PCD Patients Research Articles

P0123 The immune system of patients with immune-mediated diseases perceives dysbiotic intestinal microbial species, and IgG reactivity uncovers shared and non-shared responses across diseases

Abstract Background Immune-mediated diseases (IMIDs), like Crohn’s disease (CD), ulcerative colitis (UC), psoriatic arthritis (PsA) and type I diabetes (T1D), have common features, including intestinal microbial dysbiosis. However, it is unclear whether dysbiosis contributes to IMID pathogenesis and whether the host immune system perceives dysbiotic commensals. In CD, high IgG and T-cell responses to Lachnospiraceae-derived flagellins associate with complex disease, while Lachnospiraceae fecal abundance is decreased in CD, suggesting that individual variation in the host-microbial mutualism is important. We studied IgG responses to dysbiotic microbial species across IMIDs, and questioned whether changes in these IgG responses are homogeneous within each IMID and shared among IMIDs. Methods Using shotgun metagenomic sequencing of feces from 6 IMID cohorts (n=5650), dysbiosis was extrapolated to species level. Plasma IgG reactivity to lysates of 71 dysbiotic species was measured in adult CD (aCD, n=50), adult UC (aUC, n=50), PsA (n=100), rheumatoid arthritis (RA, n=74), T1D (n=75), healthy controls (aHC, n=97), pediatric CD (pCD, n=103), pediatric UC (pUC, n=48), pediatric HC (pHC, n=58), pediatric celiac disease (CeD, n=103) and no-CeD HC (n=68). Multiple ordinal regression analysis was performed corrected for age, sex and multiple testing. Results Anti-microbial IgG responses compared to age-matched HC were increased in aCD (2/71); pCD (46/71); PsA (3/71); RA (1/71); decreased in T1D (10/71) and pUC (1/71), and not different in CeD and aUC. Shared increased responses occurred to: Klebsiella oxytoca and Roseburia inulinivorans in aCD and pCD, Streptococcus parasanguinis and Streptococcus vestibularis in PsA and pCD, and Acidaminococcus intestini in both arthritic diseases PsA and RA. As changes were heterogeneous within each IMID, hierarchical clustering of all anti-microbial responses across adult IMIDs was performed. Clusters had a mix of IMIDs, uncovering shared response patterns across IMIDs. Although aCD and aUC patients had disease-specific responses, their overall anti-microbial response pattern was not different from other IMIDs. In contrast, pCD patients were clearly distinct from pUC and pHC, with high number of significantly increased anti-microbial IgG responses and separate hierarchical clustering, demonstrating overall increased anti-microbial responses in pCD versus aCD. Interestingly, clustering grouped pCD patients with similar clinicopathological parameters, arguing that anti-microbial IgG response patterns may relate to disease pathogenesis. Conclusion We show that the immune system perceives dysbiotic commensals and uncover shared and non-shared anti-microbial IgG responses among adult and pediatric IBD and other IMID patients.

P0933 Symptoms improvement after VAAFT procedure in patients with perianal Crohn’s disease

Abstract Background Perianal fistulas may affect about 30% of patients with Crohn’s disease (CD). Management of perianal Crohn’s disease (pCD) is difficult due to the presence of complex and recurrent fistulae unlikely to heal spontaneously or after medical-surgical treatment. . Previous studies have shown how the use of Video-Assisted Anal Fistula Treatment (VAAFT) can lead to a benefit in terms of symptom control in patients with pCD. The aim of this study is to describe the outcome of VAAFT in terms of symptomatic improvement in patients affected by pCD. Methods A retrospective study was conducted in a single centre on CD patients with perianal fistulae undergoing VAAFT procedure from July 2021 to April 2024. According to the AGA classification, all perianal fistulae were "complex". The VAAFT procedures were performed with different technical aspect. Preoperatively and 8 weeks after the perianal surgery a questionnaire on symptoms was submitted to each patient. This questionnaire evaluated several items: pad usage per day and pain, discharge and daily activity limitation on a 0-6 point Likert scale. Results 25 patients underwent 37 VAAFT procedures. Ten patients had > 1 VAAFT. The median duration of pCD was 6 years. The majority of patients underwent previous anal fistula surgery and 13 patients were on biological therapy at the time the first VAAFT. 12 (48%) had multiple or secondary tracts; an additional 17 (68%) had an abscess and 3 (12%) horseshoe fistulae. Median values of pain score (5 vs 0, p<0.001), discharge score (5 vs 2, p<0.001), daily activity limitation score (4 vs 1, p<0.001) and pads usage per day (4 vs 1, p<0.001) significantly decrease after VAAFT procedure. Of these 25, 3 patients reach an improvement in symptoms after the second VAAFT procedure. No post-procedural complication were recorded. Conclusion VAAFT is a safe, repeatable and minimally invasive procedure that can provide a reduction of symptom burden in pCD patients, affecting their quality of life.

