Epidural analgesia in labour: separating fact from fiction for autism and neurodevelopment.

Having epidural analgesia in labour has been associated with a later diagnosis of autism spectrum disorder in the offspring, resulting in concerns about childhood wellbeing. Neurodevelopmental changes are inconsistently reported in the literature, creating challenges in the interpretation of these findings. Here we explore the limitations of the current evidence base, and why findings differ between studies, concluding that the current body of evidence does not support a causal association between use of epidural analgesia in labour and autism spectrum disorder.

Epidural analgesia during labour and severe maternal morbidity: population based study.

OBJECTIVES: To determine the effect of labour epidural on severe maternal morbidity (SMM) and to explore whether this effect might be greater in women with a medical indication for epidural analgesia during labour, or with preterm labour. DESIGN: Population based study. SETTING: All NHS hospitals in Scotland. PARTICIPANTS: 567 216 women in labour at 24+0 to 42+6 weeks' gestation between 1 January 2007 and 31 December 2019, delivering vaginally or through unplanned caesarean section. MAIN OUTCOME MEASURES: The primary outcome was SMM, defined as the presence of ≥1 of 21 conditions used by the US Centers for Disease Control and Prevention (CDC) as criteria for SMM, or a critical care admission, with either occurring at any point from date of delivery to 42 days post partum (described as SMM). Secondary outcomes included a composite of ≥1 of the 21 CDC conditions and critical care admission (SMM plus critical care admission), and respiratory morbidity. RESULTS: Of the 567 216 women, 125 024 (22.0%) had epidural analgesia during labour. SMM occurred in 2412 women (4.3 per 1000 births, 95% confidence interval (CI) 4.1 to 4.4). Epidural analgesia was associated with a reduction in SMM (adjusted relative risk 0.65, 95% CI 0.50 to 0.85), SMM plus critical care admission (0.46, 0.29 to 0.73), and respiratory morbidity (0.42, 0.16 to 1.15), although the last of these was underpowered and had wide confidence intervals. Greater risk reductions in SMM were detected among women with a medical indication for epidural analgesia (0.50, 0.34 to 0.72) compared with those with no such indication (0.67, 0.43 to 1.03; P<0.001 for difference). More marked reductions in SMM were seen in women delivering preterm (0.53, 0.37 to 0.76) compared with those delivering at term or post term (1.09, 0.98 to 1.21; P<0.001 for difference). The observed reduced risk of SMM with epidural analgesia was increasingly noticeable as gestational age at birth decreased in the whole cohort, and in women with a medical indication for epidural analgesia. CONCLUSION: Epidural analgesia during labour was associated with a 35% reduction in SMM, and showed a more pronounced effect in women with medical indications for epidural analgesia and with preterm births. Expanding access to epidural analgesia for all women during labour, and particularly for those at greatest risk, could improve maternal health.

Research priorities in regional anaesthesia: an international Delphi study.

BACKGROUND: Regional anaesthesia use is growing worldwide, and there is an increasing emphasis on research in regional anaesthesia to improve patient outcomes. However, priorities for future study remain unclear. We therefore conducted an international research prioritisation exercise, setting the agenda for future investigators and funding bodies. METHODS: We invited members of specialist regional anaesthesia societies from six continents to propose research questions that they felt were unanswered. These were consolidated into representative indicative questions, and a literature review was undertaken to determine if any indicative questions were already answered by published work. Unanswered indicative questions entered a three-round modified Delphi process, whereby 29 experts in regional anaesthesia (representing all participating specialist societies) rated each indicative question for inclusion on a final high priority shortlist. If ≥75% of participants rated an indicative question as 'definitely' include in any round, it was accepted. Indicative questions rated as 'definitely' or 'probably' by <50% of participants in any round were excluded. Retained indicative questions were further ranked based on the rating score in the final Delphi round. The final research priorities were ratified by the Delphi expert group. RESULTS: There were 1318 responses from 516 people in the initial survey, from which 71 indicative questions were formed, of which 68 entered the modified Delphi process. Eleven 'highest priority' research questions were short listed, covering themes of pain management; training and assessment; clinical practice and efficacy; technology and equipment. CONCLUSIONS: We prioritised unanswered research questions in regional anaesthesia. These will inform a coordinated global research strategy for regional anaesthesia and direct investigators to address high-priority areas.

Long-term effects of neuraxial analgesia.

