Assessing quality of magnetic resonance enterography and its impact on disease assessment of ileal Crohn's disease.

BACKGROUND/AIMS: Assessment of quality of magnetic resonance enterography (MRE) in small bowel Crohn's disease (CD) activity evaluation has received little attention. We assessed the impact of bowel distention and motion artifact on MRE activity indices in ileal CD. METHODS: A cohort of patients who underwent contemporaneous MRE and colonoscopy for ileal CD assessment between 2014 and 2021 at 2 centers were audited. An abdominal radiologist blinded to clinical data reviewed each MRE, graded bowel distention and motion artifact upon a pre-specified 3-point scale and calculated the original magnetic resonance index of activity (MaRIA) and simplified MaRIA (sMaRIA), London index and CD MRE index (CDMI). Ileal endoscopic activity was graded via the Simplified Endoscopy Score for CD (SES-CD). The performance of MRE indices in discriminating active disease (SES-CD ≥3) stratified by MRE quality was measured by receiver operator characteristic analyses. RESULTS: One hundred and thirty-seven patients had MRE and colonoscopy within a median of 16 days (range, 0-30 days) with 63 (46%) exhibiting active disease (SES-CD ≥3). Forty-four MREs (32%) were deemed low quality due to motion artifact and/or moderate to poor distention. Low-quality MREs demonstrated reduced discriminative performance between ileal SES-CD ≥3 and MRE indices (MaRIA 0.838 vs. 0.634, sMaRIA 0.834 vs. 0.527, CDMI 0.850 vs. 0.595, London 0.748 vs. 0.511, P<0.05 for all). Individually the presence of any motion artifact markedly impacted the discriminative performance (e.g., sMaRIA area under the curve 0.544 vs. 0.814, P<0.05). CONCLUSIONS: Image quality parameters can significantly impact MRE disease activity interpretation. Quality metrics should be reported, enabling cautious interpretation in lower-quality studies.

Prevalence of Extraintestinal Manifestations in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a multisystem disease impacting various body systems including musculoskeletal, ocular, skin, hepatobiliary, pulmonary, cardiac, and haematological systems. The extraintestinal manifestations of IBD are frequent, common in both ulcerative colitis (UC) and Crohn's disease (CD), and impact the morbidity and mortality of patients. METHODS: The Embase, Embase classic, and PubMed databases were searched between January 1979 and December 2021. A random effects model was performed to find the pooled prevalence of joint, ocular, and skin extraintestinal manifestations of UC and CD. RESULTS: Fifty-two studies were included that reported on 352 454 patients. The prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in all IBD, UC, and CD was 24%, 27%, and 35% respectively. The prevalence between UC and CD were similar for pyoderma gangrenosum and axial joint manifestations. Ocular manifestations were found to be more common in CD than in UC. Peripheral joint manifestations and erythema nodosum were found to be more common in CD than UC. DISCUSSION: To our knowledge, this is the first meta-analysis that reports on the prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in IBD. Our results are largely consistent with figures and statements quoted in the literature. However, our findings are based on significantly larger cohort sizes. Thus, our results have the potential to better power studies and more accurately counsel patients.

The prevalence of joint, ocular, or skin extraintestinal manifestations in IBD, UC, and CD was 24%, 27%, and 35% respectively. Ocular manifestations were more common in CD. Peripheral joint manifestations and erythema nodosum were more common in CD.

Crohn's disease: an update.

Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.

DECIDE: Delphi Expert Consensus Statement on Inflammatory Bowel Disease Dysplasia Shared Management Decision-Making.

BACKGROUND AND AIMS: Inflammatory bowel disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. METHODS: Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders, and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. RESULTS: In all, 31 members [15 gastroenterologists, 14 colorectal surgeons and two nurse specialists] from nine countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. CONCLUSIONS: By consolidating evidence for best practice using literature review and key stakeholder and decision-making expert consultation, we have developed international consensus recommendations to support health care professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

Lower respiratory tract microbiome composition and community interactions in smokers.

