International Multicenter Study Research Articles

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 > 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>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 <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 >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<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<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<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.

Result of the left bundle branch area pacing data collection registry, an international multicenter study of conduction system pacing with a Tendril STS 2088 stylet-driven lead.

Left bundle branch area (LBBA) pacing (LBBAP) has been proposed as an alternative therapy option in patients indicated for cardiac pacing to treat bradycardia or heart failure. The aim of the study was to evaluate the safety and effectiveness of LBBAP in patients implanted with a Tendril 2088 stylet-driven lead. The international retrospective data collection registry included 11 sites from 5 countries globally. Patients with attempted implants of the Tendril lead in the LBBA were followed for at least 6 months post the implant attempt. The primary safety and efficacy endpoints were freedom from LBBAP lead-related serious adverse events and the composite of LBBA capture threshold of ≤2.0 V and R-wave amplitudes ≥5 mV (or ≥value at implant), respectively. Of 221 patients with attempted implants of the Tendril 2088 lead in the LBBA, 91.4% (202/221) had successful implants for LBBAP. Regardless of the LBBAP implant success, all patients were followed for at least 6 months (8.7 ± 7.3 months). Baseline characteristics: 44% female, 84% ≥65 years old, 34% coronary artery disease, and 86% of primary indications for pacemaker implant. Both primary safety and effectiveness endpoints were met (freedom from LBBAP lead-related serious adverse device effects of 99.5% and electrical performance composite success rate of 93%). The capture thresholds in LBBAP at implant and 6 months were 0.8 ± 0.3 V@0.4 ± 0.1 ms and 0.8 ± 0.3 V@0.4 ± 0.1 ms. The rate of patients with capture threshold rise ≥1 V was 1.5% through 6 months. The R-wave amplitudes in LBBAP at implant and 6 months were 9.3 ± 3.2 mV and 10.6 ± 3.0 mV. This large multicenter study demonstrates that the stylet-driven Tendril™STS 2088 lead is safe and effective for LBBAP with high success and low complication rates.

SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD) WITH CARDIAC ARREST AT PRESENTATION: A SUBANALYSIS FROM THE DISCO REGISTRY

Abstract Introduction Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients. Methods The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in–hospital bleeding. Results Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST–segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In–hospital outcomes, except for longer hospitalization, did not differ. On follow–up (average 21 months), MACE rates were similar between groups. Conclusions Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in–hospital and during long–term follow–up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10mmHg. A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15kPa and platelet count ≥ 150 × 109/L] OR SSM < 21kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25kPa OR SSM ≥ 50kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

Patterns of opioid use after surgical discharge: a multicentre, prospective cohort study in 25 countries.

Excessive opioid prescribing following surgery contributes to the growing opioid crisis. Prescribing practices are modifiable, yet data to guide appropriate prescription of opioids at surgical discharge remain sparse. This study aimed to evaluate factors associated with opioid consumption following discharge from surgery. An international prospective multicentre cohort study was performed recruiting adult patients undergoing common general, orthopaedic, gynaecological and urological surgery, with follow-up 7 days after discharge. The primary outcome measures were the quantities of prescribed and consumed opioids in oral morphine milligram equivalents. Descriptive and multivariable analyses were performed to investigate factors associated with the primary outcome measures. This analysis included 4273 patients from 144 hospitals in 25 countries. Overall, 1311 (30.7%) patients were prescribed opioids at discharge. For those patients prescribed opioids, mean (SD) 179 (240) oral morphine milligram equivalents were prescribed, yet only 81 (145) oral morphine milligram equivalents were consumed within the first 7 days after discharge. An increased dose of opioids prescribed at discharge was associated with an increased dose of opioids consumed during the follow-up period (β = 0.33 (95%CI 0.31-0.34), p < 0.001). The risk of prescribing more opioids than patients consumed increased as quantities of opioids prescribed at discharge exceeded 100 oral morphine milligram equivalents, independent of patient comorbidity, procedure and pain. Patients were prescribed more than twice the quantity of opioids they consumed in the first 7 days following discharge from surgery. Our data suggest that the current quantities of opioids provided at discharge exceed patient needs and may contribute to increasing community opioid use and circulation.

Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases

BackgroundThe combination of anti-PD-1 and anti-CTLA-4 has been associated with improvement in response and survival over anti-PD-1 monotherapy in unselected patients with advanced melanoma. Whether patients with liver metastases also benefit from the combination of anti-PD-1 and anti-CTLA-4 over anti-PD-1, is unclear. In this study, we sought to assess whether the combination of anti-PD-1 and anti-CTLA-4 leads to better response, progression-free survival and overall survival, compared with anti-PD-1 monotherapy for patients with liver metastases. MethodsWe have conducted an international multicentre retrospective study. Patients with advanced melanoma with liver metastases treated with 1st line anti-PD1 monotherapy or with anti-CTLA-4 were included. The endpoints of this study were: objective response rate, progression-free survival and overall survival. ResultsWith a median follow-up from commencement of anti-PD-1 monotherapy or in combination with anti-CTLA-4 of 47 months (95% CI, 42–51), objective response rate was higher with combination therapy (47%) versus anti-PD-1 monotherapy (35%) (p = 0.0027), while progression-free survival and overall survival were not statistically different between both treatment groups. However, on multivariable analysis with multiple imputation for missing values and adjusting for predefined variables, combination of anti-PD1 and anti-CTLA-4 was associated with higher objective response (OR 2.21, 1.46 – 3.36; p < 0.001), progression-free survival (HR 0.73, 0.57 – 0.92; p = 0.009) and overall survival (HR 0.71, 0.54 – 0.94; p = 0.018) compared to anti-PD1 monotherapy. ConclusionsFindings from this study will help guide treatment selection for patients who present with liver metastases, suggesting that combination therapy should be considered for this group of patients.

An international multi-centre study highlights a significant gap in the assessment and education provided during PCOS consultations

An international multi-centre study highlights a significant gap in the assessment and education provided during PCOS consultations

Prospective Deep Learning-based Quantitative Assessment of Coronary Plaque by CT Angiography Compared with Intravascular Ultrasound.

Coronary computed tomography angiography provides noninvasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicenter international study compared an automated deep-learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). The study included clinically stable patients with known coronary artery disease from 15 centers in the U.S. and Japan. An artificial intelligence (AI)-enabled plaque analysis service was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm. Mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. Artificial intelligence enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.[ClinicalTrails.gov identifier: NCT05138289].

Deoxyguanosine kinase deficiency: natural history and liver transplant outcome.

Autosomal recessive pathogenetic variants in the DGUOK gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance, consequently, leading to quantitative and/or qualitative impairment of mitochondrial DNA synthesis. Typically, patients present early-onset liver failure with or without neurological involvement and a clinical course rapidly progressing to death. This is an international multicentre study aiming to provide a retrospective natural history of deoxyguanosine kinase deficient patients. A systematic literature review from January 2001 to June 2023 was conducted. Physicians of research centres or clinicians all around the world caring for previously reported patients were contacted to provide followup information or additional clinical, biochemical, histological/histochemical, and molecular genetics data for unreported cases with a confirmed molecular diagnosis of deoxyguanosine kinase deficiency. A cohort of 202 genetically confirmed patients, 36 unreported, and 166 from a systematic literature review, were analyzed. Patients had a neonatal onset (≤ 1 month) in 55.7% of cases, infantile (>1 month and ≤ 1 year) in 32.3%, pediatric (>1 year and ≤18 years) in 2.5% and adult (>18 years) in 9.5%. Kaplan-Meier analysis showed statistically different survival rates (P < 0.0001) among the four age groups with the highest mortality for neonatal onset. Based on the clinical phenotype, we defined four different clinical subtypes: hepatocerebral (58.8%), isolated hepatopathy (21.9%), hepatomyoencephalopathy (9.6%), and isolated myopathy (9.6%). Muscle involvement was predominant in adult-onset cases whereas liver dysfunction causes morbidity and mortality in early-onset patients with a median survival of less than 1 year. No genotype-phenotype correlation was identified. Liver transplant significantly modified the survival rate in 26 treated patients when compared with untreated. Only six patients had additional mild neurological signs after liver transplant. In conclusion, deoxyguanosine kinase deficiency is a disease spectrum with a prevalent liver and brain tissue specificity in neonatal and infantile-onset patients and muscle tissue specificity in adult-onset cases. Our study provides clinical, molecular genetics and biochemical data for early diagnosis, clinical trial planning and immediate intervention with liver transplant and/or nucleoside supplementation.

