European Cohort Of Patients Research Articles

High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study

BackgroundFluoroquinolone antibiotics have a high potential for serious adverse drug reactions, but real-world evidence in European patient cohorts is lacking. Therefore, we aim to examine the association between fluoroquinolone exposure and potentially life-threatening adverse events stratified by age and gender in Germany.MethodsWe conducted an administrative cohort study using the active comparator new user design with a risk window up to 365 days between January 2013 and December 2019. Population-based longitudinal data from one of the largest German statutory health insurances were used. Episodes of newly dispensed fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, norfloxacin, and enoxacin) were compared to other antibiotics (amoxicillin, amoxicillin clavulanic acid, azithromycin, cefuroxime, cephalexin, clindamycin, sulfamethoxazole-trimethoprim, and doxycycline). Endpoints were defined by incident diagnoses of aortic aneurysm/dissection, cardiac arrhythmia, hepatotoxicity, and all-cause mortality. Adjusted hazard ratios were estimated from piece-wise exponential additive mixed models with smooth non-linear effects for person-time and age and adjusted for comorbidities, year and quarter at index.ResultsThe cohorts comprised 15,139,840; 11,760,159; 11,027,175; and 15,305,757 antibiotic episodes. Patients during fluoroquinolone episodes were older (59 versus 51 years) and more often female (58% versus 54%). We counted 46,502; 446,727; 19,125; and 474,411 incident endpoints. Relative risk for all-cause mortality and hepatotoxicity was high for < 40-year- and 40–69-year-old females (aHR = 1.77, 95% CI 1.55–2.03 and aHR = 1.42, 95% CI 1.32–1.53), respectively. For aortic aneurysm/dissection a nominally increased relative risk for < 40-year-old females was found (aHR = 1.42, 95% CI 0.96–2.11), although 95% CI indicates that a small relative risk reduction is also supported by the data. Relative risk for cardiac arrhythmia was increased for men aged < 40 years (aHR = 1.14, 95% CI 1.08–1.20). High relative risks for each endpoint were also identified depending on choice of active comparator, and risks increased with higher defined daily doses and shorter follow-up.ConclusionsThis study contributes real-world evidence to endpoint-specific differences of risks in patient subgroups which need to be considered to improve fluoroquinolone drug safety.

Insights and Opportunities from Multimarker Evaluation of Heart Failure: Lessons from BIOSTAT-HF.

Heart failure is a complex and heterogenous disease state that affects millions worldwide. Over recent decades, advancements in medical therapy and device implementation have significantly transformed the landscape of heart failure outcomes, while improvements in imaging modalities and greater accessibility to genome sequencing have led to increasing recognition of distinct heart failure endotypes. There is rising evidence to suggest all patients do not benefit equally from intensification of guideline directed medical therapy (GDMT). Efforts to personalize medical therapy to maximize benefits while minimizing side effects remains an ongoing challenge. We review key manuscripts from The BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), a multicenter observational study conducted across Europe, which prospectively enrolled patients with acute or worsening heart failure. BIOSTAT-CHF was designed to characterize biological pathways associated with varied patient responses to GDMT for heart failure. Utilizing a diverse cohort of European patients, the authors were able to develop risk models to predict mortality and heart failure hospitalization from clinically available data plus standard and novel biomarkers. They also utilized modeling to refine characterization of heart failure subtypes and personalization of GDMT titration. In this review we highlight key insights from the BIOSTAT-CHF cohort and how they relate to: (1) prognosis and monitoring treatment response in heart failure, (2) personalization of heart failure treatment, and (3) elucidation of biological pathways and future directions for research. These insights summarize how BIOSTAT-CHF has contributed to a deeper understanding of heart failure, focusing on using biomarkers personalizing treatment approaches, with a goal of ultimately improving patient outcomes.

Gemcitabine and docetaxel for high-risk non-muscle-invasive bladder cancer: EuroGemDoce group results.

To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment. Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews. Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres. The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols.

Recurrence after surgery for clear cell and papillary renal cell carcinoma: Head-to head comparison of validated risk scores.