The lung microbiome impacts on lung function, making any smoking-induced changes in the lung microbiome potentially significant. The complex co-occurrence and co-avoidance patterns between the bacterial taxa in the lower respiratory tract (LRT) microbiome were explored for a cohort of active (AS), former (FS) and never (NS) smokers. Bronchoalveolar lavages (BALs) were collected from 55 volunteer subjects (9 NS, 24 FS and 22 AS). The LRT microbiome composition was assessed using 16S rRNA amplicon sequencing. Identification of differentially abundant taxa and co-occurrence patterns, discriminant analysis and biomarker inferences were performed. The data show that smoking results in a loss in the diversity of the LRT microbiome, change in the co-occurrence patterns and a weakening of the tight community structure present in healthy microbiomes. The increased abundance of the genus Ralstonia in the lung microbiomes of both former and active smokers is significant. Partial least square discriminant and DESeq2 analyses suggested a compositional difference between the cohorts in the LRT microbiome. The groups were sufficiently distinct from each other to suggest that cessation of smoking may not be sufficient for the lung microbiota to return to a similar composition to that of NS. The linear discriminant analysis effect size (LEfSe) analyses identified several bacterial taxa as potential biomarkers of smoking status. Network-based clustering analysis highlighted different co-occurring and co-avoiding microbial taxa in the three groups. The analysis found a cluster of bacterial taxa that co-occur in smokers and non-smokers alike. The clusters exhibited tighter and more significant associations in NS compared to FS and AS. Higher degree of rivalry between clusters was observed in the AS. The groups were sufficiently distinct from each other to suggest that cessation of smoking may not be sufficient for the lung microbiota to return to a similar composition to that of NS.

Network meta-analysis: efficacy and safety of treatments for fistulising Crohn's disease.

INTRODUCTION: Fistulas are a debilitating complication of Crohn's disease and treatment options remain limited. There is a lack of head-to-head comparisons between treatments. To our knowledge, this is the first network meta-analysis on the efficacy of medical therapies in achieving fistula remission and maintenance of fistula closure in Crohn's disease. METHODS: Biomedical databases and the Cochrane Central Registry were searched between 1978 and 2022 for randomized controlled trials (RCTs) reporting on treatments. A network meta-analysis was performed using the frequentist model with pooled relative risks (RRs) and P -scores used to rank treatments. RESULTS: Twenty-five RCTs were included for analysis with 2239 patients included. At the 16-24 week time point, infliximab produced the only statistically significant result with the 5 mg/kg dose proving the most effective [RR, 2.30; 95% confidence interval (CI), 1.40-3.77]. At 44 weeks, ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24-4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06-3.99) and infliximab 5 mg/kg (RR, 1.68; 95% CI, 1.03-2.75) also producing a statistically significant result. CONCLUSION: Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising Crohn's disease, biologics such as ustekinumab, vedolizumab and adalimumab show promising results.

Meta-analysis: The efficacy of therapeutic drug monitoring of anti-TNF-therapy in inflammatory bowel disease.

BACKGROUND AND AIMS: This systematic review and meta-analysis aimed to determine whether the use of therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients on anti-tumour necrosis factor (anti-TNF) therapy results in improved rates of clinical and endoscopic remission, surgery, corticosteroid-free remission and hospitalisation. METHODS: MEDLINE, EMBASE, EMBASE classic, PubMed, Cochrane central databases register of controlled trials and Cochrane Specialised Trials Register were searched between 01 Janurary 1946 and 08 April 2022. Randomised controlled trials (RCTs) and prospective and retrospective observational studies were included, comparing TDM to standard of care (SOC) or reactive vs proactive TDM. Results were reported as pooled relative risks (RR) with 95% confidence intervals (95% CI). RESULTS: Twenty-six studies, including 9 RCTs, were included. Compared to SOC, proactive TDM was associated with a significantly decreased risk of treatment failure (RR 0.64, 95% CI 0.48-0.85 p<0.01), and a non-significant decrease in need for surgery (RR 0.51, 95% CI 0.25-1.02) and hospitalisation (RR 0.64, 95% CI 0.40-1.00). Furthermore compared to SOC, Proactive TDM was associated with higher rates of endoscopic remission (RR 1.19, 95% CI 0.93-1.53) and clinical remission (RR 1.07, 95% CI 0.97-1.18). Compared to reactive TDM, proactive TDM was associated with significant decreased risk of treatment failure (RR 0.46, 95% CI 0.21 = 0.98, p = 0.04) and significant reduction in hospitalisation (RR 0.33, 95% CI 0.21-0.54, p < 0.01). CONCLUSIONS: Compared to SOC, proactive TDM was associated with significant benefit in reducing treatment failure. Compared to reactive TDM, proactive TDM led to a significant reduction in hospitalisation and treatment failure. More studies with larger RCTs and standardised assays are needed to substantiate these results and validate the cost-effectiveness of TDM.

