bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADEQUACY OF SIGMOIDOSCOPY IN COMPARISION TO COLONOSCOPY TO ASSESS DISEASE ACTIVITY DURING FOLLOW UP IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Patel Sameet , Jain Shubham , Chandnani Sanjay , Debnath Prasanta , Contractor Qais , Kahmei Seemily , Kamat Rima , Rathi Pravin 
Published: January 2022

Abstract

BACKGROUND
Endoscopic remission is the current treatment target in patients with Ulcerative Colitis (UC). Literature on adequacy of sigmoidoscopy in comparison to colonoscopy to assess endoscopic and histologic activity during follow up is sparse.

METHODS
This is an interim analysis of a prospective study of patients diagnosed with UC with disease extent proximal to the sigmoid colon. Fifty adult patients underwent a complete colonoscopy with segmental biopsies. Endoscopic disease activity was graded using Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity score (UCEIS). The histological grading was done using the Nancy score, Robarts Histopathology Index (RHI) and Simplified Geboes Score (SGS). The maximum rectosigmoid disease activity was compared with the maximum disease activity in the rest of the colon.

RESULTS
Endoscopic Correlation: Sigmoidoscopic evaluation using MES showed good correlation with pan colonoscopic evaluation for disease activity with a sensitivity of 92.11%, specificity of 66.67%, accuracy of 86% (95% CI – 73.26% to 94.18%), kappa value (k) of 0.58 (p value &lt; 0.001) and Area under curve (AUC) of 0.82 (95% CI- 0.74 to 0.942). Similarly, sigmoidoscopic evaluation using UCEIS score showed good correlation with pan colonoscopic evaluation for disease activity with a sensitivity of 95.0%, specificity of 70%, accuracy of 90% (95% CI – 78.19% to 96.67%), k of 0.68 (p value &lt; 0.001) and AUC of 0.895 (95% CI- 0.805 to 0.924). Disease activity in the colon missed by performing a sigmoidoscopy using MES and UCEIS score is only 6% and 4% respectively. Histological Correlation: Histologic findings in rectosigmoid showed good correlation with histologic findings in rest of the colon using Nancy’s score [Sensitivity of 97.96%, specificity of 100%, accuracy of 98% (95% CI – 89.35% to 99.95%), k of 0.658 (p value &lt; 0.001) and AUC of 0.99 (95% CI- 0.959 to 1.0)], Simplified Geboes Score [Sensitivity of 97.92%, specificity of 100%, accuracy of 98% (95% CI – 89.35% to 99.95%), k of 0.79 (p value &lt; 0.001) and AUC of 0.99 (95% CI- 0.962 to 1.0)], and Robarts Histopathology Index [Sensitivity of 95.56%, specificity of 80%, accuracy of 94% (95% CI – 83.45% to 98.75%), k of 0.694 (p value &lt; 0.001) and AUC of 0.878 (95% CI- 0.667 to 1.0) ]. Histologic disease activity in the colon missed by performing a sigmoidoscopy using Nancy score, SGS and RHI is only 2%, 2% and 4% respectively.

CONCLUSION
In patients diagnosed with UC and having disease extent proximal to the sigmoid colon, sigmoidoscopic evaluation has good correlation with pan colonoscopic evaluation for grading endoscopic and histological disease activity. A sigmoidoscopic examination is adequate to assess the disease activity in patients with disease extent proximal to the sigmoid colon.
CORRELATION OF FECAL, PLASMA, SERUM, AND SALIVARY CALPROTECTIN TO ENDOSCOPIC AND HISTOLOGIC OUTCOMES IN PATIENTS WITH CROHN’S DISEASE
Authors: Kamp Kendra , Clark-Snustad Kindra , Saad Kamil , Tolentino Ernie , Heitkemper Margaret , Dey Neelendu , Gui Sean , Lee Scott D 
Published: January 2022

Abstract

BACKGROUND
Monitoring disease activity in Crohn’s disease is important as achieving endoscopic remission significantly improves clinical outcomes. Fecal calprotectin is a common non-invasive biomarker for monitoring disease activity. However, fecal calprotectin does not always correlate with other disease activity assessments and stool samples can be difficult to collect and inconvenient to return. Thus, we aimed to compare the association between calprotectin levels in stool, saliva, and blood, and assess to their correlation with endoscopic and histologic outcomes among patients with Crohn’s disease.

