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2.
Inflamm Bowel Dis ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38417068

ABSTRACT

BACKGROUND: Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course. METHODS: Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months. RESULTS: One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 µg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 µg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course. CONCLUSIONS: Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21267388

ABSTRACT

ObjectiveTo investigate the abrogation of COVID-19 case declines from predicted rates in the US in relationship to viral variants and mutations. DesignEpidemiological prediction and time series study of COVID-19 in the US by State. SettingCommunity testing and sequencing of COVID-19 in the US. ParticipantsTime series US COVID-19 case data from the Johns Hopkins University CSSE database. Time series US Variant and Mutation data from the GISAID database. Main outcome measuresPrimary outcomes were statistical modeling of US state deviations from epidemiological predictions, percentage of COVID-19 variants, percentage of COVID-19 mutations, and reported SARS-CoV-2 infections. ResultsDeviations in epidemiological predictions of COVID-19 case declines in the North Eastern US in March 2021 were highly positively related to percentage of B.1.526 (Iota) lineage (p < 10e - 7) and B.1.526.2 (p < 10 - 8) and the T95I mutation (p < 10e - 9). They were related inversely to B.1.427 and B.1.429 (Epsilon) and there was a trend for association with B.1.1.7 (Alpha) lineage. ConclusionDeviations from accurate predictive models are useful for investigating potential immune escape of COVID-19 variants at the population level. The B.1.526 and B.1.526.2 lineages likely have a high potential for immune escape and should be designated as variants of concern. The T95I mutation which is present in the B.1.526, B.1.526.2, and B.1.617.2 (Delta) lineages in the US warrants further investigation as a mutation of concern.

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