P0991 Laparoscopic ileocecal resection in pediatric Crohn’s disease: effect of anastomotic configuration on postoperative outcomes in the era of biologic therapy

Abstract Background Postoperative complications and recurrence (POR) frequently follow Ileocecal resection (ICR) in pediatric Crohn’s disease (pCD) patients. Evidence addressing the effect of anastomosis type on complications and POR in children remains limited. We aimed to compare laparoscopic-assisted end-to-end (ETE), side-to-side (STS), and Kono-S anastomoses and evaluate their outcomes based on the followed parameters. Methods From April 2018 to December 2023, we prospectively collected data on anastomosis configuration, colonoscopy at 6 months post-surgery, perioperative and demographic parameters from all pediatric patients referred to ICR for pCD. Complications were classified according to the Clavien–Dindo classification (CDc). Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for endoscopic recurrence (ER), defined as Rutgeerts score >1. The ETE was set as the reference. Artificial Intelligence (AI) were not used in the production of this abstract. Results Thirty-eight patients (18 females, 47.4%) were included, 14 in ETE, 10 in STS, 14 in Kono-S. No preoperative differences were observed. Median surgery durations were 151 minutes for ETE, 142 for STS (p=0.78), and 169 for Kono-S (p=0.09). Complication rate did not significantly differ. Median hospitalisations were 6.5 days for ETE, 6 for STS (p=0.85), and 6 for Kono-S (p=0.70). Neither Kono-S nor STS showed a higher risk of ER compared to ETE, with OR=1.13 (95%CI=0.21-6.16) for STS and OR=0.41 (95%CI=0.09-1.87) for Kono-S. Conclusion Kono-S and STS anastomoses demonstrated comparable complication rates to ETE, without significantly prolonging hospitalization or operation duration. Neither type of anastomosis was associated with an increased risk of ER.

Perianal Crohn’s disease across borders – understanding unmet needs to aid future global solutions

Abstract Background and aims Perianal Crohn’s disease (pCD) represents a challenging manifestation of CD, with a high symptomatic and psychological burden for patients. Epidemiologic differences in this CD phenotype have been reported across the world. At ECCO 2020, a Consortium was established to address pCD. An initial project was the development of a new classification of perianal fistulising Crohn’s disease (PFCD) (Geldof et al. LGH 2022). It has now developed “standard operating procedures” (SOPs) for clinical, radiologic and biosample collection, to facilitate consistent and collaborative research. Aims: Now, the Consortium’s goals are to expand and support low- and middle-income countries (LMICs), to 1) build data collection platforms to explore phenotypic similarities and differences across continents in PFCD regarding demographics, diagnosis (including issues around delayed diagnosis), treatments, outcomes and molecular architecture (using transcriptomic techniques); and 2) enable infrastructural developments at collaborating sites to support future IBD research and education, using PFCD as the template. Methods Collaborations have been established with Asia, South America and Africa. Data collection templates developed by the Consortium (with a data dictionary) will be used to interrogate a cohort of patients with PFCD (demographics, disease distribution, diagnosis pathways, treatment outcomes – both medical and surgical). Additionally, data will be collected from an inception cohort of patients with new PFCD. Biosample collection and banking will be conducted, prioritising new diagnosis/treatment-naïve patients and will focus on transcriptomic research (where pilot data points to differences). Anticipated impact This proposal will address each item of ECCO’s 5-year REACH strategy. It will assess time to diagnosis, equitable access and sustainable healthcare, probe pathogenic drivers of this CD-phenotype and address the holistic impact of PFCD in different parts of the world. Importantly, it will drive learning, understanding and education to improve care for pCD patients globally and establish networks and infrastructure for wider IBD research.

P0030 Multiomic Analysis Reveals Three Distinct subtypes within Perianal Crohn’s Disease, Independent of Concomitant Proctitis

Abstract Background Perianal fistulisation (pCD) affects ~20% of Crohn’s disease (CD) patients and often requires combined medical and surgical management. Despite significant progress in management of luminal CD, pCD continues to pose a major unmet need, emphasizing the importance of understanding the molecular and environmental drivers and to discover new therapeutic targets. Methods Paired biopsies from the fistula tract and rectal orifice of 81 pCD patients underwent 16S rRNA and RNA sequencing, generating multiomic profiles for both tissues. We applied Multiomics Factor Analysis (MOFA), to identify key molecular signatures, followed by hierarchical clustering1. Gene module scores were derived using Seurat to visualize expression patterns on a public single-cell RNA seq (scRNA-seq) dataset. Results The MOFA model showed minimal contribution from the microbiota but accounted for over 80% of transcriptomic variance. Unsupervised clustering based on MOFA identified three distinct patient clusters (C1, C2, C3) with unique molecular phenotypes, independent of concomitant or prior proctitis (p=1.0) (Fig 1A). C3 was associated with positive end of the primary axis of variation, showing a keratinization signature in the fistula, without signs of epithelial-mesenchymal transition (EMT) or rectal keratinization (Fig 1B). In contrast, C1 and C2 were linked to the opposite extreme of this axis, characterized by EMT signatures in the fistula and an absence of keratinization. The rectal profiles differed between these two clusters: C1 lacked keratinization in the rectum, while C2 exhibited concurrent keratinization (Fig 1B). The opposing pattern along the primary axis suggests that keratinization and EMT represent distinct, mutually exclusive processes in fistula pathology. Analysis of publicly available scRNA-seq data from psoriasis patients (a keratinization-hallmark disease) revealed significant upregulation of the pCD-specific keratinization gene signature in lesional keratinocytes compared to non-lesional samples, indicating a psoriasis-like keratinization process in pCD2 (Fig 2)2. Finally, microbial profiling showed no significant associations between bacterial genera and any of the identified clusters in either rectum or fistula (adj. p > 0.05) Conclusion Our analysis identified three distinct patient clusters in pCD, revealing diverging keratinization and EMT phenotypes in fistula. This stratification was independent of proctitis and there was little to no contribution of the microbiota. Comparing the expression profiles with the ones observed in patients with psoriasis suggests a psoriasis-like keratinization process in a subset of patients. These findings uncover potential novel mechanisms in pCD pathogenesis.