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-04.

Abstract PO3-07-09: B3 breast lesions in Asian Centers: malignant upgrade rates and risk factors

Abstract Background Lesions of uncertain malignant potential in the breast (B3 lesions) are composed of a wide spectrum of pathologies with differing risks of breast cancer. With the widespread implementation of screening programs globally, the incidence of these lesions has increased substantially. Asian women tend to have smaller and denser breasts than Western women, making identifying and treating these lesions more challenging. Previous papers quote an upgrade of B3 lesions to malignancy such as ductal carcinoma in situ (DCIS) or cancer at rates of 9.9% to 35.1%. Malignant upgrade on final histology increases patient anxiety and healthcare costs as a second surgical intervention is often required for pathological clearance or lymph node staging. This study aimed to assess the malignant upgrade rate of B3 lesions in Asian women and to evaluate any key factors that may predict the risk of a malignant upgrade. Materials and Methods A retrospective multicentre international study was done on patients at Seoul National University Hospital (SNUH), South Korea, from April 2021 to 2023, and Tan Tock Seng Hospital (TTSH), Singapore, between March 2006 and 2023. Patients who were diagnosed with a B3 lesion on initial breast core needle biopsy and underwent surgical open excision were included in the study. Results A total of 1049 patients were diagnosed with B3 lesions, with 154 (14.7%) upgrading to malignancy. The most common malignancy was DCIS, 118 (76.6%), followed by invasive ductal carcinoma (IDC), 20 (13.0%) and papillary carcinoma, 4 (2.6%). Within the types of B3 lesions, the malignant upgrade rates were found: atypical ductal hyperplasia (ADH), 88/252 (35%); intraductal papilloma (IDP) with atypia, 16/55 (29%); lobular neoplasia (LN), 9/34 (26%); and radial scar (RS), 5/21 (24%). Most patients had both ultrasound and mammographic evaluation, and all lesions in the study were graded BIRADS 4A and above. Univariate analysis showed that age &amp;gt;50 (OR 2.30 [1.61-3.31], p&amp;lt; 0.001), BMI &amp;gt;23 (OR 2.21 [1.20-4.12], p=0.01), post-menopausal status (OR 2.43 [1.34-4.34], p&amp;lt; 0.001), lesion being identified on mammography (OR 3.00 [2.04-4.51], p&amp;lt; 0.001) and presence of microcalcifications on mammography (OR 0.63 [0.41-0.98], p=0.04) were risk factors for malignant upgrade. Conclusion Based on our analysis of Asian women, post-menopausal patients with microcalcifications on mammography and a B3 biopsy result should be treated with a higher degree of suspicion for underlying malignancy. Surgical excision with adequate margins should be routinely considered for B3 lesions such as ADH, IDP with atypia, LN and RS. Avoidance of surgery or vacuum-assisted removal can be considered for younger patients with only ultrasound findings and diagnosis of FEA and IDP. Table 1. Malignant upgrade after excision Table 2. Clinical characteristics of all patients according to malignant upgrade Table 3. Univariate and multivariate analysis for malignant upgrade Citation Format: Wei Wen Ang, Ji-Jung Jung. B3 breast lesions in Asian Centers: malignant upgrade rates and risk factors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-07-09.