METHODS
Nineteen patients with Crohn’s disease were included in the data analysis. Patients collected stool, blood and saliva samples within 2 days of colonoscopy. Samples were processed and stored at -80C, then assessed for calprotectin via ELISA. The Simple Endoscopic Score – Crohn’s Disease (SES-CD) was scored at the time of colonoscopy. The biopsy sample with the most severe disease activity was assessed by a single pathologist for the Robarts Histological Index (RHI).

RESULTS
All participants had endoscopic data and blood samples (n=19), 18 had saliva samples, and 18 had stool samples. Participants had a mean age of 32.4 (SD: 7.4). Seventy percent (n=14) were female and 45% were on biologics. The median calprotectin levels were 65.4 ug/g (IQR: 8.5, 385.0) for fecal calprotectin, 23.9 ng/ml (IQR: 15.9, 40.8) for plasma calprotectin, 977.7 ng/ml (IQR: 733.3, 1207.5) for serum calprotectin, and 3761.6 ng/ml (IQR: 874.0, 8267.2) for salivary calprotectin. Correlations (as represented by Pearson’s correlation coefficients) with endoscopic disease activity (SES-CD) were 0.83 for fecal calprotectin, 0.28 for plasma calprotectin, 0.24 for serum calprotectin, and 0.02 for salivary calprotectin. Correlations with histologic disease activity (RHI) were 0.80 for fecal calprotectin, 0.56 for plasma calprotectin, 0.16 for serum calprotectin, and -0.03 for salivary calprotectin.

CONCLUSION
We present preliminary findings of the relationship between calprotectin from fecal, blood, and saliva samples with endoscopic and histologic outcomes in a small sample of patients with Crohn’s disease. Larger sample sizes are needed to further examine the possible role of blood-based calprotectin assessments. In the current study, only two participants had very high SES-CD scores which influenced our ability to understand the relationship of calprotectin to endoscopic disease activity in this subset. Of interest, plasma calprotectin had a higher correlation with histology than serum, which aligns with previous studies.
PAIN IN INFLAMMATORY BOWEL DISEASE (IBD): DOES OPIOID USE PREDICT WORSE HOSPITAL OUTCOMES?
Authors: Dasu Neethi , Khalid Yaser , Blair Brian , Foster C Jonathan 
Published: January 2022

Abstract

BACKGROUND
Opioid use has been hypothesized to be a marker for increased severity of (IBD) for patients because those patients are more likely to require surgical intervention and have uncontrolled pain. Previous studies have not compared outcomes between patients with opioid use and dependence with IBD compared to patients with IBD not using opioids. Our study aims to investigate hospital mortality, hospital length of stay (LOS), and total charges between both patient groups.

METHODS
Data were extracted from the National Inpatient Sample (NIS) 2016-2019 Database. The NIS was searched for hospitalizations for adult patients with IBD, including ulcerative colitis (UC) and Crohn’s (CD), as a principal discharge diagnosis with opioid use and dependence as a 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 for analysis.

RESULTS
Among 1,165,075 patients who had IBD, 33,195 (2.8%) had concomitant opioid usage and dependence. The adjusted odds ratio (OR) for inpatient mortality (OR +2.8, p&lt;0.018), LOS (+1.47 days, p&lt;0.0001), and total hospital charges (+8,982, p&lt;0.0001) for IBD and opioid use compared to those with only IBD were all statistically significant. Independent positive predictors of increased mortality were the following: fistula formation (OR 3.06), hematochezia (OR 2.85), electrolyte abnormalities (OR 1.48), bowel resection (OR 1.37), older age (OR 1.05) [p &lt;0.0001 for all]. Interestingly, colonoscopy (OR 0.48, p&lt;0.0001) and females (OR 0.79, p&lt;0.0001) had less mortality. Independent positive predictors of increased LOS and total hospital charges were the following: fistula formation (+4.9 days, +$53,176 p&lt;0.0001 for both), bowel obstruction (+1.2 days, +$9,228 p&lt;0.0001 for both), hematochezia (+1.0, +14,977 days, p&lt;0.0001 for both), electrolyte abnormalities (+2.0 days, +$16,793, p&lt;0.0001, for both), colonoscopy (+1.9 days, +14,796, p&lt;0.0001 for both), bowel resection (+4.5 days, +66,206, p&lt;0.0001 for both). Total charges were also increased for Asian patients (+11,388, p&lt;0.0001) and Hispanic patients (+10,177, p&lt;0.0001).

