Oral sialadenoma papilliferum with kras mutation in a patient with linear nevus sebaceous syndrome.

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome part of the epidermal nevus syndromes group, characterized by the presence of sebaceous nevi and other extracutaneous lesions genetically related to RAS family gene mutations. Sialadenoma papilliferum (SP) is a rare benign intraoral neoplasm which is usually BRAF or HRAS mutated. We report a case of a young female girl diagnosed with a LNSS who developed a SP which had a KRAS mutation. This is the first case of SP with a KRAS mutation in the context of a LNSS.

Treatment trajectories and outcomes in inflammatory bowel disease: a tertiary single-centre experience.

Background: There is an increasing diversification in the treatment landscape for inflammatory bowel diseases (IBD) leading to therapeutic challenges that can only incompletely be covered by prospective randomized double-blind trials. Real-world observations are therefore an important tool to provide insights into therapeutic strategies. Objectives: To describe the real-world treatment algorithms in an IBD referral centre. Design: Single-centre retrospective cohort study. Methods: We retrospectively analysed prospectively collected data on treatment sequences and outcomes from 502 patients with Crohn's disease (CD) and ulcerative colitis (UC) treated with infliximab, adalimumab, vedolizumab or ustekinumab at a large German tertiary referral centre. Results: Treatment decisions correlated to baseline patient characteristics. Over time, infliximab continued to be the preferred first-line option in CD and UC, although ustekinumab and vedolizumab, respectively, became increasingly important choices. Remission rates decreased with the advancement of therapy lines. Conclusion: We provide insights into the evolution of tertiary centre real-world treatment sequences that might - together with other observations - help to guide the selection of therapies in IBD. Our data also strongly underscore the unmet need for biomarkers supporting treatment decisions. Trial registration: None.

Ultrasound-guided versus Fluoro-guided Axillary Venous Access for Cardiac Implantable Electronic Devices: A Patient-Based Meta-analysis.

BACKGROUND AND AIMS: The use of ultrasound (US)-guided venous puncture for cardiac pacing/defibrillation lead placement may minimize the risk of peri-procedural complications and radiation exposure. However, none of the published studies have been sufficiently powered to recommend this approach as the standard of care. We compare the safety and efficacy of ultrasound-guided axillary venous puncture (US-AVP) versus fluoroscopy-guided access for cardiac implantable electronic devices (CIED) by performing an individual patient data meta-analysis based on previously published studies. METHODS: We conducted a thorough literature search encompassing longitudinal investigations (five randomized and one prospective studies) reporting data on Xray-guided and US-AVP for CIED procedures. The primary endpoint was to compare the safety of the two techniques. Secondary endpoints included the success rate of each technique, the necessity of switching to alternative methods, the time needed to obtain venous access, Xray exposure and the occurrence of peri-procedural complications. RESULTS: Six longitudinal eligible studies were identified including 700 patients (mean age 74.9 ±12.1 years, 68.4% males). The two approaches for venous cannulation showed a similar success rate. The use of a Xray guided approach significantly increased the risk of inadvertent arterial punctures (OR: 2.15, 95% CI: 2.10-2.21, p=0.003), after adjustment for potential confounders. Conversely, an US-AVP approach reduces time to vascular access, radiation exposure and the number of attempts to vascular access. CONCLUSIONS: The US-AVP enhances safety by reducing radiation exposure and time to vascular access while maintaining a low rate of major complications compared to the x-ray-guided approach.

Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets.

