International Multicenter Study Research Articles

DOP044 Active disease on intestinal ultrasound in pregnancy is associated with an increased risk of adverse obstetric and neonatal outcomes: an international multi-centre prospective cohort study.

Abstract Background Clinically active inflammatory bowel disease (IBD) impacts 30-50% of women antenatally1,2. Such clinically active disease is associated with an increased risk of adverse pregnancy outcomes, including preterm delivery2. However, the validity of clinical scores to assess antenatal disease activity has been questioned, whilst both faecal calprotectin (FCP) and intestinal ultrasound (IUS) are feasible and accurate in pregnancy3,4. We aimed to assess whether active disease defined by IUS may predict adverse obstetric outcomes in pregnant women with IBD. Methods This international multi-centre prospective cohort study recruited both preconception and pregnant individuals with IBD in Australia and the USA from 2017-2023. Participants underwent clinical assessments and FCP testing six months before conception, in each trimester (T1, T2, and T3), and, when feasible, six weeks postpartum. IUS was performed preconception and in T1 and T2. Clinically active disease in pregnancy was defined by a PGA>1, or a HBI>5 or SCCAI >3. A FCP>100μg/g was considered elevated, and IUS remission was defined as a bowel wall thickness of <3mm in all bowel segments, with normal bowel wall stratification, a lack of extra-mural complications, and an absence of mesenteric fat hypertrophy or hyperaemia. Univariable and multivariable binary logistic regression analyses including relevant confounders were used to determine the independent impact of IUS disease activity on obstetric outcomes. Cohen κ coefficients were used to determine agreement between FCP, IUS and clinical disease activity. Results 379 participants, 200 with Crohn’s Disease (CD), were recruited. Overall, rates of adverse obstetric outcomes were comparable to the general population (Figure 1). Maximal bowel wall thickness (BWT) >6mm in T1 was associated with a three-fold increased risk of neonatal intensive or special care unit admission (RR 3.10;1.27-7.54, p=0.013) and in T2 was associated with a four-fold increased risk of prematurity (4.51; 1.45-14.04, p=0.009). IUS hyperaemia in T2 was associated with a three-fold increase in preeclampsia risk (3.61; 1.07-12.15, p=0.038). FCP >100μg/g in T2 was associated with an increased risk of preterm delivery after adjusting for clinical disease activity (RR 2.90; 1.22-7.50, p=0.028). Agreement between clinical (HBI or SCCAI) and IUS/FCP activity during pregnancy was weak (Figure 2). Conclusion Sub-clinical disease activity identified on IUS in pregnancy is associated with an increased risk of pre-term delivery, with poor agreement between clinical symptoms and objective biomarkers of disease activity during pregnancy. IUS monitoring should be performed as part of routine antenatal IBD care and IUS remission targeted.

OP05 Efficacy and safety of autologous hematopoietic stem cell transplantation in refractory Crohn’s disease: outcomes from the international stem cell transplant consortium

Abstract Background Autologous hematopoietic stem cell transplant (HSCT) emerged as a treatment for refractory CD after several clinical studies including a randomized clinical trial (ASTIC).1,2 In CD patients at risk for bowel failure these studies demonstrated an endoscopic response in over 80% of patients with two transplant related deaths. A recent randomized trial using an alternative fludarabine-based conditioning regimen had unexpected safety outcomes with 2 deaths and renal failure secondary to thrombotic microangiopathy.3 Here we report recent long-term clinical and safety outcomes of HSCT for refractory CD using a cyclophosphamide-ATG conditioning regimen from 3 international centers. Methods Data from 100 patients was reviewed from 3 international centers (Barts Health, UK; Hospital Clinic Barcelona, Spain and Mount Sinai, US) for subjects with medically refractory CD that underwent HSCT. We compiled clinical (CDAI) and endoscopic (SES-CD) evaluations at baseline and the last documented follow-up after HSCT for 68 patients that underwent HSCT since the ASTIC trial. We further compiled additional outcomes including new initiation of advanced therapy, IBD-related surgery, need for parental nutrition, hospitalizations and death. Results As of the last follow-up (median 2 years) post-HSCT, 75% of patients had endoscopic improvement (SES CD↓50%) and 53% endoscopic remission (SESCD<4 ulcer sub-score<1) (N = 56)(Figure 1). 65% of patients were in clinical remission. 46% did not require advanced therapy following HSCT and of patients that started an advanced therapy 84% required a single therapy over 120 patient-years of follow-up (Figure 2). After HSCT there were 7 CD-related surgeries of which 2 were ileostomy reversals. No patients progressed to bowel failure and there were no long-term (>100 days post-HSCT) complications related to transplant including hospitalization, renal failure, death or malignancy. Conclusion In this multicenter international study, the majority of patients demonstrated sustained endoscopic and clinical improvement without progression to bowel failure or with long-term transplant related adverse events over 120 patient-years of follow up. These results support HSCT as a therapy for highly refractory CD patients and the need to refer these patients to international centers of expertise to prevent CD-related morbidity and mortality.