DOP047 Effectiveness of second-and-third line biologics in perianal Crohn’s disease (pCD) – a multicenter propensity score-matched study

Abstract Background Perianal involvement affects approximately 20-30% of Crohn’s Disease patients, significantly impairing their quality of life. Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are still the established biological treatment for perianal Crohn's disease (pCD). However, relapse and non-response are frequent and evidence regarding the effectiveness of 2nd- and 3rd-line biologics is limited. This study aims to compare the efficacy of 2nd- and 3rd-line biologics in patients with pCD who have previously failed 1st-line anti-TNF therapy. Methods A retrospective multicenter study of adult pCD patients who failed 1st line anti-TNF therapy. The primary outcome was defined as clinical perianal response based on physician assessment. The main secondary outcome was radiological perianal response, based on magnetic resonance imaging (MRI) or transrectal ultrasound (TRUS). Additional secondary outcomes were clinical perianal remission and radiological perianal healing. Propensity-score matching (PSM) used to address baseline clinic-demographics differences between treatments. Results 486 patients with pCD were included. Of them, 333/486 patients (68.5%) in 2nd-line and 216/263 patients (82.1%) in 3rd-line treatment-groups were matched by PSM. Figure 1 illustrates patient inclusion in the study, stratified by active versus inactive disease status and 2nd-line versus 3rd-line treatment, along with the respective rates of primary outcome achievement. 62/78 (79.5%) patients with active pCD who were treated with ustekinumab (UST) as 2nd-line biologic met the primary outcome, compared to 46/78 patients (58.9%) with VDZ (OR 4.47, 95%CI 1.94-10.28, p<0.001) and 38/78 patients (48.7%) - anti-TNF (OR 5.29, 95%CI 2.39-11.71, p<0.001). 38/49 patients (77.6%) with active pCD who were treated with UST as 3rd line met the primary outcome, compared to 29/49 patients (59.2%) with VDZ (OR 9.96, 95%CI 2.6-38.4, p<0.001) and 27/49 (55.1%) with anti TNF (OR 12.03, 95%CI 2.99-48.47, p<0.001). Patients who were treated with UST as 3rd-line biologic had higher rates of radiological response and healing than patients who were treated with VDZ (OR of 3.28 95%CI 1.07-10.07, p=0.038) and anti-TNF (OR of 2.80 95%CI 0.95-8.21, p=0.061). Conclusion Clinical perianal outcomes in patients with active perianal Crohn’s disease were more frequently achieved with ustekinumab following the failure of 1st-line anti-TNFs.

Impact of local anesthesia on ciliary dyskinesia diagnosis by digital high-speed videomicroscopy.

It was hypothesized that local anesthesia administration would not significantly affect ciliary function in nasal epithelium. A prospective, simple-blind randomized study was conducted between 2020 and 2023. The study employed digital high-speed videomicroscopy to analyze ciliary beat frequency and pattern. A cohort of 38 participants was recruited, consisting of 25 healthy volunteers and 13 referred individuals (including seven diagnosed with PCD). Selection criteria ensured the absence of chronic respiratory diseases, recent respiratory tract infections, or regular use of nasal medications. Participants underwent nasal brushing with administration of lidocaine and naphazoline nasal spray in one nostril and saline in the contralateral nostril. Ciliary beat frequency and pattern were measured using digital high-speed video microscopy. Nasal spray administration did not significantly alter ciliary beat frequency or pattern compared to saline (p = 0.841 and p = 0.125, respectively). Subgroup analysis revealed consistent results across healthy volunteers, referred patients, and PCD patients. Local anesthesia with lidocaine and naphazoline spray did not affect ciliary function outcomes. These findings support the safe use of these agents in clinical practice for PCD diagnostic procedures. Further research with larger cohorts is warranted for validation.

Preventing Recurrence of Crohn's Disease Post-Ileocaecal Surgery in Paediatric Patients: A Therapy Guide Based on Systematic Review of the Evidence.