ECCO Topical Review: Roadmap to Optimal Peri-Operative Care in IBD.

BACKGROUND AND AIMS: Despite the advances in medical therapies, a significant proportion of patients with inflammatory bowel diseases [IBD] require surgical intervention. This Topical Review aims to offer expert consensus practice recommendations for peri-operative care to optimize outcomes of IBD patients who undergo surgery. METHODS: A multidisciplinary panel of IBD healthcare providers systematically reviewed aspects relevant to peri-operative care in IBD. Consensus statements were developed using Delphi methodology. RESULTS: A total of 20 current practice positions were developed following systematic review of the current literature covering use of medication in the peri-operative period, nutritional assessment and intervention, physical and psychological rehabilitation and prehabilitation, and immediate postoperative care. CONCLUSION: Peri-operative planning and optimization of the patient are imperative to ensure favourable outcomes and reduced morbidity. This Topical Review provides practice recommendations applicable in the peri-operative period in IBD patients undergoing surgery.

Treatment adaptations and outcomes of patients experiencing inflammatory bowel disease flares during the early COVID-19 pandemic: the PREPARE-IBD multicentre cohort study.

BACKGROUND: The COVID-19 pandemic offered a unique opportunity to understand inflammatory bowel disease (IBD) management during unexpected disruption. This could help to guide practice overall. AIMS: To compare prescribing behaviour for IBD flares and outcomes during the early pandemic with pre-pandemic findings METHODS: We performed an observational cohort study comprising patients who contacted IBD teams for symptomatic flares between March and June 2020 in 60 National Health Service trusts in the United Kingdom. Data were compared with a pre-pandemic cohort after propensity-matching for age and physician global assessment of disease activity. RESULTS: We included 1864 patients in each of the pandemic and pre-pandemic cohorts. The principal findings were reduced systemic corticosteroid prescription during the pandemic in Crohn's disease (prednisolone: pandemic 26.5% vs. 37.1%; p < 0.001) and ulcerative colitis (UC) (prednisolone: pandemic 33.5% vs. 40.7%, p < 0.001), with increases in poorly bioavailable oral corticosteroids in Crohn's (pandemic 15.6% vs. 6.8%; p < 0.001) and UC (pandemic 11.8% vs. 5.2%; p < 0.001). Ustekinumab (Crohn's and UC) and vedolizumab (UC) treatment also significantly increased. Three-month steroid-free remission in each period was similar in Crohn's (pandemic 28.4% vs. 32.1%; p = 0.17) and UC (pandemic 36.4% vs. 40.2%; p = 0.095). Patients experiencing a flare and suspected COVID-19 were more likely to have moderately-to-severely active disease at 3 months than those with a flare alone. CONCLUSIONS: Despite treatment adaptations during the pandemic, steroid-free outcomes were comparable with pre-pandemic levels, although concurrent flare and suspected COVID-19 caused worse outcomes. These findings have implications for IBD management during future pandemics and for standard practice.

Ileoanal pouch cancers in ulcerative colitis and familial adenomatous polyposis: A systematic review and meta-analysis.

