Introduction

The demand for sedation during endoscopic procedures in the gastrointestinal field has increased. However, few sedatives for endoscopy are covered by Japanese national health insurance. Remimazolam is a novel, ultrashort-acting benzodiazepine drug.

Aims & Methods

This study aimed to compare the efficacy of Remimazolam and placebo in achieving successful sedation during upper gastrointestinal endoscopy in Japanese patients. We conducted a multicenter, randomized, double-blind Phase III clinical trial, including 48 Japanese patients undergoing upper gastrointestinal endoscopy. Patients were randomized to receive either Remimazolam or placebo with a ratio of 4:1. The initial Remimazolam dose was 3mg, with additional doses of 1mg as determined in the Phase II clinical trial [1]. The primary endpoint was the successful sedation rate during gastrointestinal endoscopy, determined by the Modified Observer’s Assessment of Alertness / Sedation score ≤4 before the start of endoscopy, the completion of gastrointestinal endoscopy, and two or fewer additional doses per six minutes.

Results

The Remimazolam group included 37 patients and the placebo group included 11 patients. The successful endoscopy sedation rate was significantly higher in the Remimazolam group (91.9%) compared to the placebo group (9.1%) (p<0.01). The median total Remimazolam dose was 4.0 (3.0-4.5) mg. The time from the end of endoscopy to arousal was 0.0 (0.0–0.0) minutes in the Remimazolam group and 0.0 (0.0–0.0) minutes in the placebo group. The time from the end of endoscopy to regaining the ability to walk was 5.0 (0.0–5.0) minutes in the Remimazolam group and 0.0 (0.0–0.0) minutes for the placebo group (p=0.02).

Conclusion

Remimazolam is more effective than placebo for achieving sedation during upper gastrointestinal endoscopy in Japanese patients. This study suggests that Remimazolam could be a potential option for sedation during endoscopic procedures.

References

[1] Ichijima R, Ikehara H, Maeda T, Sugita T, Horii T, Iwao A, Ogura K, Kusano C, Kondo Y, Suzuki T, Gotoda T. First dose-ranging study of remimazolam in Japanese patients undergoing gastrointestinal endoscopy: Phase II investigator-initiated clinical trial. Dig Endosc. 2022 Nov;34(7):1403-1412. doi: 10.1111/den.14365. Epub 2022 Jul 15. PMID: 35612970.

Disclosure

This study was founded by Mundi Pharma Co., Ltd. Authors declare no conflict of the interst for this study.

Introduction

Walled-off necrosis (WON) may develop in the long-term follow-up after acute pancreatitis due to acute inflammation of the pancreas. It can be managed through endoscopic, percutaneous, or surgical drainage, depending on its clinical condition. The methodology is a topic of debate due to the scarcity of data regarding the progression of asymptomatic WON in patients (1).

Aims & Methods

The aim of this study is to determine the course of asymptomatic individuals who have developed walled-off necrosis (WON) following to an episode of acute pancreatitis over a long time of observation. A retrospective evaluation was conducted on 46 (3.9%) out of 1173 patients diagnosed with acute pancreatitis between June 2016 and December 2019, who developed WON during the follow-up period. Individuals who exhibited symptoms either at the point of diagnosis or during subsequent monitoring had been determined. An analysis was made between the clinical and WON characteristics at baseline of patients who required drainage during follow-up and those who did not.

