Introduction

Despite lack of evidence, patients are kept nil by mouth for 48 to 96 hours after upper gastrointestinal bleeding (UGIB) due to fear of rebleeding. However, many trials have demonstrated the benefits of early nutrition after UGIB. We conducted a meta-analysis of randomized controlled trials to evaluate the safety and outcomes of early nutrition compared to delayed nutrition after UGIB.

Aims & Methods

The protocol was registered on PROSPERO in advance (CRD42022372306). Five databases (PubMed, Embase, CENTRAL, Scopus, and Web of Science) were searched on the 10th of November 2022 to identify randomized controlled trials that met our eligibility criteria. In-hospital and 30-day outcomes were pooled separately. Mortality rate, rebleeding rate, and length of hospital stay were the primary outcomes. The pooled risk ratio (RR), mean difference (MD), and the corresponding 95% confidence interval (CI) were calculated using a random effects model.

Results

A total of 10 trials with 1,051 patients were included in the analysis. Comparing the two groups, 7-day mortality showed no significant difference (RR=1.23, CI: 0.72 - 2.10), while there was a clear tendency for a decrease in 30-day mortality in the early nutrition group (RR=0.57, CI: 0.31 – 1.04). As for 7-day and 30-day rebleeding, there was no statistically significant difference between the two groups (RR=1.05, CI: 0.63 – 1.74 and RR=1.16, CI: 0.59 – 2.26, respectively). In addition, our analysis showed that the early nutrition group needed a reduced length of hospital stay compared to the delayed nutrition group (MD= - 1.22, CI: -2.43 to -0.01).

Conclusion

Compared with delayed nutrition, early nutrition appears to be a safe intervention and could reduce the length of hospital stay without increasing the risk of complications regarding rebleeding or mortality after upper gastrointestinal bleeding.

Disclosure

The authors declare no potential conflict of interest.

Introduction

Despite a lack of evidence, patients are often not fed for 48 to 96 hours after upper gastrointestinal bleeding (UGIB); however, many trials have demonstrated the benefits of early nutrition (EN). We conducted a meta-analysis of randomized controlled trials (RTCs) to evaluate the outcomes of EN compared to delayed nutrition (DN) after UGIB.

Aims & Methods

The protocol was registered on PROSPERO (CRD42022372306). PubMed, Embase, CENTRAL, Scopus, and Web of Science were searched on the 27^th of August 2023 to identify eligible RCTs. The primary outcomes were early (within 7 days) and late (within 30-42 days) mortality and rebleeding. Pooled risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) were calculated using a random-effects model.

Results

A total of 10 trials with 1,051 patients were included in the analysis. Early mortality was not significantly different between the two groups (RR: 1.20, CI: 0.85 – 1.71, I² = 0%), whereas late mortality was reduced to a clinically relevant extent in the EN group (RR: 0.61, CI: 0.35 – 1.06, I² = 0%). When comparing the two groups, we found no significant difference in terms of early and late rebleeding (RR: 1.04, CI: 0.66 – 1.63, I² = 0% and RR: 1.16, CI: 0.63 – 2.13, I² = 0%, respectively). Our analysis also showed that the length of hospital stay was reduced in the EN group compared to the DN group (MD: - 1.22 days, CI: - 2.43 to - 0.01, I² = 94%).

Conclusion

Compared with DN, EN (within 24 hours) appears to be a safe intervention and could reduce the length of hospital stay without increasing the risk of complications after UGIB.

Disclosure

None to declare.

Introduction

Recurrent urinary tract infections (rUTIs) affect up to 25% of women worldwide¹, with risk of antibiotic-related side effects and multi-drug resistance. Several gut pathobionts, mainly Enterobacteriaceae, are responsible for nearly 90% of all UTIs, and gut microbiome imbalance has recently appeared as a main pathogenic pathway of UTIs². Untargeted probiotics have provided conflicting results in this setting,^3-5 and current evidence does not support their use.⁶ Gut microbiome testing are emerging as a promising diagnostic tool to target microbiome and offer a personalized therapeutic strategy, but their real value is unknown.

