IDDF2023-ABS-0032 Active inflammatory bowel disease is associated with severe covid-19: a systematic review and meta-analysis

IDDF2023-ABS-0032 Figure 1 IDDF2023-ABS-0032 Figure 2 IDDF2023-ABS-0032 Figure 3 IDDF2023-ABS-0032 Figure 4COVID-19 outcomes in moderate-severe vs mild or quiescent IBD[Figure omitted. See PDF]ConclusionsPatients with IBD, particularly UC had an increased risk of developing severe COVID-19. Active IBD is associated with adverse COVID-19 outcomes, and the risk is increased with the disease activity of IBD.

PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

Mesenchymal Stem/Stromal Cells: DEVELOPMENT OF A GMP BANKING PROCESS FOR UMBILICAL CORD MESENCHYMAL STROMAL CELLS (UC-MSCS) AND USE OF UC-MSC IN CHARACTERISATION ASSAYS, FUNCTIONAL ASSAYS AND GENE EDITING STUDIES

Background & Aim: The pro-angiogenic, immunoregulatory and anti- inflammatory properties of MSCs are being exploited for the development of cellular therapies, including the treatment of graft versus host disease (GvHD), inflammatory bowel disease and COVID-19. SNBTS have developed a GMP process to bank umbilical cord MSCs (UC-MSCs) whereby we can reliably bank 100 vials of 10 million P2 UC-MSCs per cord. Each of these vials can be extensively expanded and stored for specific applications. The ultimate aim of the bank is for off-the-shelf clinical use, e.g., in GvHD or as an adjuvant therapy in Islet transplantations. Methods, Results & Conclusion(s): During process development, different basal media and supplements were screened for proliferation and MSC marker expression. Cells grown in promising media combinations were then tested for tri-lineage differentiation (identity), their chemokine/cytokine expression and T-cell inhibition (function) assessed. Medium selected for further GMP development and scale up was ultimately determined by all round performance and regulatory compliance. GMP-like UC-MSCs were shown to have immune-modulatory activity in T-cell proliferation assays at 4:1 or 16:1 ratios. Co-culture of UC-MSCs and freshly isolated leukocytes, +/- the immune activating agent LPS, show a dose dependent survival effect on leukocytes. In particular, neutrophils, which are normally very short lived in vitro demonstrated increased viability when co-cultured with UCMSCs. The survival effect was partially reproduced when UC-MSC were replaced with conditioned medium or cell lysate indicating the involvement of soluble factors. This improved neutrophil survival also correlates with results from leukocyte migration studies that demonstrate neutrophils to be the main cell type attracted to MSCs in in vitro and in vivo. Genetic modification of UC-MSC may improve their therapeutic potential. We have tested gene editing by CRISPR/Cas9 technology in primary UC-MSCS. The CXCL8 gene, highly expressed in UC-MSC, was targeted in isolates from several different donors with editing efficiencies of 78-96% observed. This translated to significant knockdown of CXCL8 protein levels in resting cells, however after stimulation levels of CXCL8 were found to be very similar in edited and non-edited UC-MSCs. This observation requires further study, but overall the results show the potential to generate future banks of primary UC-MSCS with genetically enhanced pro-angiogenic, immunoregulatory and/or anti-inflammatory activities.Copyright © 2023 International Society for Cell & Gene Therapy

Whipple's Disease, An Overlooked Diagnosis

Whipple disease is a rare multisystem inflammatory disease. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. We are reporting a case of a 46-year-old man who presented with fever, weight loss, and polyarthralgia for 2 months, and 1 month of diarrhea. The patient was thoroughly investigated for collagen diseases and COVID-19, with no definite diagnosis. A therapeutic trial by immunosuppressive drugs provided partial remission followed by a marked rebound of the symptoms. His occult blood in stool was positive and subsequent upper endoscopy with proximal small intestinal biopsies showed the pathological features of Whipple's disease. The patient showed a dramatic improvement following treatment with ceftriaxone and trimethoprim-sulfamethoxazole. Despite the rarity of Whipple's disease, its course mimics many rheumatological diseases, inflammatory bowel disease, and COVID-19 disease. It should always be a part of the differential diagnosis of obscure polyarthralgia and chronic diarrhea.Copyright © 2023 The Author(s).

