Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Effectiveness of Prehabilitation Modalities on Postoperative Outcomes Following Colorectal Cancer Surgery: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: Postoperative morbidity in patients undergoing curative colorectal cancer surgery is high. Prehabilitation has been suggested to reduce postoperative morbidity, however its effectiveness is still lacking. OBJECTIVE: The aim of this study was to investigate the effectiveness of prehabilitation in reducing postoperative morbidity and length of hospital stay in patients undergoing colorectal cancer surgery. METHODS: A comprehensive electronic search was conducted in the CINAHL, Cochrane Library, Medline, PsychINFO, AMED, and Embase databases from inception to April 2023. Randomised controlled trials testing the effectiveness of prehabilitation, including exercise, nutrition, and/or psychological interventions, compared with usual care in patients undergoing colorectal cancer surgery were included. Two independent review authors extracted relevant information and assessed the risk of bias. Random-effect meta-analyses were used to pool outcomes, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. RESULTS: A total of 23 trials were identified (N = 2475 patients), including multimodal (3 trials), exercise (3 trials), nutrition (16 trials), and psychological (1 trial) prehabilitation. There was moderate-quality evidence that preoperative nutrition significantly reduced postoperative infectious complications (relative risk 0.65, 95% confidence interval [CI] 0.45-0.94) and low-quality evidence on reducing the length of hospital stay (mean difference 0.87, 95% CI 0.17-1.58) compared with control. A single trial demonstrated an effect of multimodal prehabilitation on postoperative complication. CONCLUSION: Nutrition prehabilitation was effective in reducing infectious complications and length of hospital stay. Whether other multimodal, exercise, and psychological prehabilitation modalities improve postoperative outcomes after colorectal cancer surgery is uncertain as the current quality of evidence is low. PROTOCOL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/VW72N ).

Sustainable Calcite Scale Inhibitors via Oxidation of Lignosulfonates.

Deposition of inorganic scales in wells, flow lines, and equipment is a major problem in the water treatment, geothermal, or upstream oil and gas industries. Deployment of scale inhibitors has been adopted worldwide for oilfield scale prevention. Commercial synthetic scale inhibitors such as polymeric carboxylates and sulfonates or nonpolymeric phosphonates offer good scale inhibition performance but often suffer from one or more limitations including biodegradability, calcium compatibility, and thermal stability. Lignin-based biomaterials such as sodium lignosulfonates are natural, sustainable, and widely available polymers that are accepted for use in environmentally sensitive areas. Here we show that, although lignosulfonates perform relatively poorly as calcite scale inhibitors in dynamic tube blocking tests, oxidized lignosulfonates show a much improved inhibition effect by a factor of 20-fold. The oxidized lignosulfonates are easy to prepare in a 1-step reaction and show excellent calcium compatibility and thermal stability, useful for downhole squeeze treatments in high temperature wells. This present study unequivocally establishes oxidized lignosulfonates as a new class of sustainable green scale inhibitors, thereby bridging the gap between materials derived directly from nature and the classic synthetic polymeric scale inhibitors.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Karyotypic Reshuffling in the Genus Rhipidomys (Rodentia: Cricetidae: Sigmodontinae) Revealed by Zoo-FISH.

INTRODUCTION: Rhipidomys is the second most specious and the most widespread genus of the tribe Thomasomyini. Chromosomal data have been an important tool in the taxonomy of the group that presents low variability of diploid number (2n) and highly variable fundamental numbers (FNs). Despite such diversity, the genus has been studied mainly by classical and banding cytogenetic techniques. METHODS: This study performed a comparative study between R. emiliae (2n = 44, FN = 52), R. macrurus (2n = 44, FN = 49), R. nitela (2n = 50, FN = 71), and R. mastacalis (2n = 44, FN = 72) using chromosome painting probes of two Oryzomyini species. RESULTS: Our analysis revealed pericentric inversion as the main rearrangement involved in the karyotype evolution of the group, although tandem fusions/fissions were also detected. In addition, we detected eight syntenic associations exclusive of the genus Rhipidomys, and three syntenic associations shared between species of the tribe Thomasomyini and Oryzomyini. CONCLUSION: Comparative cytogenetic analysis by ZOO-FISH on genus Rhipidomys supports a pattern of chromosomal rearrangement already suggested by comparative G-banding. However, the results suggest that karyotype variability in the genus could also involve the occurrence of an evolutionary new centromere.