CONCLUSION
Our study shows that there is significantly increased mortality, hospital LOS, and total charges for the subpopulation of IBD patients with opioid use and dependence. The presence of fistula formation, hematochezia, electrolyte abnormalities, older age, and prior bowel resection also portends higher mortality. Pain is a common complaint in patients with IBD and leads to increased morbidity. Our study is significant because it illustrates the importance of pain management in IBD and highlights the detrimental outcomes that come with opioid use and dependence. Further randomized trials would be helpful to study this patient population.
THE IMPACT OF CARDIAC ARRHYTHMIAS ON INFLAMMATORY BOWEL DISEASE (IBD)
Authors: Dasu Neethi , Khalid Yaser , Blair Brian , Derosa Justin , Chiesa Drew 
Published: January 2022

Abstract

BACKGROUND
Chronic inflammation in patients with IBD is theorized to be a trigger for cardiac arrhythmias in this patient population. There is a paucity of studies that study the risk factors and outcomes associated with cardiac arrhythmias in patients with IBD. Our study aims to investigate hospital mortality, hospital length of stay (LOS), and total charges between both patient groups.

METHODS
Data was extracted from the National Inpatient Sample (NIS) 2016-2019 Database using ICD -10 codes. The NIS was searched for hospitalizations involving adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), as a principal discharge diagnosis. Cardiac arrhythmias, including atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation, cardiac arrest, and supraventricular tachycardias (SVT) was used as a secondary diagnosis. The primary outcome was inpatient mortality. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used for analysis.

RESULTS
Among 1,165,075 patients who had IBD, 133,270 (11.4%) had cardiac arrhythmias. The adjusted odds ratio (OR) for inpatient mortality (OR 3.44, p&lt;0.0001), hospital length of stay (LOS) (+1.78 days, p&lt;0.0001), and total hospital charges (+25,727, p&lt;0.0001) for IBD and cardiac arrhythmias compared to those patients with only IBD were all statistically significant. Independent positive predictors of increased mortality were the following: fistula formation (OR 3.02), hematochezia (OR 2.63), hypovolemia (OR 1.61), electrolyte abnormalities (OR 1.46), bowel resection (OR 1.37). Interestingly, patients undergoing colonoscopy (OR 0.48, p&lt;0.0001) had less mortality. Independent positive predictors of increased LOS and total hospital charges were the following: fistula formation (+4.9 days, +$52,890 p&lt;0.0001 for both), bowel obstruction (+1.3 days, +$10,000 p&lt;0.0001 for both), hematochezia (+1.0 days, +13,736, p&lt;0.0001 for both), electrolyte abnormalities (+1.9 days, +$15,999, p&lt;0.0001, for both), colonoscopy (+1.9 days, +14,577, p&lt;0.0001 for both), bowel resection (+4.5 days, +75,444, p&lt;0.0001 for both).

CONCLUSION
Our population-based study provides evidence that there is a significant increase in mortality, hospital LOS, and total charges for the subpopulation of IBD patients with cardiac arrhythmias. It is important to note that many patients in the IBD population have concomitant cardiac arrhythmias (&gt;10% in this study) which leads to an increased burden on the healthcare system. It is important for practitioners to recognize the risk factors associated with worsening outcomes in this patient subpopulation as early intervention can help mitigate negative outcomes. The management of IBD is complex and this study illustrates the importance of a multidisciplinary team to help maximize patient care.
COST-EFFECTIVENESS OF TOFACITINIB FOR THE TREATMENT OF MODERATE TO SEVERE ACTIVE ULCERATIVE COLITIS IN COLOMBIA
Authors: Gil Fabio , Julian-Banos Fabian , Amador Luisa , Castano Natalia , Reyes Juan 
Published: January 2022

Abstract

OBJECTIVE
To evaluate the cost-effectiveness of tofacitinib versus other treatment options currently available in Colombia for the management of adult patients with moderate-to-severe ulcerative colitis in naïve to biologics (first line) and exposed to biologics (second line).

METHODS
A Markov model was constructed with 8 weeks cycles. It simulates a cohort of patients with moderate-to-severe ulcerative colitis from a payer perspective in a 5-year horizon. The health states include remission, treatment response (without remission), active UC, and colectomy. The transition probabilities for the induction and maintenance phase were obtained from a network meta-analysis. Effectiveness was measured from quality-adjusted life-year (QALY) and the utilities were obtained from the literature. Unit costs were derived from official national sources, and these were expressed in US dollars 2021 at the average exchange rate of $3 693 COP/US. Probabilistic and deterministic sensitivity analyses were conducted. The threshold was defined as one gross domestic product ($5 391) per capita.