Ileocaecal resection (ICR) is frequent in paediatric patients with Crohn's disease (pCD). Despite rates of reoperation being low, the risk of clinical or endoscopic post-operative recurrence (POR) is high; effective medical strategies to prevent POR are thus needed. The aim of this systematic review(SR) was to identify and evaluate the published literature on post-operative medical prevention of POR in pCD to draft a possible therapy guide for pCD patients undergoing ICR. We performed an SR according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and registered it in the PROSPERO database (ID: CRD42024533855). The population, intervention, control, outcome (PICO) model was focussed on post-surgical medical prevention of POR in pCD with clearly expressed definition of recurrence (endoscopically using a standardized scoring system (e.g. Rutgeerts score) or by laboratory markers, for example, faecal calprotectin (F-CPT), C-reactive protein (CRP) or by histological findings or by clinical activity indexes [e.g. weighted paediatric Crohn's disease activity index - (w)PCDAI]. From inception until 29 February 2024, the following databases were searched: PubMed/MEDLINE, Scopus/Embase, Web of Sciences, Evidence-Based Medicine Reviews (including Cochrane), Cochrane Central Registrar of controlled Trials (CENTRAL), ClinicalTrials.gov and EudraCT. Retrieved articles were evaluated for eligibility and finally selected publications for risk of bias using ROBINS-I tool. Out of 811 publications identified by the search, only 5 fulfilled inclusion criteria of the SR. None of the studies fully answered our PICO question. The studies were overall of poor quality and the heterogeneity of the data did not allow us to perform meta-analysis, detailed statistical analysis or formal synthesis of data. Adverse events of post-operative medication were not described in any of the included studies. Existing guidelines of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), European Crohn's and Colitis Organisation (ECCO) and American Gastroenterological Association (AGA) were reviewed and paediatric therapy guide for pCD undergoing ICR was drafted with respect to recent SRs and meta-analyses in adult population and including scarce paediatric data identified by our SR. As pCD patientsundergoing ICR are a high-risk population, they should not be left untreated post-operatively. Anti-tumour necrosis factor (anti-TNF) drugs should be considered as first-line therapy in the majority of patients. Non-anti-TNF biologics should be considered in case of anti-TNF failure. Regular endoscopic monitoring starting at 6 months after the surgery and supported by regular F-CPT evaluation should be used to identify early endoscopic recurrence and to escalate the treatment. Our SR revealed that there is wide variability in treatment strategies in children, and high-quality data are generally lacking. At the moment, paediatric prophylaxis of POR should be guided by available adult evidence with respect to the high-risk nature of pCD. Extensive research in pCD should be encouraged.

Characterization of pathogenic genetic variants in Russian patients with primary ciliary dyskinesia using gene panel sequencing and transcript analysis

BackgroundPrimary ciliary dyskinesia (PCD) is a group of rare genetically heterogeneous disorders caused by defective cilia and flagella motility. The clinical phenotype of PCD patients commonly includes chronic oto-sino-pulmonary disease, infertility, and, in about half of cases, laterality defects due to randomization of left–right body asymmetry. To date, pathogenic variants in more than 50 genes responsible for motile cilia structure and assembly have been reported in such patients. While multiple population-specific mutations have been described in PCD cohorts from different countries, the data on genetic spectrum of PCD in Russian population are still extremely limited.ResultsThe present study provides a comprehensive clinical and genetic characterization of 21 Russian families with PCD living in various country regions. Anomalies of ciliary beating in patients` respiratory epithelial cells were confirmed by high-speed video microscopy. In the most cases, custom-designed panel sequencing allowed to uncover causative variants in well-known or rarely mentioned PCD-related genes, including DNAH5, DNAH11, CFAP300, LRRC6, ZMYND10, CCDC103, HYDIN, ODAD4, DNAL1, and OFD1. The variations comprised common mutations, as well as novel genetic variants, some of which probably specific for Russian patients. Additional targeted analysis of mRNA transcripts from ciliated cells enabled us to specify functional effects of newly identified genetic variants in DNAH5 (c.2052+3G>T, c.3599-2A>G), HYDIN (c.10949-2A>G, c.1797C>G), and ZMYND10 (c.510+1G>C) on splicing process. In particular, the splice site variant c.2052+3G>T, detected in four unrelated families, resulted in skipping of exon 14 in DNAH5 transcripts and, according to haplotype analysis of affected probands, was proposed as an ancestral founder mutation in Udmurt population.ConclusionsThe reported data provide a vital insight into genetic background of primary ciliary dyskinesia in the Russian population. The findings clearly illustrate the utility of gene panel sequencing coupled with transcriptional analysis in identification and clinical interpretation of novel genetic variants.

Serum Metabolites Relate to Mucosal and Transmural Inflammation in Paediatric Crohn Disease.

We aimed to identify serum metabolites associated with mucosal and transmural inflammation in paediatric Crohn disease [pCD]. In all, 56 pCD patients were included through a pre-planned sub-study of the multicentre, prospective, ImageKids cohort, designed to develop the Paediatric Inflammatory Crohn magnetic resonance enterography [MRE] Index [PICMI]. Children were included throughout their disease course when undergoing ileocolonoscopy and MRE and were followed for 18 months, when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score [SES], faecal calprotectin [FCP], and C-reactive protein [CRP], to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy [mRMR] feature selection with a j-fold cross-validation scheme identified the best subset of features and hyperparameter settings. Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve [AUC] > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in the citrate cycle [TCA cycle], aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism. We extend on recent studies, observing differences in serum metabolites between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assessment of disease severity.