Prominent tauopathy and intracellular ß-amyloid accumulation triggered by genetic deletion of cathepsin D: implications for Alzheimer disease pathogenesis.

BACKGROUND: Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid-ß protein (Aß) and the microtubule-associated protein, tau, which accumulate pathognomonically in Alzheimer disease (AD), but few studies have examined the role of CatD in the development of Aß pathology and tauopathy in vivo. METHODS: CatD knockout (KO) mice were crossed to human amyloid precursor protein (hAPP) transgenic mice, and amyloid burden was quantified by ELISA and immunohistochemistry (IHC). Tauopathy in CatD-KO mice, as initially suggested by Gallyas silver staining, was further characterized by extensive IHC and biochemical analyses. Controls included human tau transgenic mice (JNPL3) and another mouse model of a disease (Krabbe A) characterized by pronounced lysosomal dysfunction. Additional experiments examined the effects of CatD inhibition on tau catabolism in vitro and in cultured neuroblastoma cells with inducible expression of human tau. RESULTS: Deletion of CatD in hAPP transgenic mice triggers large increases in cerebral Aß, manifesting as intense, exclusively intracellular aggregates; extracellular Aß deposition, by contrast, is neither triggered by CatD deletion, nor affected in older, haploinsufficient mice. Unexpectedly, CatD-KO mice were found to develop prominent tauopathy by just ∼ 3 weeks of age, accumulating sarkosyl-insoluble, hyperphosphorylated tau exceeding the pathology present in aged JNPL3 mice. CatD-KO mice exhibit pronounced perinuclear Gallyas silver staining reminiscent of mature neurofibrillary tangles in human AD, together with widespread phospho-tau immunoreactivity. Striking increases in sarkosyl-insoluble phospho-tau (∼ 1250%) are present in CatD-KO mice but notably absent from Krabbe A mice collected at an identical antemortem interval. In vitro and in cultured cells, we show that tau catabolism is slowed by blockade of CatD proteolytic activity, including via competitive inhibition by Aß42. CONCLUSIONS: Our findings support a major role for CatD in the proteostasis of both Aß and tau in vivo. To our knowledge, the CatD-KO mouse line is the only model to develop detectable Aß accumulation and profound tauopathy in the absence of overexpression of hAPP or human tau with disease-associated mutations. Given that tauopathy emerges from disruption of CatD, which can itself be potently inhibited by Aß42, our findings suggest that impaired CatD activity may represent a key mechanism linking amyloid accumulation and tauopathy in AD.

Targeting fusion oncoproteins in childhood cancers: challenges and future opportunities for developing therapeutics.

Fusion oncoproteins are associated with childhood cancers and have proven challenging to target, aside from those that include kinases. As part of its efforts for targeting childhood cancers, the National Cancer Institute recently conducted a series on Novel Chemical Approaches for Targeting Fusion Oncoproteins. Key learnings on leading platforms and technologies that can be used to advance the development of molecular therapeutics that target fusion oncoproteins in childhood cancers are described. Recent breakthroughs in medicinal chemistry and chemical biology provide new ground and creative strategies to exploit for the development of targeted agents for improving outcomes against these recalcitrant cancers.

Mental Health Concerns During COVID-19: An Observational Study Among a Predominantly Black Community in New York City.

PURPOSE: This study examined the prevalence of mental health concerns and its association with COVID-19, selected social determinants of health, and psychosocial risk factors in a predominantly racial/ethnic minoritized neighborhood in New York City. METHODS: Adult Harlem residents (N = 393) completed an online cross-sectional survey from April to September 2021. The Patient Health Questionnaire (PHQ-4) and the Post-Traumatic Stress Disorder (PC-PTSD) were used to evaluate mental health concerns. Poisson regression with robust variance quantified the associations of interests via prevalence ratios (PR) and 95% confidence intervals (CI). RESULTS: Two-thirds (66.4%) of the residents reported experiencing mental health concerns, including PTSD (25.7%), depression (41.2%), and anxiety (48.1%). Residents with low-income housing status (PR = 1.16; 95% CI 1.01, 1.34), alcohol misuse (PR = 1.68; 95% CI 1.40, 2.01), food insecurity (PR = 1.23; 95% CI 1.07, 1.42), exposure to interpersonal violence (PR = 1.33; 95% CI 1.08, 2.65), and experience of discrimination (PR = 1.53, 95% CI 1.23-1.92) were more likely to report mental health concerns. Better community perception of the police (PR = 0.97, 95% CI 0.95, 0.99) was associated with fewer mental health concerns. No associations were observed for employment insecurity, housing insecurity, or household COVID-19 positivity with mental health concerns. CONCLUSIONS: This study showed a high prevalence of mental health concerns in a low-income racial/ethnic minoritized community, where COVID-19 and social risk factors compounded these concerns. Harlem residents face mental health risks including increased financial precarity, interpersonal violence, and discrimination exposure. Interventions are needed to address these concurrent mental health and psychosocial risk factors, particularly in racial/ethnic minoritized residents.