Results

Out of the total of 46 patients who developed WON, 4 individuals were excluded due to inadequate follow-up data, 9 patients underwent drainage at the time of diagnosis, and 2 patients lost without receiving any form of drainage intervention. During the course of the study, a total of 31 patients were followed up for a mean duration of 25.20±17.40 months. Out of these patients, 10 (32.3%) required interventional intervention within a mean duration of 122.5±152.5 days (Group 1), while the remaining 21 patients (67.7%) were monitored without any intervention. Embolization was executed on a single patient owing to the presence of a splenic artery aneurysm identified in WON, however, drainage was not carried out. Endoscopic drainage was employed in five patients, percutaneous drainage in three patients, and surgical drainage in one patient. The prevalence of biliary etiology was found to be significantly higher in Group 1 compared to Group 2 (90.0% vs 47.6%, p<0.050). The study revealed that the Intra-WON necrosis rate and initial WON size were significantly higher in patients who required drainage at follow-up. The Intra-WON necrosis rate was 68.50±28.50% compared to 38.10±26.90% in the non-drainage group (p<0.05). Similarly, the initial WON size was 125.90±46.60 mm in the drainage group compared to 89.30±45.00 mm in the non-drainage group (p<0.05).

Conclusion

Asymptomatic patients with walled-off necrosis (WON) ought to be managed conservatively through careful ongoing monitoring. It is recommended that the results obtained be validated through extensive longitudinal research.

References

1)Freeman MF, Werner J, van Santvoort HC, et al. International Multidisciplinary Panel of Speakers and Moderators. Interventions for necrotizing pancreatitis: summary of a multi-disciplinary consensus conference. Pancreas. 2012;41(8):1176-1194.

Introduction

The use of infliximab (IFX) is limited by low treatment persistence. Proactive therapeutic drug monitoring (pTDM) has been shown to increase the treatment persistence in inflammatory bowel disease (IBD) patients but the real-life data evaluating effectiveness, safety and costs of this approach are scarce.

Aims & Methods

The aim of this study was to assess survival on treatment, safety and costs of pTDM of IFX in the treatment IBD.
IBD patients who started IFX in a referral centre using pTDM between January 2018 and March 2021 were included. The main outcomes were treatment persistence, adverse events and incremental costs of pTDM.
IFX trough levels were assessed in the week 14 and subsequently every six months by commercially available ELISA kit (Ridascreen R-Biopharm) and the intensification of treatment the cut-off of 3μg/ml was used.
Costs related to the measurements of levels and the costs of intensified treatment were calculated. The costs of pTDM were compared costs of a modelled cohort using reactive TDM (rTDM) based on the data from the same cohort. The model used arbitrarily determined intensification regimen to 5mg/kg of IFX every 4 weeks in pharmacokinetically determined clinical or endoscopic loss of response. The calculation was performed for the first year of treatment.

Results

Overall, 99 patients with IBD were included (58 men – 59%; mean age 39,96 years, minimum-maximum, 20-73 years; 64% patients with Crohn´disease; mean disease duration 103 months, minimum – maximum, 8-402 months).
The treatment was intensified in 57 patients (58%). Overall treatment survival with pTDM was 87% at 6 months, 77% at one year, 66% at two years and 60% at both, the third and fourth year of treatment. There were no differences between patients on conventional regimen vs. intensified regimen with regards to adverse events.
The costs related to pTDM in this cohort of 99 patients were € 90 306,56 while the costs of the modelled cohort using rTDM were € 24 846,30. The overall incremental costs were thus € 65 460,26 with mean costs per patient for the first year of treatment of € 661,21.

Conclusion

Proactive TDM of IFX results in a steady 60% treatment persistence beyond the second year of treatment with no impact on the safety.
In the context of this solid treatment persistence, the incremental costs related to proactive TDM seem negligible when considering the costs of alternative biologicals used in case of loss of response to IFX.