Neurocognitive Changes in Patients with Post-COVID Depression.

Background: Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD, n = 25) patients using neuropsychological testing. Methods: The study involved 71 post-COVID patients with matched control groups: recovered COVID-19 individuals without complications (n = 18) and individuals without prior COVID-19 history (n = 19). A post-COVID depression group (PCD, n = 25) was identified based on psychiatric diagnosis, and a comparison group (noPCD, n = 46) included participants with neurological COVID-19 complications, excluding clinical depression. Results: The PCD patients showed gender-dependent significant cognitive impairment in the MoCA, Word Memory Test (WMT), Stroop task (SCWT), and Trail Making Test (TMT) compared to the controls and noPCD patients. Men with PCD showed worse performances on the SCWT, in MoCA attention score, and on the WMT (immediate and delayed word recall), while women with PCD showed a decline in MoCA total score, an increased processing time with less errors on the TMT, and worse immediate recall. No differences between groups in Sniffin's stick test were found. Conclusions: COVID-related direct (post-COVID symptoms) and depression-mediated (depression itself, male sex, and severity of COVID-19) predictors of decline in memory and information processing speed were identified. Our findings may help to personalize the treatment of depression, taking a patient's gender and severity of previous COVID-19 disease into account.

Skewed X-chromosome inactivation drives the proportion of DNAAF6-defective airway motile cilia and variable expressivity in primary ciliary dyskinesia

BackgroundPrimary ciliary dyskinesia (PCD) is a rare airway disorder caused by defective motile cilia. Only male patients have been reported with pathogenic mutations in X-linked DNAAF6, which result in the...

A264 IDENTIFYING CLINICAL PREDICTORS FOR SUCCESS OF EXCLUSIVE ENTERAL NUTRITION INDUCTION THERAPY IN PEDIATRIC CROHN DISEASE

Abstract Background Current treatments for IBD focus on reducing inflammation, mostly through suppression of the immune system. Exclusive enteral nutrition (EEN) is recognized as the first line therapy for mild-to-moderate luminal pediatric Crohn disease patients pCD. Although EEN is safe, as it does not suppress the immune system, it poses considerable challenges to patients, mostly due to palatability and monotony of the formula and treatment costs. Moreover, the efficacy of EEN varies greatly from patient to patient. Therefore, there is a need to distinguish between responders and non-responder patients. Aims Identify clinical features associated with efficacy of EEN induction therapy and apply machine learning to build a classifier to identify EEN non-responders. Methods The Canadian Children Inflammatory Bowel Disease Network prospectively enrolled and followed new onset pediatric IBD cases. Prospective data for 308 pCD with EEN as their first treatment for CD are available. Patients with weighted Pediatric CD Activity Indexes (wPCDAI) collected after at least 4 weeks on EEN were compiled into a dataset (n=108). For this analysis, treatment response was defined as a wPCDAI reduction of at least 12.5 points of a patient’s wPCDAI baseline score. The dataset includes 26 features for each of the 108 pCD patients at time of diagnosis. This included blood test results (Hgb, ESR, CRP, Alb, Htc, Plt), Paris Classifications, height, and weight Z-scores, as well as wPCDAI, SES-CD (simple endoscopic score, CD), PGA (physician global assessment), and Mayo scores. Odds ratios were calculated to determine whether any features were associated with response to EEN induction therapy. Then, the most relevant features were identified with regularization techniques and a machine learning classifier for predicting response to EEN was built. Results Results showed that the appropriate subset of features to include for optimal accuracy over model simplicity are n=4 (PUCAI, PGA, SES-CD scores, and hematocrit). Also, an increase in PGA score (e.g., moving from “mild disease” to “moderate disease”) was associated with an increase in the chance of EEN failure (OR 3.1, 95% CI [1.7,5.8], p=0.0001). The best classifier for predicting EEN response was a random forest consisting of 20 decision trees. The classifier achieved an area under the ROC curve of 0.75 ± 0.07 Conclusions Our results suggest that it is possible to produce a classifier capable of predicting EEN clinical remission with an accuracy over 60%. Higher PGA, PUCAI, and SES-CD scores show potential for predicting patients less likely to respond to EEN induction. This research has the potential to provide better quality of life for children who live with IBD. Funding Agencies CIHRIMAGINE SPOR Network , Women and Children's Health Research Institute

P997 New Objective Assessment of perianal Crohn’s disease, Perianal Lesion Index; PLI