Activating a high-spin iron(II) complex to thermal spin-crossover with an inert non-isomorphous molecular dopant.

[Fe(bpp)2][ClO4]2 (bpp = 2,6-bis{pyrazol-1-yl}pyridine; monoclinic, C2/c) is high-spin between 5-300 K, and crystallises with a highly distorted molecular geometry that lies along the octahedral-trigonal prismatic distortion pathway. In contrast, [Ni(bpp)2][ClO4]2 (monoclinic, P21) adopts a more regular, near-octahedral coordination geometry. Gas phase DFT minimisations (ω-B97X-D/6-311G**) of [M(bpp)2]2+ complexes show the energy penalty associated with that coordination geometry distortion runs as M2+ = Fe2+ (HS) ≈ Mn2+ (HS) < Zn2+ ≈ Co2+ (HS) ≲ Cu2+ ≪ Ni2+ ≪ Ru2+ (LS; HS = high-spin, LS = low-spin). Slowly crystallised solid solutions [FexNi1-x(bpp)2][ClO4]2 with x = 0.53 (1a) and 0.74 (2a) adopt the P21 lattice, while x = 0.87 (3a) and 0.94 (4a) are mixed-phase materials with the high-spin C2/c phase as the major component. These materials exhibit thermal spin-transitions at T½ = 250 ± 1 K which occurs gradually in 1a, and abruptly and with narrow thermal hysteresis in 2a-4a. The transition proceeds to 100% completeness in 1a and 2a; that is, the 26% Ni doping in 2a is enough to convert high-spin [Fe(bpp)2][ClO4]2 into a cooperative, fully SCO-active material. These results were confirmed crystallographically for 1a and 2a, which revealed similarities and differences between these materials and the previously published [FexNi1-x(bpp)2][BF4]2 series. Rapidly precipitated powders with the same compositions (1b-4b) mostly resemble 1a-4a, except that 2b is a mixed-phase material; 2b-4b also contain a fraction of amorphous solid in addition to the two crystal phases. The largest iron fraction that can be accommodated by the P21 phase in this system is 0.7 ± 0.1.

Link among apolipoprotein E E4, gait, and cognition in neurodegenerative diseases: ONDRI study.

INTRODUCTION: Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS: Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. RESULTS: APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non-APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain-specific poorer cognitive performances, mediated by smaller gray matter volume. DISCUSSION: Gait slowness in APOE E4 carriers with neurodegenerative diseases may indicate extensive gray matter changes associated with poor cognition. HIGHLIGHTS: APOE E4 and slow gait are risk factors for cognitive decline in neurodegenerative diseases. Slow gait and smaller gray matter volumes are associated, independently of APOE E4. Worse cognition in APOE E4 carriers with slow gait is explained by smaller GM volume. Gait slowness in APOE E4 carriers indicates poorer cognition-related brain changes.

Comparing the Kinetic Hydrate Inhibition Performance of Linear versus Branched Polymers.

Kinetic hydrate inhibitors (KHIs) are a chemical method of preventing gas hydrate plugging of oil and gas production flow lines. The main ingredient in a KHI formulation is one or more water-soluble amphiphilic polymers. Poly(N-vinyl caprolactam) (PVCap) is an unbranched polymer and a well-known industrial KHI, often used as a yardstick to compare the performance of new polymers. The effect of branching PVCap on KHI performance has been investigated by polymerizing the VCap monomer in the presence of varying amounts of trimethylolpropane triacrylate, pentaerythritol tetraacrylate, or bis-pentaerythritol hexaacrylate cross-linkers to give PVCap polymers with 3, 4, and 6 branches, respectively. If the ratio of cross-linker to VCap was too high (6:1 to 8:1), gelling and/or poor water solubility was observed, giving short polymer chains and poor KHI efficacy. For higher ratios (30:1 to 60:1), it was found that the concentration of the polymer needed to give total inhibition of structure II tetrahydrofuran hydrate crystal growth could be lowered by using tribranched rather than linear PVCap. Slow constant cooling (1 °C/h) gas hydrate experiments with a synthetic natural gas in steel rocking cells at 76 bar were also carried out. A small improvement in KHI performance was observed for one of the branched PVCaps compared with a linear PVCap. Branched and linear poly(N-isopropylmethacrylamide) (PNIPMAm) polymers were also investigated in the gas hydrate system, but there was no benefit observed when branching this polymer class.