SeroNet Pooling Project of immunocompromised populations

Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients;(b) autoimmune diseases and (c) solid organ transplant recipients (SOTR);(2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients;(b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients;(c) SOTR;(d) lupus. Method(s): For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy;SOTR;autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and diseasespecific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Result(s): Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion(s): Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations.

VACCINATIONS IN PATIENTS WITH CHRONIC INFLAMMATORY DISEASES, PATIENT KNOWLEDGE AND AWARENESS: RESULTS FROM A NORDIC SURVEY

BackgroundPatients with chronic inflammatory diseases (CID) have an increased risk for contracting infections. For patients with rheumatic diseases EULAR recommends protecting them from vaccine-preventable diseases.ObjectivesTo assess the knowledge and awareness of common vaccinations and extent of immunization among patients with CID in Denmark, Finland, Norway, Sweden (Nordics), and to identify gaps between the existing EULAR vaccination recommendations and current practice as experienced by patients.MethodsA structured anonymous online survey for patients with CID ((rheumatological disease (RD), inflammatory bowel disease (IBD) and dermatological diseases (DD)) was conducted in 2022.The survey was answered by 1748 respondents (1031 patients with RD, 543 with IBD and 563 with DD).ResultsAmong respondents, 89% were female and 58% had disease duration of above 10 years. In total, 56% were treated in specialised and 32% in primary care. Majority had ongoing systemic immunosuppressive treatment (IT) (65%). Majority of RD (59%) and IBD (66%) patients were treated in specialised care whereas minority of DD patients (38%) were treated in specialised care.Forty-nine percent (49%) responded that their healthcare professional (HCP) did not inform them about the increased risk of infection – however, 55% of the respondents believed they are somewhat or much more likely to suffer from infections than those without CID or treatment, 33% thought there is no difference and 13% did not know there is a difference.In total 68% of respondents considered it important to get vaccinated due to CID or IT. The number was particularly high in RD group (74%), although 63% stated they had not received any information regarding vaccinations at the start of their treatment.Commonly recommended vaccinations by the HCP were COVID 19 (66%), influenza (63%) and pneumococcal (45%) vaccination. When comparing respondents ≥65 and <65 years, there was a difference in how often the influenza (71% vs. 57%) and pneumococcal (57% vs. 38%), but not COVID 19 vaccination (68% vs. 65%), were recommended. In addition, 74% and 75% of respondents receiving IT were recommended influenza and COVID 19 vaccination, respectively.In total, 22% had their vaccination status checked before initiating treatment;the lowest percentage was in DD (16%) and the highest in RD (25%). However, 44% of respondents received influenza vaccination before initiation of treatment. Moreover, 62% and 74% of respondents received influenza and COVID 19 vaccination while on treatment, respectively.Eighty-six percent (86%) did not receive a vaccination plan in relation to their CID and treatment. Moreover, 64% of the respondents (RD 57%;DD 71% and IBD 66%) did not have vaccination status assessed on a regular basis. Forty-three percent (43%) were dissatisfied with the follow-up of vaccination status by their HCP. Respondents of age ≥65 years were more satisfied than the younger ones (34% vs. 25% very satisfied) and respondents with RD were more satisfied than those with IBD or DD (33% vs. 25% vs. 20%).Forty-four percent (44%) responded that the information on vaccinations related to their CID and treatment was difficult to find and 71% would like to receive more information.The respondents with RD had different level of awareness regarding EULAR vaccination recommendations. The degree of awareness among patients with RD treated with IT are presented in Figure 1.ConclusionThis Nordic survey provides insights on patients' information needs, information sources and own experiences related to recommendations on vaccinations in relation to their CID and IT. The results confirm a gap between patients' expectations and needs vs. the information they actually receive. Our findings demonstrate a need for increased awareness among patients, providers and HCP regarding EULAR vaccination recommendations in patients with RD.Reference[1]Furer V, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2020;79: 9–52.Acknowledgements:NIL.Disclosure of InterestsMeliha C Kapetanovic Grant/research support from: Received independent research grants from Roche and Pfizer, Randeep Mandla Shareholder of: Pfizer, Employee of: Current employee of Pfizer Norway, Maria Seddighzadeh Shareholder of: Pfizer, Employee of: Current employee of Pfizer Sweden, Susanne Thiesen Gren Shareholder of: Pfizer, Employee of: Current employee of Pfizer Denmark, Maaria Palmroth Consultant of: Employee of MedEngine Oy and contractor for Pfizer Oy, Employee of: Contractor for Pfizer Oy, Finland, Dan Henrohn Shareholder of: Pfizer, Employee of: Current employee of Pfizer AB, Sweden, Anne Grete Frostrup Shareholder of: Pfizer, Employee of: Current employee of Pfizer Denmark, Anna-Maria Hiltunen Consultant of: Pfizer. Employee of Nordic Healthcare Group, Jussi Ranta Consultant of: Pfizer. Employee of Nordic Healthcare Group, Anna-Kaisa Asikainen Consultant of: Pfizer. Employee of Nordic Healthcare Group, Veli-Jukka Anttila Speakers bureau: Lectures for Pfizer, MSD, Astellas, Roche, GSK, BMS, Biogen, Sandoz, Gilead, Unimedic Pharma, Boehringer-Ingelheim, Astra-Zeneca, Consultant of: Consultant for Pfizer and MSD.