Abstract Background In the previous survey, decisions of biological treatment (Bio) success for perianal Crohn’s disease (pCD) were made by the patient’s subjective improvement and physician’s assessment, so it lacks objectivity. Moreover, physicians, surgeons, and proctologists are related to treating pCD. This aspect is the difficulty of the treatment of pCD. We need a common assessment for each area’s doctor. We aimed to develop a new objective assessment of pCD, including endoscopic findings, and assess the efficacy of the newly launched Bio except anti-TNFα agents for pCD. Methods Usually, perianal abscesses and fistula are derived from ulcers in the lower rectum and anal canal, so we adapted SES-CD to the location and checked discharge and needs of setons, and finally scored it (Table 1). We named this assessment Perianal Lesion Index; PLI. We retrospectively evaluated 20 pCD patients who received Ustekinumab (UST) and Vedolizumab (VDZ) from March 2017 to March 2023 at our institute. We checked each patient’s PLI, CRP, LRG, and CDAI and compared them before starting Bio and eight weeks after initiation of Bio using a paired T-test. Finally, we used the Pearson correlation coefficient to examine the correlation between PLI and conventional serum biomarkers and CDAI. Results The male-to-female ratio was 4.0, the average age at the treatment initiation was 35. Eighteen patient’s diseases were located in the small and large intestines, 10 patients were penetrating type, and 2 patients were stenotic type. We used UST for 16 patients and VDZ for 4 patients. Seven patients were naïve for Bio, 8 patients were treated by one Bio, and 5 patients were treated by two Bio.PLI was positively correlated with CRP (r=0.59, p<0.001) but not correlated with LRG (r=0.77, p=0.077) and CDAI (r=0.35, p=0.07). The pretreatment average PLI was 8.5 and significantly decreased to 3.9 (p<0.001) 8 weeks after Bio initiation. There was a significant change in CRP (3.1 to 0.9, p =0.03) but not CDAI (193 to 147, p=0.2). There were significant PLI changes in each treatment group; the UST group’s PLI change was 8.3 to 3.1 (p<0.001), and the VDZ group's PLI was 9.5 to 8.0 (p=0.02) (Figure 1). Conclusion PLI seems to be an objective assessment for pCD, and it was positively correlated to CRP. We could assess each drug’s efficacy for pCD. Further investigation is needed to establish PLI’s accuracy, and we hope this assessment will contribute to the choices of Bio for pCD and the evaluation of its efficacy

P538 Platelet-rich stroma during surgery for treatment-refractory perianal fistulizing Crohn’s disease: long-term outcomes of a pilot study

Abstract Background Platelet-rich stroma (PRS), a combination of stromal vascular fraction and platelet-rich plasma, proved to be safe and feasible for the treatment of treatment-refractory perianal fistulizing Crohn’s disease (pCD). This study aimed to assess the long-term outcomes in patients with pCD treated with PRS. Methods Long term results from adult patients with pCD, who underwent fistula curettage, closure of the internal fistula opening and PRS injection, included in an earlier conducted pilot study (n=25) were assessed up to October 2023. The primary outcome was complete clinical closure at long-term follow-up (closure of all treated external opening[s]). Secondary outcomes comprised complete radiologic closure (absence of fluid-containing tracts on MRI), partial clinical closure (closure of ≥ 1 treated external opening[s]), recurrence (reopening of the external opening after complete clinical and/or radiological closure) and the need for unplanned re-intervention(s). Results The majority of the patients was female (56.0%)(mean age 34.4 years [SD: 0.9], and mean follow-up 3.7 years [SD: 0.6])(Table 1). 68% of the patients were concomitantly treated with a biological. During follow-up, ≥1 unplanned re-intervention(s) were necessary in 44% of the patients which were minor (e.g. incision and drainage) in the vast majority (83%)(Table 2). Complete clinical closure at long-term follow-up was reached in 88%. Complete radiologic closure was reached in 75% of patients. Partial clinical closure was reached in all patients (100%). Recurrence was reported in 8% of patients, all whom reached (partial/complete) clinical closure, whereas no recurrence was experienced in patients with complete closure on MRI. All patients with complete radiologic closure achieved clinical closure. Vice versa, patients with clinical closure achieved complete radiologic closure in 82% of the cases. Conclusion In this pilot study with treatment-refractory pCD patients treated in a tertiary referral center, all patients had benefit from surgical treatment and an additional injection of PRS. At long-term follow-up, treatment with PRS injection during surgery is promising as complete clinical and radiological closure is achieved in the majority of these patients. In addition, complete radiologic closure seems a valuable prognostic parameter for long-term success for fistula closure. Future (randomized) research is warranted to further assess the effectiveness of PRS in patients with pCD.

Newborn screening for fatty acid oxidation disorders in a southern Chinese population

