Cryptosporidiosis in individuals with inflammatory bowel disease: a scoping review protocol.

INTRODUCTION: Cryptosporidiosis is a leading cause of moderate-to-severe diarrhoea globally, and, while it is often self-limited, in immunocompromised individuals, the infection can be associated with significant morbidity and mortality. Diagnosis might be missed or delayed in patients with inflammatory bowel disease (IBD) due to similar presentation, and these patients may also be on immunosuppressive therapies, increasing their risk of infection. Additionally, gastrointestinal infection and dysbiosis may be a risk factor for IBD. Diagnosis, presentation and treatment of cryptosporidiosis in individuals with IBD, as well as any epidemiologic correlations between the two diseases, will be investigated. METHODS AND ANALYSIS: MEDLINE, Embase, Cochrane Library, CINAHL, Dissertations and Theses Global and grey literature will be searched. Joanna Briggs Institute (JBI) methodology for scoping reviews was used for the protocol and will be for the review. Two reviewers will independently screen studies and extract data. The evidence and presentation of the results will be analysed with input from the review team. Studies of cryptosporidiosis in patients with IBD will be included. Paediatric, adolescent and adult studies in all patient environments will be included. Cases in which Crohn's disease does not affect the intestine and cases in which cryptosporidial infection is not in the intestine will be excluded. ETHICS AND DISSEMINATION: Published clinical literature will be systematically reviewed, and this work does not directly involve patients. Consequently, ethical review by an institutional review board is not required. Data will be presented at academic conferences, and a culminating report will be published in a peer-reviewed journal. OPEN SCIENCE FRAMEWORK REGISTRATION: https://osf.io/j47mb.

Oral health in patients with inflammatory bowel disease: A cross-sectional survey in Sweden.

OBJECTIVES: The aim of this cross-sectional survey was to assess oral health, including prevalence of periodontitis and rate of tooth loss, in a Swedish cohort of patients with inflammatory bowel disease (IBD). METHODS: A questionnaire on general anamnestic and socio-economic aspects, IBD diagnosis, and various oral health aspects was distributed online. The analyses focused on the comparison between patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) as well as on factors associated with self-reported severe periodontitis and tooth loss. RESULTS: Analyses were based on answers from 786 patients; 415 with UC, 371 with CD, 74% female. In both disease entities, high prevalence of severe periodontitis (i.e., 38.5%) was reported, and about 19% of the population had less than 20 remaining teeth and 6.5% a poor oral health-related quality of life. CD patients tended to be more severely affected than UC patients (p > 0.05 in the adjusted analysis). Almost 90% of CD patients were aware of being entitled to a bi-annual governmental financial support for dental care due to IBD; however, 1 out of 4 UC patients did not. Furthermore, IBD patients largely believe that the interest of their physicians in any oral lesions due to IBD diagnosis is low. CONCLUSIONS: Severe periodontitis and high rate of tooth loss are frequent in Swedish IBD patients. CLINICAL RELEVANCE: Even though IBD patients receive bi-annually some special financial support for dental care, it seems this is still not sufficient and more preventive measures appear necessary.

Associations of intestinal diseases with anal diseases: a Mendelian randomization study.

Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn's disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA.

The Impact of Gastrectomy on Inflammatory Bowel Disease Risk in Gastric Cancer Patients: A Critical Analysis.

Gastrectomy, a prevalent surgical procedure for gastric cancer, results in substantial alterations to the gastrointestinal tract, including reduced gastric acid production and significant modifications to the gut microbiota. These changes can impair postoperative recovery, influence metabolic functions, and predispose patients to inflammatory bowel disease (IBD). Studies have shown an increased risk of IBD, particularly Crohn's disease (CD) and ulcerative colitis (UC), in patients following gastrectomy and bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). For instance, patients undergoing RYGB have a higher hazard ratio for developing CD, while SG patients show an increased risk for UC. The surgical alteration of the gastrointestinal tract promotes dysbiosis, with a significant increase in pathogenic bacteria and a decrease in beneficial microbial populations. This dysbiosis can impair the intestinal mucosal barrier and promote systemic inflammation. Understanding the mechanisms behind these changes and their clinical implications is essential for developing effective postoperative management strategies. Probiotics and enhanced recovery after surgery (ERAS) protocols have shown promise in mitigating these adverse effects, improving gut microbiota balance, and enhancing patient outcomes. Further research is necessary to fully elucidate the long-term impacts of gastrectomy on gastrointestinal health and to refine therapeutic approaches for postoperative care.

