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.

Efficacy of Nissen Sleeve Gastrectomy on Mid-term Barrett's Esophagus Regression.

INTRODUCTION: Sleeve gastrectomy is the most commonly performed bariatric operation globally. The main complication is GERD. In the medium term, it can increase the incidence of Barrett's esophagus (BE), which is a risk factor for esophageal adenocarcinoma. Following conventional sleeve gastrectomy, BE is noted in up to 16% of patients postoperatively. Recently, Nissen sleeve gastrectomy (NSG) has been shown to reduce the frequency of postoperative GERD compared to conventional sleeve gastrectomy. This study aims to evaluate the impact of NSG on the incidence and remission of BE in the long term. MATERIAL AND METHOD: This bicentric retrospective study included 692 patients who received NSG from September 2013 to July 2021. All patients underwent preoperative upper GI endoscopy and were then scheduled to receive upper GI endoscopy between 1 and 2 years and then between 3 and 5 years postoperatively. BE was systematically confirmed by biopsies. RESULTS: Seventy-four patients had endoscopic suspicion of BE, which was confirmed on 54/692 patients by histology. The BE lesions consisted of 18.5% intestinal metaplasia and 75.9% fundal metaplasia. Among these 54 patients, 38 underwent endoscopic investigation within 2 years postoperatively. The biopsies showed healed BE in 25/38 patients (64.1%). At 5 years, two patients had proven BE. Concerning the incidence of BE post NSG: 234 performed the follow-up endoscopy within 2 years. The incidence of de novo BE is nil. CONCLUSION: The NSG is associated with healing of known BE in approximately two-thirds of patients at 2-year follow-up. This is consistent with the GERD improvement that has been shown with NSG.

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.

Bariatric surgery provision in response to the COVID-19 pandemic: retrospective cohort study of a national registry.

BACKGROUND: When surgery resumed following the outbreak of the COVID-19 pandemic, guidelines recommended the prioritization of patients with greater obesity-related co-morbidities and/or higher body mass index. OBJECTIVE: The aim of this study was to record the effect of the pandemic on total number, patient demographics, and perioperative outcomes of elective bariatric surgery patients in the United Kingdom. SETTING AND METHODS: The United Kingdom National Bariatric Surgical Registry was used to identify patients who underwent elective bariatric surgery during the pandemic (1 yr from April 1, 2020). Characteristics of this group were compared with those of a pre-pandemic cohort. Primary outcomes were case volume, case mix, and providers. National Health Service cases were analyzed for baseline health status and perioperative outcomes. Fisher exact, χ2, and Student t tests were used as appropriate. RESULTS: The total number of cases decreased to one third of pre-pandemic volume (8615 to 2930). The decrease in operating volume varied, with 36 hospitals (45%) experiencing a 75%-100% reduction. Cases performed in the National Health Service fell from 74% to 53% (P < .0001). There was no change in baseline body mass index (45.2 ± 8.3 kg/m2 from 45.5 ± 8.3 kg/m2; P = .23) or prevalence of type 2 diabetes (26% from 26%; P = .99). Length of stay (median 2 d) and surgical complication rate (1.4% from 2.0%; relative risk = .71; 95% CI .45-1.12; P = .13) were unchanged. CONCLUSIONS: In the context of a dramatic reduction in elective bariatric surgery due to the COVID-19 pandemic, patients with more severe co-morbidities were not prioritized for surgery. These findings should inform preparation for future crises.

Gene filtering strategies for machine learning guided biomarker discovery using neonatal sepsis RNA-seq data.