The American Urology Association (AUA) recently introduced in their guidelines a subtype-agnostic, 4-tiered risk classification score to assess oncologic outcomes after surgery in patients with localized renal cell carcinoma (RCC). We provide a head-to-head comparison of the AUA score with 3, internationally validated and EAU recommended, histological-specific models. We retrieved from a prospectively-maintained database 2,560 surgically-treated patients with localized RCC in a single high-volume European center (1987-2023). Patients were classified into risk categories, according to 3 histology-specific prognostic models (i.e., Leibovich 2003, Leibovich 2018 and VENUSS). Kaplain-Meier (KM) analyses estimated 5-year progression-free (PFS) and cancer-specific (CSS) survival. Area under curves (AUCs) of each prognostic model to predict clinical progression or cancer-specific mortality (CSM) were calculated, according to histological subtypes. Overall, 2,145 (84%) patients harbored clear-cell (ccRCC), whereas 415 (16%) harbored papillary (pRCC) RCC. Within ccRCC, proportions of low vs. intermediate vs. high/very-high risk patients ranged from 57 to 58% vs. 17 to 28% vs. 6.3 to 19%, respectively. In pRCC, proportions of low vs. intermediate vs. high/very-high risk patients ranged from 54 to 73% vs. 21 to 24% vs. 4.8 to 12%, respectively. Leibovich 2018 and VENUSS exhibited the highest AUCs for clinical progression (0.805 vs. 0.884) and CSM (0.847 vs. 0.862) prediction within ccRCC vs. pRCC, respectively. The AUA model demonstrated AUCs of 0.783 vs. 0.864 for clinical progression and 0.797 vs. 0.826 for CSM in ccRCC vs. pRCC, respectively. Within a European cohort of RCC patients, the AUA prognostic stratification exhibited reliable performance. Nevertheless, histology-specific models continue to demonstrate a substantial advantage in predicting RCC outcomes.

Prevalence and relevance of H558R in the efficacy and toxicity of flecainide in patients with atrial fibrillation: a cohort study

BackgroundThe SCN5A gene polymorphism histidine-558-to-arginine (H558R) has been associated with atrial fibrillation (AF) and may affect the therapeutic effects of flecainide. This study aimed to assess the prevalence of the...

H558R: a common polymorphism may modify the efficacy and toxicity of flecainide in maintaining sinus rhythm; a cohort study

Abstract Background Certain mutations in the SCN5A gene alter the function of the type V voltage-gated cardiac sodium channel and the therapeutic effect of flecainide.(1) One such mutation, H558R, represents a polymorphism with a high prevalence associated with the development of atrial fibrillation (AF).(2–5) Purpose We aim to determine its relationship with the efficacy and adverse effects of flecainide, as well as describe for the first time its prevalence in a cohort of European patients with AF. Methods We conducted a cohort study collecting data through indirect methods, with the study being blinded to all parties involved except the statistician. Patients prescribed flecainide (dose of 100 mg/12 h) and followed up in our health area (n=450,000 people) between 2017 and 2021 were identified. A primary composite endpoint consisting of initial inefficacy and early toxicity and a secondary combined endpoint of toxicity or inefficacy during follow-up were predefined. Results Out of 104 patients who met the criteria and agreed to participate, 59 (56.4%) did not have the mutation (H558R-/-), 38 (36.5%) were heterozygous (H558R+/-), and 7 (6.7%) were homozygous (H558R+/+). This high prevalence in European patients with AF is significantly higher than that previously reported in healthy individuals (20.4% in Caucasians, 9.2% in Asians).(6) When compared with patients without the mutation, H558R+/- patients had a lower incidence of the primary endpoint (p=0.02, picture 1), with an absolute risk reduction (ARR) of -21.5% (95% confidence interval (CI): -38.4% to -4.6%) primarily due to a lower rate of initial inefficacy (ARR -18.35%, 95% CI: -1.37% to -35.3%), and a trend towards lower early toxicity (ARR -7.36; 95% CI: -19.9 to +5.2%). This difference remained in the multivariate analysis (p=0.03, table 1). Moreover, the H558R+/- genotype was associated with lower toxicity or inefficacy over an average follow-up of 492 days (p=0,04, picture 1), with a hazard ratio of 0.53 (95% CI: 0.27 to 0.999). Conclusions The H558R+/- mutation shows a marked prevalence in a selected sample of patients with AF. Its presence is clinically relevant both in terms of early efficacy or toxicity and during follow-up. If these results are confirmed, it may signify a step towards personalized treatment for patients with AF, not only from the standpoint of efficacy but also safety.Table 1.Picture 1.