Gastrointestinal Manifestations of COVID-19 and Inflammatory Bowel Disease in the COVID-19 Era: Clinical Overview and Updated Guidelines

Aim: The aim of this chapter is to discuss the gastrointestinal (GI) manifestations of coronavirus (COVID-19) and inflammatory bowel disease (IBD) in the pandemic era. Methods: The author conducted a search of the scientific literature up to June 2021 including the following databases: PubMed, Cochrane library, Google Scholar, MedLine, EMBASE, and National trials registry, using the following keywords (IBD, inflammatory bowel disease, ulcerative colitis, Crohn's disease, COVID-19, SARS-CoV2, coronavirus). Results: This chapter explained the GI associated with COVID-19 including their pathophysiology and molecular pathways, methods of diagnosis, impact on the severity of the disease, and risk of associated mortality. The chapter also outlined the role of feco-oral infection, viral shedding, the gut-lung axis, and the effect of dysbiosis on COVID-19 infection. Moreover, this chapter discussed the IBD guidelines during the pandemic, including the European Crohn's and Colitis Organization (ECCO), American Gastroenterology Association (AGA), International Organization for the Study of Inflammatory Bowel Disease (IOIBD), and Asian Pacific Association of Gastroenterology (APAGE) guidelines, to delineate the agreements and disagreements between the different guidelines. Furthermore, it discussed the implementation of telemedicine, endoscopy regulations, and vaccination programs in IBD patients. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Factors influencing sonographer-led bowel ultrasound service

The aim of this study was to investigate factors influencing UK sonographers' practice of adult bowel ultrasound. A mixed-method online questionnaire was designed and shared on social media platforms in April 2021. Research restrictions due to COVID19 limited the sample size permitted. Convenience sampling recruited thirty UK sonographers performing adult abdominal ultrasound in their practice. Quantitative data were analysed using descriptive statistics, and qualitative data were analysed using inductive thematic analysis. Quantitative data revealed that 53% (n= 16) of the participants expressed a lack of confidence in scanning the bowel, while 77%, (n = 23) indicated a high level of interest in training in bowel ultrasound. Although 63.3% (n = 19) of the participants reported a high level of confidence in scanning the bowel for suspected appendicitis, the majority (70%, n = 21) expressed lack of confidence in examining the bowel for other pathologies like inflammatory bowel disease (IBD). Inductive thematic analysis of qualitative data revealed that the participants had varying opinions on this topic. Emerging themes included training opportunities, preference of other imaging modalities, management challenges, sonographers, and radiologists' influence. Qualitative results suggested that factors influencing sonographer evaluation of the bowel include advanced levels of training, a high degree of support from radiologists, regular bowel ultrasound lists, audits, and feedback from clinicians. Based on the findings of this study, most sonographers are not confident in practising bowel ultrasound beyond the evaluation of suspected appendicitis. Surveyed sonographers were interested in expanding their roles into other areas of bowel ultrasound like examining for Crohn's and ulcerative colitis. Sonographer role extension into this area of practice is limited by various factors like chronic shortage of sonographers, increasing workload, limited training, and the perception of diminishing support from radiologists. We recommend a future study that is not limited by a small sample size.

