International Multicenter Study Research Articles

Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown.

A pilot case-control study on the fecal microbiota of pediatric functional abdominal pain-not otherwise specified and the role of early life stress.

Background: Gut microbial features and the role of early life stress in pediatric functional abdominal pain-not otherwise specified (FAP-NOS) have never been investigated before. Here, we hypothesize that early life stress is more prevalent in FAP-NOS compared to healthy controls and that fecal microbial profiles and related metabolites differ between groups. Methods: In an international multicenter case-control study, FAP-NOS patients (n = 40) were compared to healthy controls (n = 55). Stool samples and demographic and clinical data including early life traumatic events and antibiotics treatments were collected from children aged four to twelve years. Fecal microbial profiles were assessed with 16S rRNA gene amplicon sequencing. Microbial metabolite concentrations in fecal supernatant, including short-chain fatty acids and amino acids, were detected via liquid chromatography. Results: Microbial richness was increased in FAP-NOS compared to healthy controls and microbial composition (unweighted UniFrac) differed between groups. Three distinct amplicon sequencing variants and two distinct species were enriched in FAP-NOS compared to controls, with no observed changes at higher taxonomic levels. No differences in microbial metabolites and early life stress were observed between groups. Conclusion: The presented hypothesis could not be proven, with no observed differences in occurrence of early life stress, and fecal microbial metabolic profiles between pediatric FAP-NOS and healthy controls. Pediatric FAP-NOS patients exhibited mild differences in the fecal microbial community compared with controls. Further large-scale studies with high-resolution techniques are warranted to address the biological relevance of present observations.

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical,and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. The median follow-up period was 77.0months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. ClinicalTrials.gov Identifier:NCT04928573. June 16, 2021, "retrospectively registered".

Real-world assessment of multipolar and point-by-point mapping for premature ventricular contraction ablation.

We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. We included 101 children with a mean age at diagnosis of 12.8 ± 2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Chemotherapy with or without surgery for locally advanced or borderline resectable pancreatic ductal adenocarcinoma: A retrospective multicenter international study.

e16352 Background: Current clinical guidelines recommend surgery for patients with locally advanced (LA)/borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) who achieve disease control after induction therapy. However, the additional survival benefit of surgery in these patients is unknown. Methods: In this multicenter international retrospective cohort study, consecutive patients with BR/LA PDAC who achieved disease control after three to six months of induction therapy (combination chemotherapy or chemoradiotherapy) between January 2014 and July 2021 were retrospectively identified at 8 centers in Germany and Italy. Resectability status was determined by consensus in a multidisciplinary tumor board based on imaging findings, serum CA19-9, performance status and clinical response. Patient characteristics, progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox regression analysis was used to compare survival data. Results: A total of 138 patients who achieved disease control with induction therapy were analyzed. The median age at diagnosis was 66 years (range 45-82) and 43% of patients were female. 73 patients underwent surgery and 65 patients did not (median age 64 and 69 years, respectively, p = 0.02). Median OS was 20.0 months (95%CI 16.1-23.8) in the surgery group and 18.0 months (95%CI 13.6-22.4) in the nonsurgery group (hazard ratio for death, 0.90; 95%CI, 0.63 to 1.29, p = 0.57). Median PFS was 14.0 months (95%CI 8.9-19.1) in the surgery group and 15.0 months (95%CI 11.7-18.3) in the nonsurgery group (hazard ratio for disease progression, 1.04; 95%CI, 73 to 1,47, p = 0.83). The 2-year survival rates in the surgery and nonsurgery groups were 32.9% and 40.0%, respectively, with an overall odds ratio of 0.74 (95% CI: 0.37-1.47). Conclusions: In our multicenter international retrospective analysis, additional surgery did not confer a survival advantage to patients with BR/LA PDAC who achieved disease control with induction therapy.

