Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

Prospective evaluation of transoral outlet reduction (TORe) after Roux-en-Y gastric bypass (RYGB) failure.

BACKGROUND AND AIMS: Weight regain after RYGB is multifactorial including dilatation of the gastro-jejunal anastomosis. Transoral outlet reduction (TORe) procedure is a minimally invasive alternative to surgical anastomotic revision. METHODS: We conducted a prospective, multicenter, simple blind, randomized study in patients with weight regain following RYGB, comparing the efficacy of conventional nutritional and behavioral management associated with a TORe procedure (TORe group) with conventional management alone and a Sham procedure (Sham group). The main objective of this study was to evaluate the percentage of excess weight loss (%EWL) at 12 months after endoscopy. RESULTS: From January 2015 to January 2019, 73 subjects were randomized in four French Bariatric centers. The final analysis involved 50 subjects, 25 in each group, 44 women, 6 men, with an average BMI of 40.6 kg/m2. At 12 months, the average %EWL was significantly higher in the TORe group than in the Sham group (13.5 ± 14.1 vs. - 0.77 ± 17.1; p = 0.002). Cohen's d was 0.91, indicating a large effect size of the procedure on the %EWL. There was no significant difference between groups concerning the improvement of obesity-related comorbidities (diabetes and dyslipidemia) and quality of life at 12 months. We report frequent adverse events in the TORe group (20% had adverse events related to the procedure). Three adverse events were serious, including two perforations of the gastro-jejunal anastomosis after TORe group that led to the premature termination of the study. CONCLUSIONS: After RYGBP failure linked to the dilatation of the gastro-jejunal anastomosis, TORe procedure with nutritional management results in significantly higher %EWL at 12 months compared to patients with nutritional management alone. As surgery, this minimally invasive endoscopic procedure can be associated with severe adverse events.

Analysis of the effect of staple line reinforcement on leaking and bleeding after sleeve gastrectomy from the UK National Bariatric Surgery Registry.

INTRODUCTION: Sleeve gastrectomy (SG) is currently the most frequently performed procedure for obesity worldwide. Staple line reinforcement (SLR) has been suggested as a strategy to reduce the risk of staple line leak or bleeding; however, its use for SG in the United Kingdom (UK) is unknown. This study examined the effect of SLR on the development of postoperative complications from SG using a large national dataset from the UK. METHODS: Patients undergoing either primary or revision SG over 10 years from Jan 2012 to Dec 2021 were identified by the National Bariatric Surgery Registry. Comparative and logistic regression analyses were undertaken to determine the effect of SLR on staple line leak and bleeding. RESULTS: During this time, 14,231 patients underwent SG for whom there were complete data. Of these, 76.5% were female and the median age was 46 years (IQR: 36-53). The rate of surgical complications was 2.3% (n = 219/14,231). The incidence of bleeding was 1.3% (n = 179/14,231) and leak was 1.0% (n = 140/14,231). Over time, the use of SLR of any variety declined significantly from 99.7% in 2012 to 57.3% in 2021 (p < 0.001). Multivariable (adjusted) regression analysis demonstrated that neither the use of nor the type of reinforcement had any effect on the rate of bleeding or leaking. CONCLUSION: SLR for SG has declined in the UK since 2012. There were no differences in staple line leak or bleed with or without reinforcement.

Bariatric-metabolic surgery for NHS patients with type 2 diabetes in the United Kingdom National Bariatric Surgery Registry.

