scholarly journals Elevated Pretreatment Plasma Oncostatin M Is Associated With Poor Biochemical Response to Infliximab

2019 ◽  
Vol 1 (3) ◽  
Author(s):  
Phillip Minar ◽  
Christina Lehn ◽  
Yi-Ting Tsai ◽  
Kimberly Jackson ◽  
Michael J Rosen ◽  
...  

Abstract Background We hypothesized that elevations of plasma Oncostatin M (OSM) would be associated with infliximab nonresponse. Methods Plasma OSM was measured in Crohn disease patients pre-infliximab with biochemical response (>50% reduction in fecal calprotectin) as the primary outcome. Results The median OSM in biochemical responders was 86 (69–148) pg/mL compared with 166 (74–1766) pg/mL in nonresponders (P = 0.03). Plasma OSM > 143.5 pg/mL was 71% sensitive and 78% specific for biochemical nonresponse (area under the curve 0.71). Early biochemical nonremission was also associated with an elevated neutrophil CD64 expression (odds ratio 8.9, P = 0.011). Conclusions Elevated preinfliximab plasma OSM and nCD64 surface expression were both associated with poor biochemical outcomes.

2017 ◽  
Vol 24 (1) ◽  
pp. 198-208 ◽  
Author(s):  
Phillip Minar ◽  
Kimberly Jackson ◽  
Yi-Ting Tsai ◽  
Heidi Sucharew ◽  
Michael J Rosen ◽  
...  

Abstract Background In a pilot study, neutrophil CD64 surface expression was significantly elevated in newly diagnosed, pediatric-onset Crohn’s disease. We aimed to test the CD64 biomarkers (neutrophil CD64 surface expression and soluble CD64) as determinates for mucosal inflammation in a larger pediatric Crohn’s cohort with the hypotheses that the CD64 biomarkers would reliably detect intestinal inflammation and correlate with endoscopic severity scores. Methods We enrolled patients referred for colonoscopy for either suspected inflammatory bowel disease or with established Crohn’s. Neutrophil CD64 index was determined by flow cytometry using a commercial kit (Leuko64, Trillium) and soluble CD64 by ELISA (LifeSpan). Results A total of 209 patients (72 controls, 76 new inflammatory bowel disease patients, and 61 established Crohn’s) were enrolled. Both neutrophil CD64 index and soluble CD64 were significantly elevated in new Crohn’s compared with controls. The area under the curve (AUC) for neutrophil CD64 index ≥1 was 0.85 (95% confidence interval, 0.77–0.92), 75% sensitive and 89% specific for new Crohn’s. Comparatively, soluble CD64 ≥39 ng/mL was 92% sensitive and 85% specific (AUC, 0.93) for new Crohn’s. Neutrophil CD64 index, soluble CD64, and fecal calprotectin discriminated endoscopic inactive from moderate and severe activity while soluble CD64 differentiated endoscopic mild from moderate and severe activity. Neutrophil CD64 index (r = 0.46, P < 0.001) and fecal calprotectin (r = 0.55, P < 0.001) correlated well with the Simple Endoscopic Score–Crohn’s disease. Spearman correlation between the CD64 index and calprotectin was 0.39 (P < 0.001). Conclusions In a large Crohn’s disease cohort, we found that neutrophil CD64 index and soluble CD64 were significantly elevated during active gastrointestinal inflammation. 10.1093/ibd/izx022_video1 izx022.video1 5732761255001


Author(s):  
Firas Rinawi ◽  
Amanda Ricciuto ◽  
Peter C Church ◽  
Karen Frost ◽  
Eileen Crowley ◽  
...  

