Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder restricted to the esophagus that predominates in males (male:female ratio being around 3:1). The impact of patient sex on the onset, diagnosis and progression of EoE has been barely evaluated, with some reporting no or minor differences (1) while others discovered relevant changes between men and women regarding symptomatology, endoscopic findings and molecular signature (2,3).

Aims & Methods

The study aims to assess potential disparities in EoE presentation and phenotype at the moment of diagnosis, as well as to evaluate whether sex determines difference in disease progression and response to therapy. This is a cross-sectional, multicentre study that includes patients diagnosed with EoE from the EoE CONNECT registry. Demographical and clinical data were obtained from patients recruited at 37 hospitals in 4 European countries. Data extraction was conducted on March 21^st, 2024.
Quantitative (age, diagnostic delay, dysphagia symptom score, EREFS endoscopic scale, peak of eosinophils per high power field, number of previous endoscopies, and number of endoscopic dilations) and qualitative (age by groups, phenotype, country, presence of fibro-stricturing findings, atopies, treatments and symptoms) variables were compared. Statistical significance was established for p<0.05.

Results

Data from 2,976 patients (76% males) were retrieved, with no difference in female proportions among countries. Mean±SD age at diagnosis was higher for females (34.8±15.6 vs 32.7±14.8 years, p=0.007), with no differences in diagnostic delay or number of previous endoscopies before diagnosis. Proportion of women diagnosed with EoE at 60 year or older age was twice compared to men (6.4% vs 3.1%, p<0.001). Abdominal (6.6% vs 4.4%, p=0.023) and epigastric (10.6% vs 8.1%, p=0.047) pains, heartburn (27.9% vs 22.0%, p=0.003) and dysphagia (79.7% vs 73.3%, p=0.001) were significantly more frequent in females; food bolus impaction predominated in males (59.5% vs 50.1%, p<0.001). Symptoms intensity measured with the Dysphagia Symptom Score was higher in female patients (6.9±3.8 vs 6.3±4.1, p=0.003).
Endoscopic features of fibrosis (rings and/or strictures) at baseline endoscopy predominated in males (61.0% vs 51.4%, p<0.001). Accordingly, overall EREFS score and its fibrotic sub-score (2.6±1.7 vs 2.3±1.6 and 1.0±1.0 vs 0.8±1.0, respectively, p<0.001), and mixed/stricturing phenotypes were more commonly found in male compared to female patients (25.0% vs 19.3%, p=0.002). Peak eosinophil count was higher in females (median 50 vs 42 cells/HPF, p=0.005).
No differences were found for first-line treatment choice and effectiveness of anti-inflammatory therapies between men and women. In addition, 126 patients underwent 215 endoscopic dilatation procedures overall, which were slightly more common among male patients (4.5% vs 3.4%, p=0.187). In contrast, the median number of dilation procedures was higher in female compared to male EoE patients (2 vs 1; p=0.001).
Regarding concomitant atopies, no differences were noted in the prevalence of rhinitis, conjunctivitis and asthma according to sex. However, atopic dermatitis was more common in women (21.7% vs 17.8%, p=0.028).

Conclusion

Sexual dimorphism exists in EoE, as observed in other immune-mediated diseases. Despite symptoms severity scored slightly higher in females, EoE in male patients appeared earlier, more commonly with food bolus impaction and with fibro-stricturing endoscopic features at diagnosis.

References

1. Kozon I, Frandsen LT, Izgi B, et al. No gender differences in patients with eosinophilic oesophagitis. Dan Med J 2023;70(2):A06220393
2. Lynch KL, Dhalla S, Chedid V, et al. Gender is a determinative factor in the initial clinical presentation of eosinophilic esophagitis. Dis Esophagus. 2016;29(2):174-8.
3. Erwin EA, Jaramillo LM, Smith B, et al. Sex Differences in Blood Transcriptional Profiles and Clinical Phenotypes in Pediatric Patients with Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2021;9:3350-3358.e8.