AIM: Bariatric-metabolic surgery is approved by the National Institute of Health and Care Excellence (NICE) for people with severe obesity and type 2 diabetes (T2DM) (including class 1 obesity after 2014). This study analysed baseline characteristics, disease severity and operations undertaken in people with obesity and T2DM undergoing bariatric-metabolic surgery in the UK National Health Service (NHS) compared to those without T2DM. METHODS: Baseline characteristics, trends over time and operations undertaken were analysed for people undergoing primary bariatric-metabolic surgery in the NHS using the National Bariatric Surgical Registry (NBSR) for 11 years from 2009 to 2019. Clinical practice before and after the publication of the NICE guidance (2014) was examined. Multivariate logistic regression was used to determine associations with T2DM status and the procedure undertaken. RESULTS: 14,948/51,715 (28.9%) participants had T2DM, with 10,626 (71.1%) on oral hypoglycaemics, 4322 (28.9%) on insulin/other injectables, and with T2DM diagnosed 10+ years before surgery in 3876 (25.9%). Participants with T2DM, compared to those without T2DM, were associated with older age (p < 0.001), male sex (p < 0.001), poorer functional status (p < 0.001), dyslipidaemia (OR: 3.58 (CI: 3.39-3.79); p < 0.001), hypertension (OR: 2.32 (2.19-2.45); p < 0.001) and liver disease (OR: 1.73 (1.58-1.90); p < 0.001), but no difference in body mass index was noted. Fewer people receiving bariatric-metabolic surgery after 2015 had T2DM (p < 0.001), although a very small percentage increase of those with class I obesity and T2DM was noted. Gastric bypass was the commonest operation overall. T2DM status was associated with selection for gastric bypass compared to sleeve gastrectomy (p < 0.001). CONCLUSION: NHS bariatric-metabolic surgery is used for people with T2DM much later in the disease process when it is less effective. National guidance on bariatric-metabolic surgery and data from multiple RCTs have had little impact on clinical practice.

Exercise-induced responses in matrix metalloproteinases and osteopontin are not moderated by exercise format in males with overweight or obesity.

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and -3 (MMP-3), and osteopontin (OPN) are associated with adipose-tissue expansion and development of metabolic disease. The purpose of the current study was to assess the circulating concentration of these markers, along with adiponectin and glucose concentrations, in response to acute exercise in individuals with overweight or obesity. METHODS: Fourteen sedentary males with overweight or obesity (29.0 ± 3.1 kg/m2) completed two separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT) was performed on each day of the trial. Day two of each trial consisted of a single 30 min workload-matched bout of either high-intensity interval exercise (HIIE; alternating 100% and 50% of peak pulmonary oxygen uptake, [Formula: see text]O2peak) or continuous moderate intensity (CME; 60% [Formula: see text]O2peak) cycling completed 1 h prior to the OGTT. Glucose and physical activity were continuously monitored, while MMP-2, MMP-3, OPN and adiponectin were measured pre-, 0 h post-, 1 h post- and 25 h post-exercise. RESULTS: Exercise transiently increased MMP-3 and decreased OPN (both p < 0.01), but not MMP-2 or adiponectin. There were no differences in the response of inflammatory markers to the different exercise formats. Exercise increased mean daily glucose concentration and area under the glucose curve during the OGTT on Day 2 and Day 3 (main effect of time; p < 0.05). CONCLUSION: Acute cycling exercise decreased OPN, which is consistent with longer term improvements in cardiometabolic health and increased MMP-3, which is consistent with its role in tissue remodelling. Interestingly, exercise performed prior to the morning OGTT augmented the glucose concentrations in males. TRIAL REGISTRATION: ACTRN12613001086752.

Results of the ARROW survey of anti-reflux practice in the United Kingdom.

Gastro-esophageal reflux disease (GERD) is a common, significant health burden. United Kingdom guidance states that surgery should be considered for patients with a diagnosis of GERD not suitable for long-term acid suppression. There is no consensus on many aspects of patient pathways and optimal surgical technique, and an absence of information on how patients are currently selected for surgery. Further detail on the delivery of anti-reflux surgery (ARS) is required. A United Kingdom-wide survey was designed to gather surgeon opinion regarding pre-, peri- and post-operative practice of ARS. Responses were received from 155 surgeons at 57 institutions. Most agreed that endoscopy (99%), 24-hour pH monitoring (83%) and esophageal manometry (83%) were essential investigations prior to surgery. Of 57 units, 30 (53%) had access to a multidisciplinary team to discuss cases; case-loads were higher in those units (median 50 vs. 30, P < 0.024). The most popular form of fundoplication was a Nissen posterior 360° (75% of surgeons), followed by a posterior 270° Toupet (48%). Only seven surgeons stated they had no upper limit of body mass index prior to surgery. A total of 46% of respondents maintain a database of their practice and less than a fifth routinely record quality of life scores before (19%) or after (14%) surgery. While there are areas of consensus, a lack of evidence to support workup, intervention and outcome evaluation is reflected in the variability of practice. ARS patients are not receiving the same level of evidence-based care as other patient groups.