Risk of Clostridioides difficile infection in inflammatory bowel disease patients undergoing vedolizumab treatment: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent. METHOD: Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package "meta". RESULTS: Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010-0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002-0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73-2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04-0.63) for UC and 1.29 (95% CI 0.41-4.04) for CD. CONCLUSION: The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD. TRIAL REGISTRATION: The study was registered on the PROSPERO registry (CRD42023465986).

Atopic disease and inflammatory bowel disease: A bidirectional Mendelian randomization study.

Observational studies have reported associations between atopic diseases, including allergic rhinitis (AR), asthma, atopic dermatitis (AD), and inflammatory bowel disease (IBD), but the causal relationship remains unknown. We utilized pooled data from genome-wide association studies, qualified instrumental variables were screened according to the 3 hypotheses of MR, and bidirectional causality between atopic diseases and IBD was assessed using 2-sample Mendelian randomization analysis (2SMR). The results of our study suggest that AR increased the risk of Crohn disease (CD) (IVW OR = 1.19, 95% CI = 1.02-1.39, P = .026), ulcerative colitis (UC) (IVW OR = 1.14, 95% CI = 1.01-1.29, P = .031) and overall IBD (IVW OR = 1.15, 95% CI = 1.03-1.28, P = .015); Asthma increased the risk of CD (IVW OR = 7.66, 95% CI = 1.58-37.20, P = .012), UC (IVW OR = 3.81, 95% CI = 1.09-13.32, P = .036) and overall IBD (IVW OR = 5.13, 95% CI = 1.48-17.70, P = .010); AD increased the risk of CD (IVW OR = 1.19, 95% CI = 1.02-1.39, P = .023) and overall IBD (IVW OR = 1.14, 95% CI = 1.03-1.28, P = .015) risk. In reverse causality, only CD increased the risk of AR (IVW OR = 1.02, 95% CI = 1.00-1.05, P = .031). This study shows that atopic diseases of AR and asthma are causally related to IBD and its subtypes, and AD is causally related to IBD (which may be attributed to CD). Of the reverse causality, only CD was causally related to AR.

Review article: The role of the gut-brain axis in inflammatory bowel disease and its therapeutic implications.

BACKGROUND: Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting. METHODS: We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024. RESULTS: The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients. CONCLUSIONS: Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.

[A PhD completed. Oral manifestations in inflammatory bowel diseases]. / Serie: Hora est. Orale manifestaties van inflammatoire darmziekten.

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gastrointestinal tract. In addition to bowel symptoms, patients may also have oral manifestations. This thesis investigated potential associations between disease activity in the gut, oral health, salivary gland function, and saliva composition. Patients with Crohn's disease had a significantly higher DMFT index, but showed no difference in periodontal diseases compared to a healthy control group. The saliva composition in patients with active bowel disease differed from that in patients with inactive bowel disease, suggesting that saliva analysis could potentially be used in the future to determine the degree and severity of bowel disease. The knowledge of gastroenterologists and dentists regarding oral manifestations of bowel diseases was found to be limited. Gastroenterologists and dentists valued interdisciplinary patient consultation as very useful, but the frequency of consultation was considered insufficient.

Incidence of Gastric Foveolar Metaplasia in Duodenal Mucosa of the Pediatric Patients.

OBJECTIVE: The prevalence and the clinical significance of gastric foveolar metaplasia (GFM) of duodenal mucosa in pediatric patients are undetermined. The aim was to investigate the event of GFM in duodenal biopsies and its association with gastrointestinal tract disorders in pediatric patients. METHODS: We performed a chart review of the characteristics and pathologic findings in patients with GFM described in the pathology reports during 2020 to 2022. RESULTS: Sixty-five out of 3,857 patients (1.7%) had GFM observed in a total of 70/4,778 (1.5%) cases with duodenal biopsies. The ages ranged from 3 to 19 years. The duodenal bulb with GFM was identified in 65 out of 70 cases (92.9%). 17/70 (24.3%) biopsies had coexisting chronic duodenitis, and 52/70 (74.3%) had isolated GFM in duodenum. 48/70 (68.6%) cases had pathologic findings in other parts of the gastrointestinal tract, including 20 (28.6%) inflammatory bowel disease (IBD) and four (5.7%) H. pylori gastritis. Of all 4,778 cases, 136 (2.8%) and 92 (1.9%) cases were diagnosed as IBD and H. pylori gastritis, which had an odds ratio for GFM at 15.8 and 3.2 respectively (p<0.05). CONCLUSION: Both H. pylori gastritis and IBD are associated with GFM in pediatric patients, while isolated GFM itself in the duodenal bulb has limited clinical implications.