Abstract Background Data on the association between early postinduction serum adalimumab (ADA) trough levels (TLs) and objective outcomes are scarce. The aim of this study was to investigate whether early ADA TLs at weeks 4 and 8 are associated with clinical and biomarker remission at week 24 in pediatric Crohn’s disease (CD). Methods Adalimumab TLs at weeks 4 and 8 were prospectively measured in anti-TNF-naïve children initiating treatment with ADA monotherapy for luminal inflammatory CD. The primary outcome was combined clinical and biomarker remission at week 24, defined as achieving steroid-free clinical remission (Pediatric CD activity index <10) and biomarker remission (fecal calprotectin <250 µg/g and CRP <5 µg/mL). Results Among 65 patients, 39 (60%) achieved combined clinical/biomarker remission at week 24 without dose escalation. Adalimumab TLs at both weeks 4 and 8 were significantly higher in remitters vs nonremitters at week 24 (P < 0.001 and P = 0.002, respectively). Adalimumab levels at weeks 4 and 8 were good predictors of combined clinical/biomarker remission at week 24 (area under the curve, 0.887, 95% CI, 0.798–0.942; and area under the curve, 0.761, 95% CI, 0.632–0.899, respectively). The best ADA TL cutoffs at weeks 4 and 8 for predicting clinical/biomarker remission at week 24 were 22.5 µg/mL (80% sensitivity, 90% specificity, positive likelihood ratio [LR+] 8.0, negative LR [LR-] 0.2) and 12.5 µg/mL (94% sensitivity, 60% specificity, LR+ 2.4, LR- 0.1), respectively. Higher induction doses per m2 correlated positively with TLs at weeks 4 and 8. Conclusion Greater early ADA exposure is associated with superior clinical/biomarker outcomes at week 24.


Author(s):  
Elaine C Khoong ◽  
Valy Fontil ◽  
Natalie A Rivadeneira ◽  
Mekhala Hoskote ◽  
Shantanu Nundy ◽  
...  

Abstract Objective The study sought to evaluate if peer input on outpatient cases impacted diagnostic confidence. Materials and Methods This randomized trial of a peer input intervention occurred among 28 clinicians with case-level randomization. Encounters with diagnostic uncertainty were entered onto a digital platform to collect input from ≥5 clinicians. The primary outcome was diagnostic confidence. We used mixed-effects logistic regression analyses to assess for intervention impact on diagnostic confidence. Results Among the 509 cases (255 control; 254 intervention), the intervention did not impact confidence (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.999-2.12), but after adjusting for clinician and case traits, the intervention was associated with higher confidence (OR, 1.53; 95% CI, 1.01-2.32). The intervention impact was greater in cases with high uncertainty (OR, 3.23; 95% CI, 1.09- 9.52). Conclusions Peer input increased diagnostic confidence primarily in high-uncertainty cases, consistent with findings that clinicians desire input primarily in cases with continued uncertainty.


2021 ◽  
Vol 14 ◽  
pp. 175628482199474
Author(s):  
Xiaoqi Ye ◽  
Ying Wang ◽  
Harry H. X. Wang ◽  
Rui Feng ◽  
Ziyin Ye ◽  
...  

