bluuebunny/crossref_metadata_2025 huggingface dataset:
1877 Recruitment to a phase 3, RCT in Parkinson’s: strategies and association between participant characteristics and PI specialty
Authors: Henderson E J , Young G , Pendry-Brazier D , Smith M , Lloyd K , Metcalfe C , Hollingworth W , Ben-Shlomo Y
Published: January 2024

Introduction

Falls are a common complication of Parkinson’s disease, driven in part by an underlying cholinergic deficit that contributes to gait and cognitive impairment. Phase 2 studies have established that amelioration of this deficit using cholinesterase inhibitors may reduce falls.

Methods

CHIEF-PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson's Disease) is a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease that recruited from NHS sites. Relationships between the Principal Investigators’ specialty and the participants baseline characteristics were evaluated using linear, logistic and ordinal logistic regression. Cognitive impairment was defined as MoCA ≤26, while falls in the prior 12 months were separated into ordinal quartiles (1-2, 3-5, 6-12, 13+).

Results

Recruitment to CHIEF-PD commenced in January 2020 and completed in April 2023. Recruitment increased up until the start of the pandemic and thereafter there were 2 peaks. Potential participants were identified through clinic lists, databases, via national and local media and charities. 600 participants were enrolled across 38 sites. Sites enrolled between 1 and 74 participants, each. The median recruitment rate was 19 participants per month (IQR 6-27). 14 (37%) sites had Principal Investigators that were neurologists and 24 (63%) sites had PIs that were geriatricians. Most participants (76%) were over the age of 65 years. Compared with neurologists, geriatricians recruited older patients (difference in means 2.08 (95% CI 0.68, 3.48); p=0.004), with similar levels of cognitive impairment (OR 1.20 (95% CI 0.85, 1.69); p=0.293) and a lower fall rate (OR 0.46 (95% CI 0.34, 0.62); p<0.001) at baseline.

Conclusion

Recruitment of older participants to a Clinical Trial of an Investigational Medicinal Product (CTIMP) trial throughout the Covid-19 pandemic across 38 UK centres was feasible using multiple strategies. Characteristics of participants varied according to the sub-speciality of the Principal Investigator at the site.
1852 The effectiveness of structured physical activity on agitation for people living with dementia: a rapid review
Authors: McCartney A , Crosswell J , Hoe J , Rafnsson S B
Published: January 2024

Background

Managing agitation and other behavioural and psychological symptoms of dementia (BPSD) is a significant challenge and impacts on quality of life for people living with dementia. The priority is to find effective non-pharmacological interventions as drug treatments can have significant side effects.

Objectives

This review evaluates the effectiveness of structured physical activity on agitation in people living with dementia

Methods

A rapid review of the literature was carried out following PRISMA guidelines. Four electronic databases were searched (Cochrane CENTRAL, MEDLINE, CINAHL and Embase) looking for interventional studies that used a structured physical activity programme in people with a diagnosis of dementia, studied the effects of this activity on BPSD and compared this with a control group that did not follow an exercise programme.

Results

From 112 identified articles, 13 were included in this review, involving a total of 1546 participants. The results were analysed and synthesised according to the type of exercise intervention (aerobic, multicomponent or strength training) and by the frequency and intensity of the intervention. Quality assessment using CAPS guidelines indicated four studies as higher quality with seven being of moderate quality. The results showed that aerobic exercise in particular appears to be effective in reducing agitation and those studies with higher adherence to exercise tended to demonstrate more positive effects on agitation and BPSD.

Conclusions

There is evidence that physical activity can be effective in the reduction of agitation in older adults with a dementia diagnosis. Further research is needed to clarify the type of intervention that is most beneficial and strategies to make physical activity more acceptable and available to older people with dementia need to be es established.
2028 Incidence of cavum septum pellucidum on CT brain in patients referred from memory clinic, an observational pilot study
Authors: Cardle C , Jampana R
Published: January 2024

Background

Septum pellucidum is a double-membrane separating the frontal horns of the lateral ventricles of the brain. [1] Cavum septum pellucidum (CSP) refers to a potential space between these membranes. CSP is associated with some psychiatric disorders. [2] Radiological CSP has been evaluated as a possible in-vivo biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative condition affecting, particularly, retired athletes who experienced repetitive, low impact head trauma. [3]

Method

Our study evaluated the incidence of radiological CSP among a cohort undergoing investigation for cognitive impairment in memory clinic. A list of patient Community Health Index (CHI) numbers corresponding to patients referred to CT brain from a community memory clinic in North West Glasgow between October 2019 and March 2020 was generated. Approval for use of imaging for research purposes was granted by local imaging department. Images were viewed by first author following a session from second author on basic relevant anatomy. Positive cases were defined as those with a visible CSP.

Results

There were twenty-eight (n=28) cases in total. CSP was observed in one (n=1) case. Radiological CSP has been suggested as a potential biomarker for CTE. While this study does not involve review of the clinical or personal history of the subjects, it does include a cohort with clinically-relevant symptoms. We included CT only, while current evidence makes observations on MRI [3]. Locally CT is more available and the initial assessment of such patients uses CT in the first instance.