Introduction

Fecal microbiota transplantation (FMT) has been successfully used in a series of diseases in recent years. Most studies have focused on short-term risks, which are mild and generally associated with delivery methods. There have been no reports of FMT safety in the treatment of multiple diseases and long follow-up periods.

Aims & Methods

We performed a retrospective analysis of 11025 patients who underwent FMT in the Tenth People’s Hospital of Tongji University between January 2012 and December 2023. We included patients with various gastrointestinal diseases and patients with extraintestinal diseases that involved intestinal dysfunction. A questionnaire was administered to the included patients during follow-up (2 weeks, 3 months, 1 year, and 5 years after FMT) via telephone and health portal software Haodaifu app).

Results

Most adverse events during short-term follow-up (2 weeks) were related to the method of delivery. The main adverse events in the nasogastric tube group were tube-related respiratory difficulty (40.6%,include sore throat 14.1%, nasal congestion 8.7%, nasal irritation due to nasogastric intubation 17.8%) and nausea/vomiting (12.6%). In the oral capsules group, nausea and vomiting (8.9%) occurred during oral administration because the capsules are associated with a fecal smell and taste, both of which are difficult to remove completely. For colonoscopy and enema routes, the main adverse events were diarrhea (10.7%, 9.9%) and perianal discomfort (15.3%, 8.4%), respectively. Two cases in the colonoscopy group and one case in the enema group were complicated with colon perforation, but remission with conservative treatment. The most frequently reported adverse events were mild or moderate in severity and transient. Those symptoms associated with nasogastric tube administration disappeared after tube removal at the completion of treatment. Several other new symptoms were reported during short-term follow-up, although none occurred in >1% of patients. The most common symptom reported was bloating/flatulence. Although more adverse events were reported in the nasogastric tube group, most were mild. Additionally, patients are more comfortable with the upper gastrointestinal route because they could use it for enteral nutrition support or gastrointestinal imaging according to their medical needs. Based on our clinical experience, we proposed the “Tongji FMT Requirements”and implemented them in our clinic (beginning in 2019) to standardize the indications and timing of FMT treatment and to improve FMT safety. After the implementation of these requirements for 2 years, we compared safety data collected before and after implementation; The application of the requirements has effectively reduced adverse events. The short-term (mainly FMT-related diseases) incidence rate significantly decreased from 32.6% in 2017–2019 to 17.2% in 2019–2021.

Table 1.Tongji FMT Requirements

Conclusion

FMT appears safe during both short-term and long-term follow-up. The patient group that received FMT did not exhibit an increased incidence of new diseases, and the risk of infection transmission appears to be low. Considering the widespread use of FMT, there is a need for the establishment of a national clinical and patient-reported FMT safety collection system in future.

References

• 1) Kelly CR, Yen EF, Grinspan AM, et al. Fecal microbiota transplantation is highly effective in real-world practice: initial results from the fmt national registry. Gastroenterology 2021;160:183-192
• 2) Mullish BH, Quraishi MN, Segal JP, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory clostridium diffificile infection and other potential indications: Joint british society of gastroenterology (BSG) and healthcare infection society (HIS) guidelines. Gut 2018;67:1920e41
• 3) Saha S, Mara K, Pardi DS, et al. Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection. Gastroenterology 2021;160:1961-1969
• 4) Zhang S, Chen Q, Kelly CR, et al. Donor Screening for Fecal Microbiota Transplantation in China: Evaluation of 8483 Candidates. Gastroenterology 2022;162:966-968
• 5) Parenteral and Enteral Nutrition Branch of Chinese Medical Association, et al. Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation. Zhonghua Wei Chang Wai Ke Za Zhi 2020;23:5-13
• 6) Wang S, Kou C, Liu Y, et al. Rural-urban differences in the prevalence of chronic disease in northeast China. Asia Pac J Public Health 2015;27:394-406

Introduction

Metabolic-associated fatty liver disease (MAFLD) requires complex treatment based on diet and lifestyle. The understanding of the disease by patients through medical education is an element that could bring them a therapeutic benefit. Since the process is time-consuming and medical factors all over the world are under pressure to use maximum time for diagnostic and therapeutic purposes, an important role can be played by the voluntary activity carried out by medical students, under the guidance of teaching staff, devoted to this purpose.