PURPOSE OF REVIEW: This review article explores the potential longer-term implications of neuraxial analgesia in labour for both the mother and her child. RECENT FINDINGS: Neuraxial techniques for labour analgesia are well tolerated and effective, and long-term adverse sequelae are rare. Labour epidural analgesia is not independently associated with long-term headache, backache, postnatal depression or anal sphincter injury, and evidence supports that epidurals may offer protection against severe maternal morbidity, particularly in women at a higher risk of complications. However, there is an increasing awareness that postdural puncture headache may be associated with chronic headache, back pain and postnatal depression, emphasizing the need for adequate follow-up until symptoms resolve.For the neonate, a growing body of evidence refutes any association between epidural analgesia in labour and the later development of autism spectrum disorder. The clinical significance of epidural related maternal fever remains uncertain and is a research priority. SUMMARY: Women should continue to access the significant benefits of neuraxial analgesia in labour without undue concern about adverse sequelae for themselves or their offspring. Measures to prevent, appropriately manage and adequately follow-up women who have suffered complications of neuraxial analgesia, such as postdural puncture headache, are good practice and can mitigate the development of long-term sequelae.

Outcomes of total hip and knee arthroplasty in patients with haemophilia: A meta-analysis of comparative studies and clinical practice recommendations.

AIM: We aimed to compare the outcomes of total hip and knee arthroplasty (THA, TKA) in haemophilic patients compared to matched controls. METHODS: Through a literature search we identified all cohort studies comparing perioperative complications and other outcomes of THA and TKA in haemophilic patients and matched controls without haemophilia. Results of the same outcome measure assessed by two or more studies were pooled in meta-analyses; odds ratios (ORs) with 95% confidence intervals (CI) were calculated. The risk of bias in included studies and certainty of evidence of each result were assessed using the Newcastle-Ottawa scale and the GRADE tool respectively. RESULTS: A total of five retrospective studies with matched controls were included; four of them were of good and one of fair quality. Based on moderate certainty evidence, compared to matched controls, patients with haemophilia had a significantly higher incidence of the following complications after a) TKA: periprosthetic joint infection [PJI; OR 1.6 CI (1.3, 1.9)], 1-year revision/re-operation [OR 1.4 CI (1.2, 1.8)] and b) THA: major and minor 90-day complications [major OR 2.2 CI (1.7, 2.9); minor OR 1.4 CI (1.1, 1.8)], venous thromboembolism [OR 3.1 CI (2.1, 4.6)]. PJI incidence in THA was not different in haemophilia compared to controls [OR 1.5 CI (.9, 2.6)]. CONCLUSION: Our results can be used by healthcare professionals counselling patients with haemophilia considering a THA or TKA as part of the informed consent process. We provide detailed clinical recommendations for the perioperative management of THA and TKA in haemophilic patients.

Regional anaesthesia training in the UK - a national survey.

Background: Adequate training of anaesthetists in regional anaesthesia is important to ensure optimal patient access to regional anaesthesia. Methods: We undertook a national survey of UK trainee anaesthetists and Royal College of Anaesthetists (RCoA) tutors to assess experiences of training in regional anaesthesia. We performed descriptive statistics for baseline characteristics, and logistic regression of training indices and tutor confidence that their hospital could provide regional anaesthesia training at all three stages of the RCoA 2021 curriculum. Results: A total of 492 trainees (19.2%) and 114 tutors (45.2%) completed the survey. Trainees were less likely to have received training in chest/abdominal wall compared with upper/lower limb blocks {erector spinae vs femoral block (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.16-0.39), P<0.001}, or achieved >20 chest/abdominal wall blocks by Stage 3 of training (chest vs lower limb block [OR 0.09, 95% CI 0.05-0.15, P<0.001]. There was a strong association between training received, number of blocks performed (>20 vs 0-5 blocks), and self-reported ability to perform blocks independently, OR 20.9 (95% CI 9.38-53.2). 24/182 (13%) and 10/182 (5.5%) of trainees had performed ≥50 non-obstetric lumbar and thoracic epidurals, respectively, by Stage 3 training. There was a positive association between having a lead clinician for regional anaesthesia, particularly those with paid sessions, and reported confidence to provide regional anaesthesia training at all stages of the curriculum (Stage 3 OR 7.27 [95% CI 2.64-22.0]). Conclusion: Our results confirm the importance of clinical experience and access to training in regional anaesthesia, and support the introduction of departmental regional anaesthesia leads to improve equity and quality in training opportunities.

Study protocol for IMPRoVE: a multicentre prospective observational cohort study of the incidence, impact and mechanisms of perioperative right ventricular dysfunction in non-cardiac surgery.