Skin-Microbiome Assembly in Preterm Infants during the First Three Weeks of Life and Impact of Topical Coconut Oil Application.

The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, data on early-life skin-microbiome succession and potential effects of emollient skin care in preterm infants are scarce. We therefore collected skin-microbiome samples from the ear, axilla, and groin on days 1, 7, 14, and 21 from preterm infants born <30 weeks of gestation as part of a randomized clinical trial of standard skin care vs. topical coconut oil. We found that within-sample microbiome diversity was highest on day 1 after birth, with a subsequent decline and emergence of Staphylococcus genus dominance from day 7. Moreover, microbiome assembly was less diverse in infants receiving coconut oil vs. standard skin care. Our study provides novel data on preterm-infant skin-microbiome composition and highlights the modifying potential of emollient skin care.

Molecular Methodologies for Improved Polymicrobial Sepsis Diagnosis.

Polymicrobial sepsis is associated with worse patient outcomes than monomicrobial sepsis. Routinely used culture-dependent microbiological diagnostic techniques have low sensitivity, often leading to missed identification of all causative organisms. To overcome these limitations, culture-independent methods incorporating advanced molecular technologies have recently been explored. However, contamination, assay inhibition and interference from host DNA are issues that must be addressed before these methods can be relied on for routine clinical use. While the host component of the complex sepsis host-pathogen interplay is well described, less is known about the pathogen's role, including pathogen-pathogen interactions in polymicrobial sepsis. This review highlights the clinical significance of polymicrobial sepsis and addresses how promising alternative molecular microbiology methods can be improved to detect polymicrobial infections. It also discusses how the application of shotgun metagenomics can be used to uncover pathogen/pathogen interactions in polymicrobial sepsis cases and their potential role in the clinical course of this condition.

Look Who's Talking: Host and Pathogen Drivers of Staphylococcus epidermidis Virulence in Neonatal Sepsis.

Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis, a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality.

Impaired Cytokine Responses to Live Staphylococcus epidermidis in Preterm Infants Precede Gram-positive, Late-onset Sepsis.

BACKGROUND: Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS. METHODS: We conducted a prospective, observational cohort study of preterm infants (<30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay. RESULTS: Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis-induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor-α) and the regulatory cytokine IL-10. CONCLUSIONS: Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted.

The impact of cytokine levels in young South African children with and without HIV-associated acute lower respiratory infections.

Altered host immune responses are considered to play a key role in the pathogenesis of acute lower respiratory infections (ALRI). The existing literature on cytokine responses in ALRI is largely focussed on adults from developed countries and there are few reports describing the role of cytokines in childhood ALRI, particularly in African or human immunodeficiency virus (HIV)-infected populations. To measure systemic cytokine levels in blood plasma from young South African children with and without ALRI and with and without HIV to determine associations between cytokine responses and disease status and respiratory viral identification. Blood plasma samples were collected from 106 hospitalized ALRI cases and 54 non-ALRI controls less than 2 years of age. HIV status was determined. Blood plasma concentrations of 19 cytokines, 7 chemokines, and 4 growth factors (epidermal growth factor, fibroblast growth factor-basic, hepatocyte growth factor, and vascular endothelial) were measured using The Human Cytokine 30-Plex Panel. Common respiratory viruses were identified by PCR. Mean cytokine concentrations for G-CSF, interferon (IFN)-γ, interleukin (IL)-5, and MCP-1 were significantly higher in ALRI cases than in nonrespiratory controls. Within the ALRI cases, several cytokines were higher in children with a virus compared with children without a virus. Mean cytokine concentrations for IFN-α, IFN-γ, IL-4, IL-5, IL-13, tumour necrosis factor-α, and MIP-1α were significantly lower in HIV-infected cases than in HIV-uninfected cases, while IP-10 and monokine induced by interferon-γ were significantly higher in HIV-infected cases than in HIV-uninfected cases. Certain cytokines are likely to play an important role in the host immune response to ALRI. HIV-infected children have impaired inflammatory responses to respiratory infections compared with HIV-uninfected children.