Aims & Methods

A group of 250 patients with MAFLD, non-cirrhotic, diagnosed in a gastroenterology outpatient clinic, were proposed to participate in an educational program consisting of 3 sessions of 2 hours of interactive course about MAFLD (including notions of anatomy, physiology, diagnosis, evolution, prognosis, complications, risks, treatment, follow-up) in order to appreciate the contribution of medical education to the effectiveness of treatment. The patients did not receive medication but only recommendations regarding lifestyle changes and the Mediterranean diet. They were re-evaluated 6 months after the initial evaluation.

Results

Of the 250 patients, only 126 (50.4%) accepted participation in the educational plan after informed consent, a disappointing proportion; the subgroup of those who did not participate in the course was reported as a control group (the main reason of non-participation was the fact that most of these patients considered to have already enough knowledge about MAFLD), being also invited to be evaluate after 6 months. Educational presentations were given by medical students under the guidance of teaching staff (power-point presentations and informative flyers designed to fix the knowledges about disease) and patients were clinically, laboratory, ultrasound and fibroscan evaluated by attending physicians. Also a questionnaire about quality of life was completed by each patient. Finally, after 6 months, only 85 patients from the control group and 118 from the study group returned for the final evaluation. The final evaluation focused on 4 elements: 1- changes in body mass (decrease of more than 7%), 2- liver ultrasonography (reduction of the degree of steatosis), 3- laboratory analyzes (liver and metabolic tests) and 4- quality of life. In the study group, significantly better results were obtained for parameters 1, 3 and 4: (78%, 87.2%, 84.7%) compared to the reference group (38.8%, 54.1%, 62.3%) which confirms the fact that patient education is an important element in understanding the disease and its treatment. Only in parameter 2 (decrease of steatosis at ultrasonography) there were no significant differences between the two groups (50.8% vs 48.2%), probably due to the too short follow-up time of the patients.

Conclusion

Therapeutic education of patients with MAFLD can bring more efficiency to the treatment of the disease in non-cirrhotic patients, mainly on body mass control, liver laboratory tests and quality of life, if they accept to participate at educational program.

References

Koutny F, Aigner E, Datz C, Gensluckner S, Maieron A, Mega A, Iglseder B, Langthaler P, Frey V, Paulweber B, Trinka E, Wernly B. Relationships between education and non-alcoholic fatty liver disease. Eur J Intern Med. 2023 Dec;118:98-107. doi: 10.1016/j.ejim.2023.07.039. Epub 2023 Aug 3. PMID: 37541922.
Lee WM, Bae JH, Chang Y, Lee SH, Moon JE, Jeong SW, Jang JY, Kim SG, Kim HS, Yoo JJ, Kim YS. Effect of Nutrition Education in NAFLD Patients Undergoing Simultaneous Hyperlipidemia Pharmacotherapy: A Randomized Controlled Trial. Nutrients. 2021 Dec 13;13(12):4453. doi: 10.3390/nu13124453. PMID: 34960005; PMCID: PMC8709046.

Introduction

Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation (RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the general health insurance scheme population.

Aims & Methods

We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals.

Results

A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7.
Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients (P<0,0001). The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis).
Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001). This difference remained significant for patients under 65 (p<0.0073).
No significant difference for the risk of re-hospitalization after RT (p=0.84), of retransplantation during the follow-up period in RT patients (p=0.67), or for the risk of hospitalization for severe infection (p=0.97) after RT in patients from the general population compared with IBD patients. The same was true for the type of severe infections after RT (p= 0.068) and for the risk of solid and haematological cancer after RT (p=0.48). However, there was a significant difference in the type of first severe infection after RT(p=0.003), but we are waiting for the results to tell us which one.