Facial ageing . . . and other stories

When high quality photographs of the faces of 2700 middle aged and older participants in a longitudinal study were assessed by a panel without knowledge of their chronological age and medical history, people whose perceived age was lower than their chronological age were less likely to have osteoporosis, chronic obstructive pulmonary disease, hearing loss, or cataracts. Energy expenditure and incident type 2 diabetes Data from 90 000 participants in the UK Biobank study who wore an accelerometer for seven days reveal a linear relation between the amount of energy expended during physical activity and the subsequent incidence of type 2 diabetes—even after adjusting for body mass index. A study using data for 1.5 million prescriptions of PPIs in UK general practice found an increased risk of diagnosis of an inflammatory bowel disease in the first two years after treatment started.

Coronavirus disease 2019 and gastrointestinal disorders in children.

During the past 3 years, the coronavirus disease 2019 (COVID-19) pandemic has had a great impact on people all over the world. However, it has become evident that disease manifestations and severity differ across age groups. Most children have a milder disease course than adults but possibly more pronounced gastrointestinal (GI) symptoms. Given the child's developing immune system, the impact of COVID-19 on disease development may differ compared to adults. This study reviews the potential bi-directional relationship between COVID-19 and GI diseases in children, focusing on common pediatric conditions such as functional GI disorders (FGID), celiac disease (CeD), and inflammatory bowel disease (IBD). Children with GI diseases, in general, and CeD and IBD, in particular, do not seem to have an increased risk of severe COVID-19, including risks of hospitalization, critical care need, and death. While infections are considered candidate environmental factors in both CeD and IBD pathogenesis, and specific infectious agents are known triggers for FGID, there is still not sufficient evidence to implicate COVID-19 in the development of either of these diseases. However, given the scarcity of data and the possible latency period between environmental triggers and disease development, future investigations in this field are warranted.

COVID-19 vaccination in adults with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are not at increased risk of SARS-CoV-2 infection compared to the general population, and most are not at increased risk for severe disease. COVID-19 is nonetheless common, and vaccination is critical. Four safe and efficacious vaccines are now available for the prevention of COVID-19, with most data available for mRNA vaccines. Patients with IBD have a robust humoral response to vaccination with rates of seroconversion exceeding 95% following a two-dose mRNA vaccine series and 99% following a three-dose mRNA series, although those on certain therapies including anti-tumor necrosis factor α agents may have lower antibody concentrations and waning of antibodies over time. Additionally, rates of cell-mediated immune response, even in those patients with IBD who did not have evidence of humoral immunity, are high. Vaccines are safe and have not been associated with flares in disease activity. Gastroenterology providers should take an active role in ensuring patients with IBD are appropriately vaccinated against COVID-19.

The Suitability of Using the Ferret as a Model Organism in Biomedical Research

This paper reviews the literature data considering the use of the ferret as a model organism in biomedical research. The albino ferret is the most used variant from the ferret species as an animal model in biomedi-cal research. Its use as a pet is also known. Similarities have been identified between ferrets and humans in terms of the physiology and morphology of the respi-ratory system, but also on the pathogenesis or evolu-tion of some diseases on other organs and systems. Ferrets are intensively used in the study of respiratory diseases of viral nature, such as influenza and SARS-CoV, in hypersecretory respiratory disorders, such as cystic fibrosis, in the neuroendocrinology and neuro-anatomy, and even in gastric ulcer research. Through genetic engineering, transgenic ferrets have been ob-tained, such individuals reproducing the studied pa-thology much more faithfully.

