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A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.

ABSTRACT: BACKGROUND AND AIMS:Diverticulitis is the chronic inflammation of diverticula. Whether the pathophysiology of earlier-onset patients differs from later-onset patients is unknown. We profiled the colonic transcriptomes of these two patient populations to gain insight into the molecular underpinnings of diverticulitis. METHODS:We conducted deep RNA sequencing (RNA-seq) on colonic segments surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65 years old, n=13) diverticulitis patients. We used bioinformatic approaches to cluster the patients based on the relationship of differentially expressed genes and to inform on the molecular pathways that segregated the clusters. RESULTS:Principal component analysis identified three patient clusters; diverticulitis later-onset (DVT-LO), diverticulitis mixed-onset (DVT-MO), and diverticulitis earlier-onset (DVT-EO). The patients comprising DVT-EO, which was the majority of earlier-onset patients, displayed increased expression of anti-viral response genes. This finding was confirmed using an independent weighted co-expression network analysis (WGCNA) of differentially expressed genes. CONCLUSIONS:We found that the majority of patients with earlier-onset disease contained elevated expression of host genes involved in the anti-viral response. Thus, susceptibility to a viral pathogen may offer one explanation why some individuals develop diverticulitis at an earlier age.

SUBMITTER: Schieffer KM

PROVIDER: S-EPMC6340102 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.

Schieffer Kathleen M KM Kline Bryan P BP Harris Leonard R LR Deiling Sue S Koltun Walter A WA Yochum Gregory S GS

Journal of gastrointestinal and liver diseases : JGLD 20180901 3

<h4>Background and aims</h4>Diverticulitis is the chronic inflammation of diverticula. Whether the pathophysiology of earlier-onset patients differs from later-onset patients is unknown. We profiled the colonic transcriptomes of these two patient populations to gain insight into the molecular underpinnings of diverticulitis.<h4>Methods</h4>We conducted deep RNA sequencing (RNA-seq) on colonic segments surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65 years old, n= ...[more]

PMID: 30240468

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Project description:Despite professional recommendations to delay elective colon resection for patients with uncomplicated diverticulitis, early surgery (after <3 preceding episodes) appears to be common. Several factors have been suggested to contribute to early surgery, including increasing numbers of younger patients, a lower threshold to operate laparoscopically, and growing recognition of "smoldering" (or nonrecovering) diverticulitis episodes. However, the relevance of these factors in early surgery has not been well tested, and most prior studies have focused on hospitalizations, missing outpatient events and making it difficult to assess guideline adherence in earlier interventions.To describe patterns of episodes of diverticulitis before surgery and factors associated with earlier interventions using inpatient, outpatient, and antibiotic prescription claims.This investigation was a nationwide retrospective cohort study from January 1, 2009, to December 31, 2012. The dates of the analysis were July 2014 to May 2015. Participants were immunocompetent adult patients (age range, 18-64 years) with incident, uncomplicated diverticulitis.Elective colectomy for diverticulitis.Inpatient, outpatient, and antibiotic prescription claims for diverticulitis captured in the MarketScan (Truven Health Analytics) databases.Of 87?461 immunocompetent patients having at least 1 claim for diverticulitis, 6.4% (n?=?5604) underwent a resection. The final study cohort comprised 3054 nonimmunocompromised patients who underwent elective resection for uncomplicated diverticulitis, of whom 55.6% (n?=?1699) were male. Before elective surgery, they had a mean (SD) of 1.0 (0.9) inpatient claims, 1.5 (1.5) outpatient claims, and 0.5 (1.2) antibiotic prescription claims related to diverticulitis. Resection occurred after fewer than 3 episodes in 94.9% (2897 of 3054) of patients if counting inpatient claims only, in 80.5% (2459 of 3054) if counting inpatient and outpatient claims only, and in 56.3% (1720 of 3054) if counting all types of claims. Based on all types of claims, patients having surgery after fewer than 3 episodes were of similar mean age compared with patients having delayed surgery (both 47.7 years, P?=?.91), were less likely to undergo laparoscopy (65.1% [1120 of 1720] vs 70.8% [944 of 1334], P?=?.001), and had more time between the last 2 episodes preceding surgery (157 vs 96 days, P?<?.001). Patients with health maintenance organization or capitated insurance plans had lower rates of early surgery (50.1% [247 of 493] vs 57.4% [1429 of 2490], P?=?.01) than those with other insurance plan types.After considering all types of diverticulitis claims, 56.3% (1720 of 3054) of elective resections for uncomplicated diverticulitis occurred after fewer than 3 episodes. Earlier surgery was not explained by younger age, laparoscopy, time between the last 2 episodes preceding surgery, or financial risk-bearing for patients. In delivering value-added surgical care, factors driving early, elective resection for diverticulitis need to be determined.

Project description:BACKGROUND:Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases. METHODS:Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin. FINDINGS:151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85-0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02). INTERPRETATION:The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases.

Dataset Information

A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.

Publications

A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.

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