Introduction

Safe and effective sedation are important factors when performing gastrointestinal endoscopy. However, clinicians should be cautious when using sedatives in older patients because of their decreased physiological reserves. Remimazolam is an ultrashort active benzodiazepine that has attracted attention because of its efficacy. This study aimed to determine the safety and efficacy of remimazolam compared with midazolam as a sedative for diagnostic upper gastrointestinal endoscopy in older patients aged ≥65 years.

Aims & Methods

We randomly assigned patients aged ≥65 years who were scheduled for diagnostic upper gastrointestinal endoscopy. The average induction time, average recovery time, and side effect profile of patients who received remimazolam as a sedative were compared with those of patients who received midazolam.

Results

Patients who received remimazolam had shorter average induction (102.0 sec vs. 327.5 sec, p<0.001) and recovery times (5.8 min vs. 13.4 min, p<0.001) than those who received midazolam. No significant difference in side effect profiles was observed between the groups.

Conclusion

In performing upper gastrointestinal endoscopy in older patients, remimazolam can be a good alternative sedative to midazolam, whether used as monotherapy or in combination therapy.

References

Kilpatrick GJ, McIntyre MS, Cox RF, et al. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology 2007;107:60-6.
Borkett KM, Riff DS, Schwartz HI, et al. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg 2015;120:771-80.
Chernik DA, Gillings D, Laine H, et al. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol 1990;10:244-51.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a frequently employed procedure for diagnosing and treating pancreaticobiliary diseases. The selection of an appropriate sedative agent is crucial for ensuring patient comfort and procedural success. An optimal sedative should offer a predictable duration of action and a high safety profile. This study aimed to compare the efficacy and safety of remimazolam and propofol in patients undergoing ERCP procedures.

Aims & Methods

A randomized, single-blind, single center study was conducted comparing remimazolam and propofol for inpatient ERCP sedation. The study medications were administered under the supervision of the endoscopist. A total of 110 patients scheduled for ERCP were randomly assigned to receive either remimazolam or propofol. The primary endpoint was a composite of successful procedure completion and no requirement for rescue medication. Secondary endpoints included sedation efficacy, recovery time, and adverse events.

Results

Of the 110 patients randomized, 108 underwent sedation and ERCP (53 received remimazolam, 55 propofol). The primary endpoint was achieved for 100% of patients in both groups. The incidence and frequency of treatment-emergent adverse events, including desaturation, were comparable between the two groups. ERCP initiation occurred sooner in the propofol group (mean, 63.18 ± 16.56 seconds) compared to the remimazolam group (75.23 ± 32.27 seconds; p-value=0.02). Additionally, the time to full alertness after ERCP completion was significantly shorter in the propofol group than the remimazolam group (304.18 ± 146.25 vs. 448.34 ± 224.09 seconds; p-value<0.001).

Conclusion

This trial demonstrated non-inferiority of remimazolam to propofol in achieving the primary endpoint of successful ERCP completion without the need for rescue medication. The incidence and frequency of adverse events were comparable between the two groups. However, our study also revealed that propofol had a faster onset and recovery time compared to remimazolam. Although this difference may not be clinically significant, it could have practical implications in certain cases. Consequently, remimazolam can be considered a safe and effective alternative to propofol for ERCP sedation, potentially expanding clinicians’ options and improving patient outcomes. Further research is warranted to determine the optimal choice of sedative agents for various patient populations and procedures.

Introduction

Anti-tumour necrosis factor-alpha (anti-TNF-alpha) therapy is an effective treatment for the management of Crohn’s disease (CD). However, treatment failure is common.

Aims & Methods

The aim of this study was to identify predictors of anti-TNF-alpha therapy failure.
Retrospective single-center study including anti-TNF-alpha naïve patients with CD, who started on intravenous infliximab, between January 2019 and December 2021. Biochemical parameters included erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), faecal calprotectin, infliximab serum concentrations and the presence of antibodies to infliximab (ATI). Anti-TNF-alpha therapy failure was defined as the development of ATI at 6 and 12 months, absence of clinical response at 6 months, absence of clinical remission or of objective response at 12 months. Clinical response was defined as a reduction in Harvey-Bradshaw index (HBI) of ≥ 3 points comparing with initial value or HBI < 5 points if initial HBI ≥ 7 points and clinical remission as HBI ≤ 4 points. Objective response was assessed by endoscopic studies, defined by improvement of mucosal inflammation and absence of deep ulcerations, or imaging, defined as improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyper-enhancement.