Peripheral artery disease, antithrombotic treatment and outcomes in European and Asian patients with atrial aibrillation: a report from 2 prospective observational registries

Abstract Background In patients with atrial fibrillation (AF), the impact of peripheral artery disease (PAD) on oral anticoagulant (OAC) therapy use and the risk of outcomes remains unclear. Objective To analyse the epidemiology of PAD in a large cohort of European and Asian AF patients, and the impact on treatment patterns and risks of adverse outcomes. Methods We analysed AF patients from two large prospective observational registries. We identified patients with PAD as reported by the investigators. Logistic regression analysis was used to assess factor associated with the presence of PAD at baseline. OAC prescription and risk of outcomes were analyzed according to the presence of PAD, using adjusted Logistic and Cox regression analyses. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Interaction analyses were also performed according to different subgroups. Results 15,497 patients with AF (mean age 68.9, SD 11.6 years; 38.6% female, 30% from Asia) were included in the analysis. PAD was found in 941 patients (6.1%), with higher prevalence among European individuals compared to Asian (8.1% vs 1.2%, p&amp;lt;0.001). Patients with PAD were older, more likely with permanent AF, more symptomatic and with higher thromboembolic and bleeding risk. On logistic regression analysis, European patients had 6-fold higher odds of presenting with PAD compared with Asians (Figure 1, Panel A). Other comorbidities and increasing age were associated with higher odds of prevalent PAD (Figure 1 Panel A). Conversely, female sex was associated with lower odds of having PAD at baseline. With age modelled as a continuous variable, and odds of PAD at baseline, there was a non-linear relationship, with the odds of PAD increasing almost linearly until 70 years, plateauing afterwards (Figure 1 Panel B). After adjustments, PAD was associated with lower use of OAC (OR 0.69, 95% CI 0.57-0.85). On Cox regression analysis, PAD was associated with a higher risk of the primary composite outcome (HR 1.28, 95%CI: 1.08-1.52) and all-cause death (HR 1.40, 95%CI: 1.16-1.69). A significant interaction was observed between PAD and age, with greater risks of PAD found in younger patients (&amp;lt;65 years) for the primary outcome (pint=0.014, Figure 2, panel A). Consistent results were observed when we analysed the interaction between PAD and age, modelled as a restricted cubic spline, where the risk of the primary outcome followed a J-curve across age, while patients without PAD showed an approximately linear relationship (pint&amp;lt;0.001, Figure 2, Panel B). Conclusions In patients with AF, PAD is associated with lower use of OAC and higher risk of adverse outcomes, with a greater risk seen in younger patients.Figure 1Figure 2

Predictors of discordance in estimating the presence of chronic kidney disease among patients with atrial fibrillation and impact on prescription of anticoagulants and cardiovascular outcomes

