Novel, braided, self-expandable stent designed for the treatment of pulsatile tinnitus caused by intracranial venous stenosis: first-in-human experience and long-term outcomes.

BACKGROUND: Pulsatile tinnitus (PT) can be a disabling clinical condition, which may be caused by a sigmoid/transverse sinus stenosis (STSS). Intracranial venous stenting with off-label carotid or peripheral venous stents has been used successfully to treat this condition. We present the results of a cohort of patients presenting with PT treated with a novel, dedicated, braided stent for the endovascular treatment of STSS. METHODS: Twelve patients presenting with PT and associated STSS were treated at our institution (December 2022-June 2023). All clinical and procedural variables were prospectively collected. We used the Tinnitus Function Index (TFI) and the Tinnitus Handicap Inventory (THI) scores to assess the impact of PT on quality of life before and after the treatment (mean follow-up: 10.3 months). RESULTS: Twelve women (mean age: 44±16.5 years) presenting with PT and STSS were treated. Mean pretreatment TFI/THI scores were 78.8/77. The BosStent was successfully deployed in all patients. We experienced no intraprocedural/postoperative complications. Intra-stent angioplasty was performed in three cases. All patients reported a complete resolution of PT symptoms within 1 month and remained stable and PT-free at the last follow-up (mean posttreatment TFI/THI score: 7.1/5, p<0001). CONCLUSIONS: The BosStent was successfully used in a cohort of patients with PT without any intraprocedural complications. All the patients experienced a complete resolution of PT symptoms after 1 month, which was stable during the follow-up period. Further studies with larger populations will be necessary to investigate the safety and effectiveness of this novel stent for the treatment of PT with STSS.

Stent-assisted Woven EndoBridge embolization for the treatment of pulsatile tinnitus caused by an ipsilateral high-riding jugular bulb.

PURPOSE: Pulsatile tinnitus can be caused by a high-riding jugular bulb (HRJB), characterized by the superior position of the jugular bulb in the petrous temporal bone. The anatomical position and morphology of this entity make it challenging for endovascular treatment. We report our experience with two patients successfully treated with a stent-assisted Woven EndoBridge (WEB; Microvention, Tustin, CA, USA) device. MATERIALS AND METHODS: We describe two cases of HRJB in patients presenting with disabling pulsatile tinnitus. Temporary balloon occlusion of the jugular bulb prior to the intervention reduced tinnitus intensity. Both patients were subsequently treated under general anesthesia with the WEB device deployed in the HRJB which was held by a stent deployed in the sigmoid sinus. RESULTS: Both procedures were successful with good positioning of the WEB device and no procedural complications. Both patients had complete resolution of pulsatile tinnitus immediately after the procedure. Follow-up imaging showed successful occlusion of the venous cavity with a widely patent stent. CONCLUSION: Among patients with pulsatile tinnitus caused by an ipsilateral HRJB, a stent-assisted WEB device seems to be a viable endovascular option with angiographic and clinical success.

Perspectives on Remote Robotic-Assisted Stroke Treatment: A Commentary Paper.

The proved feasibility of robotic-assisted endovascular treatment of intracranial aneurysms has stimulated the idea of a potential application of remote robotics for the treatment of acute ischemic stroke. The possibility of developing a more advanced remote-controlled robotic system capable of performing a complete mechanical thrombectomy procedure would help bridge the health care gap of lack of technical expertise in isolated areas. This possibility could allow a more equitable access to mechanical thrombectomy to a larger number of patients and be a breakthrough for acute ischemic stroke care worldwide. Many aspects around the technical, human, financial, and regulatory requirements should be discussed to implement remote robotic-assisted procedures. In this State of Practice article, we aimed to outline the major challenges that must be considered, as well as proposed solutions. However, different solutions may be applied in different health care systems on the basis of the availability of human and financial resources.

How to use the Contour intrasaccular device: two illustrative cases.

Contour (Stryker, Kalamazoo, MI) is a relatively new endosaccular device for the treatment of intracranial aneurysms.1 2 Its unique cup-like shape permits treatment of most lesions, including wide-necked, irregular, and shallowed-shaped aneurysms. The sizing of the device only requires two parameters: neck size and equatorial plane (width). It must be positioned at the neck of the aneurysm with the device proximal marker in the parent artery. In our experience, dual antiplatelet therapy is usually not required for intrasaccular devices and this is also an advantage of the Contour device. We report two illustrative cases of wide-neck aneurysms in the anterior and posterior circulation, respectively (video 1). In this video we demonstrate the feasibility of this treatment in a middle cerebral artery bifurcation with atypical triangular shape and typical tip-basilar aneurysm. neurintsurg;16/3/225/V1F1V1Video 1 .