BACKGROUND: Colorectal cancer (CRC) risk is strongly affected by dietary habits with red and processed meat increasing risk, and foods rich in dietary fibres considered protective. Dietary habits also shape gut microbiota, but the role of the combination between diet, the gut microbiota, and the metabolite profile on CRC risk is still missing an unequivocal characterisation. METHODS: To investigate how gut microbiota affects diet-associated CRC risk, we fed Apc-mutated PIRC rats and azoxymethane (AOM)-induced rats the following diets: a high-risk red/processed meat-based diet (MBD), a normalised risk diet (MBD with α-tocopherol, MBDT), a low-risk pesco-vegetarian diet (PVD), and control diet. We then conducted faecal microbiota transplantation (FMT) from PIRC rats to germ-free rats treated with AOM and fed a standard diet for 3 months. We analysed multiple tumour markers and assessed the variations in the faecal microbiota using 16S rRNA gene sequencing together with targeted- and untargeted-metabolomics analyses. RESULTS: In both animal models, the PVD group exhibited significantly lower colon tumorigenesis than the MBD ones, consistent with various CRC biomarkers. Faecal microbiota and its metabolites also revealed significant diet-dependent profiles. Intriguingly, when faeces from PIRC rats fed these diets were transplanted into germ-free rats, those transplanted with MBD faeces developed a higher number of preneoplastic lesions together with distinctive diet-related bacterial and metabolic profiles. PVD determines a selection of nine taxonomic markers mainly belonging to Lachnospiraceae and Prevotellaceae families exclusively associated with at least two different animal models, and within these, four taxonomic markers were shared across all the three animal models. An inverse correlation between nonconjugated bile acids and bacterial genera mainly belonging to the Lachnospiraceae and Prevotellaceae families (representative of the PVD group) was present, suggesting a potential mechanism of action for the protective effect of these genera against CRC. CONCLUSIONS: These results highlight the protective effects of PVD while reaffirming the carcinogenic properties of MBD diets. In germ-free rats, FMT induced changes reminiscent of dietary effects, including heightened preneoplastic lesions in MBD rats and the transmission of specific diet-related bacterial and metabolic profiles. Importantly, to the best of our knowledge, this is the first study showing that diet-associated cancer risk can be transferred with faeces, establishing gut microbiota as a determinant of diet-associated CRC risk. Therefore, this study marks the pioneering demonstration of faecal transfer as a means of conveying diet-related cancer risk, firmly establishing the gut microbiota as a pivotal factor in diet-associated CRC susceptibility. Video Abstract.

Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n  = 25. RAS mutation: n  = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n  = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n  = 25. Complete response: n  = 0, partial response: n  = 14 (56%), stable disease: n  = 8 (32%), progressive disease: n  = 3 (12%), early tumor shrinkage: n  = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n  = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.

Changes in Faecal Microbiota Profile and Plasma Biomarkers following the Administration of an Antioxidant Oleuropein-Rich Leaf Extract in a Rat Model Mimicking Colorectal Cancer.

Oleuropein (OLE), a phenolic compound particularly abundant in the olive leaves, has been reported to have beneficial activities against colorectal cancer (CRC). In vitro studies suggested that these latter could be due to a modulation of the intestinal microbiota. Aiming to evaluate if OLE could affect the intestinal microbiota and the plasma metabolome, an antioxidant oleuropein-rich leaf extract (ORLE) was administered for one week to PIRC rats (F344/NTac-Apcam1137), a genetic model mimicking CRC. ORLE treatment significantly modulated the gut microbiota composition. Plasma metabolomic profiles revealed a significant predictive ability for amino acids, medium-chain fatty acids, and aldehydes. Pathway analysis revealed a significant decrease in phosphatidylcholine accumulation (LogFC = -1.67) in PIRC rats. These results suggest a significant effect of ORLE administration on faecal microbiota profiles and plasma metabolomes, thereby offering new omics-based insights into its protective role in CRC progression.

Association between Epicardial Adipose Tissue and Atrial Fibrillation in Patients with Transfusion-Dependent ß-Thalassemia.

Background: Modern treatments for transfusion-dependent ß-thalassemia (TDßT) have allowed patients to reach high life expectancy with no iron overload. Despite survival improvement, atrial fibrillation (AF) has emerged as a relevant issue. AF pathophysiology and characteristics in TDßT are different than in the general population. Epicardial adipose tissue (EAT) may play a role but its relationship with AF in patients with TDßT has not been explored. Methods: A monocentric, cross-sectional study, enrolling consecutive patients with TDßT. Epicardial adipose tissue (EAT) was evaluated at magnetic resonance. Characteristics of patients with and without history of AF were investigated. Factors independently associated with AF prevalence were analyzed. Results: A total of 116 patients were enrolled. All patients were treated with regular chelation therapy. The prevalence of AF was 29.3% (34/116). Cardiac T2* and liver iron concentration were no different between patients with and without AF. EAT thickness was significantly higher in patients with AF at left atrium, right atrium and right ventricle (5.0 vs. 4.0 mm, p < 0.01, 4.4 vs. 4.0, p = 0.02 and 5.0 vs. 4.3, p = 0.04). Patients with AF presented with older age, (53 vs. 49 years, p < 0.01), more hypothyroidism (44.1 vs. 20.7%, p = 0.01), pulmonary hypertension (23.5 vs. 2.4% p < 0.01), splenectomy (88.2 vs. 64.6%, p = 0.01), higher right and left atrial volume (61 vs. 40 and 74 vs. 43 mL, both p < 0.01). At multivariable analysis, hypothyroidism, left atrial volume and left atrial EAT were independently associated with AF (odds ratio 9.95, 1.09 and 1.91, respectively). Conclusions: In a contemporary cohort of patients with TDßT, treated with regular chelation therapy, prevalence of AF was unrelated to iron overload. EAT was independently associated with AF.