INTRODUCTION: Perioperative myocardial injury evidenced by elevated cardiac biomarkers (both natriuretic peptides and troponin) is common after major non-cardiac surgery. However, it is unclear if the rise in cardiac biomarkers represents global or more localised cardiac injury. We have previously shown isolated right ventricular (RV) dysfunction in patients following lung resection surgery, with no change in left ventricular (LV) function. Given that perioperative RV dysfunction (RVD) can manifest insidiously, we hypothesise there may be a substantial burden of covert yet clinically important perioperative RVD in other major non-cardiac surgical groups. The Incidence, impact and Mechanisms of Perioperative Right VEntricular dysfunction (IMPRoVE) study has been designed to address this knowledge gap. METHODS AND ANALYSIS: A multicentre prospective observational cohort study across four centres in the West of Scotland and London. One hundred and seventy-five patients will be recruited from five surgical specialties: thoracic, upper gastrointestinal, vascular, colorectal and orthopaedic surgery (35 patients from each group). All patients will undergo preoperative and postoperative (day 2-4) echocardiography, with contemporaneous cardiac biomarker testing. Ten patients from each surgical specialty (50 patients in total) will undergo T1-cardiovascular magnetic resonance (CMR) imaging preoperatively and postoperatively. The coprimary outcomes are the incidence of perioperative RVD (diagnosed by RV speckle tracking echocardiography) and the effect that RVD has on days alive and at home at 30 days postoperatively. Secondary outcomes include LV dysfunction and clinical outcomes informed by Standardised Endpoints in Perioperative Medicine consensus definitions. T1 CMR will be used to investigate for imaging correlates of myocardial inflammation as a possible mechanism driving perioperative RVD. ETHICS AND DISSEMINATION: Approval was gained from Oxford C Research Ethics Committee (REC reference 22/SC/0442). Findings will be disseminated by various methods including social media, international presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05827315.

Pilot Study Exploring if an Augmented Reality NeedleTrainer Device Improves Novice Performance of a Simulated Central Venous Catheter Insertion on a Phantom.

Introduction Needle insertion and visualisation skills needed for ultrasound (US)-guided procedures can be challenging to acquire. The novel NeedleTrainer device superimposes a digital holographic needle on a real-time US image display without puncturing a surface. The aim of this randomised control study was to compare the success of trainees performing a simulated central venous catheter insertion on a phantom either with or without prior NeedleTrainer device practice. Methods West of Scotland junior trainees who had not performed insertion of a central venous catheter were randomised into two groups (n=20). Participants undertook standardized online training through a pre-recorded video and training on how to handle a US probe. Group 1 had 10 minutes of supervised training with the NeedleTrainer device. Group 2 were a control group. Participants were assessed on needle insertion to a pre-defined target vein in a phantom. The outcome measures were the time taken for needle placement (secs), number of needle passes (n), operator confidence (0-10), assessor confidence (0-10), and NASA task load index score. Results The mean mental demand score in the control group was 7.65 (SD 3.5) compared to 12.8 (SD 2.2, p=0.005) in the NeedleTrainer group. There was no statistical difference between the groups in any of the other outcome measures. Discussion This was a small pilot study, and small participant numbers may have impacted the statistical significance. There is natural variation of skill within participants that could not have been controlled for. The difference in pressure needed using the NeedleTrainer compared to a real needle may impact the outcome measures.

Study protocol: examining the impacts of COVID-19 mitigation measures on pregnancy and birth outcomes in Scotland-a linked administrative data study.

INTRODUCTION: This protocol outlines aims to test the wider impacts of the COVID-19 pandemic on pregnancy and birth outcomes and inequalities in Scotland. METHOD AND ANALYSIS: We will analyse Scottish linked administrative data for pregnancies and births before (March 2010 to March 2020) and during (April 2020 to October 2020) the pandemic. The Community Health Index database will be used to link the National Records of Scotland Births and the Scottish Morbidity Record 02. The data will include about 500 000 mother-child pairs. We will investigate population-level changes in maternal behaviour (smoking at antenatal care booking, infant feeding on discharge), pregnancy and birth outcomes (birth weight, preterm birth, Apgar score, stillbirth, neonatal death, pre-eclampsia) and service use (mode of delivery, mode of anaesthesia, neonatal unit admission) during the COVID-19 pandemic using two analytical approaches. First, we will estimate interrupted times series regression models to describe changes in outcomes comparing prepandemic with pandemic periods. Second, we will analyse the effect of COVID-19 mitigation measures on our outcomes in more detail by creating cumulative exposure variables for each mother-child pair using the Oxford COVID-19 Government Response Tracker. Thus, estimating a potential dose-response relationship between exposure to mitigation measures and our outcomes of interest as well as assessing if timing of exposure during pregnancy matters. Finally, we will assess inequalities in the effect of cumulative exposure to lockdown measures on outcomes using several axes of inequality: ethnicity/mother's country of birth, area deprivation (Scottish Index of Multiple Deprivation), urban-rural classification of residence, number of previous children, maternal social position (National Statistics Socioeconomic Classification) and parental relationship status. ETHICS AND DISSEMINATION: NHS Scotland Public Benefit and Privacy Panel for Health and Social Care scrutinised and approved the use of these data (1920-0097). Results of this study will be disseminated to the research community, practitioners, policy makers and the wider public.