Conclusion

Further evidence is required to establish CSP as a reliable in vivo biomarker of CTE. [1] Das et al, in StatPearls [Internet], 2022 [2] Wang et al, J Neuropsychiatry Clin Neurosci. 2020; 32(2):175-184 [3] Alosco et al Neurotherapeutics. 2021; 18(2):772-791
scCorrector: a robust method for integrating multi-study single-cell data
Authors: Guo Zhen-Hao , Wang Yan-Bin , Wang Siguo , Zhang Qinhu , Huang De-Shuang
Published: January 2024

The advent of single-cell sequencing technologies has revolutionized cell biology studies. However, integrative analyses of diverse single-cell data face serious challenges, including technological noise, sample heterogeneity, and different modalities and species. To address these problems, we propose scCorrector, a variational autoencoder-based model that can integrate single-cell data from different studies and map them into a common space. Specifically, we designed a Study Specific Adaptive Normalization for each study in decoder to implement these features. scCorrector substantially achieves competitive and robust performance compared with state-of-the-art methods and brings novel insights under various circumstances (e.g. various batches, multi-omics, cross-species, and development stages). In addition, the integration of single-cell data and spatial data makes it possible to transfer information between different studies, which greatly expand the narrow range of genes covered by MERFISH technology. In summary, scCorrector can efficiently integrate multi-study single-cell datasets, thereby providing broad opportunities to tackle challenges emerging from noisy resources.
An objective measure of response on whole-body MRI in metastatic hormone sensitive prostate cancer treated with androgen deprivation therapy, external beam radiotherapy, and radium-223
Authors: Giacometti Valentina , Grey Arthur C , McCann Aaron J , Prise Kevin M , Hounsell Alan R , McGarry Conor K , Turner Philip G , O’Sullivan Joe M
Published: January 2024

Objectives

The aim of this study was to generate an objective method to describe MRI data to assess response in the vertebrae of patients with metastatic hormone sensitive prostate cancer (mHSPC), treated with external beam radiation therapy and systemic therapy with Radium-223 and to correlate changes with clinical outcomes.

Methods

Three sets of whole-body MRI (WBMRI) images were utilized from 25 patients from the neo-adjuvant Androgen Deprivation Therapy pelvic Radiotherapy and RADium-223 (ADRRAD) clinical trial: MRI1 (up to 28 days before Radium-223), MRI2, and MRI3 (2 and 6 months post completion of Radium-223). Radiological response was assessed based on post baseline MRI images. Vertebrae were semi-automatically contoured in the sagittal T1-weighted (T1w) acquisitions, MRI intensity was measured, and spinal cord was used to normalize the measurements. The relationship between MRI intensity vs time to biochemical progression and radiology response was investigated. Survival curves were generated and splitting measures for survival and biochemical progression investigated.

Results

Using a splitting measure of 1.8, MRI1 was found to be a reliable quantitative indicator correlating with overall survival (P = 0.023) and biochemical progression (P = 0.014). MRI (3-1) and MRI (3-2) were found to be significant indicators for patients characterized by progressive/non-progressive disease (P = 0.021, P = 0.004) and biochemical progression within/after 12 months (P = 0.007, P = 0.001).

Conclusions

We have identified a potentially useful objective measure of response on WBMRI of vertebrae containing bone metastases in mHSPC which correlates with survival/progression (prognostic) and radiology response (predictive).

Advances in knowledge

Measurements of T1w WBMRI normalized intensity may allow identifying potentially useful response biomarkers correlating with survival, radiological response and biochemical progression.
Patient-led teledermatology for skin lesion triage: a service evaluation of the DyplensTM dermoscope
Authors: Abdul Gafoor Shafiah Muna , Nelson Toby , Woodcock Emma , Adityani Btari
Published: January 2024

Despite the huge improvement in smartphone cameras, there has not been any real interest in the UK in pursuing patient-facing teledermatology within the sphere of skin lesion triage. High-specification dermoscopic images can be generated with smartphone attachments, but, to date, no formal clinical trial has been performed to establish the efficacy and feasibility of these consumer-level dermoscopes in skin lesion triage. The objectives of this study were to assess the ability of patients to capture dermoscopic images using a smartphone attachment, and to identify the safety and diagnostic accuracy of consumer-level dermoscopy in triaging out benign skin lesions from the 2-week-wait (2WW) cancer pathway. We recruited 78 patients already attending a face-to-face clinic at two locations. They were provided with instruction leaflets and asked to obtain dermoscopic and macroscopic images of their lesion(s) using their own smartphones. The images (and a brief history) were distributed to five experienced blinded assessors (consultants), who were asked to state their working diagnosis and outcome (reassurance, routine review or 2WW pathway), as they would in teledermatology. We compared their outcomes to the gold-standard in-person diagnosis and/or histological diagnosis, where available. The device achieved 100% sensitivity in diagnosing melanoma and squamous cell carcinoma (SCC). The specificity for the diagnoses of melanoma (89%) and SCC (83%) was high. The overall diagnostic accuracy was 77% for both benign and malignant lesions, The diagnostic accuracy was high for seborrhoeic keratosis (91%) and simple naevi (81%). Patient-captured dermoscopic images using bespoke smartphone attachments could be the future in safely triaging out benign lesions.
Regional GABA levels modulate abnormal resting-state network functional connectivity and cognitive impairment in multiple sclerosis
Authors: Zhang Chao , Zhang Kaihua , Hu Xin , Cai Xianyun , Chen Yufan , Gao Fei , Wang Guangbin
Published: January 2024