Abstract Background In patients with atrial fibrillation (AF), the prevalence, predictors and clinical implications of a potential discordance in estimating the presence/absence of chronic kidney disease (CKD) according to Cockroft-Gault (CG) and CKD-EPI formulas remain unclear. Objective To examine patients characterized by discordance in evaluation of renal function, specifically with regard to the threshold for defining the presence of CKD according to an estimated glomerular filtration rate (eGFR) &amp;lt; 60 ml/min, in a large cohort of European AF patients, and to assess the association with prescriptions of oral anticoagulants (OAC) and the risks of adverse outcomes. Methods Data related to AF patients enrolled in a large European observational prospective registry with an average follow up of 645.2 days were analysed. We evaluated renal function for assessing the presence of CKD according to CG and CKD-EPI formulas and we categorized the population in four groups: eGFR ≥ 60 ml/min according both to CG and CKD-EPI (Concordant ≥ 60); &amp;lt; 60 ml/min according to both formulas (Concordant &amp;lt;60); CG &amp;lt;60 ml/min and CKD-EPI ≥60 ml/min (Discordant-CKD-EPI), CG ≥ 60 ml/min and CKD-EPI &amp;lt;60 ml/min (Discordant-CG). Logistic regression analyses were used to assess factors associated with a Discordant assessment of CKD and its association with OAC therapy. Cox regression analysis was used to determine association between categories and the risk of adverse outcome. The primary endpoint was a composite of all-cause death and major adverse cardiovascular events (MACEs). Results 8.786 patients with AF (mean age 68.70, SD 11.58 years; 40.9% female) were included in the analysis. 1360 (15.5%) of them had Discordant CKD assessment: 577 (6.6%) with Discordant-CKD-EPI and 783 (8.9%) with Discordant-CG. Increasing age, female sex and coronary artery disease (CAD) were associated with Discordant-CKD-EPI, while BMI and heart failure (HF) showed an inverse association (Figure 1). Conversely, BMI and HF were factors significantly associated with Discordant-CG. Discordant-CKD-EPI patients showed lower odds of being prescribed with OAC therapy (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.54-0.95) with no significant differences regarding the type of OAC therapy (warfarin or direct oral anticoagulants). At Cox regression analysis, patients with Discordant-CKD-EPI showed a higher risk of composite endpoint events (Figure 2) and both Discordant-CKD-EPI and Discordant-CG patients were associated with a higher risk of all-cause death. Conclusions Age, BMI, female sex and comorbidities associated with AF (CAD and HF) significantly influenced the probability of having a discordant assessment of the presence of CKD, according to estimation of renal function impairment using CG or CKD-EPI formulas, respectively. A discordant assessment of CKD influenced the probability of being prescribed with OAC and was associated with a higher risk of adverse outcomes.Figure 1Figure2

Cluster-specific risk factors for suboptimal thromboprophylaxis in contemporary European cohort of patients with atrial fibrillation: the EHRA-PATHS Project

Abstract Background Oral anticoagulation (OAC) is essential to optimal thromboprophylaxis in patients with atrial fibrillation (AF). Owing to bleeding risk concerns, OAC use may be challenging in clinically complex high-risk AF patients. Comorbidities might lead to suboptimal OAC use. We assessed cluster-specific risk factors for non-prescribing OAC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was constructed using data from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific risk factors for non-prescribing OAC were identified using univariate and multivariate logistic regression analyses. Results Of 18.799 patients, 2086 (11.1%) were not prescribed with OAC. Among the three clusters (see Table), OAC non-prescribing was significantly more prevalent in Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) or Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), both P&amp;lt;0.001, with no significant difference between Clusters 2 and 3 (P=0.161). Cluster-specific multivariable risk factors for non-prescribing OAC are shown in Table. In all three clusters AF clinical type was significantly associated with OAC non-use. In Cluster 1, OAC non-use was less likely in the presence of CHA2DS2-VASc stroke risk factors, while bleeding risk factors were predominant multivariable predictors of OAC non-use among elderly (Clusters 2 and 3). Conclusion Our findings in a large contemporary European cohort suggest that different considerations prevail in treatment decision on OAC use in AF patients in clinical practice, depending on patient’s age and AF clinical type, as well as the presence and type of underlying comorbidities. Our findings could help in formulating targeted interventions to optimize stroke prevention in different subgroups of AF patients.

Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation

Abstract Background In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients. Objectives This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients. Methods A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl &amp;lt;60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves. Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2]. Conclusions Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2

Cluster-specific predictors of early rhythm control in contemporary European cohort of patients with atrial fibrillation: The EHRA-PATHS Project

