A Prospective Cohort Study of Fecal miR-223 and miR-451a as Noninvasive and Specific Biomarkers for Diagnosis of Necrotizing Enterocolitis in Preterm Infants

Neonatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Pak Cheung Ng ◽  
Kathy Yuen Yee Chan ◽  
Hugh Simon Lam ◽  
Raymond Pui On Wong ◽  
Terence Ping Yuen Ma ◽  
...  

<b><i>Objective:</i></b> The objective of this study is to evaluate the usefulness of fecal microRNA (miR)-223 and miR-451a, as novel noninvasive biomarkers for early diagnosis of necrotizing enterocolitis (NEC) in preterm infants. <b><i>Methods:</i></b> Among the top-listed target miRNAs in our previous differential microarray analysis, miR-223 and miR-451a were quantified in a pilot validation case-controlled study (NEC vs. non-NEC/nonsepsis infants; <i>n</i> = 6 in each group). A definitive prospective cohort study (<i>n</i> = 218) further assessed their clinical usefulness as noninvasive and specific diagnostic biomarkers. Fecal calprotectin was quantified in parallel for comparison. <b><i>Results:</i></b> Of 43 proven NEC cases in the cohort study, 24 (55.8%) had fecal samples recovered within the first 3 days of clinical presentation. Fecal miRNA-223 (10.5 fold), miR-451a (4.5 fold), and calprotectin (2.1 fold) concentrations were significant higher in NEC compared with the non-NEC group (<i>p</i> &#x3c; 0.009). Accepting a minimum sensitivity of 0.75, the positive predictive values (PPVs) ranged between 0.19 and 0.20. Combining fecal biomarkers and CRP (Day 1) could marginally increase the PPVs (0.31–0.34) but adversely lowered the sensitivity (0.54–0.63). <b><i>Conclusions:</i></b> Although fecal miRNA biomarkers and calprotectin concentrations were significantly higher in the NEC group, the considerable overlapping of concentrations between groups and low recovery of stool specimens within 72 h of clinical presentation rendered fecal noninvasive tests of limited clinical value in guiding diagnosis of NEC during the acute phase. A further study is underway to evaluate their roles in surveillance for predicting high-risk premature infants developing NEC.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhi-Yong Zeng ◽  
Shao-Dan Feng ◽  
Gong-Ping Chen ◽  
Jiang-Nan Wu

Abstract Background Early identification of patients who are at high risk of poor clinical outcomes is of great importance in saving the lives of patients with novel coronavirus disease 2019 (COVID-19) in the context of limited medical resources. Objective To evaluate the value of the neutrophil to lymphocyte ratio (NLR), calculated at hospital admission and in isolation, for the prediction of the subsequent presence of disease progression and serious clinical outcomes (e.g., shock, death). Methods We designed a prospective cohort study of 352 hospitalized patients with COVID-19 between January 9 and February 26, 2020, in Yichang City, Hubei Province. Patients with an NLR equal to or higher than the cutoff value derived from the receiver operating characteristic curve method were classified as the exposed group. The primary outcome was disease deterioration, defined as an increase of the clinical disease severity classification during hospitalization (e.g., moderate to severe/critical; severe to critical). The secondary outcomes were shock and death during the treatment. Results During the follow-up period, 51 (14.5%) patients’ conditions deteriorated, 15 patients (4.3%) had complicated septic shock, and 15 patients (4.3%) died. The NLR was higher in patients with deterioration than in those without deterioration (median: 5.33 vs. 2.14, P < 0.001), and higher in patients with serious clinical outcomes than in those without serious clinical outcomes (shock vs. no shock: 6.19 vs. 2.25, P < 0.001; death vs. survival: 7.19 vs. 2.25, P < 0.001). The NLR measured at hospital admission had high value in predicting subsequent disease deterioration, shock and death (all the areas under the curve > 0.80). The sensitivity of an NLR ≥ 2.6937 for predicting subsequent disease deterioration, shock and death was 82.0% (95% confidence interval, 69.0 to 91.0), 93.3% (68.0 to 100), and 92.9% (66.0 to 100), and the corresponding negative predictive values were 95.7% (93.0 to 99.2), 99.5% (98.6 to 100) and 99.5% (98.6 to 100), respectively. Conclusions The NLR measured at admission and in isolation can be used to effectively predict the subsequent presence of disease deterioration and serious clinical outcomes in patients with COVID-19.