More evidence shows that changes in functional connectivity with regard to brain networks and neurometabolite levels correlated to cognitive impairment in multiple sclerosis. However, the neurological basis underlying the relationship among neurometabolite levels, functional connectivity, and cognitive impairment remains unclear. For this purpose, we used a combination of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to study gamma-aminobutyric acid and glutamate concentrations in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus, and inter-network functional connectivity in 29 relapsing-remitting multiple sclerosis patients and 34 matched healthy controls. Neuropsychological tests were used to evaluate the cognitive function. We found that relapsing-remitting multiple sclerosis patients demonstrated significantly reduced gamma-aminobutyric acid and glutamate concentrations and aberrant functional connectivity involving cognitive-related networks compared to healthy controls, and both alterations were associated with specific cognition decline. Moreover, mediation analyses indicated that decremented hippocampus gamma-aminobutyric acid levels in relapsing-remitting multiple sclerosis patients mediated the association between inter-network functional connectivity in various components of default mode network and verbal memory deficits. In summary, our findings shed new lights on the essential function of GABAergic system abnormalities in regulating network dysconnectivity and functional connectivity in relapsing-remitting multiple sclerosis patients, suggesting potential novel approach to treatment.
Is the long-term poor prognosis of acute myocardial infarction in patients with mental illness mediated through their poor adherence with recommended healthcare?
Authors: Corrao Giovanni , Monzio Compagnoni Matteo , Conflitti Claudia , Lora Antonio
Published: January 2024

Background

Compared with patients without evidence of psychiatric symptoms, those with mental disorders experience reduced adherence with recommended healthcare and poorer clinical outcomes. This study aimed to evaluate whether the worse prognosis of patients with mental disorders after experiencing acute myocardial infarction could be fully or partially mediated by their reduced adherence to recommended healthcare.

Methods

In this retrospective cohort population-based study, 103 389 residents in the Italian Lombardy Region who experienced acute myocardial infarction in 2007–19 were identified. Among them, 1549 patients with severe mental illness (SMI) were matched with five cohort members without evidence of mental disorders (references). Recommended healthcare (cardiac medicaments and selected outpatient services) was evaluated in the year after the date of index hospital discharge. The first occurrences of cardiovascular (CV) hospital admissions and any-cause-death were considered as endpoints. Mediation analysis was performed to investigate whether post-discharge use of recommended healthcare may be considered a mediator of the relationship between healthcare exposure and endpoints occurrence.

Results

Compared with references, patients with SMI had lower adherence with recommended healthcare and adjusted risk excesses of 39% and 73% for CV hospitalizations and all-cause mortality. Mediation analysis showed that 4.1% and 11.3% of, respectively, CV hospitalizations and deaths occurred among psychiatric patients was mediated by their worse adherence to specific healthcare.

Conclusion

The reduced use of recommended outpatient healthcare by patients with SMI had only a marginal effect on their worse prognosis. Other key factors mediating the prognostic gap between patients with and without mental disorders should be investigated.
Reconciling the Dual-Faceted Mandates of Quasi-Judicial Human Rights Bodies: The Working Group on Arbitrary Detention’s Prima Facie Approach to Evidence
Authors: Gillett Matthew , Karukaya Yutaka , Marzotto Mia
Published: January 2024

Focusing on evidentiary approaches, this article examines the burdens and standards of proof applied at United Nations quasi-judicial international human rights bodies. These bodies have dual-faceted mandates, combining legal and human rights traditions and imperatives. However, they diverge in their approach to evidence. This article argues that the prima facie approach developed over the Working Group on Arbitrary Detention's 30 years of jurisprudence provides an appropriately flexible and conceptually coherent means of accommodating combined human rights and the judicial mandates. Nonetheless, this approach requires lexiconic and taxonomical tightening, and clarification of its standard of proof. Comparing the approaches taken by other quasi-judicial bodies, this article builds the impetus towards inter-institutional consistency. It reviews proposals such as wholesale reversal of the burden of proof onto Governments. It highlights the drawbacks of that unilateral type of burden and the risks that it would introduce further uncertainty for parties to proceedings, may cause onerous difficulties for claimants, and would potentially flood the human rights institutions with unsubstantiated claims.
Pregnancy Outcomes in the Ozanimod Clinical Development Program in Patients With Ulcerative Colitis, Crohn’s Disease, and Relapsing Multiple Sclerosis
Authors: Dubinsky Marla C , Charles Lorna , Selmaj Krzysztof W , Comi Giancarlo , Krakovich Anthony , Rosen Melissa , van der Woude C Janneke , Mahadevan Uma
Published: January 2024

Lay Summary

This study evaluated pregnancy outcomes in patients with ulcerative colitis, Crohn’s disease, or multiple sclerosis and in healthy volunteers treated with ozanimod. There was no increased incidence of fetal abnormalities or adverse pregnancy outcomes with ozanimod exposure during early pregnancy.
MITOCHONDRIAL TURNOVER IS ELEVATED IN RESPONSE TO INTESTINAL INFLAMMATION AND IS AMENABLE TO THERAPUTIC TARGETING VIA UROLITHIN A
Authors: Mentrup Heather , Ramos Anna , Novak Elizabeth , Ballesteros Steven , Crawford Erin , Flanagan Meredith , Mollen Kevin
Published: January 2024