RESULTS
For first line, the incremental cost-effectiveness ratio (ICER) per QALY was for tofacitinib $2 611 and for infliximab $7 652 compared to adalimumab. Sensitivity analysis showed that tofacitinib is shown as cost-effective in 52% of the iterations, followed by adalimumab 25% and infliximab 23% patients. Meanwhile, adalimumab was $27 527 compared to tofacitinib in second line. Tofacitinib was cost-effective 72% of the iterations, followed by adalimumab 28% in the sensitivity analysis. Infliximab and golimumab were not included due to data limitation in network metanalysis in second line. For both lines vedolizumab was not a cost-effective alternative under the threshold assessed.

CONCLUSION
The analysis suggests that, in Colombia, the treatment with tofacitinib for moderate-to-severe UC patients is a cost-effective option in both lines, compare with other treatment options available.
GEOGRAPHIC DIFFERENCES IN THE RISK OF SURGERY IN INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Hansen Tawnya , Mak Joyce , Underwood Fox , Windsor Joseph , King James , Quan Joshua , Buie Michael , Coward Stephanie , Frolkis Alex , Leung Alexander , Ma Christopher , Novak Kerri , Panaccione Remo , Qian Yiming , Burisch Johan , Gearry Richard , Ng Siew , Kaplan Gilaad 
Published: January 2022

Abstract

BACKGROUND
The management of inflammatory bowel disease (IBD) is associated with considerable healthcare and societal cost. A key driver of direct medical cost, remains surgery. Although the cumulative risks of surgery have been well described in countries of the Western world, surgical risk data from Asia, where IBD is rapidly emerging, is lacking.

OBJECTIVES
The primary objective was to compare the cumulative risk of surgery at 1-year after a diagnosis of Crohn’s disease (CD) and ulcerative colitis (UC) between contemporary adult population-based cohorts from the Western world and Asia. Secondarily, we estimated 5- and 10-year risks of IBD-related surgery.

METHODS
MEDLINE and EMBASE were searched for population-based studies published on or after January 1, 2000, that reported 1-, 5-, and 10-year risks of IBD-related surgery. Authors were contacted to provide previously unpublished data. Random effects models were performed to analyze temporal and regional risks of surgery for cohorts diagnosed with IBD in the year 1998 and later.

RESULTS
The initial search yielded 10,358 citations. Of those, 37 studies were used in analyses. For UC, the 1-, 5-, and 10-year risk of surgery were 1.71% (95% confidence intervals [CI]: 1.13, 2.29), 3.77% (95% CI: 2.41, 5.13), and 8.33% (95% CI: 5.03, 11.63), respectively. For CD, the 1-, 5-, and 10-year risk of surgery were 7.17% (95% CI: 5.92, 8.42), 13.63% (95% CI: 11.26, 16.00), and 24.57% (95% CI: 19.21, 29.93), respectively (Table 1; Figure 1). For CD, the 1-year risk of surgery was 7.44% (95% CI: 6.07, 8.80) and 7.22% (95% CI: 2.65, 11.78) for countries in the Western world and countries in Asia, respectively (p= 0.93). The Western 5-year risk of CD surgery (13.52%, 95% CI: 10.85, 16.19) was similar to Asia (15.95%, 95% CI: 5.48, 26.43) (p=0.66). The 1-year risk of surgery for UC was not significantly different between Western world countries (1.87%, 95% CI: 1.27, 2.47) and Asia (0.74%, 95% CI: -0.48, 1.97) (p=0.13). The pooled 5-year risk of surgery was significantly higher in countries of the Western world (4.13%, 95% CI: 2.71, 5.55) as compared to Asia (2.11%, 95% CI: 1.88, 2.33) (p=0.02). Comparison of pooled 10-year risk between countries of the Western world and Asia was not possible as there was only one Asian study published on risk of surgery 10-years after CD and UC diagnosis each.