Background and Aims: Elevated fecal calprotectin (FC) levels have been reported to correlate with histological activity in patients with ulcerative colitis (UC). However, the accuracy of FC for evaluating histological activity of UC remains to be determined. The aim of this study was to determine the accuracy of FC for evaluating histological activity of UC, based on updated definitions. Methods: Related studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. Adult participants diagnosed with UC were included when sufficient data could be extracted to calculate the accuracy of FC for evaluating histological activity. The primary outcome was histological response, and the secondary outcome was histological remission, defined according to a recently updated position paper of European Crohn’s and Colitis Organization. Statistics were pooled using bivariate mixed-effects models. The area under the curve was estimated by summary receiver-operating characteristic curves. Results: Nine studies were included, from which 1039 patients were included for the analysis of histological response and 591 patients for histological remission. For the evaluation of histological response, the pooled sensitivity, specificity, and the area under the curve were 0.69 [95% confidence interval (CI): 0.52–0.82], 0.77 (95% CI: 0.63–0.87), and 0.80 (95% CI: 0.76–0.83), respectively. For the evaluation of histological remission, the corresponding estimates were 0.76 (95% CI: 0.71–0.81), 0.71 (95% CI: 0.62–0.78), and 0.79 (95% CI: 0.75–0.82), respectively. FC had a higher accuracy in studies using Nancy Index. For histological response, the cut-off values of FC ranged from 50 to 172 µg/g, and the sensitivity was higher in studies with FC cut-off values >100 µg/g (0.77 versus 0.65). Conclusion: FC is a valuable biomarker for assessing histological activity in patients with UC. A cut-off value of 100–200 µg/g is more appropriate to spare patients from an unnecessary endoscopy and biopsy.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Almani ◽  
M Usman ◽  
M Qudrat Ullah ◽  
N Fatima ◽  
M Yousuf ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. 1. Introduction Obesity causes significant cardiovascular morbidity. Nonetheless, there is also evidence supporting obesity paradox particularly in heart failure patients. The impact of obesity on the outcomes of patients undergoing pacemaker insertion is not well studied. 2. Purpose The purpose of this study is to determine if obesity paradox exists for the patients who undergo pacemaker insertion. 3. Methods Data were extracted from the National Inpatient Sample (NIS) 2016 - 2018 Database. The NIS was searched for patients who underwent pacemaker insertion while hospitalized. The patients were divided into two groups based on presence or absence of obesity as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used to for analysis. 4. Results Of 408,040 patients who underwent pacemaker insertion, 64185 (15.7%) were obese. The adjusted odds ratio for inpatient mortality for obese patient undergoing pacemaker insertion compared to non-obese patients was 0.65 (95% CI 0.516 – 0.821, p < 0.001). Secondary outcomes are listed in table 1. 5. Conclusion Obese patients who underwent pacemaker insertion had lower inpatient mortality compared to non-obese patients. Also, obese patients undergoing pacemaker insertion were less likely to have cardiac arrest but they were more likely to develop decompensated heart failure and acute renal failure compared to non-obese patients. Outcome Without Obesity, % With Obesity, % aOR (95% CI) p-value* Primary outcome In hospital mortality 10.8 7.0 0.65 (0.516 - 0.821) <0.001* Secondary outcomes Length of stay (days), mean 5.7 6.3 0.031 (-0.105 - 0.168) # 0.654 Total hospital charges (US$), mean 121250 134757 720 (-2307 - 3747) # 0.641 Decompensated heart failure 13.3 19.2 1.53 (1.451 - 1.629) <0.001* Cardiogenic shock 2.3 2.7 1.00 (0.883 - 1.141) 0.954 IABP placement 0.5 0.6 0.98 (0.746 - 1.294) 0.898 Cardiac arrest 4.27 4.30 0.83 (0.753 - 0.920) <0.001* Acute renal failure 20.7 25.4 1.17 (1.112 - 1.231) <0.001* Abbreviations: *; statistically significant, #; adjusted mean difference, aOR: adjusted odds ratio, CI: confidence interval, IABP: Intra-aortic balloon pump.Adjusting factors: Age, race, Charlson comorbidity index, primary insurance, median household income for patient’s zip code, location and teaching status of the admitting hospital, dyslipidemia, chronic obstructive pulmonary disease, hypertension, peripheral vascular disease, diabetes mellitus, chronic kidney disease, liver disease and smoking status. Table 1: Clinical outcomes of hospitalizations for pacemaker insertion based on presence or absence of obesity, analysis of United States National Inpatient Sample from 2016 through 2018.


2020 ◽  
Vol 133 (1) ◽  
pp. 78-95 ◽  
Author(s):  
Sylvie D. Aucoin ◽  
Mike Hao ◽  
Raman Sohi ◽  
Julia Shaw ◽  
Itay Bentov ◽  
...  