Conclusion

The incidence of ESRD is significantly higher in IBD than in the general data base population, confirming the need for regular monitoring of renal function in our patients.
Survival after ESRD onset, is higher in IBD patients.
The high incidence of RT in the IBD population confirms that access to transplantation is not restricted in this
population.

References

Kirchgesner et al, Gastroenterology 2018
Meyer et al, Aliment Pharmacol Ther. 2020
Tuppin et al, Nephrol Ther 2016

Introduction

MACE is a new, non-invasive technology which approaches the diagnostic sensitivity of OGD in gastric focal lesion detection in patients with dyspepsia. [Li et al., CGH 2016] This study compared the two in the detection of focal and diffuse lesions in patients referred for the investigation of anaemia.

Aims & Methods

MACE was performed within one week before OGD using the AnX Robotica magnet system and Navicam capsule (single camera capsule, frame rate 6/sec: Wuhan, China). Following a fast, simethicone and gastric distension using 0.5-1L water, patients swallowed the capsule semi-recumbent on the left lateral side before lying supine to allow approximation of the magnet to the chest. The examination protocol included a sequence of magnet movements and patient position changes. Inspection of an anatomical location was considered complete if sufficient to exclude any significant pathology. Endoscopists performing OGD were blinded to the MACE outcome and all findings were recorded from a pre-identified diagnostic list. Data was analysed using SPSS.

Results

45 of 81 (55.5%; median age 63 (IQR 45.5- 72), 60% male) patients had pathology identified by MACE, OGD or both. Complete views were obtained by MACE in the oesophagus (72.4%), proximal stomach (93.8%), distal stomach (93.8%) and duodenum(79.6%, p<0.001) and mean examination time was 22 minutes. Findings were concordant in 17 (37.8%: gastric erosions (n=6), ulcers (n=5), oesophagitis (n=2), eroded polyps (n=2) and gastric antral vascular ectasia (n=2)). MACE alone identified pathology in 24 (53.3%: gastric erosions (n=17), angioectasia (n=4), ulcers (n=2, oesophageal and duodenal), eroded polyp (n=1) and both angioectasia and erosions (n=1). OGD identified a distal body ulcer (n=1), small (n=1) and large (n=1) oesophageal varices and oesophageal ulcers (n=1) missed by MACE and in one patient MACE identified only an oesophageal ulcer and OGD only a duodenal ulcer, each missing the pathology detected by the other. Diagnostic yield was higher for MACE than OGD (P<0.001).

Conclusion

The improved diagnostic yield of MACE compared to OGD is accounted for mainly by minor mucosal abnormalities which could, nonetheless, contribute to occult bleeding and anaemia. Although speculative this could be because of better tolerance of MACE and a longer examination time. An increased frame capture rate, with or without a second camera, is needed to improve oesophageal visualisation.

Disclosure

I herwith declare that the magnetic capsules for the study were provided by Ankon

Introduction

Tofacitinib is a relatively novel therapy for immune-mediated inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. It is a small-molecule drug that exerts its effects by inhibiting Janus kinases. Recently, concerns have been raised about the drug’s safety in terms of cardiovascular side effects and cancer risk.­­

Aims & Methods

This meta-analysis determined the risk of cancer in patients treated with tofacitinib for different clinical indications, compared to both a placebo and other therapies. We searched PubMed (accessed on november 1st 2022) for original articles regarding tofacitinib’s cancer risk when used for rheumatoid arthritis, ulcerative colitis, Crohn’s disease, psoriatic arthritis, and ankylosing spondylitis.