Abstract Background Early rhythm control (ERC) using antiarrhytmic drugs, electrical cardioversion or catheter ablation for AF within a year from first diagnosis of atrial fibrillation (AF) has been shown to reduce the risk of major adverse outcomes compared to usual care, and the effects of ERC have been suggested to be consistent across all AF subgroups with different risk profiles. We aimed to identify cluster-specific predictors of ERC in pre-defined AF clusters in contemporary European EHRA-PATHS AF cohort. Methods The EHRA-PATHS AF cohort was derived from the three prospective EurObservational Research Programme (EORP) AF registries - General Pilot, General Long-term, and AF III registry. A two-step cluster analysis was performed. A hierarchical cluster analysis with 18 variables was used to identify the optimal number of clusters, followed by a K-means cluster analysis to determine variable cluster association. Cluster-specific predictors of ERC were identified using univariate and multivariate logistic regression analyses. Results Of 18,799 patients, AF was diagnosed within 1 year in 8088 (43.0%), and 3913/8088 patients (48.4%) were treated with ERC. Among the three clusters - Cluster 1 (younger healthier AF patients) compared with Cluster 2 (Elderly with less comorbidity, mostly non-cardiovascular) and Cluster 3 (Elderly with more comorbidity, mostly cardiovascular), see Table, ERC was significantly more often used in Cluster 1 compared with Cluster 2 and Cluster 3 (both P&amp;lt;0.001), and in Cluster 2 compared with Cluster 3. Cluster-specific multivariable predictors of ERC are shown in Table. In all three clusters, asymptomatic AF (EHRA score I) and Northern Europe residence were inversely associated with ERC, while Western Europe residence was positively associated with ERC in Cluster 2 and 3. In Cluster 1, low stroke risk and hypertension were positively associated with ERC, while dilated left atrium (LA) and reduced left ventricular ejection fraction (LV EF) were negative predictors of ERC. In Cluster 2, age ≥80 years, enlarged LA, and CHA2DS2-VASc ≥2 for males and ≥3 for females were negatively associated with ERC. In Cluster 3, age ≥75 years, cardiomyopathy, liver disease, dementia and reduced LV EF were negative predictors of ERC. Conclusion Our study of a large European AF cohort showed that likelihood for ERC was greater in younger and healthier AF patients, as well as in elderly from Western Europe, while ERC was significantly less likely with increasing age and comorbidity (especially cardiovascular diseases). These findings likely reflect the lack of high-quality evidence supporting aggressive ERC in high-risk patients with AF. With increasing body of evidence favouring ERC such patients, a shift towards less selective consideration of ERC in daily practice may be expected.

Proficiency in bariatric surgery may shorten the learning curve for minimally-invasive D2 gastrectomy.

Evidence from Asian studies suggests that minimally-invasive gastrectomy achieves equivalent oncological but improved perioperative outcomes compared to open surgery. Oncological gastric resections are less frequent in European countries. Index procedures may play a role for the learning curve of minimally-invasive gastrectomy. The aim of our study was to evaluate if skills acquired in bariatric surgery allow a safe and oncologically adequate implementation of minimally-invasive gastrectomy in a cohort of european patients. In this single-center retrospective study, all patients who received primary bariatric surgery between January 2015 and December 2018 and minimally-invasive surgery for gastric cancer treated from June 2019 to January 2023 were evaluated. Primary endpoints were operation time, lymph node yield and lymph node fractions. Secondary endpoints included postoperative complications and oncological outcomes. Learning curves for two surgeons with 350 bariatric procedures and 44 minimally-invasive gastrectomies were analyzed. For bariatric surgery, the mean operation time decreased from initially 82 ± 27 to 45 ± 21min and 118 ± 28 to 81 ± 36min for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), while the complication rate remained within the international benchmark. For laparoscopic gastrectomy (n = 30), operation times decreased but then remained stable over time. Operation times for the robotic platform were longer (302 ± 60 vs. 390 ± 48min; p < 0.001) with the learning curve remaining incomplete after 14 procedures. R0 status was achieved in 95.5% of patients; the mean number of lymph nodes retrieved was 37 ± 14 with no differences between the groups. Complete mesogastric excision was more frequently achieved during the later laparoscopic cases whereas it occurred earlier for the robotic group (p = 0.004). Perioperative morbidity was comparable to the European benchmark. Textbook outcome was achieved in 54.4% of the cases. In summary, we could demonstrate a successful skill transfer from bariatric surgery to minimally-invasive laparoscopic oncological gastric surgery enabling safe and oncologically adequate minimally-invasive D2 gastrectomy in a central European patient collective.

Comprehensive clinicopathologic features in autoimmune atrophic gastritis: Insights from a European cohort of 57 patients

ContextAutoimmune atrophic gastritis (AAG) is a frequently underdiagnosed disease due to its broad-spectrum clinical presentation. The diagnosis is based on histological confirmation of corpus-restricted metaplastic chronic atrophic gastritis. ObjectiveTo thoroughly describe the histological features of a European cohort of AAG patients. DesignClinical and pathological data of 57 out of 676 patients diagnosed with AAG were reviewed. ResultsThirty-nine patients were female and eighteen were male. The mean age was 62 years. Antibodies were identified in 32/42 patients (76 %). Vitamin B12 levels were low (< 200 pg/mL) in 37/54 patients (69 %). Serum gastrin levels was elevated (> 115 pg/mL) in all cases tested. Associated autoimmune/inflammatory conditions were identified in 20/57 patients (35 %). Histologically, deep chronic inflammation was present in 46/57 (81 %) patients. Complete destruction of oxyntic glands was observed in 45/57 (79 %) patients. Pyloric metaplasia was present in 54/57 (95 %) patients, intestinal metaplasia in 51/57 (89 %) patients, and pancreatic metaplasia in 20/57 (35 %) patients. Among ECL cell proliferation, linear hyperplasia was present in all 57/57 patients, micronodular hyperplasia in 55/57 patients, and adenomatoid hyperplasia in 10/57 patients. ECL cell dysplasia was identified in 5/57 patients, and neuroendocrine microtumor in 4/57 patients. ConclusionsThe diagnosing of AAG remains challenging due to the greater variability in symptoms than previously recognized. It is important to consider chronic AAG, especially with other concurrent autoimmune conditions. The importance of accurate diagnosis and surveillance is based on the potential development of type 1 gastric neuroendocrine tumor and increased risk of gastric adenocarcinoma.

Diagnostic delays in familial Mediterranean fever: a Juvenile Inflammatory Rheumatism (JIR) cohort study.

Several studies reported that Familial Mediterranean Fever (FMF) diagnosis may be missed or delayed even in countries with a high FMF prevalence. Our aim was to study on a large cohort of European FMF patients the frequency and associated factors of diagnosis delay. Clinical data were extracted from the Juvenile Inflammatory Rheumatism (JIR)-cohort. All FMF patients fulfilled Livneh Criteria and had been sequenced for MEFV exon 10. FMF-diagnostic delay (d-FMF) was defined as the duration between the onset of the symptoms and the diagnosis of more than 10years. 960 FMF patients were enrolled: delayed diagnosis (d-FMF) was noted in 200 patients (20%). d-FMF patients were significantly older compared to non d-FMF with a median age of 46.4years old vs. 15.5 (p < 0.0001). Women displayed more d-FMF compared to men (56 vs. 47%, p = 0.03). Clinical presentation during attacks was not statistically significant except for erysipelas-like erythema, which was higher among d-FMF patients (33 vs. 22%, p = 0.0003). The presence of one or two pathogenic MEFV mutation was not different between patients. Compared to other FMF, d-FMF patients displayed significantly more AA amyloidosis (10 vs. 2.6%, p < 0.0001) and received more biotherapy (18 vs. 3.8%, p < 0.0001). Twenty percent of FMF patients had a diagnostic delay >10years, including more women. The differential diagnosis of abdominal attacks with menstrual pain may be an explanation, and erysipelas-like erythema may not be recognized as FMF by all practitioners.

Psychometric properties of the KCCQ-12 in an european cohort of patients with heart failure

Abstract Background Despite medical advances, patients with heart failure continue to suffer from poor quality of life due to worsening symptoms and functional limitations. Therefore, it is important to understand the multidimensional facets of quality of life in these patients. The Kansas City Cardiomyopathy Questionnaire is a commonly used quality of life assessment tool worldwide. However, However, there is still a lack of knowledge about its psychometric properties. Purpose The aim of this study was to investigate the psychometric properties of the KCCQ-12 and its measurement invariance in a cohort of European patients with heart failure. Methods Participants (n=510, median age=72, IQR=18, 58% males) completed the KCCQ-12 alongside measures of clinical psychosocial severity. A confirmatory factor analysis was used to establish factorial validity; internal consistency was determined using the Omega coefficient and the model-based internal consistency coefficient. Zero-order correlations between the KCCQ-12 scores and clinical and psychosocial measures were performed to test convergent validity. Multigroup confirmatory factor analysis was conducted to test measurement invariance across patients with preserved vs reduced ejection fraction. Results Confirmatory factor analysis confirmed a four-factor solution, with the domains of physical limitations, symptom frequency, quality of life, and social interference. Internal consistency was excellent (Omega coefficients ranging from 0.83 and 0.90, and internal consistency index of 0.94). The KCCQ-12 scores significantly correlated with ejection fraction, New York Heart Association class, quality of life, anxiety, depression, symptom burden, and the KCCQ-23 Overall Summary score, which adequately supported the convergent validity of the KCCQ-12. Measurement invariance was confirmed at the partial scalar and strict level. Conclusions These findings support the validity and reliability of the KCCQ-12, both in patients with reduced and preserved ejection fraction. Hence, this version can be confidently used both in research and clinical practice to measure quality of life of heart failure patients.

Psychometric analysis of the kansas city cardiomiopathy questionnaire-23 in a european population

Abstract Background People affected by heart failure (HF) often exhibit poor quality of life, which places a great deal of burden on the healthcare systems. The Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 is one of the most widespread instruments to measure quality of life in this population. So far, its psychometric properties have been investigated by a broad array of research, but the overall findings reveal inconsistency of the factorial structure and lack of rigorous psychometric testing. Objective The aim of this study was to evaluate the psychometric properties of the KCCQ-23 in a European cohort of HF patients. Methods The data used for this study were collected for the MOTIVATE-HF study, which was a three-arm, multicenter, randomized controlled trial to evaluate the effect of motivational interviewing for improving self-care in HF. A group of 510 patients (median age 74 years, IQR=18, 58% males) completed the KCCQ-23 along with clinical and psychosocial measures. Factorial validity was established with confirmatory factor analysis (CFA); omega and model-based internal consistency indexes were computed to examine the internal consistency of the scale. Convergent validity was established by correlating the KCCQ-23 scores with several clinical and psychosocial measures. Measurement invariance testing was conducted within a multigroup framework across patients with preserved vs those with reduced ejection fraction. Results Two CFA solutions were tested, which confirmed the theoretical and empirical models postulated by the original author. The internal consistency coefficients for the latent dimensions were adequate (Omega range =0.77-0.93; internal consistency coefficient =0.89-96)- KCCQ-23 scores were found to be correlated with ejection fraction, NYHA levels, quality of life, self-care confidence, anxiety and depression, and symptom burden, supporting its convergent validity. Finally, the KCCQ-23 was invariant across ejection fraction levels, both in the theoretical and empirical factor solution. Conclusion Overall, this study provides for the first time evidence that the KCCQ-23 has satisfactory psychometric properties, promoting its use in clinical settings and research to investigate the quality of life in patients with HF.

Prevalence and characteristics of vascular cognitive impairment in a European cohort of adult patients with Moyamoya angiopathy

IntroductionMoyamoya angiopathy (MMA) is associated with a high risk of stroke, but it is also increasingly recognized as leading to cognitive impairment. The aim of this study was to determine the prevalence, nature, and severity of vascular cognitive impairment no dementia (VCIND) in adults with MMA and to identify clinical and imaging factors associated with VCIND.MethodsWe conducted a retrospective study of consecutive adult patients with MMA followed in two tertiary hospitals (Toulouse and Paris Lariboisiere). All patients underwent neuropsychological assessment and brain magnetic resonance imaging (MRI). VCIND was defined as at least two variables of the same cognitive process with z-scores of < 2 standard deviations, regardless of the cognitive domain, that do not interfere in everyday life. Baseline demographic, clinical, and imaging data were compared between patients with and without VCIND.ResultsA total of 102 patients (mean age 43 years; 65% women) were included. Thirty-four patients (33.3%) had VCIND. VCIND was mild in 20/34 (59%), moderate in 8/34 (23%), and severe in 6/34 (18%) patients. Executive function was the most widely affected (25.5%), followed by attention and processing speed (24.8%). In univariable analyses, VCIND was associated with ischemic stroke at diagnosis and the presence of ischemic lesions on MRI.ConclusionsVCIND is highly prevalent in adults with MMA. Executive functions and processing speed are predominantly affected. These findings may guide clinicians in their evaluation of patients with MMA. Further research should assess the effect of revascularization therapies on cognitive functions.