Recommendations for anatomical structures to identify on ultrasound for the performance of intermediate and advanced blocks in ultrasound-guided regional anesthesia.

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for "block view" (which visualizes the block site and is maintained for needle insertion/injection). A "strong recommendation" was made if ≥75% of participants rated any structure as "definitely include" in any round. A "weak recommendation" was made if >50% of participants rated it as "definitely include" or "probably include" for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a "strong recommendation" was made for 60 structures on orientation scanning and 44 on the block view. A "weak recommendation" was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice.

Buprenorphine Compared with Methadone in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear. METHODS: We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies. RESULTS: Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable. CONCLUSIONS: Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.

Epidural analgesia in labor: A narrative review.

Lumbar epidural is the most effective form of pain relief in labor with around 30% of laboring women in the UK and 60% in the USA receiving epidural analgesia. Associations of epidural on maternal, obstetric, and neonatal outcomes have been the subject of intense study, though a number of uncertainties persist. The present narrative review explores important areas of research surrounding epidural analgesia in obstetric patients including methods of initiation and administration, choice of local anesthetic solution, and the addition of adjuvants. Key meta-analyses exploring associations of epidural analgesia on maternal and neonatal outcomes are identified and summarized.

International consensus on anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia.

There is no universally agreed set of anatomical structures that must be identified on ultrasound for the performance of ultrasound-guided regional anesthesia (UGRA) techniques. This study aimed to produce standardized recommendations for core (minimum) structures to identify during seven basic blocks. An international consensus was sought through a modified Delphi process. A long-list of anatomical structures was refined through serial review by key opinion leaders in UGRA. All rounds were conducted remotely and anonymously to facilitate equal contribution of each participant. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for the "block view" (which visualizes the block site and is maintained for needle insertion/injection). Strong recommendations for inclusion were made if ≥75% of participants rated a structure as "definitely include" in any round. Weak recommendations were made if >50% of participants rated a structure as "definitely include" or "probably include" for all rounds (but the criterion for "strong recommendation" was never met). Thirty-six participants (94.7%) completed all rounds. 128 structures were reviewed; a "strong recommendation" is made for 35 structures on orientation scanning and 28 for the block view. A "weak recommendation" is made for 36 and 20 structures, respectively. This study provides recommendations on the core (minimum) set of anatomical structures to identify during ultrasound scanning for seven basic blocks in UGRA. They are intended to support consistent practice, empower non-experts using basic UGRA techniques, and standardize teaching and research.

Anaesthesia Choice for Creation of Arteriovenous Fistula (ACCess) study protocol : a randomised controlled trial comparing primary unassisted patency at 1 year of primary arteriovenous fistulae created under regional compared to local anaesthesia.

INTRODUCTION: Arteriovenous fistulae (AVF) are the 'gold standard' vascular access for haemodialysis. Universal usage is limited, however, by a high early failure rate. Several small, single-centre studies have demonstrated better early patency rates for AVF created under regional anaesthesia (RA) compared with local anaesthesia (LA). The mechanistic hypothesis is that the sympathetic blockade associated with RA causes vasodilatation and increased blood flow through the new AVF. Despite this, considerable variation in practice exists in the UK. A high-quality, adequately powered, multicentre randomised controlled trial (RCT) is required to definitively inform practice. METHODS AND ANALYSIS: The Anaesthesia Choice for Creation of Arteriovenous Fistula (ACCess) study is a multicentre, observer-blinded RCT comparing primary radiocephalic/brachiocephalic AVF created under regional versus LA. The primary outcome is primary unassisted AVF patency at 1 year. Access-specific (eg, stenosis/thrombosis), patient-specific (including health-related quality of life) and safety secondary outcomes will be evaluated. Health economic analysis will also be undertaken. ETHICS AND DISSEMINATION: The ACCess study has been approved by the West of Scotland Research and ethics committee number 3 (20/WS/0178). Results will be published in open-access peer-reviewed journals within 12 months of completion of the trial. We will also present our findings at key national and international renal and anaesthetic meetings, and support dissemination of trial outcomes via renal patient groups. TRIAL REGISTRATION NUMBER: ISRCTN14153938. SPONSOR: NHS Greater Glasgow and Clyde GN19RE456, Protocol V.1.3 (8 May 2021), REC/IRAS ID: 290482.