Fatty acid oxidation disorders (FAODs) are a group of autosomal recessive metabolic diseases included in many newborn screening (NBS) programs, but the incidence and disease spectrum vary widely between ethnic groups. We aimed to elucidate the incidence, disease spectrum, and genetic features of FAODs in a southern Chinese population. The FAODs screening results of 643,606 newborns from 2014 to 2022 were analyzed. Ninety-two patients were eventually diagnosed with FAODs, of which 61 were PCD, 20 were MADD, 5 were SCADD, 4 were VLCADD, and 2 were CPT-IAD. The overall incidence of FAODs was 1:6996 (95% CI: 1:5814-1:8772) newborns. All PCD patients had low C0 levels during NBS, while nine patients (14.8%) had normal C0 levels during the recall review. All but one MADD patients had elevated C8, C10, and C12 levels during NBS, while eight patients (40%) had normal acylcarnitine levels during the recall review. The most frequent SLC22A5 variant was c.760C>T (p.R254*) with an allele frequency of 29.51%, followed by c.51C>G (p.F17L) (17.21%) and c.1400C>G (p.S467C) (16.39%). The most frequent ETFDH variant was c.250G>A (p.A84T) with an allelic frequency of 47.5%, followed by c.524G>A (R175H) (12.5%), c.998A>G (p.Y333C) (12.5%), and c.1657T>C (p.Y553H) (7.5%). The prevalence, disease spectrum, and genetic characteristics of FAODs in a southern Chinese population were clarified. PCD was the most common FAOD, followed by MADD. Hotspot variants were found in SLC22A5 and ETFDH genes, while the remaining FAODs showed great molecular heterogeneity. Incorporating second-tier genetic screening is critical for FAODs.

When Patients with Plasma Cell Disorders Encountered the Largest Omicron Wave (December 2022) in China: A Real-World Multicenter and Multiregional Study

Background: An unprecedented nationwide Omicron outbreak hit China in December 2022. Patients with plasma cell disorders have been confirmed to exhibit worse outcomes following COVID-19 infection, although data on the impact of Omicron on this population in China remain scarce. This study aims to report the clinical and epidemiological characteristics of plasma cell disorder patients during this major Omicron outbreak. It also analyzes the association between patient clinical characteristics and clinical course (infection, severity, hospitalization, and time to recovery) of COVID-19. Methods: We performed a multicenter and multiregional retrospective study primarily involving nine large tertiary hematology centers across nine provinces/cities in China. The study period was limited to December 1 st, 2022 - January 19 th, 2023. A total of 404 plasma cell disorder patients participated in the survey. Results: During follow-up, 342 patients had a laboratory or clinical diagnosis of COVID-19. The prevalence of COVID-19 within the study population was 76.2%. Among those with COVID-19, the majority were with multiple myeloma (325, 95.0%), and over half (201, 58.8%) were unvaccinated. At the time of COVID-19, 121 (40.1%) patients were undergoing maintenance therapy. Ninety (31.3%) patients had prior exposure to anti-CD38 monoclonal antibody, while 25 (8.7%) to CAR-T. The rates of severe illness and hospitalization were 16.4% and 20.5%, respectively. Four (5.7%) patients required ICU support and only two (2/277, 0.7%) deaths were reported. As of the data cutoff date (January 19 th, 2023), 231 (231/277, 83.4%) patients had recovered from COVID-19, with a median time to recovery of 14 days (95% CI: 13-15 days). Multivariate analysis identified age > 65 (OR 1.47, 95% CI 1.05-2.05, P = 0.02) and anti-CD38 monoclonal antibody within six months of COVID-19 (OR 1.47, 95% CI 1.03-2.09, P = 0.03) as independent risk factors for severe COVID-19 illness. Prior CAR-T therapy within six months was correlated with an increased risk of hospitalization (OR 3.49, 95% CI 1.07-11.4, P = 0.04) and prolonged time to recovery (HR 0.38, 95% CI 0.16-0.93, P = 0.03). Compared to maintenance therapy, patients at the induction or consolidation therapy stage had an elevated risk of hospitalization following COVID-19 (OR 1.55, 95% CI 1.04-2.33, P = 0.03). Notably, no significant protective effect of COVID-19 vaccination on infection or severe infection rates was observed ( P > 0.05). Conclusions: Although the impact of Omicron appears attenuated in plasma cell disorder patients, this vulnerable population still exhibits higher rates of severe illness and poorer outcomes compared to the general population. Apart from known risk factor (i.e. older age), certain treatment-related factors, including induction/consolidation therapy stage, recent anti-CD38 monoclonal antibody exposure, and prior CAR-T therapy, are associated with increased risks of severe COVID-19, hospitalization, and prolonged time to recovery. However, the protective effect of vaccination against COVID-19 is not identified. The findings from this work provide implications for the clinical management of PCD patients during the pandemic under the likely scenario of future resurgences of COVID-19.

Clinical and Genetic Characterization of Patients with Primary Ciliary Dyskinesia in Southwest Saudi Arabia: A Cross Sectional Study.