Results

Of the 2047 initial records, 22 articles describing 26 controlled studies (including 22 randomized controlled trials) were selected. In the comparison between tofacitinib and any control treatment, the relative risk (RR) for any cancer was 1.06 (95% CI, 0.86–1.31; p = 0.95). In separate comparisons between tofacitinib and either a placebo or biological therapy, no difference was found in the overall cancer risk (vs. placebo, RR = 1.04; 95% CI, 0.44–2.48; p = 0.95; vs. biological drugs, RR = 1.06; 95% CI, 0.86–1.31; p = 0.58). When tofacitinib was compared to tumor necrosis factor (TNF) inhibitors, the overall cancer RR was 1.40 (95% CI, 1.06–2.08; p = 0.02). Similarly, significant results were obtained for all cancers, except for non-melanoma skin cancer (RR = 1.47; 95% CI, 1.05–2.06; p = 0.03), and for this skin cancer alone (RR = 1.30; 95% CI, 0.22–5.83; p = 0.88).

Conclusion

In conclusion, no difference in the overall cancer risk was found between tofacitinib and either a placebo or biological drugs, while a slightly higher risk was found in patients treated with tofacitinib than anti-TNF agents. Further studies are needed to better define the cancer risk of tofacitinib therapy.

Introduction

Metabolic Associated Steatotic Liver Disease (MASLD) affects 25-30% of the European population and is projected to rise further. These patients are at increased risk for liver-related complications and higher overall mortality, emphasizing the need for early detection to improve outcomes. While abdominal ultrasound serves as the primary imaging modality for suspected liver disease, its sensitivity for diagnosing mild steatosis is inadequate, and gold-standard methods for quantifying liver steatosis infiltration, such as magnetic resonance imaging or liver biopsy are impractical for widespread use.

Aims & Methods

This study aimed to assess the diagnostic accuracy of the Attenuation Coefficient (ATT) as a complementary method to B-mode ultrasound for early detection of hepatic steatosis. Consecutive patients referred for transient elastography were prospectively enrolled. Liver steatosis was graded using a 4-point scale (normal, mild, moderate, or severe) in B-mode ultrasound for each patient, and ATT was measured in accordance with manufacturer quality criteria instructions (Fujifilm®). Additionally, the Hepato-Renal Index (HRI) was calculated for each patient, and Controlled Attenuation Parameter (CAP, Fibroscan®) was measured.

Results

A total of 128 patients, 61.7% male, with a mean age of 56.8±12.8 years, were included. Among them, 78.1% exhibited at least one cardiometabolic risk factor. The main referral indications were fibrosis assessment in viral hepatitis (42.2%), MASLD (21.9%), and alcoholic liver disease (11.7%). The median vibration-controlled elastography result was 5.8kPa. B-mode ultrasound steatosis assessment classified 44.5% as normal, 10.2% with mild steatosis, 21.1% with moderate steatosis, and 24.2% with severe steatosis. The area under the ROC curve for steatosis detection was 0.796 for HRI, 0.894 for ATT, and 0.896 for CAP, highlighting robust diagnostic performance, particularly for the latter two methods. There was a strong correlation between ATT and CAP (r=0.710). Using a CAP>248dB/m to define steatosis, the area under the ROC curve for ATT was 0.890. For an ATT cutoff value ≥0.66, Sensitivity, Specificity, Negative Predictive Value, and Positive Predictive Value were 82.7%, 77.3%, 72.3%, and 86.1%, respectively. The sensitivity of B-mode ultrasound for steatosis detection was 79.5%, increasing to 90.4% when combined with ATT measurement.

Conclusion

ATT demonstrated excellent accuracy for steatosis detection, comparable to CAP and superior to HRI. Importantly, combining B-mode ultrasound with ATT significantly improved the diagnostic sensitivity. These findings suggest that ATT has the potential to become a valuable non-invasive tool alongside ultrasound for early detection of hepatic steatosis, aiding in earlier intervention and improved patient outcomes.

References

Tamaki N, Koizumi Y, Hirooka M, et al. Novel quantitative assessment system of liver steatosis using a newly developed attenuation measurement method. Hepatol Res. 2018;48(10):821-828. doi:10.1111/hepr.13179
Bozic D, Podrug K, Mikolasevic I, Grgurevic I. Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal. Diagnostics. 2022;12(10):2287. doi:10.3390/diagnostics12102287