DOP055 Upadacitinib for induction of remission in pediatric Crohn’s disease: An international multicenter study

Abstract Background Data on upadacitinib therapy in children with Crohn’s disease (CD) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric CD. Methods A multicenter retrospective study of children treated with upadacitinib for the induction of remission of active CD from 30 centers worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN between 2022 and 2024. Demographic, clinical, laboratory, and imaging data as well as adverse events (AEs) were recorded at week 8 post induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle. Results One-hundred children (median age 15.8 [interquartile range 14.3–17.2] years) were included. All children were previously treated with biologic therapies and 89 with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) were observed in 75%, 56% and 52% of the children, respectively. Normal C-reactive protein was achieved in 68% of the children and fecal calprotectin (FC) <150 mcg/g in 58%. Combined CFR and FC remission was observed in 13/31 (42%) children with available data at 8 weeks [13% of the ITT population]. AEs were recorded in 24 children, the most frequent was acne (n=12). Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy. Conclusion Upadacitinib is an effective induction therapy for refractory pediatric CD. Efficacy should be weighed against the potential risks of AEs.

DOP051 Upadacitinib for induction of remission in pediatric Ulcerative Colitis: An international multicenter study

Abstract Background Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. Methods In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction. Results One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3–17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. The median pediatric ulcerative colitis activity index (PUCAI) decreased from 45 [33-60] to 0 [0-20] at week 8 (p < 0.001; Figure 1). Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. The median FC level declined from 1645 [628-2263] mcg/g at baseline to 140 [33-669] mcg/g at week 8 (p < 0.001) (Figure 1).Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses). Conclusion In this largest and first multicenter study on a cohort of children with UC treated with upadacitinib, upadacitinib was an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

P1064 Association of subcutaneous infliximab CT-P13 serum levels and therapeutic outcomes in patients affected by Inflammatory Bowel Disease: A retrospective international multicentric study