Aims & Methods

Our aim is to evaluate whether targeting gut microbiome is an effective strategy to prevent rUTIs derived from gut pathobionts.
In this pilot study, we included consecutive patients with rUTIs derived from gut pathobionts referring at our outpatient microbiome clinic in 2022.
All patients underwent a commercially available stool microbiome testing (XMICROGem from XBIOGem) based on 16S rRNA analysis, performed as already described⁷. Then, patients received a targeted therapy based on results of the gut microbiome testing, with the aim of restoring a balanced microbiota. Non-adsorbable antibiotics were used to downregulate pathobionts’ abundance, while prebiotics and probiotics were given to boost the abundance of specific taxa and/or to compete with pathobionts. Patients were followed up at least 12 weeks after the end of therapy.
We collected the following data of patients: age, gender, presence of gastrointestinal (GI) symptoms (assessed with GSRS), taxa responsible of UTIs; specific characteristics of gut microbiome (alpha diversity, abundance of Enterobacteriaceae, Escherichia, Klebsiella, Bifidobacteria, Akkermansia, and short-chain fatty acid producers including Lachnospiraceae, Faecalibacterium, Roseburia, Butyrivibrio); specific therapies given after testing, including non-adsorbable antibiotics, prebiotics, and probiotic strains. The primary outcome was the recurrence of UTIs, and the secondary outcome was gastrointestinal symptoms, at 12-week follow-up.

Results

Twelve patients were enrolled in the study period (n= 11 females, mean age 40 years). Of them, 11 (92%) presented with GI symptoms (67% with bloating, 50% with constipation, 50% with abdominal pain, 42% with dyspepsia, 17% with diarrhea). rUTIs were caused by E. coli in 11 patients and E. faecalis in one patient. The gut microbiome testing showed a decrease of alpha diversity in two patients (17%), of Akkermansia in eight patients (67%) and of SCFA-producers in seven patients (58%), as well as increased Proteobacteria in seven patients (58%). Moreover, Bacteroidetes were increased in four patients (33%) while Firmicutes were decreased in two patients (17%). Ten patients underwent rifaximin (83%) and two paromomycin (17%). E. coli Nissle 1917 was used in seven patients (58%), five in combination with an Enterococcus faecium-based strain,one in combination with Lactobacillus crispatus M247, and one in combination with both. Multi-strains probiotics were used in 7 patients (58%). Prebiotics were administered in seven patients. At 12-week follow-up, nine patients (75%) were free from new episodes of UTIs, and eight patients (73%) experienced an improvement of GI symptoms.

Conclusion

A precision medicine strategy based on gut microbiome testing may be a promising approach to treat rUTIs and ameliorate associated GI symptoms. Well designed, randomized and larger studies are needed to confirm our preliminary findings.

References

1. Meena, J., Thomas, C. C., Kumar, J., Raut, S. & Hari, P. Non-antibiotic interventions for prevention of urinary tract infections in children: a systematic review and meta-analysis of randomized controlled trials. Eur J Pediatr 180, 3535–3545 (2021).
2. Thänert, R. et al. Comparative Genomics of Antibiotic-Resistant Uropathogens Implicates Three Routes for Recurrence of Urinary Tract Infections. mBio 10, e01977-19 (2019).
3. Abdullatif, V. A. et al. Efficacy of Probiotics as Prophylaxis for Urinary Tract Infections in Premenopausal Women: A Systematic Review and Meta-Analysis. Cureus 13, e18843 (2021).
4. Grin, P. M., Kowalewska, P. M., Alhazzan, W. & Fox-Robichaud, A. E. Lactobacillus for preventing recurrent urinary tract infections in women: meta-analysis. Can J Urol 20, 6607–6614 (2013).
5. New, F. J., Theivendrampillai, S., Juliebø-Jones, P. & Somani, B. Role of Probiotics for Recurrent UTIs in the Twenty-First Century: a Systematic Review of Literature. Curr Urol Rep 23, 19–28 (2022).
6. EAU Guidelines on Urological Infections - THE GUIDELINE - Uroweb. Uroweb - European Association of Urology https://uroweb.org/guidelines/urological-infections/chapter/the-guideline.