INTRODUCTION: Restorative proctocolectomy results in the formation of a pouch that adapts to a more colonic phenotype. The incidence of cancer of the pouch is thought to be low with most societal guidelines differing on their recommendations for surveillance. AIMS: We conducted a systematic review with meta-analysis to report the incidence of cancer in all pouch patients. METHODS: The Embase, Embase classic and PubMed databases were searched between June 1979- June 2021. A random effects model was performed to find the pooled incidence of pouch cancer. In addition, we also looked for risk factors for pouch cancers. RESULTS: Forty-six studies were included. In 19,964 patients with Ulcerative Colitis (UC) the pooled incidence of pouch cancer was 0.0030 (95% CI: 0.0016 -0.0055). In 3741 patients with Familial Adenomatous Polyposis (FAP) the pooled incidence of pouch cancer was 0.01 (95% CI: 0.01 - 0.02). In UC most pouch cancers were found to occur in the pouch body (0.59 (95% CI: 0.29-0.84)). CONCLUSIONS: The findings suggest that the pooled incidence of pouch cancer in UC is similar to that which was previously published, and this is the first meta-analysis to report a pooled incidence for pouch cancer in FAP.

The impact of the ileoanal pouch on female fertility in ulcerative colitis: A systematic review and meta-analysis.

AIM: Ileal pouch-anal anastomosis is a restorative option for patients with ulcerative colitis (UC) requiring surgery. The primary outcome of this study was the relative risk of infertility in women with UC undergoing restorative proctocolectomy (RPC) compared to the same patients before undergoing RPC. Infertility was defined as the inability to conceive after 1 year of regular sexual intercourse without contraception. METHODS: A systematic review and meta-analysis were performed to include all relevant articles from 1946 from MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Studies included reported on the fertility rate of a cohort with UC and also reported the rate after RPC in those within the cohort who underwent surgery. This study was registered on PROSPERO (CRD42021259745). RESULTS: Thirteen studies met the inclusion criteria and accounted for 793 patients pre-pouch and 802 post-pouch. The mean and median age of the patients at analysis was 36.8 and 32.7 years respectively; and the median duration of follow-up following ileal pouch-anal anastomosis was 110.4 (68-139) months. Our results highlight that following RPC the relative risk of infertility is 4.17 (95% CI 1.99, 8.74) compared with patients before RPC who had UC. CONCLUSIONS: The findings of this meta-analysis provide an update on a previous meta-analysis published over a decade ago and results remain congruent. This suggests that despite advancements in surgical techniques the risk to fertility remains similar to a decade ago. However, further high quality studies are needed to try and decipher independent risk factors associated with a decrease in infertility.

Ambulatory care management of 69 patients with acute severe ulcerative colitis in comparison to 695 inpatients: insights from a multicentre UK cohort study.

INTRODUCTION: Acute severe ulcerative colitis (ASUC) traditionally requires inpatient hospital management for intravenous therapies and/or colectomy. Ambulatory ASUC care has not yet been evaluated in large cohorts. AIMS: We used data from PROTECT, a UK multicentre observational COVID-19 inflammatory bowel disease study, to report the extent, safety and effectiveness of ASUC ambulatory pathways. METHODS: Adults (≥18 years old) meeting Truelove and Witts criteria between 1 January 2019-1 June 2019 and 1 March 2020-30 June 2020 were recruited to PROTECT. We used demographic, disease phenotype, treatment outcomes and 3-month follow-up data. Primary outcome was rate of colectomy during the index ASUC episode. Secondary outcomes included corticosteroid response, time to and rate of rescue or primary induction therapy, response to rescue or primary induction therapy, time to colectomy, mortality, duration of inpatient treatment and hospital readmission and colectomy within 3 months of index flare. We compared outcomes in three cohorts: (1) patients treated entirely in inpatient setting; ambulatory patients subdivided into; (2) patients managed as ambulatory from diagnosis and (3) patients hospitalised and subsequently discharged to ambulatory care for continued intravenous steroids. RESULTS: 37% (22/60) participating hospitals used ambulatory pathways. Of 764 eligible patients, 695 (91%) patients received entirely inpatient care, 15 (2%) patients were managed as ambulatory from diagnosis and 54 (7%) patients were discharged to ambulatory pathways. Aside from younger age in patients treated as ambulatory from diagnosis, no significant differences in disease or patient phenotype were observed. The rate of colectomy (15.0% (104/695) vs 13.3% (2/15) vs 13.0% (7/54), respectively, p=0.96) and secondary outcomes were similar among all three cohorts. Stool culture and flexible sigmoidoscopy were less frequently performed in ambulatory cohorts. Forty per cent of patients treated as ambulatory from diagnosis required subsequent hospital admission. CONCLUSIONS: In a post hoc analysis of one of the largest ASUC cohorts collected to date, we report an emerging UK ambulatory practice which challenges treatment paradigms. However, our analysis remains underpowered to detect key outcome measures and further studies exploring clinical and cost-effectiveness as well as patient and physician acceptability are needed. TRIAL REGISTRATION NUMBER: NCT04411784.