Vaccination against COVID-19 in patients with inflammatory bowel diseases

The novel coronavirus infection (COVID-19) is characterized by a high incidence of damage not only to the bronchopulmonary system, but also to the gastrointestinal tract. The problem of patients with bowel diseases was reviewed in this research the context of the COVID-19 pandemic and the importance of vaccination this group of patients was reflected and approaches to it were described. The analysis of biomedical literature data on the problem of vaccination of patients with intestinal diseases against COVID-19 was carried out.Copyright © 2022 Sorbtsionnye i Khromatograficheskie Protsessy. All rights reserved.

Lactulose Works in the Large Bowel: But How Does It Improve Hepatic Encephalopathy in a Patient Without a Large Bowel?

Introduction: Lactulose is a non-absorbable disaccharide which acts in the large bowel, and is commonly used in the treatment of hepatic encephalopathy. We present an interesting case of altered mental status due to hepatic encephalopathy successfully managed with lactulose in a patient with history of total colectomy. Case Description/Methods: A 67-year-old male with non-alcoholic cirrhosis and inflammatory bowel disease (IBD) post total proctocolectomy with a continent ileostomy known as a Kock-pouch (K-pouch) presented to the hospital with flu like symptoms and altered mental status. He was subsequently found to be positive for COVID-19. At the time of initial evaluation, the patient was obtunded with an elevated ammonia level of 91 umol/L. Colorectal surgery was consulted as the patient was not able to empty his K-pouch. Recently, he complained of inability to catheterize and with bleeding from the stoma. Initial catheterization with a Water's tube yielded 400 cc of effluent. Nasogastric tube was placed through which he was receiving lactulose 30 mg q8 hours. The patient's mental status improved within 24 hours. The patient ultimately underwent flexible pouchoscopy with endoscopic dilation and placement of a 22 French mushroom catheter for decompression of the K-pouch. Discussion(s): Lactulose is a non-absorbable disaccharide composed of galactose and fructose. The small intestine does not have the enzymes required to breakdown lactulose so it reaches the large bowel in its original form. In the large bowel, it is metabolized by colonic bacteria into monosaccharides and then to volatile fatty acids, hydrogen and methane. Lactulose decreases both the production and absorption of ammonia mainly through the presence of gut bacteria. The question arises as to how lactulose decreased ammonia levels in this patient without a large bowel. One proposed mechanism is the translocation of bacteria normally found in the large bowel to the small intestine. Small Intestinal Bacterial Overgrowth (SIBO), is a condition causing an increased number of bacteria in the small intestine. Patients with IBD and structural abnormalities are at increased risk of developing SIBO. Lactulose is commonly used in the diagnosis through the administration of lactulose and subsequent measurements of hydrogen and methane gas in expired air. This condition, in our patient with history of ulcerative colitis and colectomy, is a proposed mechanism of the efficacy of lactulose in the treatment of hepatic encephalopathy.

Long-Term Outcomes of Treatment With and De-Escalation From a Combination of Vedolizumab and Another Biologic or Tofacitinib for Inflammatory Bowel Disease