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.

Introduction

Luminal stenoses with variable degrees of inflammatory and fibrotic components are commonly observed in patients with Crohn’s disease (CD) and may require medical, endoscopic, or surgical management.¹ Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor, demonstrated efficacy in 3 randomized, controlled, double-blind studies, and is approved for the treatment of moderately to severely active CD.^2-6 We conducted a post hoc analysis of these studies to evaluate the efficacy of UPA in patients with baseline (BL) luminal stenoses.

Aims & Methods

Patients in induction studies U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) were randomized 2:1 to receive UPA 45 mg (UPA45) or placebo (PBO) once daily (QD) for 12 weeks. Patients with clinical response were re-randomized 1:1:1 in the U-ENDURE maintenance study (NCT03345823) to receive UPA 30 mg (UPA30), UPA 15 mg (UPA15), or PBO QD for 52 weeks. The presence, location, degree of patency, and number of luminal stenoses were assessed by Simple Endoscopic Score for CD (SES-CD) narrowing component (range 0–3; patients with symptomatic stenosis were excluded). Resolution of BL stenosis and achievement of clinical remission and endoscopic response were assessed at week 12 of induction and week 52 of maintenance.

Results

One-third of patients (33.0% [337/1021]) had stenoses at induction BL (UPA45: 34.1% [230/674]; PBO: 30.8% [107/347]). BL demographics and disease characteristics were generally similar in patients with or without stenoses. BL stenoses occurred most frequently in the ileum (161 stenoses) followed by the right colon, transverse colon, sigmoid and left colon, and rectum (116, 39, 53, and 33 stenoses, respectively). At week 12, resolution rates of BL stenosis were nominally greater in the sigmoid and left colon and numerically greater in the ileum, transverse colon, and rectum among patients receiving UPA45 vs PBO (Table). UPA45 showed nominally greater efficacy compared with PBO in achieving clinical remission and endoscopic response in patients with or without BL stenoses (Table). Of the 502 patients in the maintenance population, 35.3% (n = 177) had stenoses at induction BL (UPA30: 34.5% [58/168]; UPA15: 35.6% [60/169]; PBO: 35.8% [59/165]). Narrowing was most frequent in the ileum (82 stenoses) followed by the right colon, transverse colon, sigmoid and left colon, and rectum (56, 21, 27, and 20 stenoses, respectively). By week 52, resolution rates of BL stenosis were nominally greater in the sigmoid and left colon and numerically greater in the ileum, right colon, transverse colon, and rectum among patients receiving UPA30 vs PBO (Table). Numerically greater rates of right colon, sigmoid and left colon, and rectum stenosis resolution occurred among patients receiving UPA15 vs PBO (Table). Nominally or numerically greater proportions of patients, with or without BL stenoses, achieved clinical remission and endoscopic response at week 52 with UPA30 and UPA15 vs PBO (Table).

Conclusion

Among patients with moderately to severely active CD, UPA induction and maintenance treatment improved the narrowing component of BL luminal stenoses, and clinical and endoscopic outcomes for patients with or without stenoses.

References

1. Bettenworth D, et al. Gut. 2019;68:1115–1126.
2. Loftus E, et al. United European Gastroenterol J. 2022;10(S8):103.
3. Colombel JF, et al. Gastroenterology. 2022;162(7):S-1394.
4. Panés J, et al. Am J Gastroenterol. 2022;117:S10.
5. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf
6. RINVOQ. Summary of Product Characteristics. AbbVie Inc.; 2023. Accessed 27 March 2023. https://www.medicines.org.uk/emc/product/12830/smpc.

