Effect of Chemotherapy on the Microbiota and Metabolome of Human Milk: A Case Report

BACKGROUND: Human milk is an important source of bacteria for the developing infant and has been shown to influence the bacterial composition of the neonatal gut, which in turn can affect disease risk later in life. Human milk is also an important source of nutrients, influencing bacterial composition but also directly affecting the host. While recent studies have emphasized the adverse effects of antibiotic therapy on the infant microbiota, the effects of maternal chemotherapy have not been previously studied. Here we report the effects of drug administration on the microbiota and metabolome of human milk. METHODS: Mature milk was collected every two weeks over a four month period from a lactating woman undergoing chemotherapy for Hodgkin\u27s lymphoma. Mature milk was also collected from healthy lactating women for comparison. Microbial profiles were analyzed by 16S sequencing and the metabolome by gas chromatography-mass spectrometry. FINDINGS: Chemotherapy caused a significant deviation from a healthy microbial and metabolomic profile, with depletion of genera Bifidobacterium, Eubacterium, Staphylococcus and Cloacibacterium in favor of Acinetobacter, Xanthomonadaceae and Stenotrophomonas. The metabolites docosahexaenoic acid and inositol known for their beneficial effects were also decreased. CONCLUSION: With milk contents being critical for shaping infant immunity and development, consideration needs to be given to the impact of drugs administered to the mother and the long-term potential consequences for the health of the infant

Efficacy and safety of carbon dioxide insufflation for brain protection for patients undergoing planned left-sided open heart valve surgery:protocol for a multicentre, placebo-controlled, blinded, randomised controlled trial (the CO2 Study)

Introduction: Brain injury is common following open heart valve surgery. Carbon dioxide insufflation (CDI) has been proposed to reduce the incidence of brain injury by reducing the number of air microemboli entering the bloodstream in surgery. The CO2 Study will evaluate the efficacy and safety of CDI in patients undergoing planned left-sided open heart valve surgery. Methods and analysis: The CO2 Study is a multicentre, blinded, placebo-controlled, randomised controlled trial. Seven-hundred and four patients aged 50 years and over undergoing planned left-sided heart valve surgery will be recruited to the study, from at least eight UK National Health Service hospitals, and randomised in a 1:1 ratio to receive CDI or medical air insufflation (placebo) in addition to standard de-airing. Insufflation will be delivered at a flow rate of 5 L/min from before the initiation of cardiopulmonary bypass until 10 min after cardiopulmonary bypass weaning. Participants will be followed up until 3 months post-surgery. The primary outcome is acute ischaemic brain injury within 10 days post-surgery based on new brain lesions identified with diffusion-weighted MRI or clinical evidence of permanent brain injury according to the current definition of stroke. Ethics and dissemination: The study was approved by the East Midlands–Nottingham 2 Research Ethics Committee in June 2020 and the Medicines and Healthcare products Regulatory Agency in May 2020. All participants will provide written informed consent prior to undertaking any study assessments. Consent will be obtained by the principal investigator or a delegated member of the research team who has been trained in the study and undergone Good Clinical Practice training. Results will be disseminated through peer-reviewed publications and presentations at national and international meetings. Study participants will be informed of results through study notifications and patient organisations. Trial registration number: ISRCTN30671536

TOPCAT and Gaia

TOPCAT, and its command line counterpart STILTS, are powerful tools for working with large source catalogues. ESA's Gaia mission, most recently with its second data release, is producing source catalogues of unprecedented quality for more than a billion sources. This paper presents some examples of how TOPCAT and STILTS can be used for analysis of Gaia data.Comment: 4 pages, 2 figures; to appear in the Proceedings of ADASS 2018, Astronomical Society of the Pacific (ASP) Conference Serie

Ubx Regulates Differential Enlargement and Diversification of Insect Hind Legs

Differential enlargement of hind (T3) legs represents one of the hallmarks of insect evolution. However, the actual mechanism(s) responsible are yet to be determined. To address this issue, we have now studied the molecular basis of T3 leg enlargement in Oncopeltus fasciatus (milkweed bug) and Acheta domesticus (house cricket). In Oncopeltus, the T3 tibia displays a moderate increase in size, whereas in Acheta, the T3 femur, tibia, and tarsus are all greatly enlarged. Here, we show that the hox gene Ultrabithorax (Ubx) is expressed in the enlarged segments of hind legs. Furthermore, we demonstrate that depletion of Ubx during embryogenesis has a primary effect in T3 legs and causes shortening of leg segments that are enlarged in a wild type. This result shows that Ubx is regulating the differential growth and enlargement of T3 legs in both Oncopeltus and Acheta. The emerging view suggests that Ubx was co-opted for a novel role in regulating leg growth and that the transcriptional modification of its expression may be a universal mechanism for the evolutionary diversification of insect hind legs

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]