Abstract Background The association between therapeutic outcomes and serum levels associated with the use of subcutaneous (SC) IFX CT-P13 in patients with inflammatory bowel disease [IBD] has been poorly studied. We aimed to define SC-IFX thresholds associated with therapeutic outcomes. Methods Patients receiving SC-IFX who had at least one therapeutic drug monitoring [TDM] were enrolled. Therapeutic outcomes were assessed as follows: clinical remission [HBI <5, SCCAI ≤2]; fecal calprotectin [FCAL] remission [<250 mg/g]; C-reactive protein [CRP] remission [CRP <5 mg/L]; deep remission [clinical + biomarker remission]. Chi-squared test for trend was used to analyze serum levels quartile data. Results 177 patients [54% male; 67% Crohn’s disease; Weight ≥ 80 kg 51%; 7% active smoker; 39% on immunosuppressants [IMM]; 9% on steroids; 26% with previous biologic exposure] from 4 centres had a total of 263 TDM measurements. Of these, were available 242 concurrent clinical measurement, 244 CRP and 152 FCAL.Median duration of SC treatment at time of TDM was 24 months (4-135). Proportion of patients achieving outcomes is described in table 1. The median IFX serum level was significantly higher in patients with clinical remission as well as in those with clinical and CRP remission (Figure 1), compared with patients who did not reach these targets. Conversely, there was no significant difference for the FCAL, clinical and FCAL, clinical and CRP and FCAL outcomes. In univariate analysis of factors associated with clinical remission (p<0.1) were sex, concomitant IMM, concomitant steroids, and previous biologic exposure and were included in a multivariate analysis in which only concomitant IMM showed remained significant [OR 0,1796 CI 95% 0,028-0,633]. Quartile analysis showed better outcome on higher drug levels for clinical remission, but not for other outcomes. Based on the ROC analysis and the Youden index, the cut-off levels for the therapeutic outcomes were respectively: clinical remission 12.85 mg/ml [sensitivity 0.85, specificity 0.5]; FCAL remission 11.8 mg/ml [sensitivity 0.82, specificity 0.32]; clinical and CRP remission 14.55 mg/ml [sensitivity 0.77, specificity 0.44]; clinical and FCAL remission 12.05 mg/ml [sensitivity 0.85, specificity 0.35]; clinical, CRP and FCAL remission12.05 mg/ml [sensitivity 0.85, specificity 0.33]. Conclusion An association between drug levels and clinical outcomes was identified in patients with IBD treated with SC IFX. Clinical remission was associated with a level of 12.8 mg/ml but the association between higher drug levels and deeper remission that has been described previously was not seen. References Roblin X, Nancey S, Papamichael K, et al. Higher Serum Infliximab Concentrations Following Subcutaneous Dosing are Associated with Deep Remission in Patients with Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(5):679-685. doi:10.1093/ecco-jcc/jjad188 Iborra M, Caballol B, Garrido A, et al. Subcutaneous infliximab cut-off points in patients with inflammatory bowel disease. Data from the ENEIDA registry. J Crohns Colitis. Published online August 22, 2024. doi:10.1093/ecco-jcc/jjae127

Feasibility and inter-reporter variability of submaximal outcomes derived from cardiopulmonary exercise testing in people with advanced cystic fibrosis lung disease

BackgroundCardiopulmonary exercise testing (CPET) provides prognostic information in people with advanced cystic fibrosis lung disease (pwACFLD). This project aimed to ascertain feasibility and inter-reporter variability in the identification of submaximal CPET outcomes for pwACFLD as potential predictors of prognosis where no peak exercise data are available.MethodsWe utilised data from an international retrospective multicentre study involving pwACFLD, for whom raw CPET data were available. Two experienced operators independently reviewed and analysed CPET tests with a focus on three pre-defined measures: oxygen uptake (V̇O2) at the anaerobic threshold (AT), the breathing reserve index at the AT (BRIAT), and the slope of the minute ventilation to carbon dioxide production ratio (V̇E/V̇CO2-slope). We calculated intra-class correlation coefficients (ICC) with their 95% confidence intervals (CI), and limits of agreement using the Bland-Altman method.ResultsThe original cohort included 174 pwACFLD. Among those, raw CPET data were available for 101 individuals, of which 89 tests were of sufficient technical quality for submaximal analysis. In 72 out of 89 technically-acceptable tests (81%), the AT could be confidently identified by both operators. Furthermore, ICCs indicated good-to-excellent inter-reporter agreement for V̇O2at the AT [ICC (95% CI) 0.79 (0.62 to 0.88)], the V̇E/V̇CO2-slope [0.95, 0.93 to 0.97)], and BRIAT [0.76, 0.63 to 0.85].ConclusionsSubmaximal CPET data can be reliably obtained in most pwACFLD by trained CPET operators. Future studies may ascertain the prognostic value of submaximal CPET outcomes in pwACFLD.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery. Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC. International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated. Overall, 2,282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction=0.003) and higher serum CA19-9 (Pinteraction=0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction=0.43), splenic vein (Pinteraction=0.30), retroperitoneal (Pinteraction=0.84), and multivisceral (Pinteraction=0.96) involvement. Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke

ObjectivesTo investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in...