Disclosure

WR has served as a speaker and/or consultant and/or an advisory member for AbbVie, Amgen, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Bioclinica, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celgene, Celltrion, Eli Lilly, Falk Pharma GmbH, Ferring, Janssen, Galapagos Medice, Gatehouse Bio Inc., Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Landos Biopharma, Medahead, MedImmune, Microbiotica, Mitsubishi Tanabe Pharma Corporation, MSD, Roche, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pharmacosmos, Pfizer, Pharmacosmos, Protagonist, Provention, Quell Therapeutics, Sandoz, Seres Therapeutics, Setpointmedical, Shire, Sigmoid, Sublimity, Takeda, Teva Pharma, Therakos, Theravance, and Zealand; and has received research funding from AbbVie, Janssen, MSD, Sandoz, Sanofi, and Takeda.
RA has served as a speaker or consultant, or received research grants from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Falk Foundation, Ferring, Galapagos, Gilead, InDex Pharmaceuticals, Janssen-Cilag, Kliniksa, Lilly, MSD Sharp & Dohme, Novartis, Pandion Therapeutics, Pfizer, Roche Pharma, Samsung Bioepsis, Takeda Pharma, Tillotts Pharma, and Viatris.
VJ has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena Pharmaceuticals, Asieris, Bristol-Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Galapagos, GSK, Genentech, Gilead, Janssen, Lilly, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, and Topivert; and speaker fees from, AbbVie, Ferring, Galapagos, Janssen, Pfizer, Shire, and Takeda.
JP has received financial support for research from AbbVie and Pfizer; lecture fees from AbbVie, Ferring, Janssen, and Takeda; and consultancy fees from AbbVie, Arena Pharmaceuticals, Athos, Boehringer Ingelheim, Celltrion, Ferring, Galapagos, Genentech, GSK, Janssen, Mirum, Morphic, Origo, Pandion, Pfizer, Protagonist, Revolo, Robarts, Roche, Takeda, Theravance, and Wassermann.
EVL has received consultancy honoraria from AbbVie, Alvotech, Amgen, Arena, Avalo Therapeutics, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota Biosciences, Iterative Scopes, Janssen, Morphic, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Sun Pharma, Surrozen, Takeda, and UCB; and has received research support from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Receptos, Robarts Clinical Trials, Takeda, Theravance, and UCB.
SH reports no disclosures.
MTA has received consulting fees from Arena AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Celsius, Eli Lilly Pharmaceuticals, Gilead, Janssen, Microba, Pfizer, Prometheus Biosciences, UCB Biopharma, WebMD Global, and Focus Medical.
FR has received consulting/advisory board fees from Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Janssen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, and 89Bio.
VPR, EM, ED, SIA, and AG are employees or contractors of AbbVie and may own stock and/or options.
JFC has received research grants from AbbVie, Janssen, and Takeda; payment for lectures from AbbVie, Amgen, Ferring, Shire, and Takeda; consulting fees from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enterome, Ferring, Genentech, Janssen, Medimmune, Merck, Novartis, Pfizer, Protagonist Therapeutics, Sandoz, Second Genome, Seres Therapeutics, Shire, Takeda, Theradiag, and Theravance; and holds stock options in Genfit and Intestinal Biotech Development.
Funding
AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial. Medical writing support was provided by Tracy Wetter, PhD, and Akua Adu-Boahene, MD, MPH, of JB Ashtin, and funded by AbbVie.

Introduction

Differential diagnosis of solid pancreatic tumours (SPT) is a clinical challenge. Development of advanced imaging techniques associated with EUS, such as elastography and contrast enhancement, has been a step forward in this context. EUS-guided detective flow imaging (DFI) is a very recent technology allowing the evaluation of microvascularization and low-velocity blood flow without the need of contrast agents.

Aims & Methods

Aim of our study was to evaluate the findings obtained by EUS-DFI in SPT and compare them with contrast enhanced harmonic EUS (CEH-EUS).
Methods: A prospective, single-centre, observational study in patients who underwent EUS for the evaluation of SPT was designed. Procedures were performed with a linear echoendoscope (Fujifilm 740UT) attached to the ultrasound system Arietta 850. Lesions were characterized according to the vascularization pattern (hypervascular, isovascular and hypovascular) described with both methods. Final diagnosis was based on histology after EUS-guided biopsy. Data area shown as mean ± SD and percentage.