Inflammatory bowel disease (IBD) is a complex, multifactorial set of diseases defined by chronic and relapsing inflammation of the gut. Changes in oxidative stress, inflammation, and metabolism are central to the disease process, linking mitochondrial health to IBD pathogenesis. Mitophagy is a quality-control mechanism that selectively removes dysfunctional mitochondria. Multiple mitophagy pathways co-exist in the intestine, including the canonical PINK1/PARKIN pathway and NIX. We have previously shown that NIX is increased in IBD, removing damaged mitochondria in the epithelium. Whether this translates to a physiologic increase in mitochondrial turnover remains unanswered. We hypothesized that mitophagy within the intestinal epithelium represents a key homeostatic response to inflammation. To study this hypothesis, we employed the use of a novel transgenic mouse expressing the pH-dependent fluorescent protein, mt-Keima, tethered to the mitochondria. Adult mt-Keima mice were subjected to chemically induced colitis (3% DSS) for 7 days to induce intestinal inflammation. In vivo mitophagic flux, measured via live-cell confocal microscopy, was increased nearly 4-fold (n=3, p<0.05) in DSS-treated animals compared to controls. Despite this consistent elevation, NIX expression varied in both human and mouse tissue, suggesting that other mitophagy pathways, like PARKIN, may be involved. Interestingly, activated PARKIN (pSer65-PARKIN) was higher in inflamed tissues of humans and mice as compared to controls, though variation was present. To determine the functional importance of PARKIN, Parkin-/- mice were subjected to a 7-day treatment of 2% DSS. These mice developed a more severe colitis, suggesting that Parkin-mediated mitophagy contributes to the mitochondrial damage response in IBD. These data collectively indicate that mitophagy is elevated in IBD, and both NIX and PARKIN likely work in parallel to respond to the elevated mitophagic demand. Interestingly, both NIX and pSer65-PARKIN expression are co-expressed in human control tissues, while both were generally expressed in inflamed biopsies, and at higher levels. We speculate that the mechanism of mitophagy may not necessarily be important, but that it is elevated in response to intestinal inflammation. To address this aim, we administered a known mitophagy inducer, urolithin A, to mice on a 7-day course of DSS. Urolithin A + DSS-treated mice had elevated NIX and pSer65-PARKIN expression compared to vehicle + DSS controls. This elevation correlated with decreased disease activity and improved O2 mitochondria respiration. We conclude that mitophagy is an imperative homeostatic response to remove superfluously damaged mitochondria in IBD and is amenable to therapeutic intervention. Elevating mitophagic flux might be a potential therapeutic option to help improve disease outcomes in IBD.
DIETARY INTERVENTION AS A NOVEL TOOL TO IMPROVE DIAGNOSTIC ACCURACY OF PATENCY CAPSULE IN CROHN'S DISEASE PATIENTS
Authors: Asher Adi Talan , Ukashi Offir , Lahat Adi , Kopylov Uri , Eliakim Rami , Ben-Horin Shomron
Published: January 2024

INTRODUCTION AND AIM

Patency capsule (PC) is a recommended procedure to confirm that the gastrointestinal tract is patent before ingestion of video capsule endoscopy (VCE). However, in some patients non-expelled PC may be due to slow transit time and not due to small bowel stricture. We examined if a nutritional intervention during the PC test which we introduced into routine clinical practice could improve passed PC rate and reduce false positive results.

METHODS

A retrospective study of patients who were subjected to standard protocol of PC procedure or to a nutrition-modified protocol of PC. Nutritional-modification comprised individualized dietary advice on the consumption of personally-convicted laxative foods after PC ingestion. Imaging study at 30 hours post-ingestion was performed to ascertain passage of PC in patients who did not visually see a passed PC in stool.

RESULTS

A total of 49 Crohn's patients who ingested PC were included (median age 33.7, 28.6% with previous intestinal resection). 26 patients followed the nutrition-modified personalized protocol and 23 did not (15 for technical reasons, eight for non-compliance). In total, 38 PC passed and 11 failed. Patients on dietary modification had significantly reduced rate of a failed PC compared to patients receiving standard protocol (7.7% versus 39.13%, respectively, odds ratio 0.13, 95% [CI] 0.0244-0.687, P value = 0.016). All patients with a passed PC subsequently ingested a VCE without complications.

CONCLUSION

Personalized nutritional intervention to promote colonic transit time may serve as a novel practical easy-to-follow dietary tool, in order to improve the diagnostic accuracy of patency capsule. Prospective controlled trials are warranted to corroborate these findings.

Study flowchart. CD, Crohn’s disease; CT: Computed tomography; PC: Patency capsule.

Percentage (%) of patients with failed PC with nutrition protocol or with standard protocol.
REAL WORLD EFFECTIVENESS OF JAK INHIBITOR UPADACITINIB IN ULCERATIVE COLITIS VERSUS CROHN’S DISEASE IN AN IBD TERTIARY CARE CENTER
Authors: Bhatia Karan , Mahadevan Uma
Published: January 2024

BACKGROUND

Upadacitinib is a selective Janus kinase inhibitor approved for the management of Crohn’s Disease (CD) and Ulcerative Colitis (UC).

AIMS

To compare response to upadacitinib between patients with UC and CD in a real world tertiary care center.

METHODS

Retrospective cohort study of adult patients with CD vs UC seen at UCSF Colitis and Crohn’s Disease Center from 2019-2023. The primary outcome was endoscopic remission as noted in post-induction staging scope. Endoscopic remission was assessed using SES-CD and Mayo scores for CD and UC, respectively. Outcomes were assessed at 3 or 6 months after starting upadacitinib for UC and CD, respectively. Failure was considered failure to meet remission criteria, change in medications shortly after induction, or surgery.

RESULTS

A total of 60 patients were reviewed, 26 with Crohn’s Disease and 34 with Ulcerative Colitis, who had taken Upadacitinib and had post-induction follow up data in EHR review. 10 patients with CD achieved remission (38.5%) compared to 17 patients with UC (50%). This difference was found to be nonsignificant (P=0.38).

CONCLUSION

In this real-world cohort of IBD patients seen at a tertiary care center, there was no significant difference in response between patients with CD or UC.
PROTECTIVE ROLE OF SAFFRON TO REDUCE INFLAMMATION AND IMPROVE CLINICAL MANIFESTATIONS IN ULCERATIVE COLITIS PATIENTS
Authors: Ashktorab Hassan , Roghani Roham Salman , Rohgani Hassan , Chirumamilla Lakshmi , Farjana Nasrin , Rashid Mudasir , Aduli Farshad , Kibreab Angesom , Laiyemo Adeyinka , Challa Suryanarayana Reddy , Oppong-Twene Philip , Brim Hassan
Published: January 2024

BACKGROUND

We studied saffron as an additional intervention to improve clinical manifestations of Ulcerative colitis (UC) patients.