Validation of the Iwate scoring system for the stratification of laparoscopic liver resections: an international multicenter study

Validation of the Iwate scoring system for the stratification of laparoscopic liver resections: an international multicenter study

Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study

Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study

Amniocentesis in Pregnancies at or Beyond 24 Weeks: An International Multicenter Study

(Abstracted from Am J Obstet Gynecol 2024:S0002-9378(24)00693-8) Amniocentesis, a standard method for obtaining fetal samples for genetic testing since the 1970s, is typically performed between 15 and 22 weeks of gestation. While useful for detecting chromosomal or single-gene fetal disorders, it carries low-incidence risks such as pregnancy loss, preterm prelabor rupture of membranes, chorioamnionitis, and fetal needle injury.

Comparison of two aspirin doses for the prophylaxis of pre-eclampsia in twin pregnancy: a multicentre retrospective study with propensity score matching.

Aspirin has proved its efficacy in reducing the rate of preeclampsia in singleton pregnancy, however, there is discrepancy about the efficient dosage that should be used. While some societies recommend daily 75-81mg, others recommend higher dosage (160mg). This discrepancy is due to the lack of randomized controlled studies that compare these two dosages. Moreover, there remains a considerable gap in our knowledge concerning the appropriate prophylactic aspirin dosage for twin pregnancies. This study aimed to assess the efficacy of various aspirin prophylaxis dosages in the prevention of preeclampsia and hypertensive disorders of pregnancy (HDP) in twin pregnancies. This was an international multicentre retrospective cohort study that was conducted in three European centers. We included all twin pregnancies with 2 live fetuses at 13 weeks of gestation (WG). We excluded fetal malformations, twin-twin transfusion syndrome, twin anemia polycythemia sequence, twin reversed arterial perfusion sequence, twin pregnancies at onset but continued as singletons (vanishing twin/arrest before 13 WG), and loss of follow-up. Patients were categorized into three groups: no aspirin, daily 80-100mg aspirin, and daily 160mg aspirin. Primary outcomes were the incidence of preeclampsia and HDP, whereas secondary outcomes were small-for-gestational age, postpartum hemorrhage>1000 mL, antenatal bleeding of obstetrical origin, thrombocytopenia, miscarriage, intrauterine fetal demise (IUFD), neonatal death, and gastritis. Propensity score matching and multivariate analyses were conducted to assess outcomes including pre-eclampsia, gestational hypertension, maternal complications, and gastritis. Propensity score matching was used to balance the three groups of study. Cox regression models were done for each outcome after matching to compare the three groups. A p-value<0.05 was considered statistically significant. A total of 1907 twin pregnancies were included: 1423 (74,62%) received no aspirin, 212 (11.12%) received 80-100 mg, and 272 (14.26%) received 160 mg. After using propensity score matching for maternal age, body mass index, race, parity, history of preeclampsia, chronic hypertension, diabetes mellitus, thrombophilia, spontaneous conception, and type of twin pregnancy, the three groups were adequately balanced (absolute standardized difference [ASD] <15%), except for age and thrombophilia (ASD 22.1% and 16.4% respectively). The administration of aspirin 160mg decreased the hazard ratio (HR) for preeclampsia to 0.63 and for HDP to 0.56, whereas the administration of aspirin 80-100mg failed to decrease both HR below 1. In addition, aspirin 160mg decreased the risk for preeclampsia <34 WG. No significant increase for aspirin-related complications, such as bleeding or thrombocytopenia, or other obstetrical outcomes was observed with the higher dose of aspirin. The use of 160 mg aspirin for the prevention of hypertensive disorders of pregnancy may offer superior outcomes in twin pregnancies, with no discernible rise in complications when compared to aspirin doses ranging from 80-100 mg. Further research should explore long-term impacts and refine dosage strategies for optimal outcomes in twin pregnancies.