Amniocentesis in pregnancies at or beyond 24 weeks: an international multicenter study

BackgroundAmniocentesis for genetic diagnosis is most commonly done between 15 and 22 weeks of gestation, but can be performed at later gestational ages. The safety and genetic diagnostic accuracy of amniocentesis have been well-established through numerous large-scale, multicenter studies for procedures before 24 weeks, but comprehensive data on late amniocentesis remain sparse. ObjectivesTo evaluate the indications, diagnostic yield, safety, and maternal and fetal outcomes associated with amniocentesis performed at or beyond 24 weeks of gestation. Study DesignWe conducted an international, multicenter retrospective cohort study examining pregnant individuals who underwent amniocentesis for prenatal diagnostic testing at gestational ages between 24w0d and 36w6d. The study, spanning from 2011 to 2022, involved nine referral centers. We included singleton or twin pregnancies with documented outcomes, excluding cases where other invasive procedures were performed during pregnancy or if amniocentesis was conducted for obstetric indications. We analyzed indications for late amniocentesis, types of genetic tests performed, their results, and the diagnostic yield, along with pregnancy outcomes and post-procedure complications. ResultsOf the 752 pregnant individuals included in our study, late amniocentesis was primarily performed for the prenatal diagnosis of structural anomalies (91.6%), followed by suspected fetal infection (2.3%) and high-risk findings from cell-free DNA screening (1.9%). The median gestational age at the time of the procedure was 28w5d, and 98.3% of pregnant individuals received results of genetic testing before birth or pregnancy termination. The diagnostic yield was 22.9%, and a diagnosis was made 2.4 times more often for fetuses with anomalies in multiple organ systems (36.4%) compared to those with anomalies in a single organ system (15.3%). Additionally, the diagnostic yield varied depending on the specific organ system involved, with the highest yield for musculoskeletal anomalies (36.7%) and hydrops fetalis (36.4%) when a single organ system or entity was affected. The most prevalent genetic diagnoses were aneuploidies (46.8%), followed by copy number variants (26.3%) and monogenic disorders (22.2%). The median gestational age at delivery was 38w3d, with an average of 59 days between the procedure and delivery date. The overall complication rate within two weeks post-procedure was 1.2%. We found no significant difference in the rate of preterm delivery between pregnant individuals undergoing amniocentesis between 24-28 weeks and those between 28-32 weeks, reinforcing the procedure's safety across these gestational periods. ConclusionsLate amniocentesis, at or after 24 weeks gestation, especially for pregnancies complicated by multiple congenital anomalies, has a high diagnostic yield and a low complication rate, underscoring its clinical utility. It provides pregnant individuals and their providers with a comprehensive diagnostic evaluation and results before delivery, enabling informed counseling and optimized perinatal and neonatal care planning.

Comprehensive analysis of adverse events associated with transmural use of LAMS in patients with liver cirrhosis: International multicenter study

Comprehensive analysis of adverse events associated with transmural use of LAMS in patients with liver cirrhosis: International multicenter study

First-line systemic therapy following adjuvant immunotherapy in renal cell carcinoma (RCC): An international multi-center study.

First-line systemic therapy following adjuvant immunotherapy in renal cell carcinoma (RCC): An international multi-center study.

The management of complicated colorectal cancer in older patients in a global perspective after COVID-19: the CO-OLDER WSES project.

Colorectal (CRC) cancer is becoming a disease of the elderly. Ageing is the most significant risk factor for presenting CRC. Early diagnosis of CRC and management is the best way in achieving good outcomes and longer survival but patients aged ≥75 years are usually not screened for CRC. This group of patients is often required to be managed when they are symptomatic in the emergency setting with high morbidity and mortality rates. Our main aim is to provide clinical data about the management of elderly patients presenting complicated colorectal cancer who required emergency surgical management to improve their care. The management of complicated COlorectal cancer in OLDER patients (CO-OLDER; ClinicalTrials.gov ID: NCT05788224; evaluated by the local ethical committee CPP EST III-France with the national number 2023-A01094-41) in the emergency setting project provides carrying out an observational multicenter international cohort study aimed to collect data about patients aged ≥75 years to assess modifiable risk factors for negative outcomes and mortality correlated to the emergency surgical management of this group of patients at risk admitted with a complicated (obstructed and perforated) CRC. The CO-OLDER protocol was approved by Institutional Review Board and released. Each CO-OLDER collaborator is asked to enroll ≥25 patients over a study period from 1st January 2018 to 30th October 2023. Data will be analyzed comparing two periods of study: before and after the COVID-19 pandemic. A sample size of 240 prospectively enrolled patients with obstructed colorectal cancer in a 5-month period was calculated. The secured database for entering anonymized data will be available for the period necessary to achieve the highest possible participation. One hundred eighty hospitals asked to be a CO-OLDER collaborator, with 36 potentially involved countries over the world. The CO-OLDER project aims to improve the management of elderly people presenting with a complicated colorectal cancer in the emergency setting. Our observational global study can provide valuable data on the effectiveness of different management strategies in improving primary assessment, management and outcomes for elderly patients with obstructed or perforated colorectal cancer in the emergency setting, guiding clinical decision-making. This information can help healthcare providers make informed decisions about the best course of action for these patients.