Green-house gas fluxes and soil microbial functional genes abundance in saturated and drained peatlands in South-West Iceland.

The drainage of peatlands followed by land use conversion significantly impacts on the fluxes of green-house gases (GHGs, i.e. CO2, CH4, and N2O) to and from the atmosphere, driven by changes in soil properties and microbial communities. In this study, we compared saturated peatlands with drained ones used for sheep grazing or cultivated, which are common in South-West Iceland. These areas exhibit different degrees of soil saturation and nitrogen (N) content, reflecting the anthropic pressure gradient. We aimed at covering knowledge gaps about lack of estimates on N2O fluxes and drainage, by assessing the emissions of GHGs, and the impact of land conversion on these emissions. Moreover, we investigated soil microbial community functional diversity, and its connection with processes contributing to GHGs emission. GHGs emissions differed between saturated and drained peatlands, with increased soil respiration rates (CO2 emissions) and N mineralization (N2O), consistent with the trend of anthropogenic pressure. Drainage drastically reduced methane (CH4) emissions but increased CO2 emissions, resulting in a higher global warming potential (GWP). Cultivation, involving occasional tillage and fertilization, further increased N2O emissions, mediated by higher N availability and conditions favorable to nitrification. Functional genes mirrored the overall trend, showing a shift from prevalent methanogenic archaea (mcrA) in saturated peatlands to nitrifiers (amoA) in drained-cultivated areas. Environmental variables and nutrient content were critical factors affecting community composition in both environments, which overall affected the GHGs emissions and the relative contribution of the three gases.

A COVID-19 specific multiparametric and ECG-based score for the prediction of in-hospital mortality: ELCOVID score.

We aimed to develop and validate a COVID-19 specific scoring system, also including some ECG features, to predict all-cause in-hospital mortality at admission. Patients were retrieved from the ELCOVID study (ClinicalTrials.gov identifier: NCT04367129), a prospective, multicenter Italian study enrolling COVID-19 patients between May to September 2020. For the model validation, we randomly selected two-thirds of participants to create a derivation dataset and we used the remaining one-third of participants as the validation set. Over the study period, 1014 hospitalized COVID-19 patients (mean age 74 years, 61% males) met the inclusion criteria and were included in this analysis. During a median follow-up of 12 (IQR 7-22) days, 359 (35%) patients died. Age (HR 2.25 [95%CI 1.72-2.94], p < 0.001), delirium (HR 2.03 [2.14-3.61], p = 0.012), platelets (HR 0.91 [0.83-0.98], p = 0.018), D-dimer level (HR 1.18 [1.01-1.31], p = 0.002), signs of right ventricular strain (RVS) (HR 1.47 [1.02-2.13], p = 0.039) and ECG signs of previous myocardial necrosis (HR 2.28 [1.23-4.21], p = 0.009) were independently associated to in-hospital all-cause mortality. The derived risk-scoring system, namely EL COVID score, showed a moderate discriminatory capacity and good calibration. A cut-off score of ≥ 4 had a sensitivity of 78.4% and 65.2% specificity in predicting all-cause in-hospital mortality. ELCOVID score represents a valid, reliable, sensitive, and inexpensive scoring system that can be used for the prognostication of COVID-19 patients at admission and may allow the earlier identification of patients having a higher mortality risk who may be benefit from more aggressive treatments and closer monitoring.

Prognostic Electrocardiographic Signs in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a rare cardiac disease, characterized by the progressive replacement of myocardial tissue with fibrous and fatty deposits. It can involve both the right and left ventricles. It is associated with the development of life-threatening arrhythmias and culminates in sudden cardiac death. Electrocardiography (ECG) has emerged as a pivotal tool, offering diagnostic insights and prognostic information. The specific ECG abnormalities observed in ACM not only contribute to early detection but also hold the key to the prediction of the likelihood of severe complications. The recognition of these nuanced ECG manifestations has become imperative for clinicians as it guides them in the formulation of tailored therapeutic strategies that address both the present symptoms and the potential future risks.

Direct healthcare costs of oral cancer: A retrospective study from a tertiary care center.