Contrast-enhanced US of High-Risk Indeterminate Focal Liver Observations Categorized as LR-4 or LR-M at CT/MRI.

Background Indeterminate focal liver observations in patients at risk for hepatocellular carcinoma (HCC) may require invasive biopsy or follow-up, which could lead to delays in definitive categorization and to postponement of treatment. Purpose To examine clinical effect of contrast-enhanced US (CEUS) in participants with high-risk indeterminate liver observations categorized as Liver Imaging Reporting and Data System (LI-RADS) category LR-4 (probably HCC) or LI-RADS category LR-M (probably or definitely malignant but not HCC specific) at CT or MRI. Materials and Methods This was a secondary analysis of a prospective international multicenter validation study for CEUS LI-RADS (January 2018 to August 2021). CEUS was performed within 4 weeks of CT or MRI. Tissue histologic and CT or MRI follow-up data were used as reference standards. Clinical effect of CEUS for HCC was evaluated in observations 10 mm or larger categorized as CT/MRI LR-4 and LR-M. Results Included were 109 participants (mean age, 64.3 years ± 8.3 [SD]; 68.8% [75 of 109] male participants) with 113 observations (≥10 mm) categorized as CT/MRI LR-4 (53.1%; 60 of 113) or LR-M (46.9%; 53 of 113). CEUS resulted in management recommendation changes in 33.6% (95% CI: 25, 43; 38 of 113) of observations; among these, 95% (95% CI: 82, 99; 36 of 38) were correct. A total of 30.1% (34 of 113) of CT/MRI LR-4 and LR-M observations were categorized at CEUS as LI-RADS category LR-5 (definite HCC), making biopsy unnecessary; 94% (32 of 34) of these categorizations were correct. Of CT/MRI LR-4 observations, 7% (four of 60) were categorized as CEUS LR-M; subsequent biopsy confirmed non-HCC malignancy in all participants. Clinical impact of CEUS was more substantial for observations 20 mm or larger (n = 68); CEUS helped appropriately categorize both LR-5 and LR-M lesions as HCC and non-HCC malignancies, respectively, and resulted in management recommendation changes in 40% (27 of 68) of observations with 100% accuracy. Conclusion CEUS resolved some high-risk indeterminate liver observations (categorized as LR-4 and LR-M at CT or MRI), with particularly high clinical impact for observations measuring at least 20 mm. Clinical trial registration no. NCT03318380 © RSNA, 2025 Supplemental material is available for this article.

Genome-wide meta-analysis associates donor-recipient non-HLA genetic mismatch with acute cellular rejection post-liver transplantation.

Acute cellular rejection (ACR) remains a common complication causing significant morbidity post-liver transplantation. Non-human leukocyte antigen (non-HLA) mismatches were associated with an increased risk of ACR in kidney transplantation. Therefore, we hypothesized that donor-recipient non-HLA genetic mismatch is associated with increased ACR incidence post-liver transplantation. We conducted an international multicenter case-control genome-wide association study of donor-recipient liver transplant pairs in 3 independent cohorts, totaling 1846 pairs. To assess genetic mismatch burden, we calculated sum scores for single-nucleotide polymorphism (SNP) mismatch based on all non-HLA functional SNPs, specifically SNPs coding for transmembrane or secreted proteins as they more likely affect the immune system. We analyzed the association between the non-HLA mismatch scores and ACR in a multivariable Cox regression model per cohort, followed by a weighted meta-analysis. During the first year post-transplantation, 90 of 689 (13%), 161 of 720 (22%), and 48 of 437 (11%) recipients experienced ACR in cohorts 1-3, respectively. Weighted meta-analyses showed that higher mismatch in functional non-HLA SNPs was associated with an increased incidence of ACR (HR 5.99; 95% CI: 1.39-20.08; p=0.011). Moreover, we found a larger effect of mismatch in SNPs coding for transmembrane or secreted proteins on ACR (HR 7.54; 95% CI 1.95-28.79; p=0.003). Sensitivity analyses showed that imputed HLA mismatch did not affect the associations between both non-HLA mismatch scores and ACR. Donor-recipient mismatch of functional non-HLA SNPs overall and, especially, of SNPs encoding transmembrane or secreted proteins correlated with 1-year ACR post-liver transplantation. Identifying high-risk immunological burdens between pairs may prevent early graft rejection and aid in personalizing immunosuppressive therapy. Future studies are, however, needed to validate our findings using a genotyped HLA cohort.