Introduction: There are scant data on long-term outcomes of treatment of inflammatory bowel disease (IBD) with a combination of advanced therapies, including after de-escalation. Method(s): We identified patients with IBD at a tertiary center who began therapy with vedolizumab (VDZ) in combination with another advanced therapy (biologic or JAK inhibitor) between 2016 and 2020 and examined their outcomes through 6/1/22. We defined biochemical remission as CRP, 5 mg/L and calprotectin < 150 mcg/g, and endoscopic remission as Mayo endoscopic subscore 0 or simple endoscopic score for Crohn's disease (CD) 0. Short-term outcomes of this cohort were previously reported. Result(s): Fourteen patients with a median of 322 (IQR 251-322) weeks of follow up were identified. 10 had ulcerative colitis, 3 CD, and 1 indeterminate colitis. VDZ was combined with tofacitinib in 9 patients, ustekinumab in 3 and adalimumab in 2. Median time on combination therapy was 94 weeks (IQR 17-133). Eight patients achieved objective remission (3 biochemical, 5 endoscopic), 1 changed combination with subsequent endoscopic remission, 2 had primary non-response, 1 had secondary non-response, 1 stopped within 1 month due to reported adverse effect (paresthesia), and 1 lacked follow-up data. Eight patients de-escalated to a single agent, 4 at physician direction and 4 due to insurance denial. Before de-escalation, 6 had objective remission (2 biochemical, 4 endoscopic). After de-escalation, 3 patients maintained objective remission (2 biochemical, 1 endoscopic), 3 had disease flare, of which 1 required colectomy, and 2 lacked data. All 3 patients with disease flare had de-escalated following an insurance denial. Two patients remained on combination therapy through follow up: 1 has endoscopic remission after changing one drug of their combination and 1 has ongoing moderate endoscopic disease despite combination therapy. There were 2 infections requiring hospitalization (rotavirus, C. difficile), and 8 non-serious infections (5 mild SARS-COV-2, 1 peristomal cellulitis, 1 pneumonia, 1 sinus) while on combination therapy. Conclusion(s): In long-term follow up of this small cohort, there were no new signals on effectiveness or safety of combining advanced agents. De-escalation to a single agent was tolerated in half of patients with follow-up data;all patients who flared following de-escalation had adjusted therapy due to insurance denial. More data is needed to inform de-escalation decisions.

Knowledge About Preventive Health Guidelines for Inflammatory Bowel Diseases in Patients: A Quality Improvement Project

Introduction: Preventive care guidelines for patients with Inflammatory Bowel Disease (IBD) emphasize the need for a patient-centered interdisciplinary approach, with assessment and management of the patient's physical and mental health as well as the IBD. There is no data about compliance with current IBD preventive care guidelines in Puerto Rico. This study aims to evaluate current IBD preventive care in the clinic, and knowledge among patients and gastroenterologists about the preventive care guidelines. The 3-phase study includes retrospective medical record review, an anonymous online survey of gastroenterologists, and an anonymous survey of patients. We report the results of the patient survey. Method(s): Adult patients with an established diagnosis of at least 6 months of ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis (IC), were recruited from the IBD Clinics and through IBDrelated social media. Questionnaires were filled in the clinic and online using Google forms. Statistical analysis was performed using descriptive statistics. Comparisons of proportions and means between groups was based on Fisher's exact and chi square tests. The study was approved by the MSC IRB. Result(s): 83 patients completed the survey, 42 from the clinics and 41 through social media. 60% had CD, 47.4% were diagnosed more than 10 years ago, 57.9% were younger than 38 years old and 68% were on immunosuppressants/biologics. 83.13% and 60.24% of patients knew that COVID and Influenza vaccines were indicated, respectively. However only 42.17%, 36.14%, 32.53% and 31.33% of patients knew about indications for HPV, pneumococcal, varicella and zoster vaccines, respectively. There was a significant difference about knowledge regarding screening for latent TB (p=0.019), anxiety and depression (p= 0.03) and smoking status (p=0.033) between CD and UC/IC patients, as shown in Table. Conclusion(s): Our study showed a significant lack of knowledge about IBD preventive care in patients. Strategies to improve patient education are needed. The results of the review of records from the clinic as well as the knowledge of gastroenterologists will point out other deficiencies in the healthcare system and help design methods to improve patient care. Another aspect that needs to be explored is access to preventive measures such as vaccines. (Table Presented).