BMJ ◽  
2017 ◽  
pp. j1039 ◽  
Author(s):  
Colm P Travers ◽  
Reese H Clark ◽  
Alan R Spitzer ◽  
Abhik Das ◽  
Thomas J Garite ◽  
...  

2014 ◽  
Vol 218 (6) ◽  
pp. 1148-1155 ◽  
Author(s):  
Melissa A. Hull ◽  
Jeremy G. Fisher ◽  
Ivan M. Gutierrez ◽  
Brian A. Jones ◽  
Kuang Horng Kang ◽  
...  

2017 ◽  
Vol 210 (6) ◽  
pp. 429-436 ◽  
Author(s):  
Leah Quinlivan ◽  
Jayne Cooper ◽  
Declan Meehan ◽  
Damien Longson ◽  
John Potokar ◽  
...  

BackgroundScales are widely used in psychiatric assessments following self-harm. Robust evidence for their diagnostic use is lacking.AimsTo evaluate the performance of risk scales (Manchester Self-Harm Rule, ReACT Self-Harm Rule, SAD PERSONS scale, Modified SAD PERSONS scale, Barratt Impulsiveness Scale); and patient and clinician estimates of risk in identifying patients who repeat self-harm within 6 months.MethodA multisite prospective cohort study was conducted of adults aged 18 years and over referred to liaison psychiatry services following self-harm. Scale a priori cut-offs were evaluated using diagnostic accuracy statistics. The area under the curve (AUC) was used to determine optimal cut-offs and compare global accuracy.ResultsIn total, 483 episodes of self-harm were included in the study. The episode-based 6-month repetition rate was 30% (n = 145). Sensitivity ranged from 1% (95% CI 0–5) for the SAD PERSONS scale, to 97% (95% CI 93–99) for the Manchester Self-Harm Rule. Positive predictive values ranged from 13% (95% CI 2–47) for the Modified SAD PERSONS Scale to 47% (95% CI 41–53) for the clinician assessment of risk. The AUC ranged from 0.55 (95% CI 0.50–0.61) for the SAD PERSONS scale to 0.74 (95% CI 0.69–0.79) for the clinician global scale. The remaining scales performed significantly worse than clinician and patient estimates of risk (P < 0.001).ConclusionsRisk scales following self-harm have limited clinical utility and may waste valuable resources. Most scales performed no better than clinician or patient ratings of risk. Some performed considerably worse. Positive predictive values were modest. In line with national guidelines, risk scales should not be used to determine patient management or predict self-harm.


Cephalalgia ◽  
2016 ◽  
Vol 38 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Jasna J Zidverc-Trajkovic ◽  
Tatjana Pekmezovic ◽  
Zagorka Jovanovic ◽  
Aleksandra Pavlovic ◽  
Milija Mijajlovic ◽  
...  

Objective To evaluate long-term predictors of remission in patients with medication-overuse headache (MOH) by prospective cohort study. Background Knowledge regarding long-term predictors of MOH outcome is limited. Methods Two hundred and forty MOH patients recruited from 2000 to 2005 were included in a one-year follow-up study and then subsequently followed until 31 December 2013. The median follow-up was three years (interquartile range, three years). Predictive values of selected variables were assessed by the Cox proportional hazard regression model. Results At the end of follow-up, 102 (42.5%) patients were in remission. The most important predictors of remission were lower number of headache days per month before the one-year follow-up (HR-hazard ratio = 0.936, 95% confidence interval (CI) 0.884–0.990, p = 0.021) and efficient initial drug withdrawal (HR = 0.136, 95% CI 0.042–0.444, p = 0.001). Refractory MOH was observed in seven (2.9%) and MOH relapse in 131 patients (54.6%). Conclusions Outcome at the one-year follow-up is a reliable predictor of MOH long-term remission.


Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Brian J. Anderson ◽  
Carolyn S. Calfee ◽  
Kathleen D. Liu ◽  
John P. Reilly ◽  
Kirsten N. Kangelaris ◽  
...  

Abstract Background Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors. Methods In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies. Measurements and main results An admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor. Conclusions Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.


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