informée par les patientes, permettant aux femmes d'accéder à des informations précises sur la perte de grossesse précoce. Cette ressource gratuite et accessible au public a été lancée en mai 2022 à l'hôpital Mount Sinai de Toronto et a été partagée avec les services d'urgence de tout le Canada.

Does body mass index impact assisted reproductive technology treatment outcomes in gestational carriers.

BACKGROUND: The purpose of this study was to assess whether increased body mass index (BMI) negatively affects assisted reproductive technology (ART) outcomes among gestational carriers. METHODS: A retrospective matched case-control cohort, including all gestational carrier (GC) cycles performed at CReATe Fertility Centre (Toronto, ON, Canada) between 2003 and 2016. SETTING: A Canadian fertility clinic, with a large surrogacy program. PATIENTS: All gestational carriers that had undergone a cycle completed to a transfer at our clinic, and had BMI and outcome data available, were matched by BMI to infertile patients treated at our clinic during the same years provided they had undergone a cycle completed to a transfer, and had outcomes data available. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical pregnancies rates, miscarriage rates and live birth rates. RESULTS: BMI was not a reliable prediction factor of any of the measured outcomes. Importantly, the gestational carrier population had better outcomes and a significantly lower overall incidence of maternal, fetal and neonatal complications when compared with infertile patients, treated at our clinic during the same years. CONCLUSION: BMI is not a reliable predictor of outcomes among gestational carriers.

Progression of the first stage of spontaneous labour.

This chapter reviews and compiles the most recent published evidence assessing the overall labour duration and patterns of progression for both nulliparous and parous women, as well as the accuracy of the alert and action lines in the World Health Organization (WHO) partograph for the identification of women at risk of birth complications. Systematic reviews of observational studies reporting on the duration of the first and the second stages of labour, and on cervical dilatation patterns for women with low risk of complications with 'normal' perinatal outcomes were identified and updated. The accuracy of the alert (1 cm/h) and action lines of the cervicograph in the partogram to predict adverse birth outcomes among women in first stage of labour was also reviewed, questioning the appropriateness of considering cervical dilatation over time as an isolated indicator to define labour progression or arrest.

Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis.

BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic agents can prevent PPH, and are routinely recommended. The current World Health Organization (WHO) recommendation for preventing PPH is 10 IU (international units) of intramuscular or intravenous oxytocin. There are several uterotonic agents for preventing PPH but there is still uncertainty about which agent is most effective with the least side effects. This is an update of a Cochrane Review which was first published in April 2018 and was updated to incorporate results from a recent large WHO trial. OBJECTIVES: To identify the most effective uterotonic agent(s) to prevent PPH with the least side effects, and generate a ranking according to their effectiveness and side-effect profile. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (24 May 2018), and reference lists of retrieved studies. SELECTION CRITERIA: All randomised controlled trials or cluster-randomised trials comparing the effectiveness and side effects of uterotonic agents with other uterotonic agents, placebo or no treatment for preventing PPH were eligible for inclusion. Quasi-randomised trials were excluded. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. DATA COLLECTION AND ANALYSIS: At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. Secondary outcomes included blood loss and related outcomes, morbidity outcomes, maternal well-being and satisfaction and side effects. Primary outcomes were also reported for pre-specified subgroups, stratifying by mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of administration. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available agents. MAIN RESULTS: The network meta-analysis included 196 trials (135,559 women) involving seven uterotonic agents and placebo or no treatment, conducted across 53 countries (including high-, middle- and low-income countries). Most trials were performed in a hospital setting (187/196, 95.4%) with women undergoing a vaginal birth (71.5%, 140/196).Relative effects from the network meta-analysis suggested that all agents were effective for preventing PPH ≥ 500 mL when compared with placebo or no treatment. The three highest ranked uterotonic agents for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, misoprostol plus oxytocin combination and carbetocin. There is evidence that ergometrine plus oxytocin (RR 0.70, 95% CI 0.59 to 0.84, moderate certainty), carbetocin (RR 0.72, 95% CI 0.56 to 0.93, moderate certainty) and misoprostol plus oxytocin (RR 0.70, 95% CI 0.58 to 0.86, low certainty) may reduce PPH ≥ 500 mL compared with oxytocin. Low-certainty evidence suggests that misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin.All agents except ergometrine and injectable prostaglandins were effective for preventing PPH ≥ 1000 mL when compared with placebo or no treatment. High-certainty evidence suggests that ergometrine plus oxytocin (RR 0.83, 95% CI 0.66 to 1.03) and misoprostol plus oxytocin (RR 0.88, 95% CI 0.70 to 1.11) make little or no difference in the outcome of PPH ≥ 1000 mL compared with oxytocin. Low-certainty evidence suggests that ergometrine may make little or no difference to this outcome compared with oxytocin meanwhile the evidence on carbetocin was of very low certainty. High-certainty evidence suggests that misoprostol is less effective in preventing PPH ≥ 1000 mL when compared with oxytocin (RR 1.19, 95% CI 1.01 to 1.42). Despite the comparable relative treatment effects between all uterotonics (except misoprostol) and oxytocin, ergometrine plus oxytocin, misoprostol plus oxytocin combinations and carbetocin were the highest ranked agents for PPH ≥ 1000 mL.Misoprostol plus oxytocin reduces the use of additional uterotonics (RR 0.56, 95% CI 0.42 to 0.73, high certainty) and probably also reduces the risk of blood transfusion (RR 0.51, 95% CI 0.37 to 0.70, moderate certainty) when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe morbidity as these outcomes were rare in the included randomised trials where they were reported.The two combination regimens were associated with important side effects. When compared with oxytocin, misoprostol plus oxytocin combination increases the likelihood of vomiting (RR 2.11, 95% CI 1.39 to 3.18, high certainty) and fever (RR 3.14, 95% CI 2.20 to 4.49, moderate certainty). Ergometrine plus oxytocin increases the likelihood of vomiting (RR 2.93, 95% CI 2.08 to 4.13, moderate certainty) and may make little or no difference to the risk of hypertension, however absolute effects varied considerably and the certainty of the evidence was low for this outcome.Subgroup analyses did not reveal important subgroup differences by mode of birth (caesarean versus vaginal birth), setting (hospital versus community), risk of PPH (high versus low risk for PPH), dose of misoprostol (≥ 600 mcg versus < 600 mcg) and regimen of oxytocin (bolus versus bolus plus infusion versus infusion only). AUTHORS' CONCLUSIONS: All agents were generally effective for preventing PPH when compared with placebo or no treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional desirable effects compared with the current standard oxytocin. The two combination regimens, however, are associated with significant side effects. Carbetocin may be more effective than oxytocin for some outcomes without an increase in side effects.