International multicenter validation of AI-driven ultrasound detection of ovarian cancer

Ovarian lesions are common and often incidentally detected. A critical shortage of expert ultrasound examiners has raised concerns of unnecessary interventions and delayed cancer diagnoses. Deep learning has shown promising results in the detection of ovarian cancer in ultrasound images; however, external validation is lacking. In this international multicenter retrospective study, we developed and validated transformer-based neural network models using a comprehensive dataset of 17,119 ultrasound images from 3,652 patients across 20 centers in eight countries. Using a leave-one-center-out cross-validation scheme, for each center in turn, we trained a model using data from the remaining centers. The models demonstrated robust performance across centers, ultrasound systems, histological diagnoses and patient age groups, significantly outperforming both expert and non-expert examiners on all evaluated metrics, namely F1 score, sensitivity, specificity, accuracy, Cohen’s kappa, Matthew’s correlation coefficient, diagnostic odds ratio and Youden’s J statistic. Furthermore, in a retrospective triage simulation, artificial intelligence (AI)-driven diagnostic support reduced referrals to experts by 63% while significantly surpassing the diagnostic performance of the current practice. These results show that transformer-based models exhibit strong generalization and above human expert-level diagnostic accuracy, with the potential to alleviate the shortage of expert ultrasound examiners and improve patient outcomes.

Prophylactic anticoagulation in children receiving home parenteral nutrition: an international prospective multicenter study

Prophylactic anticoagulation in children receiving home parenteral nutrition: an international prospective multicenter study

Incorporation of the Central Vein Sign into the McDonald Criteria

BackgroundDiagnosis of multiple sclerosis (MS) frequently relies on MRI dissemination in time (DIT) and space (DIS), as codified in 2017 McDonald criteria (McD 2017). The central vein sign (CVS) is a proposed MS diagnostic biomarker, but its optimal incorporation into McD 2017 has not been extensively studied. ObjectiveEvaluate the diagnostic performance of several methods incorporating CVS into McD 2017 radiological DIS criteria. MethodsData were obtained from the CAVS-MS Pilot, a cross-sectional, international multi-center study conducted by the North American Imaging in MS Cooperative (NAIMS) that recruited adults referred for suspicion/diagnosis of demyelinating disease. Diagnostic performance of methods incorporating CVS into McD 2017 radiological DIS were evaluated by comparing sensitivity, specificity, and accuracy. Results78 participants (37 MS, 41 others) were included. For MS diagnosis, sensitivity, specificity, and accuracy of DIS based on brain imaging (DIS-B) alone was 92%, 69%, and 78%. Requiring at least one lesion with CVS in any brain location in addition to DIS-B increased specificity (sensitivity 92%, specificity 81%, accuracy 86%). Presence of 2 deep white matter lesions with CVS as an additional topography for DIS-B had higher sensitivity (sensitivity 97%, specificity 59%, accuracy 77%). ConclusionsIncorporation of CVS in McD 2017 DIS criteria can be used to improve diagnostic accuracy. Validation in additional prospective studies is needed.

Risk of Cancer and Reoperation After Ileorectal Anastomosis and Ileal Pouch-Anal Anastomosis in Familial Adenomatous Polyposis.