Plasma secretory phospholipase A2 as an early marker for late-onset sepsis in preterm infants-a pilot study.

Preterm infants are particularly susceptible to bacterial late-onset sepsis (LOS). Diagnosis by blood culture and inflammatory markers have sub-optimal sensitivity and specificity and prolonged reporting times. There is an urgent need for more rapid, accurate adjunctive diagnostics in LOS to improve management and minimise antibiotic exposure. We measured the diagnostic performance of secretory phospholipase A2 type IIA (sPLA2-IIA) in very preterm infants (<30 weeks gestational age) with suspected LOS. Plasma sPLA2-IIA levels were elevated in infants with LOS (n = 28) compared to those without LOS (n = 21; median 30,970 vs. 2534 pg/ml, p < 0.0001). The mean area under the curve was 0.884 (95% CI: 0.771, 0.977) with a sensitivity of 0.907 (95% CI: 0.667, 1.00) and specificity of 0.804 (95% CI: 0.600, 1.00). The positive and negative predictive values were 0.833 (95% CI: 0.664, 0.927) and 0.842 (95% CI: 0.624, 0.945), respectively. This pilot study suggests that sPLA2-IIA may have clinical utility for the early diagnosis of LOS in very preterm infants, potentially informing clinical management and antibiotic stewardship.

A multicenter prospective audit to investigate the current management of patients undergoing anti-reflux surgery in the UK: Audit & Review of Anti-Reflux Operations & Workup.

BACKGROUND: There are a variety of surgical and endoscopic interventions available to treat gastroesophageal reflux disease. There is, however, no consensus on which approach is best.The aim of this national audit is to describe the current variation in the UK clinical practice in relation to anti-reflux surgery (ARS) and to report adherence to available clinical guidelines. METHODS: This national audit will be conducted at centers across the UK using the secure online web platform ALEA. The study will comprise two parts: a registration questionnaire and a prospective multicenter audit of ARS. All participating centers will be required to complete the registration questionnaire comprising details regarding pre-, peri-, and post-operative care pathways and whether or not these are standardized within each center. Following this, a 12-month multicenter prospective audit will be undertaken to capture data including patient demographics, predominant symptoms, preoperative investigations, surgery indication, intraoperative details, and postoperative outcomes within the first 90 days.Local teams will retain access to their own data to facilitate local quality improvement. The full dataset will be reported at national and international scientific congresses and will contribute to peer-reviewed publications and national quality improvement initiatives. CONCLUSIONS: This study will identify and explore variation in the processes and outcomes following ARS within the UK using a collaborative cohort methodology. The results generated by this audit will facilitate local and national quality improvement initiatives and generate new possibilities for future research in anti-reflux interventions.

Vancomycin Is Protective in a Neonatal Mouse Model of Staphylococcus epidermidis-Potentiated Hypoxic-Ischemic Brain Injury.

Infection is correlated with increased risk of neurodevelopmental sequelae in preterm infants. In modeling neonatal brain injury, Toll-like receptor agonists have often been used to mimic infections and induce inflammation. Using the most common cause of bacteremia in preterm infants, Staphylococcus epidermidis, we present a more clinically relevant neonatal mouse model that addresses the combined effects of bacterial infection together with subsequent hypoxic-ischemic brain insult. Currently, there is no neuroprotective treatment for the preterm population. Hence, we tested the neuroprotective effects of vancomycin with and without adjunct therapy using the anti-inflammatory agent pentoxifylline. We characterized the effects of S. epidermidis infection on the inflammatory response in the periphery and the brain, as well as the physiological changes in the central nervous system that might affect neurodevelopmental outcomes. Intraperitoneal injection of postnatal day 4 mice with a live clinical isolate of S. epidermidis led to bacteremia and induction of proinflammatory cytokines in the blood, as well as transient elevations of neutrophil and monocyte chemotactic cytokines and caspase 3 activity in the brain. When hypoxia-ischemia was induced postinfection, more severe brain damage was observed in infected animals than in saline-injected controls. This infection-induced inflammation and potentiated brain injury was inoculum dose dependent and was alleviated by the antibiotic vancomycin. Pentoxifylline did not provide any additional neuroprotective effect. Thus, we show for the first time that live S. epidermidis potentiates hypoxic-ischemic preterm brain injury and that peripheral inhibition of inflammation with antibiotics, such as vancomycin, reduces the extent of brain injury.

Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.

BACKGROUND: Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life. METHODS: Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay. RESULTS: cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1ß, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis. CONCLUSIONS: The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.

Acceptable outcomes after fundoplication-different views are held by patients, GPs, and surgeons.

Antireflux surgery aims to improve quality of life. However, whether patients and clinicians agree on what this means, and what is an acceptable outcome following fundoplication, is unknown. This study used clinical scenarios pertinent to laparoscopic fundoplication for gastroesophageal reflux to define acceptable outcomes from the perspective of patients, surgeons, and general practitioners (GPs). Patients who had previously undergone a laparoscopic fundoplication, general practitioners, and esophagogastric surgeons were invited to rank 11 clinical scenarios of outcomes following laparoscopic fundoplication for acceptability. Clinicopathological and practice variables were collated for patients and clinicians, respectively. GPs and esophagogastric surgeons additionally were asked to estimate postfundoplication outcome probabilities. Descriptive and multivariate statistical analyses were undertaken to examine for associations with acceptability. Reponses were received from 331 patients (36.4% response rate), 93 GPs (13.4% response), and 60 surgeons (36.4% response). Bloating and inability to belch was less acceptable and dysphagia requiring intervention more acceptable to patients compared to clinicians. On regression analysis, female patients found bloating to be less acceptable (OR: 0.51 [95%CI: 0.29-0.91]; P = 0.022), but dysphagia more acceptable (OR: 1.93 [95%CI: 1.17-3.21]; P = 0.011). Postfundoplication estimation of reflux resolution was higher and that of bloating was lower for GPs compared to esophagogastric surgeons. Patients and clinicians have different appreciations of an acceptable outcome following antireflux surgery. Female patients are more concerned about wind-related side effects than male patients. The opposite holds true for dysphagia. Surgeons and GPs differ in their estimation of event probability for patient recovery following antireflux surgery, and this might explain their differing considerations of acceptable outcomes.

Intraoperative Sentinel Node Mapping in the Colon: Potential and Pitfalls.

Sentinel lymph node mapping (SLNM) may play a significant role in future delivery of colon cancer surgery because of an increase in early-stage, node-negative disease due to national bowel cancer screening programmes. Traditionally, colon lymphatic drainage has not been thought relevant as the operative approach cannot be tailored. Recent advances in local and endoscopic risk-reducing interventions for colonic malignancy have caused a rethink in approach. SLNM was initially attempted with blue dye techniques with limited success. Technological improvement has allowed surgeons to use near-infrared (NIR) light and NIR active tracers such as indocyanine green. This review provides an overview of the current status of intraoperative lymph node mapping in the colon, identifies challenges to the delivery of the techniques, and discusses potential solutions that may help SLNM play a role in improving the delivery of surgical care for patients with colon cancer.

Erratum to: Enhanced Recovery After Surgery Interactive Audit System: 10 Years' Experience with an International Web-Based Clinical and Research Perioperative Care Database.

[This corrects the article DOI: 10.1055/s-0038-1673357.].

Enhanced Recovery After Surgery Interactive Audit System: 10 Years' Experience with an International Web-Based Clinical and Research Perioperative Care Database.

The Enhanced Recovery After Surgery (ERAS) is a managed care program that has shown the ability to reduce complications following elective colorectal surgery. In 2006, the ERAS ® Society developed the ERAS ® Interactive Audit System (EIAS), which has allowed centers in over 20 countries to enter perioperative patient data to benchmark against international practice within the audit system and act as a stimulus for quality improvement. The de-identified patient data are coded in SQL (a relational database), stored on secure servers, and data governance aspects have been secured in all involved countries. A collaborative approach is undertaken within involved units toward research questions with published cohort data from the audit system having demonstrated the importance of overall compliance on improving patient outcomes and less cost of care. The EIAS has shown that collaborative clinical effort can drive quality improvement in a short time frame in an international context.

Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis.

Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here, we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and postchallenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis-exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis-exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens.