European Registry Research Articles

THU-167 Diagnostic and therapeutic trends in primary biliary cholangitis: insights from the european reference network registry (R-LIVER)

THU-167 Diagnostic and therapeutic trends in primary biliary cholangitis: insights from the european reference network registry (R-LIVER)

P122 The quality of the data in the European Cystic Fibrosis Society Patient Registry as assessed through source data verification from 2018 to 2024

P122 The quality of the data in the European Cystic Fibrosis Society Patient Registry as assessed through source data verification from 2018 to 2024

WS02.05 Assessment of respiratory infection following initiation of elexacaftor/tezacaftor/ivacaftor using the European Cystic Fibrosis Society patient registry

WS02.05 Assessment of respiratory infection following initiation of elexacaftor/tezacaftor/ivacaftor using the European Cystic Fibrosis Society patient registry

Guideline-Directed Medical Therapy and Survival After TEER for Secondary Mitral Regurgitation With Right Ventricular Impairment

BackgroundRight ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients. ObjectivesThe aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort. MethodsWithin the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular–to–pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMTtit) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years. ResultsAmong 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMTtit showed a significantly higher long-term survival vs the 729 patients not on GDMTtit (61.8% vs 36.0%; P < 0.00001). Propensity score–matched analysis confirmed a significant association between GDMTtit and higher survival (61.0% vs 43.1%; P = 0.018). GDMTtit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMTtit vs those not on GDMTtit). Its association with better outcomes was confirmed among all subgroups analyzed. ConclusionsIn patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

American College of Rheumatology and Food and Drug Administration Summit: Summary of the Meeting, May 17-18, 2022.

The American College of Rheumatology and the US Food and Drug Administration co-sponsored a public meeting in May 2022 about challenges in the clinical development of drugs for rheumatoid arthritis (RA) and psoriatic arthritis (PsA), focusing on innovative clinical trial designs, outcome measures, and data collection methods. Recommendations include early dose-ranging studies and use of active comparators. Challenges and opportunities in assessing long-term safety by leveraging real-world data from electronic health records (EHRs) and claims data are discussed, along with insights from European registries and the evolving role of real-world evidence and artificial intelligence in regulatory evaluations. Endpoints for assessing disease activity and outcome measures used in RA and PsA trials are explored, emphasizing challenges in defining remission, assessing clinical response, and evaluating structural progression. The need for outcome measures that better reflect treatment targets and the potential of advanced imaging in future trials are highlighted. Challenges with placebo-controlled trials in RA are discussed and use of non-inferiority clinical trial design, in which new drugs are evaluated with active comparators, is proposed. Pragmatic trials in RA and PsA, employing decentralized approaches, are highlighted for their real-world relevance and administrative efficiencies. Strategies for identifying at-risk populations for RA and the challenges of using EHRs and insurance claims data in drug development are discussed. Registry data and digital health technologies show promise in bridging the gap between clinical trials and real-world effectiveness.

#2278 EUROCYS, a European cystinuria registry

Abstract Background and Aims Cystinuria (OMIM 220100) is a rare autosomal recessive disorder in which high urinary cystine excretion leads to formation of cystine stones due to its low solubility at normal urinary pH. Retrospective series have been published but precise data to guide long term optimal management of these patients are lacking. Our goal was to collect consistent and comparative prospective clinical, biological, genetic and radiological data from patients (children and adults) with cystinuria followed in European centers. Method We developed EUROCYS, a multidisciplinary, European, multicenter registry of patients with cystinuria in which demographic, clinical, surgical, biological, genetic, radiological and therapeutic data are collected longitudinally. These data are recorded via the European Rare Kidney Disease Registry (ERKReg) platform. Results Enrolment started in July 2021. To date, 269 patients have been included at 29 different centers in 8 European countries. Mean age at diagnosis was 18.7 years (SD 17.3) and mean age at inclusion was 35.4 years (20.2). 86.9% of patients had less than 9 calculi extractions reported, 11.0% had between 10 to 19, and 2.0% had more than 20. 61.4% (418/680) were treated by ureteroscopy, 16.2% (110/680) by shock wave lithotripsy and 16.0% (109/680) by percutaneous nephrolithotomy. 39% of patients had a new stone expulsion or surgery during the last 12 months. At the inclusion visit, mean urinary pH was below the recommended level at 6, 8 (0.8). Only 16.3% of patients had a urinary pH between 7.5 and 8: 77.2% of patients had a urinary pH below 7.5 and 6.3% above 8. In adults, mean 24-hour urinary volume was 2653 mL (1077). 34.9% had a target urine volume above 3000 ml. Under treatment, spot urine cystine concentration was 345.5 mg/l (255.2) and 44.8% of patients had a concentration below target concentration (250 mg/l). Mean sodium urinary excretion was 147 mmol/24 h (67). Only 29% of patients had a sodium urinary excretion below 100 mmol/24 h. As alkalinizing agent, 87.2% of patients received potassium citrate, 16.3% sodium bicarbonate and 9.1% potassium bicarbonate. As cystine binding drug, 71 patients (26.7%) were treated with Tiopronin and 3 experienced serious adverse events (hematological, cutaneous, proteinuria). 15 (5.6%) were treated with D-Penicillamine and 2 had adverse events (proteinuria and gastrointestinal). In adults, mean eGFR at inclusion was 82.1 ml/min/1.73 m² (26.3): 40.9% of patients were at chronic kidney disease (CKD) stage 1, 40.1% at CKD2, 16.7% at CKD3, 0.7% at CKD 4 and 1.5% at CKD5. Conclusion The EUROCYS registry shows real life data on cystinuria patients followed in European centers. Despite alkalinizing treatment, most patients do not reach the recommended urinary pH level and only one third have an adequate urinary volume. This registry will allow analyzing the impact of adhesion to recommendations on disease activity.

#1196 C3G and ic-MPGN across the life span: findings from the European Rare Kidney Disease Registry

Abstract Background and Aims C3 glomerulopathy (C3G) and immune complex-membranoproliferative glomerulonephritis (ic-MPGN) are two complement-mediated rare kidney disorders affecting both adults and children for which innovative therapies are under development. Due to the low prevalence and difficult diagnosis of the diseases, demographic and kidney outcome data are scarce. To obtain such information, we interrogated the European Rare Kidney Disease Registry (ERKReg), a Pan-European database of patients with rare kidney diseases treated at specialized adult and pediatric nephrology centers. Method Data on all patients diagnosed with C3G or ic-MPGN were extracted from the ERKReg database, to which more than 22, 000 incident and prevalent patients with rare kidney diseases were enrolled between October 2018 and December 2023. After exclusion of 32 patients with reported disease onset prior to 1998 to ensure compliance with contemporaneous diagnostic and treatment standards, 225 C3G and 173 ic-MPGN patients from 32 pediatric and 12 adult nephrology units in 16 European countries were available for analysis. Among these, 20.4% of C3G and 10.4% of ic-MPGN were incident patients who were enrolled either within 3 months of diagnosis or had diagnostic confirmation of suspected disease during prospective follow-up in ERKReg. Kaplan Meier actuarial survival analysis was performed to calculate time to kidney failure. Survival rates are given as median estimates and 95% confidence intervals. The impact of disease type and age at disease onset on kidney survival was assessed by Cox regression analysis. Results Overall, 80.9% of C3G and 33.5% of ic-MPGN patients had disease onset in childhood; the median (IQR) age at diagnosis was 12.4 (8.4-16.2) years for C3G and 38.9 (12.1-57.6) years for ic-MPGN. Genetic variants in CFH, CFHR1/3/5 and CFB were identified in 13 C3G (10.7% of tested) and 4 (14.8% of tested) ic-MPGN patients, and CFH autoantibodies in another 7 (17% of tested) C3G patients. Among the incident patients, 71.7% presented in CKD1 and 6.5% in CKD4/5 for C3G, as compared to 27.8% CKD1 and 27.7% CKD4/5 for ic-MPGN. Nephrotic-range proteinuria was present in 34% of incident C3G and 44% of ic-MPGN patients respectively. At last observation, 7.8% of childhood-onset and 17.1% of adult-onset C3G patients were on kidney replacement therapy (KRT) (thereof 71% and 86% with functioning transplant, respectively). For ic-MPGN at last observation, 14.6% of childhood-onset and 38.9% of adult-onset received KRT (thereof 62.5% and 69.0% with functioning graft, respectively). Kidney survival rates are given in the table below: The risk of progression to kidney failure within the observation period was approximately 60% higher in ic-MPGN vs. C3G (HR: 1.6; CI 95%: 0.9-2.8; p = 0.06) and was twice as high in patients with adult vs. pediatric disease onset (HR: 2.0; CI 95%: 1.2-3.3; P = .01). Conclusion C3G tends to manifest at earlier age than ic-MPGN. Altered complement regulation can be identified in subsets of patients with both disorders. Functional kidney impairment at first disease manifestation is more common and progression to kidney failure occurs more rapidly with ic-MPGN vs. C3G. Disease onset at adult age is associated with a more rapid disease progression compared to childhood-onset disease.

#1276 Clinical practice of complement inhibitor use in hemolytic uremic syndrome: findings from the European rare kidney disease registry

Abstract Background and Aims Over the last decade, significant advancements have emerged in the field of rare kidney diseases, notably the introduction of C5 inhibitor therapy. The C5 inhibition has transformed the prognosis for atypical Hemolytic Uremic Syndrome (aHUS), offering improved clinical outcomes. However, despite these advancements, the utilization of C5 inhibitor therapy varies significantly, with disparities in treatment duration, reasons for discontinuation, and consideration of extending treatment to patients with infectious HUS (iHUS). This variability is further compounded by the considerable cost associated with C5 inhibitor treatment. Method This retrospective cohort study utilized data from the ERKNet Registry. The study cohort comprised 608 HUS patients enrolled in the ERKNet Registry between November 2018 and September 2023. The dataset encompassed patient demographics, disease and diagnostic records, medication profiles, dialysis or transplantation requirements, kidney function monitoring at the last visit, and clinical outcomes. Results Among 230 aHUS patients, 23 underwent kidney transplantation. 11 received C5 inhibitor therapy before kidney failure. The majority of these patients had genetic aHUS with various mutations (3 CFH, 2 CFI, and 1 CD46). The only death in the study was from this group of patients, unresponsive to C5 Inhibition. Out of 175 aHUS patients treated with Eculizumab, 23 (13%) transitioned to Ravulizumab. Among 104 patients who discontinued C5 inhibitors, 14 (14%) had to resume treatment, half of them with genetic aHUS, with 3 cases of CD46 mutations, 2 cases CFHR5 mutations, and one each involving mutations in CFI and C3. Only two patients required dialysis.. Among 371 iHUS patients, 82 (22%) received C5 Inhibitor treatment. Conclusion In the context of aHUS, we found that discontinuing C5 inhibitors is generally safe, with a slightly higher relapse rate in patients with complement gene variants, though most relapses were mild, requiring dialysis in only a few cases. Long-term follow-up revealed a return to normal kidney function following TMA relapses. Transitioning from Eculizumab to Ravulizumab exhibited promising outcomes, with no relapses or kidney failures in 23 patients. Our analysis of C5 inhibitor use in iHUS emphasized its association with more severe disease progression. While some studies question C5 inhibitors' acute-phase efficacy, others report remarkable improvements in patients unresponsive to other treatments. Overall, our findings underscore the safety of discontinuation practices, the potential benefits of Ravulizumab, and the ongoing need for further research on C5 inhibitor treatment in iHUS.

Mechanical circulatory support in patients with congenital heart disease: a European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study.

This study aims to explore characteristics and clinical outcomes of patients with congenital heart disease (CHD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). This is a retrospective study of EUROMACS participants receiving MCS as bridge-to-transplant, possible bridge-to-transplant, or rescue therapy/bridge-to-recovery from 2011 to 2023 (n = 5340). Adult and paediatric cohorts were analysed separately. The primary outcome was mortality on MCS; secondary outcomes included recovery, transplant and complications including bleeding, cerebrovascular events, and sepsis. Among adult patients, mortality at 1-year was 33.3% among the CHD cohort vs 22.1% in the non-CHD cohort. Adult CHD patients had higher hazards of mortality within the first year after MCS implantation [hazard ratios 1.98, 95% confidence interval (CI) 1.35-2.91, P < 0.001] and bleeding events (subdistribution hazard ratios 2.10, 95% CI 1.40-3.16, P < 0.001) compared with non-CHD patients. Both associations remained significant after accounting for multiple mediators. Among paediatric patients, mortality at 1 year was 22.1% in the CHD cohort vs 17.3% in the non-CHD cohort (hazard ratios 1.39, 95% CI 0.83-2.32, P = 0.213). Adult and paediatric patients with CHD on MCS have higher adverse event risk compared with non-CHD MCS patients, though children did not have greater risk of mortality. As the number of CHD patients requiring advanced heart failure management continues to grow, these findings can enhance informed decision-making. Registry name: EUROMACS.

EuReCa – The European Registry of Cardiac Arrest and the related studies

Out-of-hospital cardiac arrest (OHCA) is a major health issue throughout Europe. Due to limited knowledge about the epidemiology of OHCA in Europe, in 2011, the European Registry of Cardiac Arrest (EuReCa) project was established. Initially based on existing resuscitation registries in a few countries, the network expanded and in October 2014 the EuReCa ONE study was launched, bringing together 27 countries and showing that appropriate data acquisition (10,682 cases submitted) is feasible within Europe. EuReCa TWO was conducted from October to December 2017 and included 37,054 cases. EuReCa THREE data collection was carried out from September to November 2022 and data analysis is currently being conducted. EuReCa TWO and THREE studies generated more robust data, with both studies covering 3-month periods in 28 countries, respectively. While EuReCa TWO focused on the bystander, EuReCa THREE investigated the impact of time-related aspects (time from call to scene, time at scene, transport times and other) on resuscitation outcomes. EuReCa is a network supporting countries in their ambition to establishing continuously running registries as quality management tools and for scientific work.

#2744 Analysis of bacteremia and mortality in patients with tunneled catheter for hemodialysis: a 14-years observational study

Abstract Background and Aims Infections are a leading cause of morbidity and mortality in hemodialysis patients. Tunneled catheters (TC) have been associated with increased risk of infection and death, but mortality rates are not widely reported. Our study aimed to analyse catheter infection-free survival and mortality of patients with this vascular access. Method This is a retrospective study of all TC inserted during the period of 1 January 2005 to 31 December 2019. The TC were inserted by nephrologists, following a preimplantation protocol agreed with the Infectious Diseases Service. Patients were followed up from the tunneled catheter insertion until the study end date (December 31, 2020), TC related bacteremia or died. Results In the 14-year period under study, 406 TC were implanted in 325 patients. A total of 85 tunneled catheter related bacteremia were diagnosed, resulting in an incidence of 0.40 per 1000 catheter days (81.1% after 6 months of implantation). The predominant microorganisms isolated were Gram-positive organisms: Staphylococcus epidermidis (48.4%); Staphylococcus aureus (28.0%). During the study, a total of 145 patients had the TC removed or exchanged due different causes. The main reasons for catheter removal were the adequate development and use of the arteriovenous fistula (48, 33.1%) and discharge from hemodialysis due to recovery of renal function, transfer to peritoneal dialysis or renal transplantation (47, 32.4%). Only in 26 (17.9%) patients, the TC was removed due to bacteremia at a median of 4.8 (1.0-8.0) days from the bacteremia. The median time to catheter removal for non-infection-related reasons was 448 (185-910) days, without significant differences with the TC related bacteremia group [430 (116-695)] (p=0.83). The 30-day mortality rate from the first TC related bacteremia was 8.7%. During the study period, a total of 168 (51.7%) patients died for different causes. Conclusion The incidence of bacteremia in our study was low and did not seem to have a relevant impact on catheter survival. The global mortality rate was similar to that reported in European registries for patients on renal replacement therapy. An implantation and management protocol, strict in prophylactic measures, could reduce the incidence of bacteremia and reduce its morbidity and mortality.

Clinicopathological Characteristics and Disease Chronicity in Glomerular Diseases: A Decade-Long Study at Romania's Largest Kidney Biopsy Reference Center.

Glomerular diseases (GDs), significant causes of end-stage kidney disease, are better understood through epidemiological studies based on kidney biopsies (KBs), which provide important insights into their prevalence and characteristics. This study aims to analyze the clinicopathological features of GDs diagnosed from 2008 to 2017 at Romania's largest reference center. In this decade-long study, 1254 adult patients diagnosed with GDs were included. The local previously validated renal histopathological prognostic score was calculated for each KB using four histopathologic lesions: global glomerulosclerosis, tubular atrophy, interstitial fibrosis and fibrocellular/fibrous crescents. The mean patient age was 50 years, with a male predominance (57%). The primary referral reasons were nephrotic syndrome (46%), nephritic syndrome (37%), chronic kidney disease (12%), asymptomatic urinary abnormalities (4%), and acute kidney injury (1%). Immunoglobulin A nephropathy (IgAN) was the most frequently diagnosed GD (20%), aligning with frequencies reported in European registries. Diabetic glomerular nephropathy was the most common secondary GD (10%). It also presented the highest median renal histopathological prognostic score (2), indicating a poorer prognosis. Lower eGFR and higher proteinuria were independently associated with higher scores. This decade-long study highlights IgAN as the most frequent GD diagnosed by KB. Diabetic glomerular nephropathy was identified as the most common secondary GD. The renal histopathological prognostic score, notably high in diabetic glomerular nephropathy patients, was correlated with lower eGFR and higher proteinuria, underlining its clinical relevance.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation

BackgroundSystemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries.MethodsData of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients.ResultsClinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria.ConclusionsPatients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response

Objective To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. Method Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. Results Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63–80%) than at MASES sites (mainly axial; 82–100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. Conclusion Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Post-Conceptional Exposure to Clomiphene Citrate and Congenital Malformations: A Cohort Study.

Clomiphene citrate is an ovulation inductor for which inadvertent post-conceptional exposures may occur in early pregnancy. In preclinical studies, post-conceptional exposures showed a teratogenic effect in different species. In humans, to date, little is known about the outcomes of inadvertently post-conceptionally exposed pregnancies. The objectives of our study were to assess the association between post-conceptional exposures to clomiphene citrate and major and minor congenital malformations in the offspring. A retrospective cohort study of prospectively ascertained cases was undertaken, based on clinical data from the Centre de Référence sur les Agents Tératogènes (CRAT), Paris, France. Women with post-conceptional exposure to clomiphene citrate (n = 309), and unexposed pregnant women (n = 1236, 1:4 ratio) with prospectively collected data, known pregnancy outcome and delivery date prior to 01/02/2022, were matched by calendar year. An adjudication committee classified major and minor congenital malformations according to the EUROCAT (European Registration of Congenital Anomalies and Twins) classification. Among post-conceptional exposed women, no increased risk of major malformation was found (crude relative risk = 0.64, 95% confidence interval 0.19-2.15) as compared to unexposed women. Three major and ten minor congenital malformations were reported in the exposed group. An increased risk of minor malformations was found (crude relative risk = 4.05, 95% confidence interval 1.70-9.64) although there was no specific clinical pattern. Post-conceptional exposure to clomiphene citrate was not associated with an increased risk of major congenital malformations. Given potential confounding and information biases, the results about minor malformations should be interpreted with caution as no specific clinical pattern was identified.

Prospective, multi-country, observational study of patients with endogenous Cushing's syndrome exposed to Ketoconazole (using the existing European Registry on Cushing's Syndrome (ERCUSYN)), to assess drug use, safety and effectiveness

Prospective, multi-country, observational study of patients with endogenous Cushing's syndrome exposed to Ketoconazole (using the existing European Registry on Cushing's Syndrome (ERCUSYN)), to assess drug use, safety and effectiveness

Abstract PO4-08-08: Is it time for a European BRCA Mutation Registry? An Italian experience

Abstract Background: Knowledge of BRCA 1/2 mutation plays an important role in cancer care. The National Plan to improve BRCA detection in order to increase access to target agents and ameliorate the prevention strategy has several implementations in the Italian regions. Recent guidelines are considering extending genetic testing to a larger population, regardless of family history. We present our experience in Apulia Region on the detection of BRCA 1/2 and its clinical implication at the regional level, to underline the importance of spreading the extension of BRCA detection at the regional level and to propose the creation of a European register for BRCA patients, based on population-based BRCA 1/2 testing. Methods: This is an observational study conducted at a Familiar Cancer Service of the Lecce Hospital. Participants completed a questionnaire (socio-demographic epidemiology of cancer and lifestyle factors), genetic counseling and BRCA testing. Notably, genetic testing for BRCA mutations was carried out based on family cancer history since 2018, according to the Italian cancer guidelines (AIOM) and related updates in 2019 and 2023. A mutational analysis of exons and adjacent intronic regions of BRCA1/BRCA2 genes was performed by Sanger sequencing and MiSeq Illumina NGS platform. Results: Between 2014 and May 2023 a total of 4365 patients were enrolled in the study, of whom 2426 (56%) was evaluable for BRCA detection, 18% men (n=440) and 82% female (n=1986). Median age at diagnosis was 57 yrs. 65% of patients had a cancer diagnosis (n=1575) and 35% were healthy carriers (n=851). In particular, breast cancer (BC) was present in 63% of patients (n=1048), ovarian cancer (OC) in 21% (n=352), pancreatic cancer in 5% (n=85), prostate cancer in 4% (n=65), melanoma in 1% (n=13), and other cancers in 6% (n=92). The table 1 (uploaded) shows the results of patients with BC (n=1048) The presence of BRCA mutation is observed in 20.52% of BC patients (1:4.87). Conclusion These data confirm that BRCA mutation detection is an emerging need to improve prevention and early diagnosis according to the European Beating Cancer Plan. Therefore, it is crucial to improve this topic at regional level until the creation of a shared BRCA registry among European countries. Table. Citation Format: Elisabetta De Matteis, Mariangela Ciccarese, Paolo Tarantino, Tiziana Grassi, Francesco Bagordo, Emanuele Rizzo, Maria Rosaria Tumolo, Graziana Ronzino, Maria Rita De Giorgio, Salvatore Mauro, Nicola Di Renzo. Is it time for a European BRCA Mutation Registry? An Italian experience [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 PO4-08-08.

Real-world evidence evaluation of LDL-C among hospitalized patients: a population-based observational study in the timeframe 2021-2022

Aims. European registries and retrospective cohorts highlighted the lack of low-density lipoprotein-cholesterol (LDL-C) goal achievement in many very high-risk patients. Hospitalized patients are often frail, and frailty is associated with all-cause mortality and cardiovascular mortality. Aim of this study is to evaluate LDL-C levels in a Real-World setting of inpatients, identify cardiovascular risk categories and highlight treatment gaps in the implementation of LDL-C control. Methods. This retrospective, observational study included all the adult patients admitted at an Italian hospital between 2021-2022 and with LDL-C values available during hospitalization. Disease-related real-world data were collected from Hospital Information Systems using automated data extraction strategies and through the implementation of a patient-centered data repository (the Dyslipidemia Data Mart). Assessment of cardiovascular risk profiles, LDL-C target achievement according to the 2019 ESC/EAS guidelines and lipid-lowering therapies (LLT) use were performed. Results. 13,834 patients were included: 17.15%, 13.72%, 16.82% and 49.76% were low (L), moderate (M), high (H) and very high-risk (VH) patients, respectively. The percentage of in-target patients was progressively lower moving towards worse categories (78.79% in L, 58.38% in M, 33.3% in H and 21.37% in VH). Among LLT treated patients in VH category, in-target are 28.48%; 47.6.% in H, 69.12% in M and 68.47% in L. The impact of monotherapies and combination therapies on target achievement was also analyzed. Conclusions. This study depicts LDL-C control among an entire population of inpatients, highlighting relevant gaps especially in VH category. Future efforts must aim to reduce the cardiovascular risk of these subjects.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. To determine which factors influence compliance with treatment. A systematic prospective non-interventional registry (Hp-EuReg) of theclinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 usingtheAEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p<0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor+clarithromycin+amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p<0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p<0.001). Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.