Machine learning (ML) algorithms are powerful tools that are increasingly being used for sepsis biomarker discovery in RNA-Seq data. RNA-Seq datasets contain multiple sources and types of noise (operator, technical and non-systematic) that may bias ML classification. Normalisation and independent gene filtering approaches described in RNA-Seq workflows account for some of this variability and are typically only targeted at differential expression analysis rather than ML applications. Pre-processing normalisation steps significantly reduce the number of variables in the data and thereby increase the power of statistical testing, but can potentially discard valuable and insightful classification features. A systematic assessment of applying transcript level filtering on the robustness and stability of ML based RNA-seq classification remains to be fully explored. In this report we examine the impact of filtering out low count transcripts and those with influential outliers read counts on downstream ML analysis for sepsis biomarker discovery using elastic net regularised logistic regression, L1-reguarlised support vector machines and random forests. We demonstrate that applying a systematic objective strategy for removal of uninformative and potentially biasing biomarkers representing up to 60% of transcripts in different sample size datasets, including two illustrative neonatal sepsis cohorts, leads to substantial improvements in classification performance, higher stability of the resulting gene signatures, and better agreement with previously reported sepsis biomarkers. We also demonstrate that the performance uplift from gene filtering depends on the ML classifier chosen, with L1-regularlised support vector machines showing the greatest performance improvements with our experimental data.

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.

A Video-Based Review of Important Technical Concepts in the Nissen-Sleeve Gastrectomy.

PURPOSE: The development of gastroesophageal reflux disease (GERD) is a commonly encountered scenario after sleeve gastrectomy. A recently reported technical amendment to incorporate a Nissen fundoplication is discussed in this multimedia article focussing on optimising outcomes and reducing complications. MATERIALS AND METHODS: An intraoperative video has been edited to demonstrate the Nissen-Sleeve Gastrectomy and important technical considerations in its technical performance. RESULTS: Gastrolysis is performed proximally from 6 cm proximal to the pylorus. Routine full mediastinal mobilisation of the oesophagus (5 cm) is completed. Cruroplasty is routinely performed. A short Nissen fundoplication is completed calibrated on a 37 French bougie and then sleeve gastrectomy is performed. Our team's experience suggests that careful manipulation of the fundus and using reproducible measurements of the fundus are key to completing the fundoplication whilst minimising complications. A control test with mobilisation of the bougie through the wrap is recommended at the end of the procedure. CONCLUSION: The Nissen-Sleeve Gastrectomy, as presented in this video, is safe and has good short-term efficacy outcomes. Longer term and randomised studies are ongoing.

Clinical characteristics of patients undergoing primary bariatric surgery in the United Kingdom based on the National Bariatric Surgery Registry.

Baseline demographic characteristics and operations undertaken for patients having bariatric surgery in the United Kingdom are largely unknown. This study aimed to describe the profile of patients having primary bariatric surgery in the National Health Service (NHS) or by self-pay, and associated operations performed for both pathways. The National Bariatric Surgery Registry dataset for 5 years between January 2015 and December 2019 was used. 34 580 patients underwent primary bariatric surgery, of which 75.9% were NHS patients. Mean patient age and initial body mass index were significantly higher for NHS compared to self-pay patients (mean age 45.8 ± 11.3 [SD] vs. 43.0 ± 12.0 years and initial body mass index 48.0 ± 7.9 vs. 42.9 ± 7.3 kg/m2 , p < .001). NHS patients were more likely to have obesity-related complications compared to self-pay patients: prevalence of Type 2 diabetes mellitus 27.7% versus 8.3%, hypertension 37.1% versus 20.1%, obstructive sleep apnoea 27.4% versus 8.9%, severely impaired functional status 19.3% versus 13.9%, musculoskeletal pain 32.5% versus 20.1% and being on medication for depression 31.0% versus 25.9%, respectively (all p < .001). Gastric bypass was the most commonly performed primary NHS bariatric operation 57.2%, but sleeve gastrectomy predominated in self-pay patients 48.7% (both p < .001). In contrast to self-pay patients, NHS patients are receiving bariatric surgery only once they are older and at a much more advanced stage of obesity-related disease complications.

Prevalence of Overweight and Obesity in France: The 2020 Obepi-Roche Study by the "Ligue Contre l'Obésité".

Obepi-Roche 2020 by the "Ligue Contre l'Obésité" (League Against Obesity) estimated overweight and obesity prevalence in France. The adopted methodology was chosen to be as similar as possible to that of a series of quota-based surveys conducted every three years from 1997 to 2012 (Obepi-Roche studies). The 2020 survey was conducted online from 24th September to 5th October 2020 by the Odoxa polling institute on a sample of metropolitan French subjects aged 18 years or over. Participants (n = 9598) self-measured their height and weight according to detailed instructions. Prevalence estimates were produced for all categories of body mass index. The prevalence of excess weight was 47.3% (17.0% of subjects with obesity), with higher values in the north and east of France. When comparing these 2020 estimates to previous Obepi-Roche estimates in order to visualize trends since 1997, it appeared that overweight fluctuated around 30%, and obesity prevalence increased steadily at a rapid pace. The increase was even steeper in the youngest age groups and for severe and complex obesity. Given the slightly different methodologies between the 1997-2012 studies and the 2020 survey, the worrying trends in obesity prevalence since 1997 must be confirmed, calling for a reedition of the Obepi-Roche series.

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.

A systems biology approach to better understand human tick-borne diseases.

Tick-borne diseases (TBDs) are a growing global health concern. Despite extensive studies, ill-defined tick-associated pathologies remain with unknown aetiologies. Human immunological responses after tick bite, and inter-individual variations of immune-response phenotypes, are not well characterised. Current reductive experimental methodologies limit our understanding of more complex tick-associated illness, which results from the interactions between the host, tick, and microbes. An unbiased, systems-level integration of clinical metadata and biological host data - obtained via transcriptomics, proteomics, and metabolomics - offers to drive the data-informed generation of testable hypotheses in TBDs. Advanced computational tools have rendered meaningful analysis of such large data sets feasible. This review highlights the advantages of integrative system biology approaches as essential for understanding the complex pathobiology of TBDs.

Tough Talks Virtual Simulation HIV Disclosure Intervention for Young Men Who Have Sex With Men: Development and Usability Testing.

BACKGROUND: HIV status disclosure is an important decision with barriers specific to young men who have sex with men (YMSM), who have the highest rates of new HIV infections in the United States. Behavioral and social determinants of the difficulty to disclose can include fear of rejection, stigma, loss of financial stability, and lack of communication skills. Once able to disclose, a person may have increased access to social support and improved informed risk reduction conversations and medication adherence. Despite the known challenges and advantages of disclosure, there are few effective tools supporting this behavior. OBJECTIVE: To address this gap in disclosure interventions, the Tough Talks (TT) app, an mHealth intervention using artificial intelligence (AI)-facilitated role-playing scenarios, was developed for YMSM. This paper reports stages of development of the integrated app and results of the usability testing. METHODS: Building on the successful development and testing of a stand-alone interactive dialogue feature in phases 1-3, we conducted additional formative research to further refine and enhance the disclosure scenarios and develop and situate them within the context of a comprehensive intervention app to support disclosure. We assessed the new iteration for acceptability and relevance in a usability study with 8 YMSM with HIV. Participants completed a presurvey, app modules, and a semistructured qualitative interview. RESULTS: TT content and activities were based on social cognitive theory and disclosure process model framework and expanded to a 4-module curriculum. The AI-facilitated scenarios used dialogue from an utterance database developed using language crowdsourced through a comic book contest. In usability testing, YMSM reported high satisfaction with TT, with 98% (31/33) of activities receiving positive ratings. Participants found the AI-facilitated scenarios and activities to be representative and relevant to their lived experiences, although they noted difficulty having nuanced disclosure conversations with the AI. CONCLUSIONS: TT was an engaging and practical intervention for self-disclosure among YMSM with HIV. Facilitating informed disclosure decisions has the potential to impact engagement in sexual risk behaviors and HIV care. More information is needed about the ideal environment, technical assistance, and clinical support for an mHealth disclosure intervention. TT is being tested as a scalable intervention in a multisite randomized controlled trial to address outstanding questions on accessibility and effect on viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov NCT03414372; https://clinicaltrials.gov/ct2/show/NCT03414372.

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.

Assessing the Activity of Antimicrobial Peptides Against Common Marine Bacteria Located in Rotifer (Brachionus plicatilis) Cultures.