Patients' and health professionals' research priorities for chronic pain associated with inflammatory bowel disease: a co-produced sequential mixed methods Delphi consensus study.

OBJECTIVE: Chronic pain in inflammatory bowel disease (IBD) is common and detrimental to quality of life. Recent Cochrane reviews identified a multitude of randomised controlled trial interventions, but the certainty of the findings is low or very low. We set out to reach a patient and professional co-produced Delphi consensus on treatment priorities, key outcomes and propose a model for understanding our findings. METHODS: An online survey was co-produced with Crohn's and Colitis UK and sent to patients and healthcare professionals in two phases, for prioritisation of treatments and outcome measures. Phase three consisted of four online group interviews, where patients and healthcare professionals discussed the rationale of their choices. Transcripts were combined with the free text data from the Delphi surveys and analysed through a three-phase qualitative technique. RESULTS: The phase 1 survey was completed by 128 participants (73 patients, 3 carers and 53 health professionals). Diet was the top priority for both patients (n=26/73, 36.1%) and healthcare professionals (n=29/52, 56.9%). Phase 2 was completed by 68 participants. FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, stress management therapy and relaxation therapy were the top three consensus priorities. Phase 3 group interviews were attended by 13 patients and 5 healthcare professionals. Key themes included: The patient as an individual, beliefs and experiences, disease activity influencing therapy choice, accessibility barriers and quality of life. CONCLUSION: Low FODMAP diet, followed by psychological therapies were the highest-rated research priorities for healthcare professionals and patients. Funding bodies and researchers should consider these findings, alongside the model for understanding our findings, when making research decisions.

Distinct clinical outcomes linked to peripheral arthritis and dactylitis in axial spondyloarthritis: findings from a retrospective Irish cohort.

INTRODUCTION: Axial spondyloarthritis (AxSpA) is a chronic inflammatory condition primarily affecting the axial skeleton. Peripheral features such as peripheral arthritis (PA) and dactylitis are common in AxSpA disease. This study aimed to investigate the independent impact of these manifestations on patient presentation and disease outcomes within an Irish AxSpA cohort. METHODS: 912 Irish AxSpA patients were analyzed in this study. Disease outcomes in patients with and without peripheral arthritis or dactylitis were compared using univariate and multivariate methods. The prevalence of extra-spinal manifestations was further assessed in relation to AxSpA disease duration. RESULTS: 30.2% of patients reported PA, while 6.6% had dactylitis. PA and dactylitis were strongly linked, with 70% of patients presenting with dactylitis also showing features of PA. Psoriasis was more common in both patients with PA (OR 2.2, P < 0.001) and dactylitis (OR 3.38, P < 0.001). Dactylitis, but not PA was strongly linked to uveitis (OR 2.91, P < 0.001) and inflammatory bowel disease (OR 3.15, P < 0.001), while PA was associated with worse patient functioning and reduced quality of life. PA, but not dactylitis was linked with increased AxSpA disease duration. DISCUSSION: Despite high concurrence of PA and dactylitis in AxSpA patients, each manifestation is independently associated with worse outcomes. While some of these overlapped, several outcomes are specific to either PA or dactylitis. Due to its strong association with uveitis and inflammatory bowel disease, an early presentation of dactylitis may represent a unique subset of patients and serve as a valuable predictive marker for the later onset of these conditions.

Risk of inflammatory bowel disease following hospitalisation with infectious mononucleosis: nationwide cohort study from Denmark.