Association of Epidural Analgesia in Women in Labor With Neonatal and Childhood Outcomes in a Population Cohort.

Importance: Although use of epidural analgesia during labor is safe, detailed information about its association with neonatal and child outcomes is limited. Objective: To investigate the association of labor epidural analgesia with neonatal outcomes and childhood development during the first 1000 days of life. Design, Setting, and Participants: This population-based cohort study used Scottish National Health Service hospital administrative data of all 435 281 singleton live births in Scotland between January 1, 2007, and December 31, 2016, with follow-up over the first 1000 days of life. All 435 281 mother-infant pairs delivering between 24 weeks 0 days and 43 weeks 6 days' gestation who were in active labor with cephalic presentation and who delivered vaginally or via unplanned cesarean delivery were included. Stillbirths and infants with known congenital anomalies were excluded. Data were analyzed between August 1, 2020, and July 23, 2021. Exposures: Epidural analgesia in labor. Main Outcomes and Measures: Neonatal outcomes included resuscitation, Apgar score less than 7 at 5 minutes, and neonatal unit admission. Childhood development measures (gross and fine motor function, communication, and social functioning) were obtained from standardized national childhood surveillance assessments performed at 2 years. Results: This study included a total of 435 281 live births with cephalic presentation in labor (median gestational age at delivery, 40 weeks [IQR, 39-41 weeks]; 221 153 male infants [50.8%]), of which 94 323 (21.7%) had labor epidural. Epidural analgesia was associated with a reduction in spontaneous vaginal deliveries (confounder-adjusted [Cadj] relative risk [RR], 0.46; 95% CI, 0.42-0.50), an increased risk of neonatal resuscitation (Cadj RR, 1.07; 95% CI, 1.03-1.11), and an increased risk of neonatal unit admission (Cadj RR, 1.14; 95% CI, 1.11-1.17). With additional analysis for mediation by mode of delivery (CMadj), these associations were reversed (CMadj RR, 0.83; 95% CI, 0.79-0.86 for neonatal resuscitation and CMadj RR, 0.94; 95% CI, 0.91-0.97 for neonatal unit admission). Epidural analgesia was associated with a reduced risk of an Apgar score less than 7 at 5 minutes in both confounder and confounder/mediation analyses. Epidural analgesia was associated with a reduced risk of having developmental concern in any domain at 2 years in confounder and confounder/mediation analyses (CMadj RR, 0.96; 95% CI, 0.93-0.98), with specifically fewer concerns regarding communication (CMadj RR, 0.96; 95% CI, 0.93-0.99) and fine motor skills (CMadj RR, 0.89; 95% CI, 0.82-0.97). Conclusions and Relevance: The results of this cohort study suggest that labor epidural analgesia is not independently associated with adverse neonatal or childhood development outcomes. Associations with neonatal resuscitation and admission were likely mediated by mode of delivery.

Neonatal and early childhood outcomes following maternal anesthesia for cesarean section: a population-based cohort study.