The aim of this study was to retrospectively evaluate the direct costs of OSCC treatment and postsurgical surveillance in a tertiary hospital in northeast Italy. Sixty-three consecutive patients surgically treated for primitive OSCC at S. Orsola Hospital in Bologna (Italy) between January 2018 and January 2020 were analyzed. Billing records of the Emilia Romagna healthcare system and institutional costs were used to derive specific costs for the following clinical categories: operating theatre costs, intensive and ordinary hospitalization, radiotherapy, chemotherapy, postsurgical complications, visits, and examinations during the follow-up period. The study population comprised 17 OSCC patients classified at stage I, 14 at stage II, eight at stage III, and 24 at stage IV. The estimated mean total direct cost for OSCC treatment and postsurgical surveillance was €26 338.48 per patient (stage I: €10 733, stage II: €19 642.9, stage III: €30 361.4, stage IV: €39 957.2). An advanced diagnosis (stages III and IV), complex surgical procedure, and loco-regional recurrences resulted in variables that were significantly associated with a higher cost of OSCC treatment and postsurgical surveillance. Redirection of funds used for OSCC treatment to screening measures may be an effective strategy to improve overall health outcomes and optimize national health resources.

Heart Failure-Related Death in Subjects With Atrial Fibrillation in the United States, 1999 to 2020.

BACKGROUND: Population-based data on heart failure (HF)-related death in patients with atrial fibrillation (AF) are lacking. We assessed HF-related death in people with AF in the United States over the past 21 years and examined differences by age, sex, race, ethnicity, urbanization, and census region. METHODS AND RESULTS: Data were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research to determine trends in age-adjusted mortality rates per 100 000 people, due to HF-related death among subjects with AF aged ≥15 years. To calculate nationwide annual trends, we assessed the average annual percent change (AAPC) and annual percent change with relative 95% CIs using joinpoint regression. Between 1999 and 2020, 916 685 HF-related deaths (396 205 men and 520 480 women) occurred among US adults having a concomitant AF. The overall age-adjusted mortality rates increased (AAPC: +4.1% [95% CI, 3.8-4.4]; P<0.001), especially after 2011 (annual percent change, +6.8% [95% CI, 6.2-7.4]; P<0.001) in men (AAPC, +4.8% [95% CI, 4.4-5.1]; P<0.001), in White subjects (AAPC: +4.2% [95% CI, 3.9 to 4.6]; P<0.001) and in subjects aged <65 years (AAPC: +7.5% [95% CI, 6.7-8.4]; P<0.001). The higher percentage of deaths were registered in the South (32.8%). During the first year of the COVID-19 pandemic, a significant excess in HF-related deaths among patients with AF aged >65 years was observed. CONCLUSIONS: A worrying increase in the HF-related mortality rate among patients with AF has been observed in the United States over the past 2 decades.

Cardiac conduction disorders in young adults: Clinical characteristics and genetic background of an underestimated population.

BACKGROUND: Cardiac conduction disorder (CCD) in patients <50 years old is a rare and mostly unknown condition. OBJECTIVE: We aimed to assess clinical characteristics and genetic background of patients <50 years old with CCD of unknown origin. METHODS: We retrospectively reviewed a consecutive series of patients with a diagnosis of CCD before the age of 50 years referred to our center between January 2019 and December 2021. Patients underwent complete clinical examination and genetic evaluation. RESULTS: We enrolled 39 patients with a median age of 40 years (28-47 years) at the onset of symptoms. A cardiac implantable electronic device was implanted in 69% of the patients. In 15 of 39 CCD index patients (38%), we found a total of 13 different gene variations (3 pathogenic, 6 likely pathogenic, and 4 variants of uncertain significance), mostly in 3 genes (SCN5A, TRPM4, and LMNA). In our cohort, genetic testing led to the decision to implant an implantable cardioverter-defibrillator in 2 patients for the increased risk of sudden cardiac death. CONCLUSION: Patients with the occurrence of CCD before the age of 50 years present with a high rate of pathologic gene variations, mostly in 3 genes (SCN5A, TRPM4, and LMNA). The presence of pathogenic variations may add information about the prognosis and lead to an individualized therapeutic approach.

Interventricular Septal Hematoma Complicating Left Bundle Branch Area Pacing: A Case Report-The Devil Is Not So Black as He Is Painted.

BACKGROUND: This case report outlines the presentation of an emerging complication arising from left bundle branch area pacing (LBBAP). CASE SUMMARY: A 43-year-old male with no history of cardiac problems experienced recurrent episodes of syncope with no prodromal symptoms. During monitoring in the emergency department, the patient underwent an episode of asystole, leading to LBBAP implantation. The procedure encountered technical challenges, resulting in an interventricular septal hematoma and subsequent ventricular arrhythmias. Despite initial concerns, conservative management led to resolution, demonstrated through echocardiographic follow-ups. DISCUSSION: This report underscores the significance of ventricular arrhythmias as indicators of interventricular septal hematoma, providing insights into its diagnosis, management, and implications for LBBAP procedures.