METHODS

This is a study at Yazd university where 30 UC patients were randomly assigned to placebo (n=9), low (n=9, 25 mg), or high dose saffron (n=12, 50mg), two times a day for 8 weeks. Hemoglobin, platelet levels, CRP, ESR, and fecal calprotectin along with clinical data Simple Clinical Colitis Activity Index (SCCAI), Partial Mayo Score, and Hamilton Depression Anxiety Score (HDRS) were recorded at baseline and completion of treatment. For validation, we recruited 3 UC patients at Howard University who received 50mg of Saffron twice daily for 8 weeks, two underwent a wash-out period and received saffron for a second cycle. Inflammatory markers, CRP, stool calprotectin, and the cytokines from PMA/ionomycin stimulated PBMCs, at baseline and 8 weeks Saffron treatment were compared. 16S rDNA analysis was performed on stool DNA for gut microbiome.

RESULTS

In Yazd study of 30 patients, all participants completed the study successfully. The high dose group showed significant improvement in HDRS score (p=0.001), SCCAI (p=0.04), Partial Mayo score (p=0.01), fecal calprotectin (p=0.009), and CRP (p=0.001) compared to baseline. The low dose group also improved in HDRS score (p=0.01; Table 1, Fig 1). No adverse events were reported. In HU data, saffron improved Partial Mayo Score, health related quality of life and HDRS. Pro-inflammatory cytokines TNFα, INFγ, IL-6, IL-2, IL-17a decreased while anti-inflammatory IL-10, TGF-β increased. Fecal calprotectin levels of 228 μg/g and 169 μg/g decreased to 63 μg/g and 16 μg/g in two individual patients, respectively. After the wash-out period, fecal calprotectin increased. A second saffron treatment cycle reduced it again further validating the causal relationship. Saffron led to a decrease in gamma Proteobacteria, and enrichment in Ruminococcaceae.

CONCLUSION

This study demonstrates that saffron led to improvements in clinical response including reduction in partial Mayo scores, HDRS scores, and inflammatory markers such as fecal calprotectin and CRP. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with UC.

Table 1. Basic characteristics, clinical variables, and laboratory variables among the study participants in three arms of the clinical trial.

Figure 1 Effect of Saffron on quality of life and Inflammatory markers.
COMPARING MAGNETIC RESONANCE ENTEROGRAPHY AND ENDOSCOPY FINDINGS TO QUANTATATIVE MAGENTIC RESONANCE IMAGING IN PEDIATRIC CROHN’S DISEASE
Authors: McSorley Brianna , Plunk Matthew , Challa Sai Alekha , Pan Amy , Menys Alex , Noe Joshua
Published: January 2024

BACKGROUND

In pediatric Crohn’s disease, endoscopy has remained the gold standard for diagnosis; however, Magnetic Resonance Enterography (MRE) is able to show inflammation of the bowel that a gastroenterologist cannot reach with endoscopy. For a standard MRE, a patient needs to ingest oral contrast, receive intravenous (IV) contrast and a spasmolytic agent, and hold his/her breath during portions of the study, which can be challenging in younger children. As shown in previous studies, quantitative Magnetic Resonance Imaging (MRI) can evaluate bowel motility in children with Crohn’s disease, showing that as motility decreases in the bowel, inflammation increases. A motility score obtained from GIQuant software (Motilent, UK) may allow existing MRE protocols to be shortened and can be done with free-breathing techniques and without IV contrast and the spasmolytic agent.

AIM

Our primary aim is to demonstrate that quantitative MRI, which uses the cine image to develop a motility score from GIQuant software, is as effective as standard MRE in assessing inflammation of the bowel. We secondarily hypothesize that the motility score will inversely correlate to the Endoscopic Biopsy Acute Histologic Inflammatory Score (eAIS), the Crohn’s Disease Endoscopic Index of Severity (CDEIS) score, and the MR Index of Activity (MaRIA) score.

METHODS

This was a retrospective study of 50 pediatric patients from Children’s Wisconsin with ileal and/ or cecal Crohn’s disease who underwent endoscopy and MRE within 7 days of each other without exposure to therapy. Cine images were used from patients’ previously obtained MREs to obtain a motility score using GIQuant. A cine image and GIQuant map example is shown in Figure 1. The relationships between motility score and MaRIA, eAIS, and CDEIS were then calculated by Spearman’s rank correlation coefficient (ρ).

RESULTS

MaRIA and motility scores inversely correlated (ρ = -0.66, p <.0001), which is seen in Figure 2. MaRIA positively correlated with CDEIS (ρ = 0.30, p= 0.03) and eAIS (ρ = 0.26, p = 0.07). The motility score showed a non-significant negative correlation with CDEIS (ρ = -0.17, p = 0.24) and eAIS (ρ = -0.23, p =0.11).

CONCLUSION

Quantitative MRI is as effective as standard MRE in identifying inflammation of the bowel in Crohn’s disease. The cine image is obtained much faster than standard MRE and without the use of intravenous contrast, spasmolytic agent, and breath-holding techniques, which is crucial for children who are too young to cooperate with current MRE protocols.