Results

44 patients were included (mean age 67 years, range 24-88, 23 males). Mean tumour size was 26.1 ± 15.7 mm. Fourteen (31.8%) lesions were located in the head of the pancreas, 19 (43.2%) in the body, 9 (20.5%) in the tail and 2 (4.5%) in the uncinate process. Final diagnosis was adenocarcinoma in 24 patients (54.5%), neuroendocrine tumour in 13 (29.5%), inflammatory mass in 3 (6.8%), autoimmune pancreatitis in 1 (2.3%), pancreatic necrosis in 1 (2.3%), accessory spleen in 1 (2.3%) and lipoma in 1 (2.3%). Agreement regarding the vascular pattern of SPT between CEH-EUS and EUS-DFI was reached in 97.7% of the cases. All adenocarcinomas were hypovascular, inflammatory masses and autoimmune pancreatitis isovascular, pancreatic necrosis avascular, and accessory spleen and lipoma hypervascular at both CEH-EUS and EUS-DFI. All 13 neuroendocrine tumours were hypervascular at CEH-EUS, 12 of them (90%) at EUS-DFI.

Conclusion

EUS-DFI allows evaluating the microvascular pattern of SPT with a similar accuracy than CEH-EUS, but without the need of using contrast agents.

Disclosure

Julio Iglesias-Garcia. Advisor Pentax, FujiFilm, Mediglobe

Introduction

Pancreatic acinar cystic transformation (ACT) was first described in 2000. Its initially supposed pre-neoplastic nature was reconsidered in the WHO Classification 2019. Its current management prone to a non-surgical approach, and so rare cases of histopathological diagnosis have been obtained since. Radiological diagnostic criteria have been proposed to differentiate ACT from Branch-duct Intraductal Papillary Mucinous Neoplasms (BD-IPMN) (Delavaud et al., 2014): 1) ≥ 5 cysts, 2) clustered peripheral small cysts, 3) cyst calcifications and 4) no communication with the main pancreatic duct.

Aims & Methods

The aims of this study were to describe the clinical and radiological characteristics of patients with a presumed diagnosis of ACT in imaging and to assess the role of these known radiological criteria in case of possible differential diagnoses. In this single-centre retrospective study (2003-2021), consecutive patients with a presumed diagnosis of ACT in the coding database were included. Patients without an available imaging (CT or MRI) for expert radiological centralized review were excluded. A group of “typical” diagnosis of ACT was defined as the absence of differential diagnosis to be evoked. A group of “uncertain” diagnosis of ACT was defined as other possible differential diagnoses.

Results

A total of 64 patients were included (35 male patients [55%]). Median age of diagnosis was of 60 (IQR 47-67) years. ACT diagnosis was “typical” for 35 (55%) patients and was “uncertain” for 29 (45%) patients. In the “typical” group, 91.4% of patients presented ≥3 radiological criteria versus 96.6% in the “uncertain” group (p=0.61). There were more calcifications and <10 cysts in the “uncertain” group compared to the “typical” group (86% versus 66%, p = 0.041 et 24% versus 6%, p = 0.06, respectively). In the “uncertain” group, the main differential diagnoses suggested were: 16 (55%) BD-IPMN and 7 (24%) calcified chronic pancreatitis (CCP). A pathological confirmation of ACT was obtained for three patients from which two were in the “uncertain” group.

Conclusion

ACT displays an heterogenous morphological imaging presentation reflecting a challenge for accurate non-invasive diagnosis. The published diagnostic radiological criteria seem not to be sufficient, especially in case of calcifications or/and <10 cysts.

References

Delavaud C, d’Assignies G, Cros J, et al. CT and MR imaging of multilocular acinar cell cystadenoma: comparison with branch duct intraductal papillary mucinous neoplasia (IPMNs). Eur Radiol 2014; 24: 2128–2136

Disclosure

No conflict of interest to be disclosed