Comparative Study of Lesions Obtained through Radiofrequency between the Irrigated Ablation Catheter with a Flexible Tip and the Non-Irrigated Catheter in Ex Vivo Porcine Hearts.

BACKGROUND: At the same conditions of delivered power and contact force, open-irrigated radiofrequency ablation catheters are believed to create deeper lesions, while non-irrigated ones produce shallower lesions. This ex vivo study aims to directly compare the lesion dimensions and characteristics of an irrigated ablation catheter with a flexible tip and a non-irrigated solid-tip catheter. METHODS: Radiofrequency lesions were induced on porcine myocardial slabs using both open-tip irrigated and non-irrigated standard 4 mm catheters at three power settings (20 W, 30 W, and 40 W), maintaining a fixed contact force of 10 gr. A lesion assessment was conducted including the lesion depth, depth at the maximum diameter, and lesion surface diameters, with the subsequent calculation of the lesion volume and area being undertaken. RESULTS: Irrigated catheters produced lesions with significantly higher superficial widths at all power levels (3.8 vs. 4.4 mm at 20 W; 3.9 mm vs. 4.4 mm at 30 W; 3.8 mm vs. 4.5 mm at 40 W; p = 0.001, p = 0.019, p = 0.003, respectively). Non-irrigated catheters resulted in significantly higher superficial areas at all power levels (23 mm2 vs. 18 mm2 at 20 W; 25 mm2 vs. 19 mm2 at 30 W; 26 mm2 vs. 19 mm2 at 40 W; p = 0.001, p = 0.005, p = 0.001, respectively). Irrigated catheters showed significantly higher values of lesion maximum depth at 40 W (4.6 mm vs. 5.5 mm; p = 0.007), while non-irrigated catheters had a significantly higher calculated volume at 20 W (202 µL vs. 134 µL; p = 0.002). CONCLUSIONS: Radiofrequency ablation using an irrigated catheter with a flexible tip has the potential to generate smaller superficial lesion areas compared with those obtained using a non-irrigated catheter.

Etrolizumab-s fails to control E-Cadherin-dependent co-stimulation of highly activated cytotoxic T cells.

Despite promising preclinical and earlier clinical data, a recent phase III trial on the anti-ß7 integrin antibody etrolizumab in Crohn's disease (CD) did not reach its primary endpoint. The mechanisms leading to this outcome are not well understood. Here we characterize the ß7+ T cell compartment from patients with CD in comparison to cells from individuals without inflammatory bowel disease. By flow cytometric, transcriptomic and functional profiling of circulating T cells, we find that triple-integrin-expressing (α4+ß7+ß1hi) T cells have the potential to home to the gut despite α4ß7 blockade and have a specific cytotoxic signature. A subset of triple-integrin-expressing cells readily acquires αE expression and could be co-stimulated via E-Cadherin-αEß7 interactions in vitro. Etrolizumab-s fails to block such αEß7 signalling at high levels of T cell stimulation. Consistently, in CD patients treated with etrolizumab, T cell activation correlates with cytotoxic signatures. Collectively, our findings might add one important piece to the puzzle to explain phase III trial results with etrolizumab, while they also highlight that αEß7 remains an interesting target for future therapeutic approaches in inflammatory bowel disease.

The Great Gobi A Strictly Protected Area: Characterization of Soil Bacterial Communities from Four Oases.

Understanding how microbial communities survive in extreme environmental pressure is critical for interpreting ecological patterns and microbial diversity. Great Gobi A Strictly Protected Area represents an intriguing model for studying the bacterial community since it is a protected and intact wild area of the Mongolian desert. In this work, the composition of a bacterial community of the soil from four oases was characterized by extracting total DNA and sequencing through the Illumina NovaSeq platform. In addition, the soil's chemical and physical properties were determined, and their influence on shaping the microbial communities was evaluated. The results showed a high variability of bacterial composition among oases. Moreover, combining specific chemical and physical parameters significantly shapes the bacterial community among oases. Data obtained suggested that the oases were highly variable in physiochemical parameters and bacterial communities despite the similar extreme climate conditions. Moreover, core functional microbiome were constituted by aerobic chemoheterotrophy and chemoheterotrophy, mainly contributed by the most abundant bacteria, such as Actinobacteriota, Pseudomonadota, and Firmicutes. This result supposes a metabolic flexibility for sustaining life in deserts. Furthermore, as the inhabitants of the extreme regions are likely to produce new chemical compounds, isolation of key taxa is thus encouraged.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.