Disclosure

nothing to disclose

Clinical Case Summary

Familial intrahepatic cholestasis is a heterogeneous group of genetic diseases with autosomal recessive transmission. BSEP (Bile-Salt Export Pump) is the main bile acid export pump in hepatocytes. Mutations in the gene encoding BSEP, ABCB11, are associated with heterogeneous clinical phenotypes ranging from diseases with a benign course to severe forms requiring liver transplantation. Here we report the case of a 17-year-old girl admitted to our Clinic because of severe jaundice and itching. She reported a similar episode 2 years earlier with spontaneous recovery. Family history is positive for cholelithiasis. On admission, laboratory tests showed: total and direct bilirubin values of 24.5 mg/dl and 18.9 mg/dl, AST 307 IU/L and ALT 238 IU/L, respectively. GammaGT was normal. Viral, autoimmune, metabolic causes, and biliary obstruction were excluded. Liver biopsy showed a picture of hepatocellular and intracanalicular cholestasis with cholestatic rosettes, inflammatory activity, and mild portal and pericellular fibrosis. Immunohistochemical staining for BSEP showed only weak diffuse expression. Genetic testing documented compound heterozygosity of the ABCB11 gene with the variants c.1460G>A - p(Arg487His) of paternal origin and c2599C>T -(Gln867*) of maternal origin. Genetic testing of relatives is also ongoing. The patient was treated with ursodesoxycholic acid, cholestyramine and cetirizine for 4 months with disappearance of jaundice and pruritus and normalization of bilirubin levels. Follow-up at 1 year was free of events without therapy. This is the first time that the c2599C>T -(Gln867*) variant has been described in a patient with familial intrahepatic cholestasis. Application of the "temporal test" will allow this new variant to be attributed to the BRIC2 form rather than PFIC2.

Clinical Case Summary

Psoriasis and Inflammatory Bowel Disease (IBD) overlap in epidemiology and immune mechanisms. Biologics have been used to treat both conditions. Interleukin-17 inhibitors (anti-IL-17) play a vital role in the approach of refractory psoriasis, but paradoxal gastrointestinal effects may occur.
A 67-year-old woman with chronic plaque psoriasis and arthritis refractory to methotrexate (MTX) and ustekinumab, at that moment under Ixekizumab (anti-IL-17), presented to the emergency room with chronic abdominal pain, diarrhea (>10 bowel movements/day) and rectal bleeding. Blood workup showed normocytic normochromic anemia (9,9g/dL) and elevated C-reactive protein (181mg/L). Clostridioides difficile toxin test and stool cultures were negative. Computed tomography showed sigmoid colon and rectum wall thickening and densification of the surrounding fat. Endoscopy revealed deep ulcers in the rectum and sigmoid.
The main diagnostic hypothesis were severe inflammatory proctocolitis triggered by anti-IL-17 and infectious colitis (including cytomegalovirus (CMV) infection). Clinical, endoscopic and histopathologic findings supported a Crohn’s-like colitis possibly triggered by Ixekizumab. Histopathology revealed chronic inflammation and excluded CMV infection.
Ixekizumab was discontinued; clinical remission was induced with Infliximab (IFX), after corticosteroid (CT) failure. Six weeks later, she was admitted with cellulitis. CT was rapidly tapered. Due to her medical background as well as clinical, biologic and endoscopic improvement, after a multidisciplinary discussion, it was decided to maintain IFX in association with MTX. Further follow-up revealed clinical remission and endoscopic response.
The increasing use of anti-IL-17 in psoriatic patients led to the report of rare cases of IBD onset in this population. This case suggests a possible association between anti-IL-17 therapies and de novo IBD, highlighting the need of surveillance of patients under these therapies.

References

Endoscopic images (total of 4 pictures); photographs of lower limbs (total of 5 pictures).