A review of the therapeutic management of Crohn's disease.

Crohn's disease is a chronic inflammatory, relapsing-remitting, and progressive gastrointestinal disorder with an often-negative impact on the physical, emotional, and psychological well-being. Over the past two decades, the medical compendium for the treatment of Crohn's disease has increased significantly, enabling treatment beyond symptoms. Indeed, early and timely use of effective medical therapy has been reflected by improved outcomes with reduction in surgery and ability to achieve clinical and endoscopic remission, reduce corticosteroid dependance, and prevent long-term complications in more patients. In this review, we discuss the key milestones in the medical management of Crohn's disease.

Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium.

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Prevalence of pouchitis in both ulcerative colitis and familial adenomatous polyposis: A systematic review and meta-analysis.

AIM: Pouchitis is a clinically significant complication of ileal pouch-anal anastomosis with its prevalence varying in the literature. Pouchitis is thought to occur more commonly in patients with ulcerative colitis (UC) than in patients with familial adenomatous polyposis (FAP). We conducted a systematic review with meta-analysis of all published literature to report the prevalence of pouchitis in all pouch patients as well as specifically in UC and FAP. We also investigated the prevalence of acute and chronic pouchitis in UC and FAP. METHODS: A meta-analysis was conducted by searching the Embase, Embase Classic and PubMed databases between 1978 and 2021 exploring the prevalence of pouchitis in UC and FAP. We then performed a random effects model in order to find the pooled prevalence of pouchitis and used odds ratios to report differences in the prevalence of pouchitis in UC and FAP. RESULTS: Fifty-nine full papers and conference abstracts were included in the meta-analysis comprising 18 117 patients with UC and 860 with FAP. The prevalence of pouchitis in UC was 0.32 (95% CI 0.27-0.37) and in FAP was found to be 0.06 (95% CI 0.03-0.15). The odds ratio of pouchitis in UC patients compared with FAP patients was 4.95 (95% CI 3.17-7.72, P < 0.0001). CONCLUSIONS: Our findings support the consensus that the prevalence of pouchitis is higher in UC than in FAP. More significantly our findings suggest that the true prevalence of pouchitis is higher than commonly reported in the literature. This literature may help counsel patients prior to undergoing restorative proctocolectomy.

Are we addressing the top 10 research priorities in IBD?

BACKGROUND: Since publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK. METHODS: The ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD. RESULTS: Of 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn's disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn's disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1. CONCLUSIONS: This study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders' viewpoints on needs for expanded knowledge in IBD, particularly the patients' perspective.

Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

An Unusual Cause of Gastrointestinal Perforation in an Adolescent Patient With Beta-Thalassemia on Deferasirox and SARS-CoV-2 Infection.

Chelation therapy is recognized as a safe and effective treatment option in patients with beta-thalassemia with iron overload. We report an 18-year-old male with acute abdomen and gastrointestinal bleeding with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection secondary to gastric perforation due to chelation therapy. This patient had a prolonged intensive care stay with complications of SARS-CoV-2 and a small bowel obstruction post-surgery that resolved after conservative management. Given the acute presentation, chelation therapy use and concomitant SARS-CoV-2 infection, clinicians should keep an open mind on the differential diagnosis of acute abdomen in patients with beta-thalassemia.