EBioMedicine
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Randomized Controlled Trial Clinical Trial
Short- and long-term impacts of azithromycin treatment on the gut microbiota in children: A double-blind, randomized, placebo-controlled trial.
Macrolides are commonly prescribed for respiratory infections and asthma-like episodes in children. While their clinical benefits have been proved, concerns regarding the side-effects of their therapeutic use have been raised. Here we assess the short- and long-term impacts of azithromycin on the gut microbiota of young children. ⋯ Azithromycin treatment induced a perturbation in the gut microbiota 14 days after randomization but did not have long-lasting effects on the gut microbiota composition. However, it should be noted that our analyses included a limited number of fecal samples for the placebo treated group at age 4 years. FUND: Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation, China Scholarship Council.
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Multiple studies have made robust associations between differential DNA methylation and exposure to cigarette smoke. But whether a DNA methylation phenotype is established immediately upon exposure, or only after prolonged exposure is less well-established. Here, we assess DNA methylation patterns from peripheral blood samples in current smokers in response to dose and duration of exposure, along with the effects of smoking cessation on DNA methylation in former smokers. ⋯ Our findings suggest that smoking-associated DNA methylation changes are a result of prolonged exposure to cigarette smoke, and can be reversed following cessation. The length of time in which these signatures are established and recovered is dose dependent. Should DNA methylation-based signatures of smoking status be predictive of smoking-related health outcomes, our findings may provide an additional criterion on which to stratify risk.
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Multicenter Study
Development and validation of a radiomics signature for clinically significant portal hypertension in cirrhosis (CHESS1701): a prospective multicenter study.
Clinically significant portal hypertension (CSPH) is associated with an incremental risk of esophageal varices and overt clinical decompensations. However, hepatic venous pressure gradient (HVPG) measurement, the gold standard for defining CSPH (HVPG≥10 mm Hg) is invasive and therefore not suitable for routine clinical practice. This study aims to develop and validate a radiomics-based model as a noninvasive method for accurate detection of CSPH in cirrhosis. ⋯ Intraclass correlation coefficients for inter- and intra-observer agreement were 0·92-0·99 and 0·97-0·99, respectively. A radiomics signature was developed and prospectively validated as an accurate method for noninvasive detection of CSPH in cirrhosis. The tool of rHVPG assessment can facilitate the identification of CSPH rapidly when invasive transjugular procedure is not available.
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Randomized Controlled Trial
Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942.
Interleukin-13 (IL-13) is a key mediator of T-helper-cell-type-2 (Th-2)-driven asthma, the inhibition of which may improve treatment outcomes. We examined the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of VR942, a dry-powder formulation containing CDP7766, a high-affinity anti-human-IL-13 antigen-binding antibody fragment being developed for the treatment of asthma. ⋯ Study funding and funding for the medical writing and editorial support for preparation of the manuscript were split equally between the two study co-funders (Vectura Ltd and UCB Pharma).
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Preoperative lymph node (LN) status is important for the treatment of bladder cancer (BCa). However, a proportion of patients are at high risk for inaccurate clinical nodal staging by current methods. Here, we report an accurate magnetic resonance imaging (MRI)-based radiomics signature for the individual preoperative prediction of LN metastasis in BCa. ⋯ The MRI-based radiomics nomogram has the potential to be used as a non-invasive tool for individualized preoperative prediction of LN metastasis in BCa. External validation is further required prior to clinical implementation.