Results

A total of 53 CD patients were included, 30 were female (56.6%), with a mean age at the beginning of treatment of 39 ± 2 years. Considering the Montreal classification, 31 patients had ileal disease (58.5%), 7 colonic (13.2%) and 15 ileocolonic disease (28.3%); 22 patients had nonstricturing, nonpenetrating disease (41.5%), 22 stricturing (41.5%) and 9 penetrating disease (17.0%). Eleven patients had perianal disease (20.8%). A total of 26 patients (49.1%) were treated with combination of anti-TNF-alpha and immunomodulatory therapy (thiopurine or methotrexate). Anti-TNF-alpha therapy failure occurred in 21 patients (39.6%). At 6 months, the development of ATI occurred in 6 patients (11.3%) and absence of clinical response in 9 patients (17.0%). At 12 months, absence of clinical remission was seen in 13.6% of patients and absence of objective response in 27.0% of patients.
At 6 months, the development of ATI was significantly higher in patients with lower infliximab serum concentrations at week 14 (with antibodies 5.9±3.2 µg/mL vs without 14.3±7.7 µg/mL, p<0.001). Additionally, the development of ATI was significantly higher in patients with a higher initial value of ESR (with antibodies median 35 vs without median 13, p=0.045). The infliximab serum concentrations at week 14 (AUC 0.828; p=0.009; sensitivity 0.833 and specificity 0.404 for values ≤11.6) and the initial value of ESR (AUC 0.754; p=0.045; sensitivity 0.833 and specificity 0.468 for values ≥15) had very good and good discriminative capacity, respectively, in predicting the development of ATI. No statistically significant differences were found in initial values of CRP and faecal calprotectin, between both groups. Moreover, the other definers of anti-TNF-alpha therapy failure were not associated with the combination with immunomodulatory therapy, infliximab serum concentrations at week 14 or initial values of ESR, CRP and faecal calprotectin.

Conclusion

Infliximab serum concentration after induction therapy is the most important factor in the development of ATI, influencing treatment response, regardless of the combination of anti-TNF-alpha therapy with immunomodulatory therapy. A higher initial value of ESR can also predict the development of ATI.

Introduction

IgG4-related disease of the liver, pancreas, and bile ducts (IgG4-HPB) can lead to fibrosis and organ damage. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and Enhanced liver fibrosis (ELF) score are validated, non-invasive methods for measuring liver fibrosis in other chronic liver diseases, but little is known about their utility in IgG4-HPB.

Aims & Methods

The aim of this study is to assess LSM using Fibroscan® and ELF in patients with IgG4-HPB. This is a retrospective observational cohort of patients meeting the ACR/EULAR classification criteria for IgG4-Related Disease at Oxford University Hospitals. Clinical data collected included demographics, organ involvement, clinical flares, serum biomarkers and organ damage. LSM was recorded in 55 IgG4-HPB patients, and sequential LSM was recorded in 32 patients. Serum ELF was measured in 23 patients. Wilcoxon rank, Mann-Whitney U, and Fisher’s exact tests were performed.

Results

Ninety-seven patients with IgG4-HPB were included; median age was 68 years ±19, and 79% were male. Among the entire cohort, 69% had established organ dysfunction and/or damage and, when subdivided by organ involvement, damage was present in 72% of those with liver and biliary disease (IgG4-HB) and 65% of those with pancreatic disease only (IgG4-AIP) (Table 1).