Clinical Case Summary

Extra intestinal digestive involvement of tuberculosis (TB) remains a rare entity, even in endemic countries.3 cases of extra intestinal digestive TB in immunocompetent patients are reported.
Case 1: A 50-year-old man was admitted for exploration of weight loss and weakness, with chronic abdominal pain. A computed tomography (CT) scan of the abdomen showed multiple hypodense hepatics and splenic nodules; an ultrasound-guided percutaneous liver biopsy was performed. The patient was diagnosed to have primary hepatosplenic TB. Images:
1:CT scan:multiple lesions in the liver and spleen
2:Liver tissue showing granulomatos reaction)
Case 2: A 24-year-old woman,admitted for exploration of chronic epigastralgia.Abdominal and pelvic CT scan and pancreaticobiliary Magnetic Resonance Imaging (MRI)showed a mass at the isthmus and tail of the pancreas associated with adenopathies.The endoscopic ultrasound (EUS)showed a cystic lesion at the pancreatic corporal-caudal junction. Given the strong suspicion of a pseudo papillary and solid tumor of the pancreas,a caudal splenopancreatectomy was decided. Intraoperatively, exploration revealed,whitish pinhead-sized lesions disseminated over the entire pancreatic parenchyma,suggesting pancreatic TB.An anatomopathological examination of an adenopathy confirmed the diagnosis of TB. Images:
1:MRI showing a mixed lesion in the pancreas
2:EUS image showing the heterogeneous lesion of the pancreas)
Case 3: a 28-year-old man, was admitted for exploration of abdominal pain with fever and weight loss.The physical examination found an abdominal tenderness and hepatomegaly.Hepatic nodular lesions were revealed on CT and MRI.The diagnosis of hepatic tuberculosis was confirmed after anatomopathological analysis of the biopsies of the hepatic nodules obtained during laparoscopy. images:
1: Abdominal CT scan:multiple hypodense hepatic lesions
2: A hepatic MRI:a dysmorphic liver,with heterogeneous lesions)

Introduction

Living with inflammatory bowel disease (IBD) affects physical, psychological and social dimensions, limiting the ability to engage in daily activities. It is a lifelong illness that mainly affects patients of working age, with a significant impact on their professional life. In fact, the maintenance and promotion of employees is one of the important social goals and can be considered as a determinants of health for IBD patients.
The aim of the study was to analyze the impact of disease on the working life among IBD patients and to characterize the breadth of challenges they experience in their workplace.

Aims & Methods

We conducted a cross-sectional study including patients followed for IBD and exercising a professional activity, over a 9-months period. We collected sociodemographic, clinico-biological and evolutionary data. Then, we performed a survey among these patients using a self-report questionnaires on employment status, IBD-related difficulties at work and sick leave.

Results

A total of 45 patients were included: 80% had Crohn disease (CD) and 20% had ulcerative colitis (UC). The mean age was 44 ± 12 years [extreme: 20-72 years], the sex-ratio M/F was 0.73 and the average of follow-up was 9 years [extreme: 1-18 years]. Civil servants represented 33% of the total population, those in the private sector 47%, and those in the liberal profession 20%. The most important socio-professional category was manual workers with 51%. Thirty-seven patients (82%) developed their disease after being employed with a mean delay of 11.8 years. The average number of working hours per week was 38.8 ± 11 hours [extreme: 9-60 hours]. The majority of the employees worked full time (85%), only seven subjects worked part-time, two of them because of their IBD. One in three patients (N=14) claimed to have been exposed to at least one harmful agent during their professional career, mainly organic solvents and chemicals. The main complaint reported by the patients during the daily exercise of the work was about physical fatigue which was omnipresent in the majority of the workers (69%). The digestive symptoms were mainly abdominal pain (53%) evaluated according to VAS with a mean intensity of 2.8 [0 - 10], subocclusive syndrome (40%), presence of diarrhea (38%), incontinence and fecal impaction (22%) which was worsened by the absence of accessible restrooms (33%). Psychological repercussions such as anxiety and depression were mentioned in 27% of cases. The average absenteeism during the last twelve months was 49.6 days [extreme: 0-240 days] and the average number of hospitalization days was 30.7 [extreme: 0-150 days]. Twenty patients (44%) claimed that they were subject to a salary restriction during their professional career because of their illness. Among the patients interrogated, a minority (5 people) had alreadỳ benefited from a contact with the occupational medicine and health service.

Conclusion

IBD has a negative impact on the working life of patients, due to uncomfortable symptoms, days of absenteeism, and unadapted workplaces, which can affect career plans, professional achievement, and income. Appropriate supports and accommodations to the workplace are needed in order to improve their working experience.