Eligibility of Asian and European registry patients for phase III trials in heart failure with reduced ejection fraction.

Traditional approaches to designing clinical trials for heart failure (HF) have historically relied on expertise and past practices. However, the evolving landscape of healthcare, marked by the advent of novel data science applications and increased data availability, offers a compelling opportunity to transition towards a data-driven paradigm in trial design. This research aims to evaluate the scope and determinants of disparities between clinical trials and registries by leveraging natural language processing for the analysis of trial eligibility criteria. The findings contribute to the establishment of a robust design framework for guiding future HF trials. Interventional phase III trials registered for HF on ClinicalTrials.gov as of the end of 2021 were identified. Natural language processing was used to extract and structure the eligibility criteria for quantitative analysis. The most common criteria for HF with reduced ejection fraction (HFrEF) were applied to estimate patient eligibility as a proportion of registry patients in the ASIAN-HF (N=4868) and BIOSTAT-CHF registries (N=2545). Of the 375 phase III trials for HF, 163 HFrEF trials were identified. In these trials, the most frequently encountered inclusion criteria were New York Heart Association (NYHA) functional class (69%), worsening HF (23%), and natriuretic peptides (18%), whereas the most frequent comorbidity-based exclusion criteria were acute coronary syndrome (64%), renal disease (55%), and valvular heart disease (47%). On average, 20% of registry patients were eligible for HFrEF trials. Eligibility distributions did not differ (P=0.18) between Asian [median eligibility 0.20, interquartile range (IQR) 0.08-0.43] and European registry populations (median 0.17, IQR 0.06-0.39). With time, HFrEF trials became more restrictive, where patient eligibility declined from 0.40 in 1985-2005 to 0.19 in 2016-2022 (P=0.03). When frequency among trials is taken into consideration, the eligibility criteria that were most restrictive were prior myocardial infarction, NYHA class, age, and prior HF hospitalization. Based on 14 trial criteria, only one-fifth of registry patients were eligible for phase III HFrEF trials. Overall eligibility rates did not differ between the Asian and European patient cohorts.

Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study.

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/μL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug.

Performance of HAS-BLED and DOAC scores to predict major bleeding events in atrial fibrillation patients treated with direct oral anticoagulants: A report from a prospective European observational registry

BackgroundThe DOAC score has been recently proposed for bleeding risk stratification of patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). ObjectiveTo compare the performance of HAS-BLED and DOAC score in predicting major bleeding events in a contemporary cohort of European AF patients treated with DOAC. MethodsWe included patients derived from a prospective observational registry of European AF patients. HAS-BLED and DOAC scores were calculated as per the original schemes. Our primary endpoint was major bleeding events. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the scores. ResultsA total of 2834 AF patients (median age [IQR] 69 [62–77] years; 39.6 % female) treated with DOAC were included in the analysis. According to the HAS-BLED score, 577 patients (20.4 %) were categorized as very low risk of bleeding, as compared to 1276 (45.0 %) according to DOAC score. A total of 55 major bleeding events occurred with an overall incidence of 1.04 per 100 patient-years. Both scores showed only a modest ability for the prediction of bleeding events (HAS-BLED area under the curve [AUC], 0.65, 95 % confidence interval [CI] 0.55–0.70; DOAC score AUC 0.62, 95 % CI 0.59–0.71, p for difference = 0.332]. At calibration analysis, the DOAC score showed modest calibration, especially for patients at high risk, when compared to HAS-BLED. ConclusionIn a contemporary cohort of DOAC-treated AF patients, both HAS-BLED and DOAC scores only modestly predicted the occurrence of major bleeding events. Our results do not support the preferential use of DOAC score over HAS-BLED.