Publications by authors named "Simeng Lin"
The hypoblast is an essential extraembryonic tissue set aside within the inner cell mass in the blastocyst. Research with human embryos is challenging. Thus, stem cell models that reproduce hypoblast differentiation provide valuable alternatives.
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- The study aimed to evaluate the effectiveness of two medications, infliximab and adalimumab, for treating patients with active Crohn's disease over three years and to identify what factors contribute to treatment failure.
- It involved a large cohort of patients across the UK, tracking their responses to anti-TNF therapy and analyzing reasons for loss of effectiveness.
- Findings showed that remission rates declined over time for both medications, with around 40% of patients on infliximab and about 35% on adalimumab remaining in remission by the end of Year 1, suggesting ongoing challenges in maintaining treatment effectiveness.
Article Synopsis
- - This study aimed to see if gene expression of TREM-1 in whole blood could predict how well patients with ulcerative colitis (UC) or Crohn's disease (CD) would respond to anti-TNF therapy, specifically adalimumab.
- - The research involved analyzing TREM-1 gene expression through RNA sequencing in patients from clinical trials and comparing their responses at different time points, finding no strong predictive value initially, but some associations at Week 52 for UC patients.
- - Overall, TREM-1 gene expression did not reliably predict treatment responses in either UC or CD patients, indicating a need for further investigations into potential blood-based markers for predicting responses to anti-TNF therapy.
Article Synopsis
- The study investigated blood gene expression differences between primary responders and non-responders to anti-TNF therapy for inflammatory bowel disease, aiming to identify any potential biomarkers for treatment response.
- Conducted through the PANTS study in the UK, researchers analyzed RNA sequencing data from 324 Crohn's disease patients before and after starting anti-TNF treatment, focusing on changes in gene expression over time.
- Results showed that certain immune-related gene expressions were higher in responders, but the ability to predict which patients would respond based on baseline data was limited, indicating a need for improvement in predictive methods.
Article Synopsis
- Anti-tumor necrosis factor (TNF) treatment failure in patients with inflammatory bowel disease (IBD) often stems from low drug levels, prompting researchers to explore epigenetic biomarkers in blood that could help optimize treatment from the beginning.
- The study analyzed DNA methylation from 1,104 blood samples of 385 patients at different intervals during anti-TNF therapy to compare profiles of those who responded positively to treatment against those who did not.
- Key findings included 4,999 differentially methylated positions (DMPs) related to immune processes, with 323 DMPs at baseline linked to better drug concentrations at week 14; researchers identified specific DMPs associated with both low drug effectiveness and primary
Article Synopsis
- * The study employed a high-throughput method to analyze changes in serum IgG N-glycome composition in 198 CD patients during 14 weeks of anti-TNF treatment, finding significant shifts indicating reduced inflammation.
- * While IgG N-glycan patterns may provide insights into treatment outcomes, they cannot reliably predict which patients will be non-responsive to anti-TNF therapy before treatment begins.
Article Synopsis
- Vitamin D plays a crucial role in immune function, and past research suggested its low levels might lead to ineffective treatment with anti-TNF therapies in Crohn's disease patients.
- This study measured vitamin D levels in over 1,100 patients undergoing treatment with infliximab and adalimumab to assess if these levels could predict treatment outcomes.
- The findings showed that while vitamin D deficiency is prevalent among these patients, it did not significantly predict non-response or non-remission to anti-TNF therapy within 14 weeks or 54 weeks, contrasting earlier studies' results.
Article Synopsis
- Patients with inflammatory bowel disease (IBD) on anti-TNF therapy show reduced immune responses to SARS-CoV-2 vaccines, and the study investigates how gut microbiota and its metabolites might influence this.
- The research involved analyzing fecal and serum samples from IBD patients who received the SARS-CoV-2 vaccine, using various advanced techniques to assess microbial composition and metabolomic profiles.
- Results revealed that lower gut microbiota diversity correlates with poorer vaccine responses; specific microbes like Bilophila are linked to better responses, whereas others like Streptococcus are linked to worse outcomes.
Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.
Lancet Gastroenterol Hepatol
February 2023
Background: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.
View Article and Find Full Text PDFImplications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.
Aliment Pharmacol Ther
October 2022
Article Synopsis
- Anti-drug antibodies linked to treatment failure in inflammatory bowel disease (IBD) patients on anti-TNF agents were analyzed in a large UK study involving 1058 participants.
- The study found that patients who developed antibodies to their first anti-TNF drug were more likely to also develop antibodies to their second anti-TNF drug, indicating a potential pattern of immunogenicity across different treatments.
- Introducing an immunomodulator when switching anti-TNF therapies boosted treatment persistence in patients with immunogenicity, suggesting that combined therapies may enhance outcomes in IBD management.