BACKGROUND: The fetus is vulnerable to maternal drug exposure. We determined associations of exposure to spinal, epidural, or general anesthesia on neonatal and childhood development outcomes during the first 1000 days of life. METHODS: Population-based study of all singleton, cesarean livebirths of 24+0 to 43+6 weeks gestation between January 2007 and December 2016 in Scotland, stratified by urgency with follow-up to age 2 years. Models were adjusted for: maternal age, weight, ethnicity, socioeconomic status, smoking, drug-use, induction, parity, previous cesarean or abortion, pre-eclampsia, gestation, birth weight, and sex. RESULTS: 140 866 mothers underwent cesarean section (41.2% (57,971/140,866) elective, 58.8% (82,895/140,866) emergency) with general anesthesia used in 3.2% (1877/57,971) elective and 9.8% (8158/82,895) of emergency cases. In elective cases, general anesthesia versus spinal was associated with: neonatal resuscitation (crude event rate 16.2% vs 1.9% (adjusted RR 8.20, 95% CI 7.20 to 9.33), Apgar <7 at 5 min (4.6% vs 0.4% (adjRR 11.44, 95% CI 8.88 to 14.75)), and neonatal admission (8.6% vs 4.9% (adjRR 1.65, 95% CI 1.40 to 1.94)). Associations were similar in emergencies; resuscitation (32.2% vs 12.3% (adjRR 2.40, 95% CI 2.30 to 2.50)), Apgar <7 (12.6% vs 2.8% (adjRR 3.87, 95% CI 3.56 to 4.20), and admission (31.6% vs 19.9% (adjRR 1.20, 95% CI 1.15 to 1.25). There was a weak association between general anesthesia in emergency cases and having ≥1 concern noted in developmental assessment at 2 years (21.0% vs 16.5% (adjRR 1.08, 95% CI 1.01 to 1.16)). CONCLUSIONS: General anesthesia for cesarean section, irrespective of urgency, is associated with neonatal resuscitation, low Apgar, and neonatal unit admission. Associations were strongest in non-urgent cases and at term. Further evaluation of long-term outcomes is warranted.

Intercellular Communication in the Nervous System Goes Viral.

Viruses and transposable elements are major drivers of evolution and make up over half the sequences in the human genome. In some cases, these elements are co-opted to perform biological functions for the host. Recent studies made the surprising observation that the neuronal gene Arc forms virus-like protein capsids that can transfer RNA between neurons to mediate a novel intercellular communication pathway. Phylogenetic analyses showed that mammalian Arc is derived from an ancient retrotransposon of the Ty3/gypsy family and contains homology to the retroviral Gag polyproteins. The Drosophila Arc homologs, which are independently derived from the same family of retrotransposons, also mediate cell-to-cell signaling of RNA at the neuromuscular junction; a striking example of convergent evolution. Here we propose an Arc 'life cycle', based on what is known about retroviral Gag, and discuss how elucidating these biological processes may lead to novel insights into brain plasticity and memory.

The effect of anesthesia on the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colorectal cancer in the context of an enhanced recovery pathway: A prospective cohort study.

ABSTRACT: There are reports that the use of regional anesthesia (RA) may be associated with better perioperative surgical stress response in cancer patients compared with general anesthetics (GA). However, the role of anesthesia on the magnitude of the postoperative systemic inflammatory response (SIR) in colorectal cancer patients, within an enhanced recovery pathway (ERP), is not clear.The aim of the present study was to examine the effect of anesthesia, within an enhanced recovery pathway, on the magnitude of the postoperative SIR in patients undergoing elective surgery for colorectal cancer.Database of 507 patients who underwent elective open or laparoscopic colorectal cancer surgery between 2015 and 2019 at a single center was studied. The anesthetic technique used was categorized into either GA or GA + RA using a prospective proforma. The relationship between each anesthetic technique and perioperative clinicopathological characteristics was examined using binary logistic regression analysis.The majority of patients were male (54%), younger than 65 years (41%), either normal or overweight (64%), and were nonsmokers (47%). Also, the majority of patients underwent open surgery (60%) and received mainly general + regional anesthetic technique (80%). On univariate analysis, GA + RA was associated with a lower day 4 CRP (≤150/>150 mg/L) concentration. On day 4, postoperative CRP was associated with anesthetic technique [odds ratio (OR) 0.58; confidence interval (CI) 0.31-1.07; P = .086], age (OR 0.70; CI 0.50-0.98; P = .043), sex (OR 1.15; CI 0.95-2.52; P = .074), smoking (OR 1.57; CI 1.13-2.19; P = .006), preoperative mGPS (OR 1.55; CI 1.15-2.10; P = .004), and preoperative dexamethasone (OR 0.70; CI 0.47-1.03; P = .072). On multivariate analysis, day 4 postoperative CRP was independently associated with anesthetic technique (OR 0.56; CI 0.32-0.97; P = .039), age (OR 0.74; CI 0.55-0.99; P = .045), smoking (OR 1.58; CI 1.18-2.12; P = .002), preoperative mGPS (OR 1.41; CI 1.08-1.84; P = .012), and preoperative dexamethasone (OR 0.68; CI 0.50-0.92; P = .014).There was a modest but an independent association between RA and a lower magnitude of the postoperative SIR. Future work is warranted with multicenter RCT to precisely clarify the relationship between anesthesia and the magnitude of the postoperative SIR.