45MO Management of stage I ovarian Sertoli-Leydig cell tumors: Prognostic factors from a multicenter international retrospective study

45MO Management of stage I ovarian Sertoli-Leydig cell tumors: Prognostic factors from a multicenter international retrospective study

Nodular number as a prognostic indicator in hepatic resection for intermediate-stage hepatocellular carcinoma: An international multicenter observational study.

e16271 Background: The role of hepatic resection in treating Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) is a subject of ongoing debate. This study aims to assess the prognostic significance of the number of nodular HCC in patients undergoing hepatic resection for intermediate-stage (BCLC stage B) HCC. Methods: An analysis was conducted using data from a multicenter database of patients who underwent curative-intent resection for BCLC intermediate-stage HCC. Patients were classified into binodular and tri(+)nodular (≥ 3 nodules) groups based on the number of tumor nodules. Long-term overall survival (OS) and recurrence-free survival (RFS) were compared between these groups. Univariate and multivariate Cox-regression analyses identified risk factors for OS and RFS. Additional comparisons were made with outcomes in patients with uninodular large HCC (single nodule &gt; 5 cm; BCLC stage A). Results: Of the 338 patients with BCLC intermediate-stage HCC, 187 (55.3%) had binodular and 151 (44.7%) had tri(+)nodular disease. Patients with binodular HCC showed significantly better median OS (49.6 months) and RFS (22.2 months) compared to those with tri(+)nodular HCC (33.5 and 13.7 months, P = 0.036 and 0.009, respectively), and outcomes comparable to those with uninodular large HCC (59.8 and 26.8 months, P = 0.144 and 0.311, respectively). Multivariate analyses indicated that binodular HCC was independently associated with improved OS and RFS following hepatic resection in BCLC intermediate-stage HCC. Conclusions: Patients with binodular HCC exhibit more favorable survival outcomes post-resection of BCLC intermediate-stage HCC compared to those with tri(+)nodular HCC, akin to outcomes observed in BCLC early-stage uninodular large HCC. These findings highlight the prognostic relevance of nodular number in stratifying and guiding surgical decisions for intermediate-stage HCC. [Table: see text]

Ventricular arrhythmias associated with electrical cardioversion for atrial fibrillation, a multicenter study