International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

Detection of Felis catus Gammaherpesvirus 1 in Domestic Cat Saliva: Prevalence, Risk Factors, and Attempted Virus Isolation.

Felis catus gammaherpesvirus 1 (FcaGHV1) infects domestic cats worldwide, yet it has not been successfully propagated in cell culture, and little is known about how it is shed and transmitted. To investigate the salivary shedding of FcaGHV1, we quantified FcaGHV1 DNA in feline saliva by qPCR. For FcaGHV1-positive saliva, we sequenced a portion of the viral glycoprotein B (gB) gene and attempted to isolate the infectious virus by passage in several felid and non-felid cell lines. We detected FcaGHV1 DNA in 45/227 (19.8%) saliva samples with variable viral DNA loads from less than 100 to greater than 3 million copies/mL (median 4884 copies/mL). Multiple saliva samples collected from an infected cat over a two-month period were consistently positive, indicating that chronic shedding can occur for at least two months. Cat age, sex, and health status were not associated with shedding prevalence or viral DNA load in saliva. Feral status was also not associated with shedding prevalence. However, feral cats had significantly higher FcaGHV1 DNA load than non-feral cats. Sequencing of FcaGHV1 gB showed low sequence diversity and >99.5% nucleotide identity to the worldwide consensus FcaGHV1 gB sequence. We did not detect virus replication during the passage of FcaGHV1-positive saliva in cell culture, as indicated by consistently negative qPCR on cell lysate and supernatant. To our knowledge, these data show for the first time that cats in Canada are infected with FcaGHV1. The data further suggest that shedding of FcaGHV1 in saliva is common, can occur chronically over an extended period of time, and may occur at higher levels in feral compared to non-feral cats.

In vivo activity of the second-generation proteasome inhibitor ixazomib against pediatric T-cell acute lymphoblastic leukemia xenografts.

The overall survival rate of patients with T-cell acute lymphoblastic leukemia (T-ALL) is now 90%, although patients with relapsed T-ALL face poor prognosis. The ubiquitin-proteasome system maintains normal protein homeostasis, and aberrations in this pathway are associated with T-ALL. Here we demonstrate the in vitro and in vivo activity of ixazomib, a second-generation orally available, reversible, and selective proteasome inhibitor against pediatric T-ALL cell lines and patient-derived xenografts (PDXs) grown orthotopically in immunodeficient NOD.Cg-PrkdcscidIL2rgtm1Wjl/SzJAusb (NSG) mice. Ixazomib was highly potent in vitro, with half-maximal inhibitory concentration (IC50) values in the low nanomolar range. As a monotherapy, ixazomib significantly extended mouse event-free survival of five out of eight T-ALL PDXs in vivo.

Preparing for and Not Waiting for Surgery.

Cancer surgery is an essential treatment strategy but can disrupt patients' physical and psychological health. With worldwide demand for surgery expected to increase, this review aims to raise awareness of this global public health concern, present a stepwise framework for preoperative risk evaluation, and propose the adoption of personalised prehabilitation to mitigate risk. Perioperative medicine is a growing speciality that aims to improve clinical outcome by preparing patients for the stress associated with surgery. Preparation should begin at contemplation of surgery, with universal screening for established risk factors, physical fitness, nutritional status, psychological health, and, where applicable, frailty and cognitive function. Patients at risk should undergo a formal assessment with a qualified healthcare professional which informs meaningful shared decision-making discussion and personalised prehabilitation prescription incorporating, where indicated, exercise, nutrition, psychological support, 'surgery schools', and referral to existing local services. The foundational principles of prehabilitation can be adapted to local context, culture, and population. Clinical services should be co-designed with all stakeholders, including patient representatives, and require careful mapping of patient pathways and use of multi-disciplinary professional input. Future research should optimise prehabilitation interventions, adopting standardised outcome measures and robust health economic evaluation.

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.