Infectious mononucleosis (IM) is suspected to be associated with inflammatory bowel disease (IBD) development. Using a Danish nationwide cohort of people developing severe IM and their age-, sex-, and socioeconomic (SES) index-matched counterparts, we investigated the subsequent risk of IBD, Crohn's disease (CD), or ulcerative colitis (UC) development from 1977 to 2021. Among 39,684 severe IM patients we find a sex-, age-, and SES index-adjusted HR for IBD of 1.35 (95% CI: 1.22-1.49). This significantly increased risk was seen for both CD (HR: 1.56; 95% CI: 1.34-1.83) and to a lesser extent UC (HR: 1.23; 95% CI: 1.08-1.40) and remains following negative control matching with a cohort diagnosed with Chlamydia trachomatis infection (HR: 1.39; 95% CI: 1.01-1.91). Those with severe IM at 0-9 years had a particularly increased risk for CD (HR: 1.77; 95% CI: 1.26-2.49). Here we show an increased risk for IBD diagnosis following IM hospitalisation, indicating an association between severe EBV disease and later IBD development. Further exploration of the potential factors contributing to IBD susceptibility following EBV disease is warranted.

Inflammatory bowel diseases and spondyloarthritis: a focus on female patients.

OBJECTIVE: Ulcerative colitis and Crohn's disease are chronic inflammatory diseases and represent the two most important types of inflammatory bowel diseases (IBD), while spondyloarthritis (SpA) comprises a heterogeneous group of systemic inflammatory chronic rheumatic diseases, including peripheral SpA and axial SpA. Joint manifestations are the most commonly observed extraintestinal manifestations, and they can precede or not the diagnosis of IBD. Notably, in women, misdiagnoses of IBD as irritable bowel syndrome and SpA as fibromyalgia are common, leading to delayed diagnoses, increased disease burden, and poorer prognoses. This narrative review emphasizes the critical role of diagnostic tools in facilitating early referrals of IBD patients with suspected SpA and vice versa to rheumatologists and gastroenterologists, respectively. Special attention is given to the multidisciplinary approach for more effective management of these conditions, particularly in female patients. METHODS: In this narrative review, we critically evaluated the literature on this topic, focusing on papers written in English that address female issues in IBD and SpA. RESULTS: IBD and SpA are chronic inflammatory disorders often occurring in the same patients. Female patients are often misdiagnosed, and this delay in diagnosis is associated with a higher disease burden and a poorer prognosis. CONCLUSIONS: A multidisciplinary approach is needed to enable early referral between gastroenterologists and rheumatologists, as this means a better prognosis for patients with a reduction in the economic and social burden associated with IBD and SpA.

Prevalence and risk factors of sleep disorders in inflammatory bowel disease: a cross-sectional study.

BACKGROUND: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD). METHODS: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients. RESULTS: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor. CONCLUSION: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors.

Insights into the Two Most Common Cancers of Primitive Gut-Derived Structures and Their Microbial Connections.

The gastrointestinal and respiratory systems are closely linked in different ways, including from the embryological, anatomical, cellular, and physiological angles. The highest number (and various types) of microorganisms live in the large intestine/colon, and constitute the normal microbiota in healthy people. Adverse alterations of the microbiota or dysbiosis can lead to chronic inflammation. If this detrimental condition persists, a sequence of pathological events can occur, such as inflammatory bowel disease, dysplasia or premalignant changes, and finally, cancer. One of the most commonly identified bacteria in both inflammatory bowel disease and colon cancer is Escherichia coli. On the other hand, patients with inflammatory bowel disease are at risk of several other diseases-both intestinal (such as malnutrition and intestinal obstruction, besides cancer) and extraintestinal (such as arthritis, bronchiectasis, and cancer risk). Cancers of the lung and colon are the two most common malignancies occurring worldwide (except for female breast cancer). Like the bacterial role in colon cancer, many studies have shown a link between chronic Chlamydia pneumoniae infection and lung cancer. However, in colon cancer, genotoxic colibactin-producing E. coli belonging to the B2 phylogroup may promote tumorigenesis. Furthermore, E. coli is believed to play an important role in the dissemination of cancer cells from the primary colonic site. Currently, seven enteric pathogenic E. coli subtypes have been described. Conversely, three Chlamydiae can cause infections in humans (C. trachomatis may increase the risk of cervical and ovarian cancers). Nonetheless, striking genomic plasticity and genetic modifications allow E. coli to constantly adjust to the surrounding environment. Consequently, E. coli becomes resistant to antibiotics and difficult to manage. To solve this problem, scientists are thinking of utilizing suitable lytic bacteriophages (viruses that infect and kill bacteria). Several bacteriophages of E. coli and Chlamydia species are being evaluated for this purpose.