Loss of Bifidobacteria in Lyme Disease: Cause or Effect

Introduction: Lyme disease is a poorly understood condition which starts with a rash but may continue with chronic fatigue and neurological symptoms. Approximately 1 in 5 early Lyme disease patients have GI symptoms, such as nausea, anorexia, abdominal pain, or diarrhea. Lyme disease is thought to be cased by microbes in the spirochetes phylum transmitted by black legged ticks. Lyme-related healthcare costs in America exceed 1.3 billion dollars annually. Bifidobacteria are known for their beneficial probiotic actions within the human gut microbiome. Their numbers are reduced in severe COVID-19, Clostridioides difficile infection and Inflammatory Bowel Disease. To our knowledge Bifidobacteria levels have not been studied in Lyme disease patients. Given the importance of Bifidobacterium abundance in other diseases, we focused on relative abundance of Bifidobacterium in fecal samples of patients with Lyme disease compared to controls. Method(s): Fecal samples were assessed for relative abundance of Bifidobacterium in Healthy Control subjects without Lyme disease (n=20) compared to patients with Lyme disease (n=39). The average symptom duration in patients with Lyme disease was 5 years and none were on antibiotics 2 weeks prior to sample collection (range of symptoms from 1 month to 20 years, all treated initially with antibiotics).Metagenomics Next Generation sequencing was performed on fecal samples, where DNA samples were extracted and normalized for library downstream analysis using Shotgun Methodology. Mann- Whitney Statistical test was used for comparison. This study was IRB approved. Result(s): Relative Abundance of bifidobacteria was significantly decreased (p< 0.0001) in patients with Lyme disease. Median and interquartile range (IQR) were: Control (Median:4.175%;IQR:1.72-10.27%) and Lyme disease (Median:0.0014%;IQR:0.00%-0.96%)(Figure). 30/39 Lyme disease patients (77%) were found to possess < 1% relative abundance of Bifidobacterium in their stool sample. Of interest only 1/39 samples showed presence of Spirochetes in stool samples. Conclusion(s): This is the first study that demonstrates low levels of Bifidobacteria in patients with chronic Lyme disease. These results raise three questions;whether the disease was caused by 1. the original microbe creating loss of Bifidobacterium 2. baseline low Bifidobacteria due likely to either diet or medications or 3. excessive treatment. Given Lyme disease comprises a gut dysbiosis issue, therapies should also aim at restoration of depleted Bifidobacteria. (Figure Presented).

Prevention of Venous Thromboembolism in IBD Patients May Not Be Associated With Prophylaxis Rates

Introduction: Patients with inflammatory bowel disease (IBD) harbor a higher risk of deep venous thrombosis and venous thromboembolism (VTE) compared to healthy individuals. Previous studies, including a large meta-analysis, estimate the risk of VTE incidence to be almost 2-3 times baseline. Guidelines, therefore, recommend VTE prophylaxis in most inpatients with IBD. While previous studies have demonstrated less than ideal adherence with these guidelines, we sought to determine the rate of VTE prophylaxis at an academic medical center. Method(s): A retrospective chart review of inpatients with Crohn's disease or ulcerative colitis admitted to a tertiary medical center in Bronx, NY from 1/2015 to 2/2020 was performed. All patients who were admitted with a primary gynecological or psychiatric disorder, COVID infection, or known hypercoagulable disorder were excluded. Orders for pharmacologic and mechanical VTE prophylaxis at any point during the patient's admission were ed. Using ICD10 codes, IBD patients with acute VTE variations were identified. Clinical and demographic variables were analyzed for their association with VTE prophylaxis. Two-sample t-tests and Fisher's exact tests were used as appropriate. A p-value < 0.05 was considered statistically significant. Result(s): A total of 1670 patients with IBD were identified among whom 1280 (76.7%) were prescribed either pharmacological or mechanical VTE prophylaxis during their hospital admission. 70 patients were excluded from the analysis of development of VTE because their diagnosis of VTE was prior to their admission date. Older age (p<.0001), higher BMI (p<.0001), female sex (p=.001), havingMedicare insurance (p<.0001) were associated with VTE prophylaxis ordering (see Table). There was a VTE incidence of 6.2% (n=98/1600) of the IBD patients in our cohort, with 3/388 patients (0.8%) not being prescribed prophylaxis and 95/1212 (7.8%) being prescribed prophylaxis (p< 0.001). Conclusion(s): Contrary to other studies, we show that VTE prophylaxis rates may not be associated with a reduction in VTE incidence during hospitalization. While bias by indication may be contributing to this finding with those at greatest risk more likely to receive prophylaxis, other factors may be involved. Further studies are warranted. (Table Presented).