Figure 1 MRE cine image with the Region of Interest in the terminal ileum identified via the polygon and the resulting Motility Map produced by GIQuant

Figure 2 MaRIA and Motility scores of each patient in our cohort
SOCIOECONOMIC DISPARITIES IN HOSPITALIZATION AND OUTCOMES OF EOSINOPHILIC COLITIS: A FIVE-YEAR NATIONAL ANALYSIS
Authors: Karki Bibek , Kandel Pujan , Belbase Samjhana , Ghimire Calvin , McDonald Philip , Elbedawi Mamoon
Published: January 2024

BACKGROUND

Eosinophilic colitis (EoC) is a rare gastrointestinal inflammation of the colon due to an altered hypersensitivity reaction characterized by eosinophilic infiltration into the colonic wall. Patients usually present with abdominal pain, diarrhea, and weight loss.

METHODS

We used the National Inpatient Sample (NIS) database to conduct a retrospective study of hospitalized adult patients with eosinophilic colitis using the validated ICD-10 diagnosis codes between January 1, 2016, and December 31, 2020.

RESULTS

We identified 4353 cases of eosinophilic colitis using the NIS database. There were 748, 776, 889, 934, and 1,006 eosinophilic colitis cases diagnosed in 2016, 2017, 2018, 2019, and 2020 respectively. Males were more likely to be hospitalized due to eosinophilic colitis than females (51.8% vs. 48.2%). Moreover, there was a significantly higher prevalence of eosinophilic colitis among the white population, with 81.7% in Whites, 8.1% in Blacks, 6.3% in Hispanics, and 1.3% in Asians. 26.5% of those patients had Medicare, 15.7% had Medicaid, and 50.6% had private/HMO insurance. About 20.7% of patients had a median household income of $45,999 or less, 23.6% had $46,000-58,999, and 55.6% had $59,000 or more. Based on hospital location, 30.3% of the cases were in the South, 27.5% in the Midwest, 23.4% in the West, and 18.8% in the Northeast. The majority of patients admitted for eosinophilic colitis were recorded in urban teaching hospitals (77.8%) compared to 17.6% in urban nonteaching hospitals and 4.6% in rural areas. Only 16.5% of the patients with eosinophilic colitis had a Charlson Comorbidity Index of 3 or higher.

CONCLUSION

Based on the national inpatient sample over 5 years, males and whites are more likely to be hospitalized with eosinophilic. The report suggests that eosinophilic colitis is common among patients with high median household income and has a better prognosis.
UNIQUE MONOCYTE EXPRESSION SIGNATURE IN A STXBP2 MUTATION CAUSING INFANTILE ONSET VEO-IBD AND HLH
Authors: Baccarella Alyssa , Dawany Noor , Conrad Maire , Heimall Jennifer , Bunin Nancy , Gaddipati Shreya , Cohen Maya , Pickering Oliver , Borodyanskaya Yelizaveta , Sullivan Kathleen , Kelsen Judith
Published: January 2024

Mutations in syntaxin-binding-protein-2 (STXBP2) can result in NK cell dysfunction leading to a hyperinflammatory state including familial HLH and infantile onset inflammatory bowel disease (IBD). While the function of STXBP2 in NK cells and cytotoxic T cells has been well described, it is highly expressed in monocytes with unclear relevance. We report the case of an infant who presented with severe infantile onset diarrhea with an identified pathogenic mutation in STXBP2. We sought to utilize scRNA-Seq to study the impact of STXBP2 deficiency on monocyte transcription, with the goal of generating insight into the pathogenesis of disease.

METHODS: Trio whole exome sequencing was performed. PBMCs were collected from the described patient (case), and two control groups: 3 patients with VEO-IBD, and 3 age matched healthy controls. Single cell RNA-Seq was performed using the 10x platform and data analysis was done using Seurat in R.

RESULTS: A male infant presented at 1 week of age with diarrhea and metabolic acidosis. Endoscopic evaluation at 4 weeks of age showed histologic findings of colitis and marked epithelial cell changes, including cell rounding. WES identified a homozygous pathogenic mutation in STXBP2. Due to significant risk of HLH, he underwent evaluation for stem cell transplant. However, in the interim he developed severe HLH requiring ICU level care. He recovered following aggressive treatment and underwent HSCT at 4 months of age and retransplant for graft failure at 11 months of age. He is currently in endoscopic remission off therapy.

We analyzed PBMCs from the case patient using single cell RNA-Seq, as compared to patients with VEO-IBD and age-matched controls. STXBP2 expression was most enriched in monocyte populations and reduced in the case patient compared to controls. 231 and 187 genes were differentially expressed in the case monocytes as compared to both controls. The case patient had a paucity of non-classical monocytes. Within the classical monocytes, differentially expressed genes showed enrichment of host defense, cytokine processes, and apoptotic processes. Within the intermediate monocytes, differentially expressed genes showed enrichment of chemotaxis pathways, antigen presentation and T cell activation processes.

CONCLUSIONS: Mutations in STXBP2 are a life-threatening cause of fHLH and infantile onset IBD. We report a case of infantile onset IBD due to a homozygous mutation in STXBP2 with resolution of disease post HSCT. Transcriptional analysis of PBMCs from this patient reveals a paucity of non-classical monocytes in the peripheral blood, and differential regulation of genes implicated in host defenses, antigen presentation, chemotaxis and apoptosis. These results may suggest the role of monocyte function in pathogenesis of STXBP2 and in other forms of IBD.
COST PER REMISSION FOR MIRIKIZUMAB VS USTEKINUMAB IN THE MAINTENANCE PHASE FOR MODERATELY-TO-SEVERELY ACTIVE ULCERATIVE COLITIS TREATMENT FROM THE UNITED STATES COMMERCIAL PAYER PERSPECTIVE
Authors: Gulati Ankit , Kane Sunanda , Mittal Neha , Creveling Thomas , Bires Nicholas , Fisher Deborah , Chanan Neha , Koushik Amit Kumar , Upadhyay Navneet
Published: January 2024