	Overall cohort (n = 97)	HPB cohort (n = 57)	AIP cohort (n = 40)	p-value
Median age (IQR)	67.5 (19)	68.5 (19)	65.5 (18)	0.91
Men	77 (79%)	44 (77%)	33 (82%)	0.61
Established organ damage	67 (69%)	41 (72%)	26 (65%)	>0.99
Diabetes	33 (34%)	26 (46%)	12 (29%)	0.14
Cardiometabolic disease	41 (42%)	22 (39%)	20 (49%)	0.11
MASLD	19 (20%)	13 (23%)	6 (15%)	0.59
Mean cumulative steroid dose (SD)	7326 (17468)	9012 (21263)	4260 (3074)	0.32
Median number of flares (IQR)	1 (2)	1 (2)	0 (1)	0.25

LSM was recorded in 55 patients: IgG4-HB (n = 38) had a higher mean LSM compared with IgG4-AIP (n = 17) (6.1 kPa vs 5 kPa, p = 0.04). IgG4-HB were risk-stratified by LSM: 66% had LSM <8kPa, 21% had LSM ≥8 but <12kPa, and 13% had LSM ≥12kPa. There was a higher prevalence of metabolic associated steatotic liver disease (MASLD) and its metabolic factors (diabetes, hypertension, hypercholesterolemia, and ischaemic heart disease) in those with more advanced liver fibrosis (LSM≥12 kPa). Furthermore, survival analysis showed that patients with LSM ≥ 8kPa develop organ damage faster than those with LSM < 8kPa (p=0.0086).

In longitudinal analysis, 32 patients with IgG4-HPB had serial LSMs. Of those with IgG4-HB (n = 22), 23% showed an increase in LSM over a median of 2 years (IQR 1-4). The proportion of patients meeting criteria for MASLD increased from 20% to 25% over a median of two years. In those with paired readings during active disease and remission (n = 8), there was no discernible variation in LSM.

Twenty-three patients with IgG4-HPB had an ELF test and were stratified by the score: 13/23 (56%) <9.8 and 10/23 (43%) ≥9.8. ELF accurately identified patients with more significant liver fibrosis; no patient with LSM ≥ 8kPA was seen in the <9.8 group (p = 0.0021). There was no association of ELF with disease activity or serum biomarkers.

Conclusion

This is the first study assessing the role of LSM by Fibroscan® and of ELF score in patients with IgG4-HPB. An increased LSM over time was associated with the accumulation of cardiometabolic risk factors, evidence of MASLD, and end-organ damage, while ELF score ruled out advanced fibrosis in this cohort concurrently.

Disclosure

EC: Speaking Fees: Horizon Therapeutics, Advanz (Intercept), Albireo, Dr Falk Pharma, Gilead, GSK; Consulting Fees: Advanz (Intercept), Horizon Therapeutics, Ipsen, Mirum, Moderna, Sanofi, Zenus Pharma; Grant Support: Jansen, Innovate UK, PSC Support, Wellcome Trust; Institutional Funding Support: BRC Oxford NIHR (UK), Oxford Charitable Fund, Research Capability Fund.
SK, RM and CM have nothing to declare.

Introduction

Diverticulosis was once regarded as an uncommon anatomic variant with different types of complication, Faecal calprotectin (FC) is a cytoplasmic antimicrobial
compound prominent in granulocytes, monocytes, and macrophages (1).

Aims & Methods

we aim to assess the fecal calprotectin values in colonic diferticulosis as a non invasive marker of disease severity.

Results

We enrolled in this study 360 consecutive patients who had undergone a total colonoscopy and MSCT on Abdomen and complete laboratory investigation including fecal calportectin, Age was distributed as 46.61±11.57 with minimum 15 and maximum 80 years and regard sex distribution female were majority with 59.7% fecal calportectin significantly positive correlated with CRP, NIS and Hinchey classification. Mild diverticulosis showed Significant area under curve with cutoff >65 and with sensitivity 97.0%and specificity 82.8%. moderate diverticuosis showed Significant area under curve with cutoff >162 <175 and with sensitivity 83.3%and specificity 96.0%. Severe Significant area under curve with cutoff >175 and with sensitivity 85.0%and specificity 92.5%.

Conclusion

Faecal calprotectin (FC) is inflammatory marker considered as a stronger predictor of diverticulosis diseases in Non IBD Patients.

References

(1) Roseth AG, Fagerhol M, Aadland E, Schjonsby H (1992) Assessment of neutrophil dominating protein calprotectin in feces. A methodological study. Scand J Gastroenterol 27:793–798