Primary ciliary dyskinesia (PCD, MIM 244400) is an inherited ciliopathy disorder characterized by recurrent sinopulmonary infections, subfertility, and laterality defects. The true incidence of PCD in Saudi Arabia is not known, but it is likely underdiagnosed due to the high prevalence of consanguineous marriages. In this study, we aim to study the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia to provide guidance to clinicians and researchers studying PCD. This was a cross-sectional study conducted between 2019 and 2023 in Abha Maternity and Children's Hospital. Twenty-eight patients with clinically diagnosed PCD were recruited. The diagnosis of PCD was confirmed via whole-exome sequencing. A total of 28 patients from 20 families were identified and recruited for this study. The median age of patients was 7.5 years (IQR = 3, 13 years). The people of different sexes were evenly distributed, and 18 patients (64%) had neonatal respiratory distress (NRD). The median age of diagnosis was 5.5 years (IQR = 2, 11 years), while the age when the first symptoms appeared was 3 months old (IQR = 1, 6 months). The prevalence of a chronic wet cough, chronic rhinosinusitis, ear infections were 100% (n = 28), 78.6% (n = 22), and 67.9% (19), respectively. The most common gene in our study was DNAH5, which represented 17.9% (five out of twenty-eight) of the cases. Furthermore, the remaining pathogenic variants included: 14.3% with RSPH9 in four individuals (three families), 14.3% with DNAI2 in four individuals (two families), and 10.7% with LRRC56 in three individuals (one family). The most common findings on the chest CT scans were consolidation (seen in all patients), mucus plugging (seen in 95%), and bronchiectasis (seen in 77%). In the patients with bronchiectasis, the most commonly affected lobes were the right lower lobe (88%) and left lower lobe (76%). The patients with PCD and situs inversus were more likely to experience NRD than the patients with PCD and situs solitus. The median PICADAR score in the patients with PCD and situs inversus (median: 11.5; Q1: 10-Q3: 12.5) was significantly higher compared to those with PCD and situs solitus (median: 7.5; Q1: 5.8-Q3: 8) (U = 10.5; p < 0.001). This study provides preliminary data on the clinical and genetic characteristics of PCD patients in the southwestern region of Saudi Arabia. We found that DNAH5 and RSPH9 genes were the most common genes among the studied population. Furthermore, PCD should be considered for each child with early NRD and laterality defects, and further confirmatory tests are recommended. These findings also highlight the need for greater awareness of the disease in daily clinical practice to facilitate early diagnosis and avoid irreversible lung damage.

Airway microbiota correlated with pulmonary exacerbation in primary ciliary dyskinesia patients.

Primary ciliary dyskinesia (PCD) is characterized by symptoms such as productive cough, rhinitis, and recurrent infections in both the upper and lower airways, which can lead to chronic infection, bronchiectasis, and decreased pulmonary function. Our study aimed to analyze the diversity and composition of the microbiota in the respiratory tract and investigate the correlation of the microbiota with pulmonary exacerbation in PCD patients. This study employed 16S rRNA amplicon sequencing to explore the microbiota present in both bronchoalveolar lavage fluid (BALF) and sputum samples collected from PCD patients. Eighty-five airway samples (17 BALF and 68 sputum samples) were collected from 72 patients aged 2 months to 60 years. Significantly lower sputum microbiota diversity and richness were found in the pulmonary exacerbation group than in the pulmonary stabilization group; additionally, the relative abundance of Pseudomonas increased when pulmonary exacerbation occurred. There was a positive correlation between pulmonary exacerbation and the relative abundance of Pseudomonas, while Streptococcus, Moraxella, and Haemophilus showed a negative correlation. Although there was no significant difference in the sputum microbiota diversity and composition in children aged 6-18 years with pulmonary exacerbation, Pseudomonas increased during pulmonary exacerbation. BALF samples of pediatric patients with pulmonary exacerbation had a lower microbiota diversity and richness; furthermore, Pseudomonas had a higher abundance and a moderate distinguishing effect. We found that microbiota beta diversity and dominance were decreased during pulmonary exacerbation. Additionally, Pseudomonas had a higher abundance and moderate distinguishing effect in pediatric patients with pulmonary exacerbation. IMPORTANCE PCD is a rare disease characterized by productive cough, rhinitis, and recurrent infections of the upper and lower airways. Because the diagnosis of PCD is often delayed, patients receive more antibiotics, experience a heavier financial burden, and have a worse prognosis; thus, it is very important to identify the pathogeny and use the correct antibiotic. In this large single-center study of PCD microbiota, we identified an outline of the bacterial microbes from the respiratory tract; furthermore, we found that the microbiota diversity in pediatric sputum was richer than that in pediatric BALF through sequencing, indicating a heterogeneous community structure. The microbiota diversity and richness were lower during pulmonary exacerbation than during pulmonary stabilization. A significantly higher abundance of Pseudomonas had a moderate distinguishing effect for lung exacerbation, which attracted more attention for the study of Pseudomonas therapy in pediatric patients with PCD.

Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD, ORPHA:244) is a group of rare genetic disorders characterized by dysfunction of motile cilia. It is phenotypically and genetically heterogeneous, with more than 50 genes involved. Thanks to genetic, clinical, and functional characterization, immense progress has been made in the understanding and diagnosis of PCD. Nevertheless, it is underdiagnosed due to the heterogeneous phenotype and complexity of diagnosis. This review aims to help clinicians navigate this heterogeneous group of diseases. Here, we describe the broad spectrum of phenotypes associated with PCD and address pitfalls and difficult-to-interpret findings to avoid misinterpretation. Review of literature CONCLUSION: PCD diagnosis is complex and requires integration of history, clinical picture, imaging, functional and structural analysis of motile cilia and, if available, genetic analysis to make a definitive diagnosis. It is critical that we continue to expand our knowledge of this group of rare disorders to improve the identification of PCD patients and to develop evidence-based therapeutic approaches.