Abstract Background Cases of ventricular arrhythmias (VAs) associated with QT prolongation after electrical cardioversion (ECV) for atrial fibrillation have been reported. Purpose To assess the incidence, timing and clinical characteristics of patients with VAs post-ECV for AF. Methods This is a multicenter international study. Seventy-seven centers were approached. Data was received from 13 worldwide centers. VAs included were torsades de pointes (TdP), NSPVT&amp;gt;3 beats or SCD within 7 days of ECV. The total number of ECVs performed at each center during the time period for which data was sent was provided. Results VAs occurred after ECV at an estimated incidence of 0.16%, range 0- 1.3% at different centers. Twenty-three patients with VAs were identified from 8 European centers, from 2008-2023, of whom 18 (78%) were from 2019-2023. There were 13 (56.5%) females, aged 71+11 years, mean LVEF=45+9%. AF duration prior to ECV was 72+65 days. Antiarrhythmic drugs (AADs) used prior to ECV were amiodarone in 9 (39%), sotalol in 4 (17%), class Ic in 3 (13%), beta blockers in 19 (83%), CCB in 1(4%) and digoxin in 4 (17%) patients. Five (22%) patients received QT prolonging drugs other then AADs. Baseline hypokalemia &amp;lt;3.5mmol/L was seen in 3(13%) patients (range 2.9-3.4mmol/L). ECV was elective, urgent and emergent in 10 (43%), 12 (52%) and 1(4%) patient, respectively. The arrhythmias documented were TdP in 17(74%), NSPVT &amp;gt;3 beats in 5(22%) and 1(4%) SCD. Arrhythmia documentation was available in 19 (83%) patients. Baseline mean HR pre-ECV was 115+30bpm and QT 388+61ms, both significantly differed from post-ECV mean HR which was 58+11bpm and QT 469+63ms, P&amp;lt;0.0001. Arrhythmia occurred 45+54 hours post-ECV, median 28.5 hours, range 5 minutes- 10 days. Figure 1 demonstrates an example of serial ECG changes from baseline to TdP occurrence. An arrhythmic storm occurred in 11 (48%) patients. Arrhythmia reoccurred in 9 (39%) patients, mean 13.25 + 15 (range 0.5-48) hours after the index event. The arrhythmias which reoccurred were TdP in 5 (22%), VF in 2 (9%), NSPVT in 1 (4%) and monomorphic VT in 1 (4%) patient. Acute therapy with DCCV was needed in 10 (43%) patients. AADs were discontinued in 16 patients. IV electrolytes were helpful in arrhythmia control in 16 (89%) of 18 patients, IV isoproterenol was helpful in 1 (25%) of 4 patients, temporary pacing with arrhythmia control in 2(40%) of 5 patients in whom it was used. ICD was implanted in 7 patients and a pacemaker in 4 others. Two (8.7%) patients expired, 1 died suddenly at home 12 hours after ECV and 1 suffered from acute heart failure and fatal TdP 72 hours after ECV while hospitalized. Conclusion VAs associated with QT prolongation after ECV for AF occur mainly 24-48 hours after ECV and may reoccur. Prolonged monitoring prior to discharge should be considered for prevention of fatal outcomes in patients with any evidence of QT prolongation following ECV.Figure 1

Impact of functional gene groups on outcomes after ablation of ventricular tachycardia in patients with inherited left ventricular cardiomyopathy: an international multicentre study

Abstract Background Advances in genetic testing has enabled identification of pathogenic variants of different functional gene groups associated with non-dilated left ventricular cardiomyopathy (NDLCM)/dilated cardiomyopathy (DCM) and ventricular tachycardia (VT). However, there is limited data on the impact of functional groups on VT ablation outcome. Aim We aimed to assess the impact of likely pathogenic/pathogenic variants (LP/Pv) of different functional gene groups on heart failure (HF) outcomes and VT recurrence in patients with NDLCM/DCM after VT ablation. Methods Patients with NDLCM/DCM who underwent genetic testing (next-generation sequencing) and were referred for VT ablation were enrolled at 6 participating centers. Patients were followed for VT recurrence, HF-related adverse outcomes (death, left ventricular assist device [LVAD], or heart transplantation due to HF), and all-cause mortality. Results A total of 239 patients (age 55±14yrs; male n=193; LVEF 40±12%; amiodarone at admission n=103; ICD n=180) were included. LP/Pv were identified in 128 patients (54%), predominantly found in genes encoding sarcomeric (n=36/128, [28%]; titin n=20, myosin binding protein C n=12), followed by nuclear membrane (n=27/128, [22%]; lamin A/C; n=26), desmosomal (n=23/128, [18%]; desmoplakin n=11, plakophilin n=9), cytoskeleton (n=12/128, [9%]; filamin C n=8), and sarcoplasmic reticulum proteins (n=12/128, [9%]; phospholamban n=10). Variants of unknown significance (n=32) were grouped with patients who tested negative. Acute complete ablation success, defined as non-VT inducibility of any sustained monomorphic VT, was achieved in 113 patients (47%), 63 (56%) with LP/Pv. During a median follow-up of 32 months, 108 patients (45%) had VT recurrence, 41 (17%) had HF-related adverse outcomes (death with/without LVAD in 34, LVAD in 2, heart transplantation in 5) and 47 (20%) died. Patients with LP/Pv were more likely to have VT recurrence, HF-related adverse outcomes and had a higher mortality compared to those without (VT, 68 [53%] vs. 40 [36%]; HF-related adverse outcomes, 30 [23%] vs. 11 [10%]; mortality, 30 [23%] vs. 17 [15%]; log-rank, P&amp;lt;0.01 for all). As compared to patients without LP/Pv, those with LP/Pv in genes encoding nuclear membrane or sarcomeric proteins had significantly worse (P&amp;lt;0.01 for both) and those with LP/Pv in genes encoding desmosomal proteins had similar HF and VT recurrence outcomes (Figure). Of interest, patients with LP/Pv in genes encoding cytoskeleton proteins had favorable HF-related adverse outcomes, but worse VT recurrence (P=0.02) compared to those without LP/Pv (Figure). Conclusion In patients with NDLCM/DCM and VT, the impact of LP/Pv on HF and VT-recurrence outcomes after ablation differs across functional groups. Integrating genetic testing in the comprehensive evaluation of patients with NDLCM/DCM undergoing VT ablation may facilitate personalized ablation strategies and early consideration of alternative HF treatments.