To prevent colorectal cancer, most patients with familial adenomatous polyposis (FAP) undergo (procto)colectomy with ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA). After surgery, these patients remain at risk of developing cancer in the remnant rectum or rectal cuff/pouch. We aimed to compare the long-term risk of cancer after IRA or IPAA in FAP. We performed an international multicenter historical cohort study of FAP patients undergoing IRA or IPAA from 1990 to 2023. The proportion of patients developing cancer after surgery was estimated using the Kaplan-Meier method. (Procto)colectomy was performed in 685 patients (53.6% female); 366 (53.4%) had IRA, and 319 (46.6%) had IPAA. Median age at IRA and IPAA was 23 and 27 years, and the median follow-up was 12 and 15 years, respectively. Overall, 8 patients (2.2%) developed rectal and/or rectal cuff/pouch cancer after IRA and 0.9% after IPAA. The estimated 10- and 20-year cancer incidence after IRA vs IPAA was 1.6% vs 0.4% and 2.5% vs 0.9%, respectively (log-rank P = 0.15). Reoperations, mainly for extensive polyposis, were performed in 39 (10.7%) patients with an IRA and 24 (7.5%) patients after IPAA. The number of postoperative endoscopic surveillance endoscopies was higher in patients with an IRA compared with those with an IPAA ( P < 0.001). Over the past 3 decades, few patients were diagnosed with cancer in the rectum or rectal cuff/pouch after (procto)colectomy in FAP. This might be due to an improved selection of the type of (procto)colectomy and close endoscopic surveillance including prophylactic polypectomies.

Standardizing and Classifying Anterior Cruciate Ligament Injuries: An International Multicenter Study Using a Mobile Application.

Background/Objectives: This international multicenter study aimed to assess the effectiveness of the Pivot-Shift Meter (PSM) mobile application in diagnosing and classifying anterior cruciate ligament (ACL) injuries, emphasizing the need for standardization to improve diagnostic precision and treatment outcomes. Methods: ACL evaluations were conducted by eight experienced orthopedic surgeons across five Latin American countries (Bolivia, Chile, Colombia, Ecuador, and Mexico). The PSM app utilized smartphone gyroscopes and accelerometers to standardize the pivot-shift test. Data analysis from 224 control tests and 399 standardized tests included non-parametric statistical methods, such as the Mann-Whitney U test for group comparisons and chi-square tests for categorical associations, alongside neural network modeling for injury grade classification. Results: Statistical analysis demonstrated significant differences between standardized and control tests, confirming the effectiveness of the standardization. The neural network model achieved high classification accuracy (94.7%), with precision, recall, and F1 scores exceeding 90%. Receiver Operating Characteristic (ROC) analysis yielded an area under the curve of 0.80, indicating reliable diagnostic accuracy. Conclusions: The PSM mobile application, combined with standardized pivot-shift techniques, is a reliable tool for diagnosing and classifying ACL injuries. Its high performance in predicting injury grades makes it a valuable addition to clinical practice for enhancing diagnostic precision and informing treatment planning.

Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study

Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site. Outcomes included local recurrence (LR), progression-free survival (PFS), and overall survival (OS). Cumulative incidence analysis was used for LR, Kaplan–Meier estimates for PFS and OS. Covariables included patient, disease, and SRT characteristics. We performed univariable and multivariable analyses (MVA). Among 444 patients, 751 metastases were treated with SRT. Of these, 73% were intracranial and 27% extracranial lesions. Oligometastatic disease (OMD) was present in 66% of the patients. LR after two years occurred significantly more often in intracranial (25%) versus extracranial lesions (7%). In MVA of patients with OMD treated for intracranial sites, higher performance status was significantly associated with longer PFS. Further, higher performance status, biologic subtype (HR-pos./HER2-pos.), and MDT to all sites were significantly associated with longer OS. In MVA of oligometastatic patients treated for extracranial sites, biologic subtype (HR-neg./HER2-pos.) and synchronous metastasis were associated with significantly longer PFS, whereas higher grading was associated with significantly shorter PFS. Moreover, biologic subtype (HR-neg./HER2-neg.) was associated with significantly shorter OS. In conclusion, the role of MDT for breast cancer may vary per clinical scenario. Patients with OMD treated for intracranial lesions who had MDT to all sites showed superior OS. Our results should be validated prospectively.