Background A barrier to routine preoperative frailty assessment is the large number of frailty instruments described. Previous systematic reviews estimate the association of frailty with outcomes, but none have evaluated outcomes at the individual instrument level or specific to clinical assessment of frailty, which must combine accuracy with feasibility to support clinical practice. Methods The authors conducted a preregistered systematic review (CRD42019107551) of studies prospectively applying a frailty instrument in a clinical setting before surgery. Medline, Excerpta Medica Database, Cochrane Library and the Comprehensive Index to Nursing and Allied Health Literature, and Cochrane databases were searched using a peer-reviewed strategy. All stages of the review were completed in duplicate. The primary outcome was mortality and secondary outcomes reflected routinely collected and patient-centered measures; feasibility measures were also collected. Effect estimates were pooled using random-effects models or narratively synthesized. Risk of bias was assessed. Results Seventy studies were included; 45 contributed to meta-analyses. Frailty was defined using 35 different instruments; five were meta-analyzed, with the Fried Phenotype having the largest number of studies. Most strongly associated with: mortality and nonfavorable discharge was the Clinical Frailty Scale (odds ratio, 4.89; 95% CI, 1.83 to 13.05 and odds ratio, 6.31; 95% CI, 4.00 to 9.94, respectively); complications was associated with the Edmonton Frail Scale (odds ratio, 2.93; 95% CI, 1.52 to 5.65); and delirium was associated with the Frailty Phenotype (odds ratio, 3.79; 95% CI, 1.75 to 8.22). The Clinical Frailty Scale had the highest reported measures of feasibility. Conclusions Clinicians should consider accuracy and feasibility when choosing a frailty instrument. Strong evidence in both domains support the Clinical Frailty Scale, while the Fried Phenotype may require a trade-off of accuracy with lower feasibility. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


2015 ◽  
Author(s):  
Edward L. Barnes ◽  
Jonathan S. Levine

Inflammatory bowel disease (IBD) is composed of two major subtypes, ulcerative colitis (UC) and Crohn disease (CD). These chronic disorders, characterized by inflammation of the gastrointestinal tract, demonstrate a variety of clinical features, including intestinal and extraintestinal manifestations during periods of relapse and remission over many years. This review examines the clinical features of IBD, including the extraintestinal manifestations and diagnosis. Figures include examples of images conducted via computed tomography (CT), magnetic resonance imaging, and position emission tomography (PET)/CT. Tables list the location frequencies of UC and CD at the time of diagnosis, extraintestinal manifestations of IBD, differential diagnosis of UC and CD, and clinical utility of fecal calprotectin in the evaluation and management of IBD. This review contains 4 highly rendered figures, 5 tables, and 48 references. 


2019 ◽  
Vol 37 (03) ◽  
pp. 341-348 ◽  
Author(s):  
Michelle C. Starr ◽  
Louis Boohaker ◽  
Laurie C. Eldredge ◽  
Shina Menon ◽  
Russell Griffin ◽  
...  

Abstract Objective This study aimed to evaluate the association between acute kidney injury (AKI) and bronchopulmonary dysplasia (BPD) in infants born <32 weeks of gestational age (GA). Study Design Present study is a secondary analysis of premature infants born at <32 weeks of GA in the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) retrospective cohort (n = 546). We stratified by gestational age and used logistic regression to determine association between AKI and moderate or severe BPD/mortality. Results Moderate or severe BPD occurred in 214 of 546 (39%) infants, while death occurred in 32 of 546 (6%); the composite of moderate or severe BPD/death occurred in 246 of 546 (45%). For infants born ≤29 weeks of gestation, the adjusted odds ratio (OR) of AKI and the primary outcome was 1.15 (95% confidence interval [CI] = 0.47–2.86; p = 0.76). Infants born between 29 and 32 weeks of gestation with AKI had four-fold higher odds of moderate or severe BPD/death that remained after controlling for multiple factors (adjusted OR = 4.21, 95% CI: 2.07–8.61; p < 0.001). Conclusion Neonates born between 29 and 32 weeks who develop AKI had a higher likelihood of moderate or severe BPD/death than those without AKI. Further studies are needed to validate our findings and evaluate mechanisms of multiorgan injury.


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