CONCLUSIONS
During the 21st century the risk of early surgery 1-year after the diagnosis for CD and UC was similar in countries of the Western world as compared to Asia. Long-term (10-year data) was lacking for Asian countries. Future studies are needed to generate more robust long-term estimates for risks of IBD-surgery in Asia.
NOVEL CONTRIBUTIONS OF CLAUDIN-4 TO EPITHELIAL BARRIER REGULATION AND COLITIS
Authors: Shashikanth Nitesh , Liu Yunuo , Xing Tiaosi , Turner Jerrold 
Published: January 2022

Abstract
Intestinal barrier dysfunction is linked to human IBD and contributes to progression of experimental, immune-mediated colitis. Claudin family tight junction proteins are critical determinants of epithelial paracellular permeability and barrier function. Expression of one of these, claudin-2, a pore-forming claudin, is specifically upregulated in IBD. We have shown that claudin-2 overexpression or, conversely, channel inhibition, augment or attenuate, respectively, immune-mediated colitis severity. We sought to understand claudin contributions to barrier function using in vitro and in vivo models.
Claudin-4 overexpression has been shown to reduce cation permeability in vitro, leading to the conclusion that this protein is a barrier-forming claudin. We found, however, that, in the absence of claudin-2 expression, neither knockout nor overexpression of claudin-4 affected barrier function. Instead, claudin-4 specifically suppressed claudin-2 pore function by destabilizing claudin-2 polymers and disrupting claudin-2 anchoring at the tight junction. Thus, claudin-4 is not barrier-forming but is the first pore-regulating claudin.
Together with observations that claudin-2 exacerbates colitis in vivo and that claudin-4 antagonizes claudin-2 function in vitro led us to hypothesize that intestinal epithelial claudin-4 knockout would exacerbate colitis. Knockout mice were, however, protected from both immune-mediated and DSS-induced chemical colitis. Conversely, transgenic claudin-4 overexpression exacerbated colitis. Preliminary in vitro studies suggest that claudin-4 may limit collective migration and epithelial wound repair.
As a whole, our studies require a reconsideration of claudin functional classifications and reveal unanticipated contributions of claudin-4 to barrier regulation and epithelial wound repair. The relationship between these functions and claudin-4 downregulation in human IBD remains to be explored.
PLIN2 IS AN ARYL HYDROCARBON RECEPTOR TRANSCRIPTIONAL TARGET AND MAY CONTRIBUTE TO MUCOSAL RESTITUTION
Authors: Davis Deanna , Ciorba Matthew , Alvarado David 
Published: January 2022

Abstract

INTRODUCTION
Dysregulated barrier function contributes to the pathogenesis in inflammatory bowel diseases (Crohn’s (CD) and ulcerative colitis (UC)). The cytosolic transcription factor aryl hydrocarbon receptor (AHR) is activated by both endogenous and exogenous ligands, and functionally contributes to maintaining mucosal homeostasis. Recently, we demonstrated that AHR activity promotes a pro-restitutive program in small intestine, but this pathway is disrupted in Crohn’s disease. In this study, we sought to identify genetic loci associated with AHR pathway dysfunction and to identify candidate downstream effectors linking AHR activity to mucosal healing.

METHODS
Organoid lines were established with biopsies from healthy patients (N=4) and patients with IBD (CD=4, UC=5) and from mice with intact Ahr (WT) or Ahr null (KO). Genomic DNA was isolated and genotyped with a custom GSA SNP chip. Organoids were differentiated and treated with AHR agonist 6-Formylindolo[3,2-b]carbazole (FICZ) or vehicle. Expression of AHR transcriptional target cytochrome P450 1A1 (CYP1A1) was determined by quantitative realtime (qRT) PCR and was used to measure AHR activity. Genomic association analysis was performed using PLINK with cell lines with high (&gt;3 fold) CYP1A1 expression as controls and cells with low CYP1A1 expression as cases.

RESULTS
Using human organoids, nine genetic variants were associated with low AHR activity (p&lt;5x10-8). One variant, rs12338361, has been identified as an expression quantitative trait locus (eQTL) for Perilipin 2 (PLIN2) in other tissues. PLIN2 is involved in lipid droplet formation and trafficking in the liver, but has also been shown to be a PPARγ effector and reduce inflammation by lowering the release of TNFa in the intestine. In WT mouse organoids, expression of Plin2 was increased in response to FICZ treatment (∼50% increase). This upregulation was dependent on Ahr, as Plin2 expression did not increase in KO mouse organoids (∼7% increase). Expression of PLIN2 was assessed in human organoids treated with FICZ and was found to correlate with AHR activity (r=0.953, p=4.896 x 10-7).

CONCLUSIONS
PLIN2 is a transcriptional target of AHR and may contribute to AHR-mediated epithelial restitution through activation of the PPARγ pathway. This may represent a novel method of controlling inflammation in the intestinal epithelium.