Objective: Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD.
Design: Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study.
Article Synopsis
- The study investigates the relationship between the serum free triiodothyronine-to-thyroxine (fT3/fT4) ratio and treatment effectiveness in Crohn's disease patients receiving infliximab or adalimumab.
- It found that a lower fT3/fT4 ratio is linked to female sex, corticosteroid use, and more severe disease, and it can predict primary non-response (PNR) to treatment at week 14.
- However, the fT3/fT4 ratio was not associated with non-remission outcomes at week 54, suggesting its predictive value is limited to early treatment responses.
The COVID-19 pandemic has raised considerable concerns that patients with inflammatory bowel disease (IBD), particularly those treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 acquisition, develop worse outcomes following COVID-19, and have suboptimal vaccine response compared with the general population. In this review, we summarise data on the risk of COVID-19 and associated outcomes, and latest guidance on SARS-CoV-2 vaccines in patients with IBD. Emerging evidence suggests that commonly used medications for IBD, such as corticosteroids but not biologicals, were associated with adverse outcomes to COVID-19.
View Article and Find Full Text PDFAnti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.
View Article and Find Full Text PDFAs an important carbon (C) storage in biological soil crusts (BSCs), exopolysaccharides (EPSs) are not only a part of the desert C cycle, but also the key materials for cyanobacteria to resist desert stress. In this study, the influence of initial N concentrations (10, 25 and 50 mg L designated as N10, N25 and N50 respectively) on Microcoleus vaginatusis growth and the excretion of EPSs including RPS (released exopolysaccharides) and CPS (capsule exopolysaccharides) were evaluated at different growth periods. In logarithmic period, higher ratio of biomass to EPSs indicated by (DW-CPS)/EPSs was observed in the N50 group with the highest N concentration (about 40 mg L) in the medium, while no difference was observed among the three groups in stationary period when the N concentrations of medium were lower than 25 mg L.
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- * Data from over 11,000 patients showed that those on infliximab and adalimumab had lower seroprevalence rates for SARS-CoV-2 compared to those on vedolizumab, indicating potential differences in immune response.
- * Higher rates of seropositivity were found in patients with undetectable anti-TNF drug levels, suggesting that the presence of these drugs may hinder the body’s ability to produce antibodies after infection.
Article Synopsis
- The COVID-19 pandemic prompted a shift to telemedicine for patients with chronic inflammatory disorders, highlighting a need for innovative methods of remote therapeutic drug monitoring, such as low-volume intracapillary blood sampling done at home.* -
- A study comparing patient-led intracapillary sampling (fingerpricks) to traditional venepuncture found that the new method was equivalent in measuring drug levels and was well-accepted by patients, with 69% preferring it over traditional methods.* -
- During the first UK lockdown, requests for therapeutic drug monitoring of adalimumab decreased significantly, while those for infliximab remained stable; over 75% of patients successfully returned two blood samples within 14 days for analysis
Objective: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.
Design: Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody.
Objective: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.
Design: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections.
Background: Colonoscopic surveillance in patients with inflammatory bowel disease (IBD) leads to earlier detection of colorectal cancer (CRC) and reduces CRC-associated mortality. However, it is limited by poor adherence in practice.
Aim: To identify missed opportunities to detect IBD-associated CRC at our hospital METHODS: We undertook root-cause analyses to identify patients with missed opportunities to diagnose IBD-associated CRC.
Quality improvement project identifies factors associated with delay in IBD diagnosis.
Aliment Pharmacol Ther
August 2020
Background: Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking.
Aim: To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD.
Methods: This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services.
Background: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS].
Methods: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure.
Objective: To determine the diagnostic accuracy of calprotectin to diagnose inflammatory bowel disease (IBD) in children in whom general practitioners (GPs) suspected IBD.
Design: Prospective observational cohort study of a new calprotectin-based primary care referral pathway.
Setting: 48 GP practices and gastroenterology secondary care services at the Royal Devon and Exeter NHS Foundation Trust in the South-West of England, UK.
Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study.
Lancet Gastroenterol Hepatol
May 2019
Background: Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal.
Methods: The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study.
Long-term outcomes in patients diagnosed with bile-acid diarrhoea.
Eur J Gastroenterol Hepatol
February 2016
Objective: Bile-acid diarrhoea (BAD) is a recognized cause of chronic diarrhoea; however, its detection remains suboptimal. Currently, there is a paucity of follow-up studies evaluating BAD. This work evaluates the natural history of BAD by examining individuals diagnosed with BAD [7 days of Se-homocholic acid taurine (SeHCAT) retention<10%] and determining the use of and response to bile-acid sequestrants (BAS).
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