The multicenter ablate-by-LAW study: personalized paroxysmal atrial fibrillation ablation according to the local left atrial wall thickness

Abstract Background Personalized radiofrequency (RF) catheter ablation for paroxysmal atrial fibrillation (PAF), tailoring the ablation index (AI) to the local left atrial wall thickness (LAWT), has proven to be an efficient procedure with high arrhythmia-free survival rates. However, to date, only monocentric experiences have been reported in the literature. Purpose The present study sought to report a multicenter experience in order to assess the safety, efficacy, and efficiency, of a LAWT-guided personalized pulmonary vein isolation (PVI) approach for PAF ablation (ClinicalTrials.gov, NCT04218604). Methods We conducted an international multicenter prospective study at five tertiary hospitals (two in Spain, one in Italy, one in Germany, and one in the United States). Consecutive patients referred for first-time RF catheter ablation of PAF were prospectively enrolled from November 2020 to September 2022. In all patients a three-dimensional map of LAWT were obtained from preprocedural multidetector computed tomography (MDCT)-derived data postprocessing. LAWT was categorized into 1 mm layers and AI was titrated according to the LAWT. All procedures were performed under general anesthesia, utilizing high-rate low-tidal volume (HR-LTV) ventilation (Figure 1). All antiarrhythmic drugs were discontinued following the 3-month blanking period. The primary endpoint was freedom from any documented sustained atrial arrhythmia at 12-month follow-up, regardless of symptoms. Results One hundred and nine patients (60.1±9.4 years, 64.2% male) were prospectively enrolled. The mean LA diameter was 38.7±5.8 mm and the mean left ventricular ejection fraction was 60.7±4.7%. The median procedure time was 61.7 minutes (IQR 48.4–83.8), and the median RF application time was 13.9 minutes (IQR 12.3–16.8). The mean number of VisiTags was 63.2 ± 18. First-pass PVI was achieved in the 83.5% of patients. The median fluoroscopy time was 61.5 seconds (IQR 22.5–197.5). In 94 (86.2%) patients, ablation was performed with a single femoral venous puncture. At 12-month follow-up, the rate of freedom from any documented atrial arrhythmia was 93.4% (Figure 1). Two (1.8%) patients died during follow-up, one from unknown cause three months after the procedure, and another from complications following multiple trauma after falling from a ladder. One patient (0.9%) developed femoral artery pseudoaneurysm, with no other serious procedure-related complications. Conclusion The Ablate-by-LAW multicenter study proved that a personalized PAF ablation protocol, tailoring the AI to the local LAWT is highly efficient and achieved a high acute first-pass PVI rates. The study reported a high 12-month survival-free from any documented sustained atrial arrhythmias, exceeding 90%, and an exceptionally low incidence of serious procedure-related complications.

