Citations

Abstract Background and Aims Over 10% of patients with Crohn’s disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn’s disease patients with permanent ileostomy. Methods MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

Abstract Background Histologic inflammation persists in up to 1/4 of patients with Crohn’s disease (CD) despite endoscopic mucosal healing. Histologic and combined endoscopic-histologic endpoints are evolving measures of treatment efficacy in CD; however, the impact of histologic healing on long-term outcomes and disease progression is unknown. Week (W) 52 data comparing mirikizumab (Miri) vs placebo (PBO) in the randomized, double-blind, placebo- and active-controlled, treat-through Phase 3 VIVID-1 trial in patients with moderately-to-severely active CD (NCT03926130) were reported previously.1 Methods The main objective was to evaluate the association of W12 histologic response and W12 histologic remission with W52 clinical and endoscopic outcomes in VIVID-1. Two biopsy specimens from each of 5 intestinal segments (1 ileal and 4 colonic) were obtained from the edge of the ulcers, or the most inflamed mucosa from randomized patients at screening, W12, and W52. All analyses were post hoc and among patients with active histologic disease (defined as a Robarts Histopathology Index >0 and a Global Histologic Disease Activity Score >0) at baseline. Results At W12, treatment with Miri resulted in statistically significantly higher rates of achieving histologic response and histologic remission vs. PBO (Figure). At W12, 62.1% of patients had agreement (k=0.27 [fair]) between histologic response and endoscopic response, with a greater percentage achieving histologic over endoscopic response (59.0% vs. 38.8%)*. Significantly greater proportions of patients who achieved histologic response at W12 also achieved histologic response, histologic remission, endoscopic response, endoscopic remission, combined CDAI (Crohn’s Disease Activity Index) remission and endoscopic response, and normalisation of faecal calprotectin levels ≤250 µg/g and ≤150 µg/g at W52 (Table). Similar associations were observed between W12 histologic remission and W52 outcomes. Conclusion Histologic response seems to be an early objective sign of anti-inflammatory response and was significantly associated with one-year endoscopic and histologic outcomes, as well as biomarker normalisation. *Observed data References 1.Jairath V, et al. Presented at: UEGW 2024. OP131.

Abstract Background A passive dosimeter framework for the measurement of dose in carbon ion beams has yet to be characterized or implemented for regular use. Purpose This work determined the dose calculation correction factors for absorbed dose in thermoluminescent dosimeters (TLDs) in a therapeutic carbon ion beam. TLD could be a useful tool for remote audits, particularly in the context of clinical trials as new protocols are developed for carbon ion radiotherapy. Methods TLD‐100 were irradiated in a carbon ion beam at the Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia, Italy. The dose correction factors for linearity, fading, and beam quality were characterized. Fading was characterized from 5 to 100 days post‐irradiation. For linearity, the TLDs were irradiated to absorbed doses ranging from 1 to 15 Gy in both the entrance of a high‐energy pristine carbon ion peak and the center of a 2 cm spread‐out Bragg peak. For beam quality, the TLD was irradiated to the same absorbed dose (3 Gy) in several pristine carbon ion Bragg peaks, as well as in several spread‐out Bragg peaks. Each correction factor was calculated and compared to photon correction factors. The correction factors were also compared between high and low dose‐averaged linear energy transfer (LET D ) in the carbon ion beams. The absorbed dose was compared between ion chamber and TLD‐100 in the several tissue substitute phantom materials, applying the carbon ion TLD correction factors. Results There was no statistically significant difference in the TLD fading correction factor between photons, low LET D carbon ion beams, or high LET D carbon ion beams. The TLD linearity correction factor did differ between photons, low LET D carbon ions, and high LET D carbon ions. The beam quality correction factor was large and changed linearly with LET D . The overall uncertainty of the carbon ion absorbed dose calculation was 3.9% at the one‐sigma level, driven largely by a 3.5% uncertainty in the beam quality correction. TLD measurements were within 1.2% of ion chamber measurements in the phantom material for polyethylene, solid water (Gammex and Sun Nuclear), acrylic, blue water, and techtron HPV. TLD measurements in balsa wood were within 3.0% and cork was 6.6% low compared to ion chamber. Conclusion TLD‐100 can be used for passive dosimetry in a therapeutic carbon ion beam. Importantly, the linearity and beam quality correction factors are both different from photon therapy, and dependent on LET D of the carbon ion beam. This opens the possibility of TLD use for carbon ion output audits, phantom audits, and in vivo dose measurements, but may be subject to more complicated management and slightly larger uncertainties than are achieved in photon beams.

OBJECTIVE Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients. METHODS TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding. RESULTS From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1–2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7–1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2–1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4–13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1–7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4–7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9–3.6] per 100 patient-years; 2.0 [95% CI 1.3–2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6–2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1–8.9], p < 0.001), large (HR 2.6 [95% CI 1.1–6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2–5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1–4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7–4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0–4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0–3.2) per 100 patient-years. CONCLUSIONS Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.