BACKGROUND

In phase 3 studies, mirikizumab (MIRI), an IL-23p19 antibody, demonstrated efficacy vs placebo in adult patients with moderately-to-severely active ulcerative colitis (UC). It is being developed for the United States Food and Drug Administration approval for the treatment of UC. Ustekinumab (USTE), an IL-12/23p40 antibody, is currently the most utilized second line treatment in UC patients. Physicians may prescribe MIRI in a similar placement to USTE, and payers may compare them when making formulary decisions for IL-23 inhibitors. Given the need for continued maintenance therapy to manage UC, it is of interest to evaluate the relative cost-efficiency of MIRI vs USTE. We estimated and compared the cost of MIRI vs USTE for achieving remission in one additional patient during the maintenance phase in biologic/Janus kinase inhibitor (JAKi)-experienced patients with UC.

METHODS

This study used a network meta-analysis (NMA) of published randomized controlled trials of maintenance phase therapy to derive the number needed to treat (NNT) for achieving clinical remission among those who responded to induction therapy. In NMA, clinical remission was defined as a total Mayo score of ≤2 points, with no individual sub-score >1. An Excel-based analytic model was developed to estimate cost per additional patient achieving clinical remission at the end of maintenance trial period. The model included the cost of maintenance therapy from a US commercial payer perspective and the NNT of achieving clinical remission for MIRI and USTE in the biologic/JAKi-experienced population. Wholesale Acquisition Cost (WAC) of USTE was taken from Micromedex Redbook. A scenario with USTE biosimilar was also considered where NNT was considered the same as USTE, but the WAC was considered 50% lower than the current WAC of USTE.

RESULTS

The costs per biologic/JAKi-experienced patient achieving clinical remission during the maintenance phase were $501,472 and $1,027,799 for MIRI and USTE. The lower cost per remission for MIRI in maintenance was the result of both lower relative NNT and lower anticipated WAC of MIRI compared to USTE. The scenario also resulted in a comparable cost per remission for MIRI vs a USTE biosimilar.

CONCLUSION

MIRI is projected to have a lower cost per remission during maintenance therapy compared to USTE. Given the need for long-term treatment for this chronic condition, MIRI appears to be a cost-efficient treatment option based on its lower NNT and anticipated acquisition cost in the maintenance phase.
DEVELOPING A SCORING SYSTEM TO PREDICT CHRONIC OPIOID USE AMONG ADOLESCENTS AND YOUNG ADULTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Balbale Salva , Huang Lynn , Raval Mehul
Published: January 2024

BACKGROUND

Chronic, or long-term, opioid use is associated with higher risk of addiction and death as well as poor inflammatory bowel disease (IBD) outcomes. Recent data estimate that up to 20% of adolescents and young adults (AYA) with IBD may be chronic opioid users. Models to predict chronic opioid use among AYA with IBD may support identification, clinical management, and follow-up of patients at high risk of opioid dependence. We aimed to develop a clinical predictive model based on administrative data for chronic opioid use among AYA with IBD.

METHODS

We performed a retrospective analysis of AYA patients between 15-29 years treated at a tertiary academic center for IBD management from 3/2018-12/2021. Univariate regression was performed to identify individual predictors of chronic opioid use. Multivariate regression was performed using variables with p-values <0.15 in univariate regression. Variables significant after adjustment were included in a simple scoring system. Point estimates for chronic opioid use risk probabilities were derived using the percentage of chronic opioid users in our analytic cohort assigned that prognostic score. 95% confidence intervals were estimated using a bootstrapping technique with 1000 replications.

RESULTS

Our final cohort included 575 unique AYA patients with IBD. Patients were, on average, 23 years old (IQR 20-26) and 69% of the cohort was female. 41% had a diagnosis of Crohn’s disease, 25% with ulcerative colitis and 64% with indeterminate colitis. Patients’ mean age at index IBD diagnosis was approximately 22 years and over half (56%) had undergone prior IBD surgery. Following adjustment, eleven factors were associated with the highest odds of chronic opioid use, including: public insurance coverage, non-digestive or non-gastrointestinal (GI) surgery, outpatient prescription receipt for weaker opioids (i.e. codeine/tramadol), and concurrent depression and post-traumatic stress disorder (PTSD) diagnoses (Figure 1). Prognostic scores ranged from 1-9 (mean: 5, SD=2.7). Patients were stratified into three risk categories by prognostic score (1-4; 5-7; 8-9) with associated risk scores of 52.1% (95% CI: 48.9-55.2%), 68.6% (66.5-71.1%), 86.2% (76.6%-94.4%), respectively (Figure 2).

CONCLUSIONS

We developed a practical scoring system to stratify AYA with IBD by chronic opioid use risk. Future directions include understanding the relationship between these risk factors and their influence on chronic use. Risk factors most associated with chronic opioid use among AYA with IBD included: public insurance coverage, undergoing a non-digestive surgical procedure, and having concurrent diagnoses of depression and PTSD. Findings will directly inform targeted opioid reduction initiatives for this vulnerable population.

Figure 1 Final risk factors associated with development of prognostic score.