Evaluation of the potential use of protoporphyrins as biomarkers of anemic disease in human urine from inflammatory bowel disease patients.

Protoporphyrins are organic compounds with cyclic structure that are synthesised by a wide variety of organisms. In humans, these compounds are detected in blood and urine, with significantly higher levels in blood. Their potential as biomarkers of anemia and other diseases is currently being investigated, as their levels change according to the biochemical processes associated with the disease. The most widely used biomarker of anemia is serum ferritin, but it is unreliable in patients with inflammatory bowel disease (IBD) because its levels can be altered by acute inflammation and/or infections. There is therefore a need to look for new markers to help diagnose anemia in IBD patients. This work develops and validates a method for the determination of three protoporphyrins in human urine: protoporphyrin IX (PPIX), protoporphyrin IX complex with Zn (ZnPPIX) and protoporphyrin IX complex with Fe (II) (FePPIX), the latter also known as heme. The aim is to evaluate their potential as biomarkers of anemic disease in patients diagnosed with IBD. The proposed analytical method is based on high performance liquid chromatography (HPLC) with dual detection based on photodiode array (PDA) and fluorescence (FD). Quantification of the analytes at very low concentrations is possible due to the efficient preconcentration provided by dispersive liquid-liquid microextraction (DLLME) and the sensitivity of the detection systems. The method was validated by evaluating linearity (25-1000 ng mL-1), matrix effect, sensitivity (limits of quantification were between 5 and 11 ng mL-1), selectivity, accuracy, carry-over, dilution integrity, stability and precision (< 12.1 %). Finally, statistical analyses applied to the sample quantification results showed these three markers, together with five clinical markers, were significantly different between anemic and non-anemic IBD patients.

Frailty: An Underappreciated Risk Factor for IBD Complications.

PURPOSE OF REVIEW: The prevalence of IBD in older adults is rapidly growing. Older adults with IBD are underrepresented in research and clinical trials and yet at great risk for adverse events. Therefore, understanding advanced aged associated constructs in older adults can be critical to improving the management of older adults with IBD. RECENT FINDINGS: In this review, we present recent studies on frailty in IBD. We identify 4 major themes in the literature: studies that describe frailty in patients with IBD, studies that report on consequences of frailty, studies of frailty as a risk stratification modality, and studies of frailty as an exposure and outcome. In reviewing the literature, we discuss the heterogeneity that exists and outline future directions to ensure appropriate applications for frailty in the field of IBD.

Meta-analysis: Risk of lymphoma in patients with inflammatory bowel disease in population-based cohort studies.

BACKGROUND: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. AIMS: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. METHODS: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population-based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random-effects meta-analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21-1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06-1.53]) and non-Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20-1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27-1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09-1.35]) (p for interaction = 0.026). Meta-regression demonstrated that mean age of patients, study year, mean study follow-up duration, and percentages of immunomodulators and biologics use did not influence study outcome. CONCLUSIONS: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non-Hodgkin's lymphoma.

Navigating the pharmacotherapeutic management of comorbid inflammatory bowel disease and primary sclerosing cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is the most specific hepatobiliary extraintestinal manifestation in inflammatory bowel disease (IBD). PSC ultimately has a poor prognosis, with disease progression resulting in liver cirrhosis and subsequent liver failure. While there is current data for the medical management of IBD, the optimal approach for concurrent PSC-IBD is unclear. AREAS COVERED: This review focuses on the current literature of pharmacotherapy in the PSC-IBD population including anti-tumor necrosis factor agents, vedolizumab, JAK inhibitors, IL-12/23 inhibitors, and thiopurines. Regarding PSC-IBD, it focuses on effectiveness of IBD therapies on liver biochemistry and IBD activity as well as the advent of clinically relevant liver outcomes and safety. The authors also address the need for further advances in research. EXPERT OPINION: The longer-term data for pharmacological management for IBD is well established. In the concomitant PSC-IBD population there is no drug to date that has effectively reduced disease related morbidity and mortality outcomes. There are limitations in the current, mostly retrospective data on IBD drugs in PSC-IBD with respect to samples sizes, heterogenous outcomes, and lack of a high-quality surrogate endpoint in PSC. However, current data for adalimumab offers encouraging results which require further exploration with larger prospective studies.