Duration of spontaneous labour in 'low-risk' women with 'normal' perinatal outcomes: A systematic review.

BACKGROUND: Despite decades of research, the concept of normality in labour in terms of its progression and duration is not universal or standardized. However, in clinical practice, it is important to define the boundaries that distinguish what is normal from what is abnormal to enable women and care providers have a shared understanding of what to expect and when labour interventions are justified. OBJECTIVES: To synthesise available evidence on the duration of latent and active first stage and the second stage of spontaneous labour in women at low risk of complications with 'normal' perinatal outcomes. SEARCH STRATEGY: PubMed, EMBASE, CINAHL, POPLINE, Global Health Library, and reference lists of eligible studies. SELECTION CRITERIA: Observational studies and other study designs. DATA COLLECTION AND ANALYSIS: Four authors extracted data on: maternal characteristics; labour interventions; duration of latent first stage, active first stage, and second stage of labour; and the definitions of onset of latent and active first stage, and second stage where reported. Heterogeneity in the included studies precluded meta-analysis and data were presented descriptively. MAIN RESULTS: Thirty-seven studies reporting the duration of first and/or second stages of labour for 208,000 women met our inclusion criteria. Among nulliparous women, the median duration of active first stage (when the starting reference point was 4 cm) ranged from 3.7-5.9 h (95th percentiles: 14.5-16.7 h). With active phase starting from 5 cm, the median duration was from 3.8-4.3 h (95th percentiles: 11.3-12.7 h). The median duration of second stage ranged from 14 to 66 min (95th percentiles: 65-138 min) and from 6 to 12 min (95th percentiles: 58-76 min) in nulliparous and parous women, respectively. Sensitivity analyses excluding first and second stage interventions did not significantly impact on these findings CONCLUSIONS: The duration of spontaneous labour in women with good perinatal outcomes varies from one woman to another. Some women may experience labour for longer than previously thought, and still achieve a vaginal birth without adverse perinatal outcomes. Our findings question the rigid limits currently applied in clinical practice for the assessment of prolonged first or second stage that warrant obstetric intervention.

Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2.

Cellular identity in metazoan organisms is frequently established through lineage-specifying transcription factors, which control their own expression through transcriptional positive feedback, while antagonizing the developmental networks of competing lineages. Here, we have uncovered a distinct positive feedback loop that arises from the reciprocal stabilization of the tyrosine kinase ABL and the transcriptional coactivator TAZ. Moreover, we determined that this loop is required for osteoblast differentiation and embryonic skeletal formation. ABL potentiated the assembly and activation of the RUNX2-TAZ master transcription factor complex that is required for osteoblastogenesis, while antagonizing PPARγ-mediated adipogenesis. ABL also enhanced TAZ nuclear localization and the formation of the TAZ-TEAD complex that is required for osteoblast expansion. Last, we have provided genetic data showing that regulation of the ABL-TAZ amplification loop lies downstream of the adaptor protein 3BP2, which is mutated in the craniofacial dysmorphia syndrome cherubism. Our study demonstrates an interplay between ABL and TAZ that controls the mesenchymal maturation program toward the osteoblast lineage and is mechanistically distinct from the established model of lineage-specific maturation.

Collagen modifications in postmenopausal osteoporosis: advanced glycation endproducts may affect bone volume, structure and quality.

The classic model of postmenopausal osteoporosis (PM-OP) starts with the depletion of estrogen, which in turn stimulates imbalanced bone remodeling, resulting in loss of bone mass/volume. Clinically, this leads to fractures because of structural weakness. Recent work has begun to provide a more complete picture of the mechanisms of PM-OP involving oxidative stress and collagen modifications known as advanced glycation endproducts (AGEs). On one hand, AGEs may drive imbalanced bone remodeling through signaling mediated by the receptor for AGEs (RAGE), stimulating resorption and inhibiting formation. On the other hand, AGEs are associated with degraded bone material quality. Oxidative stress promotes the formation of AGEs, inhibits normal enzymatically derived crosslinking and can degrade collagen structure, thereby reducing fracture resistance. Notably, there are multiple positive feedback loops that can exacerbate the mechanisms of PM-OP associated with oxidative stress and AGEs. Anti-oxidant therapies may have the potential to inhibit the oxidative stress based mechanisms of this disease.

External causes of metabolic disorders.

Common medical conditions, such as head trauma, malignancy,and pregnancy may be associated with rarely seen metabolic emergencies that require prompt recognition and therapy. Although care of the primary disorder is the focus of initial management,identification of the associated endocrinopathy is important. These clinical syndromes, although uncommon, must be considered when evaluating patients, as prompt treatment may minimize the mortality and morbidity of these conditions.