#664 Childhood Takayasu arteritis: a multicentre retrospective study

Abstract Background and Aims Takayasu arteritis (TA) is a rare, large vessel vasculitis affecting mainly the aorta and its major branches. Data on paediatric TA (pTA) is very scarce. The aim of this study was to characterize clinical presentation, therapy and outcome of pTA in a global study population. Method We conducted an international multicentre retrospective observational study of children diagnosed with pTA. Inclusion criteria were an age of less than 18 years at initial presentation in the year 2000 or more recently. Clinical data were collected from patients’ charts by the treating paediatric rheumatologist or nephrologist; data were fully anonymised for analysis purposes. Follow-up data was collected up to 2 years after diagnosis. Results 198 patients from 20 countries were included (76% female). The median age at disease onset was 12 years. Arterial hypertension (67%), a difference in pulses between limbs (65%) and fatigue (66%) were the most common symptoms at presentation. The gastrointestinal system was the second most affected organ system. The median eGFR (estimated glomerular filtration rate) at baseline was 105 ml/min/1.73 m2. Renal artery stenosis was documented in 58% of all patients and in 37% there was need for an invasive renovascular procedure. In 25 of 32 (78%) patients who had either a positron emission tomography–magnetic resonance imaging (PET-MRI) or PET-computed tomography (CT) there was evidence of active inflammation mainly of the aorta. 67% of all patients showed thickened wall abnormalities and 31% had arterial dilatations in a major vessel on any one or more anatomical imaging modality such as ultrasound, CT or MRI. Immunosuppressive treatment was primarily steroids, cyclophosphamide and methotrexate, 37% of all patients were treated with monoclonal antibodies of which 65% received an anti-tumor necrosis factor (TNF) antibody, 31% an anti-Interleukin 6 (IL-6) antibody and 4% an anti-B-cell antibody. Dialysis was necessary in 7% and one patient underwent kidney transplantation. Seven patient deaths (4%) were documented at the most recent follow-up. The renal function after two years was median eGFR 102 ml/min/1.73 m2, with 67% showing normal function, 31% presenting with chronic kidney disease (CKD) stage 1, 1% with stage 2, 1% with stage 3 and no patients showed stages 4 and 5. A quarter of the patients (27%) were still symptomatic at the 2-year follow-up. The median systolic blood pressure was 117 (interquartile range 107–125) mmHg. 64% of all patients still had antihypertensive treatment, and 87% were still on immunosuppressive therapy. Conclusion Our study represents the largest paediatric cohort of children diagnosed with Takayasu arteritis. Several organ systems were involved at onset and the clinical spectrum was highly variable. We will in our further analyses in more detail describe the outcome in relation to presenting symptoms and treatment.

An international, multicenter, survey-based analysis of practice and management of acute liver failure.

Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and hepatic encephalopathy in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. A total of 267 physicians completed the survey with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians were specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred and fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver- or transplant- intensive care unit (p<0.001). Median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, one week in 37.6%, and more than one week in 9.6% (p<0.001). Deceased-donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of ALF patients, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring hepatic encephalopathy and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare multicenter studies are valuable to identify global practice.

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) &amp;gt;75th percentile, 2) 75th-25th percentile, and 3) &amp;lt;25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (&amp;gt;75th, 75th-25th, and &amp;lt;25th groups, respectively). Results in the cross-section analysis (T1) &amp;lt;25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the &amp;gt;75th group. Using hierarchical linear modeling, the &amp;lt;25th exhibited higher cf-PWV than the &amp;gt;75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the &amp;lt;25th group compared to the &amp;gt;75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in &amp;lt;25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

Prognostic factors in uterine adenosarcoma: subanalysis of the SARCUT study.

The purpose of the study was to analyse the role of prognostic factorson the risk of recurrence and overall survival of patients with uterine adenosarcoma. A retrospective international multicentre study involving 46 centres collected 32 cases of uterine adenosarcoma, and these cases were included in the present subanalysis. Clinical and demographic features and tumour characteristics were gathered, as well as information on treatment and relapse. Disease-free and overall survival were analysed. The 5-year disease-free survival (DFS) was 85.3% and the 5-year overall survival (OS) rate was 89.5%. The risk factors significantly associated with overall survival were age (HR 1.09, 95% CI 1.03-1.15; p = 0.004) and FIGO stage II-III (HR 17.75, 95% CI 2.87-109.93; p = 0.002). Patients who experienced early relapse (within 12 months) had a tumour size >30mm and advanced stage. The majority of recurred cases were treated with radiotherapy or surgery and obtained a good response rate. The most significant prognostic factors in uterine adenosarcoma were age and FIGO stage and, indirectly, tumour size at diagnosis. The use of secondary surgery and/or radiotherapy could help in prolonging the disease-free status of the patients.

Local Excision for organ preservation in early REctal cancer with No Adjuvant treatment (LORENA Trial): prospective observational study protocol

IntroductionLocal resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME. Patients and methodAn international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI +/− endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy. DiscussionThe prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information.The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients.Trial registration number: NCT05927584.