Figure 2 Percent of chronic opioid users by prognostic score.
DIFFERENCE IN HEALTHCARE OUTCOMES BETWEEN PUBLIC AND PRIVATE PAYERS FOR PATIENTS ADMITTED WITH CROHN'S DISEASE
Authors: Salazar Miguel , Flocco Gianina , Al-Smadi Khaled , Hammami Bader , Saffouri George
Published: January 2024

BACKGROUND

In countries where health coverage is not universal, there is ample evidence of disparities in healthcare, often associated with insurance. Crohn’s disease (CD) is a complex chronic disease with potential for significant morbidity if the content or delivery of healthcare is suboptimal. However, the literature related to primary payers and CD remains lacking.

METHODS

We queried the National Inpatient Sample (NIS)from 2016-2019 using ICD10-CM/PCS codes to identify hospital discharges with a diagnosis of CD. Patients were subsequently stratified based on insurance (Medicare, Medicaid, Private, and No insurance). Observations were categorized into two groups, private and public (Medicare and Medicaid) insurance. Patients without insurance were excluded from the study. In-hospital mortality, total hospital cost, length of stay, and in-hospital complications were evaluated. Multivariate logistic regression analysis was conducted to adjust for confounders.

RESULTS

A total of 135,075 discharges with diagnosis of CD were identified with a primary payer insurance, of which 70,275(52.1%) had private insurance and 64,800 (47.9%) public. Patients with private insurance were more likely to be white (68.9% vs 78.4%; P<0.01), have lower Charlson score (46.1% vs 59.1%; P<0.01), belong to the higher income bracket (16.7% vs 29.6%; P<0.01), be admitted to a teaching institution (74.2% vs 79.4%; P<0.01), and be in an urban setting (92.2% vs 95.5%; P<0.01). Patients with private insurance were less likely to require parenteral nutrition (5.9% vs 5.3%; P=0.04), have severe malnutrition (8.8% vs 6.4%; P<0.01), abuse EtOH (1.7% vs 0.8%; P<0.01), use tobacco (1.4% vs 1.1%; P<0.01), use cannabis (4.2% vs 2.3%; P<0.01), have iron deficiency anemia (13.4% vs 11.6%; P<0.01), and die during hospitalization (0.4% vs 0.1%; P<0.01).

On multivariate analysis, there was lower mortality in patients with a private primary payer [0.28; (P<0.01)], shorter LOS (5.8 vs 4.9 days mean days; P<0.01), and lower healthcare charges [ -3,903 US$; (P<0.01)]. Overall, those with private insurance had lower in-hospital complications such as respiratory failure [aOR 0.75; (P=0.05)], endotracheal intubation [aOR 0.50; (P<0.01)], prolonged mechanical ventilation [aOR 0.36;(P<0.01)], hemodialysis [aOR 0.34; (P<0.01)], acute kidney injury [aOR 0.72; (P<0.01)], and venous thromboembolism [aOR 0.54; (P<0.01)]. However, they had higher rates of surgical interventions including small bowel resection [aOR 1.57; (P<0.01)], large bowel resection [aOR 1.58; (P<0.01)], laparoscopic surgery [aOR 2.44; (P<0.01)], and to require conversion to open surgery [aOR 1.55; (P<0.01)].

CONCLUSIONS

Our findings suggest that primary public payers were independently associated with higher morbidity and mortality in patients admitted with CD.
REVOLUTIONIZING IBD MANAGEMENT: HOW DO CHATGPT & GOOGLE BARD STAND UP IN OFFERING COMPREHENSIVE MANAGEMENT SOLUTIONS?
Authors: Mohan Raj Mohan Ram , Natt Dilman , Joy Melvin , Magam Sai Reshma , Magam Sai Greeshma , Desai Jiten , Jiyani Rucha , Mustacchia Paul
Published: January 2024

INTRODUCTION

Artificial Intelligence (AI) has notably transformed the realm of healthcare, especially in diagnosing and treating Inflammatory Bowel Disease (IBD) and other digestive disorders. Essential AI tools, such as ChatGPT and Google Bard, can interpret endoscopic imagery, analyze diverse samples, simplify administrative duties, and assist in assessing medical images and the automation of devices. By individualizing treatments and forecasting adverse reactions, these AI applications have notably enhanced the management of digestive diseases. Integrating such AI technologies empowers patients to make knowledgeable choices by evaluating customized treatment alternatives.

METHODS

The study's objective was to evaluate the precision of two widely used Chat Bots, Chat GPT and Google BARD, in responding to queries related to medical management. Each bot was tasked with answering a series of questions, and the responses were scored on a 1-10 Likert scale, with 1 denoting high accuracy. To uphold impartial judgment, two unbiased assessors reviewed each bot's replies. The purpose of this research was to illuminate the competencies of these chatbots by systematically analyzing their performance in aspects of accuracy and dependability. Employing two evaluators and utilizing the Likert scale approach helped mitigate potential biases, corroborating the findings.

RESULTS

Our study compared the proficiency of Chat GPT and Google BARD in medical management. Chat GPT demonstrated superior performance, achieving 71% in accuracy as opposed to Google BARD’s 39% (p = 0.032) and 58% versus 29% in the reliability of medical information (p = 0.021). This research underscores the pivotal importance of accuracy and reliability in the creation of IBD chatbots. While Chat GPT showed commendable results, signifying its promise as a trustworthy resource, it also highlighted the imperative need for ongoing research and advancement in this domain.

DISCUSSION

AI has significantly reshaped healthcare, particularly aiding in the diagnosis and management of IBD. ChatGPT and Google Bard are key AI tools that analyze medical images, assess samples, and optimize tasks. Our research evaluated the precision and dependability of these chatbots in the sphere of medical management. ChatGPT surpassed Google Bard, securing 71% in accuracy and 58% in reliability of information. While ChatGPT showcases substantial potential as a reliable AI instrument in IBD management, the results also accentuate the continual necessity for exploration and advancement in this area.