Rotifers are used as the first feed for marine fish larvae and are grown in large cultures that have high loads of organic matter and heterotrophic bacteria; these bacteria are passed on to the developing fish larvae and can potentially lead to bacterial infections. A modified minimum inhibitory concentration (MIC) protocol for antimicrobial peptides was used to determine the potency of ten antimicrobial peptides (AMPs) in artificial seawater relevant to a rotifer culture (salinity of 25‰) against common marine pathogens. All of the AMPs had antimicrobial activity against the bacterial isolates when the salt concentration was approximately zero. However, in high salt concentrations, the majority of the AMPs had an MIC value greater than 65 µg mL-1 in artificial seawater (25‰). The only exceptions were 2009 (32.5 µg mL-1) and 3002 (32.5 µg mL-1) against Vibrio rotiferianus and Tenacibaculum discolor, respectively. The selected synthetic AMPs were not effective at reducing the bacterial load in brackish salt concentrations of a typical commercial rotifer culture (25‰).

Composition of early life leukocyte populations in preterm infants with and without late-onset sepsis.

BACKGROUND: Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). AIM: To characterise and compare leukocyte populations in preterm infants with and without LOS during the first month of life. STUDY DESIGN: Single-centre prospective observational cohort study. PARTICIPANTS: Infants born <30 weeks gestational age (GA). OUTCOME MEASURES: Peripheral blood samples were collected at 1, 7, 14, 21 and 28 days of life. Leukocyte populations were characterised using 5-fluorophore-6-marker flow cytometry. Absolute leukocyte counts and frequency of total CD45+ leukocytes of each population were adjusted for GA, birth weight z-scores, sex and total leukocyte count. RESULTS: Of 119 preterm infants enrolled, 43 (36%) had confirmed or clinical LOS, with a median onset at 13 days (range 6-26). Compared to infants without LOS, the adjusted counts and frequency of neutrophils, basophils and non-cytotoxic T lymphocytes were generally lower and immature granulocytes were higher over the first month of life in infants who developed LOS. Specific time point comparisons identified lower adjusted neutrophil counts on the first day of life in those infants who developed LOS more than a week later, compared to those without LOS, albeit levels were within the normal age-adjusted range. Non-cytotoxic T lymphocyte counts and/or frequencies were lower in infants following LOS on days 21 and 28 when compared to those who did not develop LOS. CONCLUSION: Changes in non-cytotoxic T lymphocytes occurred following LOS suggesting sepsis-induced immune suppression.

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.

Network Meta-Analysis of Metabolic Surgery Procedures for the Treatment of Obesity and Diabetes.

BACKGROUND: Metabolic surgery is part of a well-established treatment intensification strategy for obesity and its related comorbidities including type 2 diabetes (T2DM). Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are the most commonly performed metabolic surgeries worldwide, but comparative efficacy is uncertain. This study employed network meta-analysis to compare weight loss, T2DM remission and perioperative complications in adults between RYGB, SG and OAGB. METHODS: MEDLINE, EMBASE, trial registries were searched for randomised trials comparing RYGB, SG and OAGB. Study outcomes were excess weight loss (at 1, 2 and 3-5 years), trial-defined T2DM remission at any time point and perioperative complications. RESULTS: Twenty randomised controlled trials were included involving 1803 patients investigating the three metabolic surgical interventions. RYGB was the index for comparison. The excess weight loss (EWL) demonstrated minor differences at 1 and 2 years, but no differences between interventions at 3-5 years. T2DM remission was more likely to occur with either RYGB or OAGB when compared to SG. Perioperative complications were higher with RYGB when compared to either SG or OAGB. Two-way analysis of EWL and T2DM remission against the risk of perioperative complications demonstrated OAGB was the most positive on this assessment at all time points. CONCLUSION: OAGB offers comparable metabolic control through weight loss and T2DM remission to RYGB and SG whilst minimising perioperative complications. Registration number: CRD42020199779 (https:// www.crd.york.ac.uk/PROSPERO ).