Endovascular treatment of wide-neck bifurcation aneurysms: the eCLIPs device.

The endovascular clip system device, eCLIPs (eVasc, Vancouver, British Columbia, Canada), was introduced almost a decade ago for the treatment of wide-neck bifurcation aneurysms,1-3 which represent a challenge for both endovascular and surgical approaches. Several techniques and devices (intrasaccular or intra-arterial) have been introduced and are currently available in order to improve the technical and clinical outcomes of aneurysm embolization. Flow diversion and flow disruption have shown controversial results in this subtype of aneurysm. In this video we present the use of the eCLIPs device to treat a ruptured, wide-neck aneurysm of the top of the basilar artery. The decisional approach, technical details, and the different steps of the endovascular treatment are described. The final part of the video is dedicated to the characteristics of the device for re-endothelialization4 and flow diversion (video 1).5 neurintsurg;16/3/229/V1F1V1Video 1 .

Defining the optimal size of an aspiration catheter in relation to the arterial diameter during mechanical thrombectomy for stroke.

BACKGROUND: Mechanical thrombectomy for acute ischemic stroke is effective and includes different technical approaches. Operators use direct aspiration, a stent retriever, or a combination of both. Direct aspiration can be performed with various catheters of different sizes depending on the diameter of the occluded vessel. PURPOSE: We studied the relationship between the catheter diameter in regards to the occluded vessel diameter and the rate of successful recanalization. MATERIALS AND METHODS: We conducted a retrospective, monocentric study on a series of consecutive patients treated with mechanical thrombectomy. For each procedure, we extracted each attempt that used direct aspiration and rated the attempt as successful or unsuccessful. We also measured the occluded artery diameter and calculated the ratio between the occluded artery and the aspiration catheter diameters. We tested the association between the diameter ratio and the recanalization status. We also performed inter-rater agreement for the arterial diameter measurement between three interventional neuroradiologists. RESULTS: We included 119 patients with 201 attempts of direct aspiration. A higher diameter ratio was associated with a higher recanalization rate. The analysis in terciles showed that the odds of success were 4.80 higher when the ratio was >0.71 vs <0.54 (p < 0.01). Inter-rater agreement showed near-perfect intraclass correlation with 0.93 (0.91-0.94) consistency and 0.92 (0.90-0.94) absolute agreement. CONCLUSIONS: We demonstrated an association between higher recanalization and a diameter of ratio >0.71 between the aspiration catheter and the occluded artery. These results could guide intraoperative decisions regarding the appropriate selection of aspiration catheters during mechanical thrombectomy increasing the rate of successful recanalisation. A larger study could provide additional data to further specify the optimal ratio.

Rescue intracranial permanent stenting for refractory occlusion following thrombectomy: a propensity matched analysis.

BACKGROUND: Rescue intracranial stenting (RIS) can be used in refractory large vessel occlusion (LVO) after mechanical thrombectomy (MT). We aimed to assess the safety and efficacy of RIS versus a propensity matched sample of patients with persistent LVO. METHODS: We retrospectively analysed a multicenter retrospective pooled cohort of patients with anterior LVO (2015-2021) treated with MT, and identified patients with at least three passes and a modified Thrombolysis In Cerebral Infarction (mTICI) score of 0 to 2a. Propensity score matching was used to account for determinants of outcome in patients with or without RIS. The study outcomes included 3 months modified Rankin Scale (mRS) and symptomatic hemorrhagic transformation (HT). RESULTS: 420 patients with a refractory anterior occlusion were included, of which 101 were treated with RIS (mean age 69 years). Favorable outcome (mRS 0-2) was more frequent in patients with a patent stent at day 1 (53% vs 6%, P<0.001), which was independently associated with an early dual antiplatelet regimen (P<0.05). In the propensity matched sample, patients treated with RIS versus without RIS had similar rates of favorable outcomes (36.8% vs 30.3%, P=0.606). Patients with RIS showed a favorable shift in the overall mRS distributions (common adjusted OR 0.74, 95% CI 0.60 to 0.91, P=0.006). Symptomatic HT was marginally more frequent in the RIS group (9% vs 3%, P=0.07), and there was no difference in 3-month mortality. CONCLUSION: In selected patients with a refractory intracranial occlusion despite at least three thrombectomy passes, RIS may be associated with an overall shift towards more favorable clinical outcome, and no significant increase in the odds of symptomatic HT or death.

Deep learning-based cerebral aneurysm segmentation and morphological analysis with three-dimensional rotational angiography.

BACKGROUND: The morphological assessment of cerebral aneurysms based on cerebral angiography is an essential step when planning strategy and device selection in endovascular treatment, but manual evaluation by human raters only has moderate interrater/intrarater reliability. METHODS: We collected data for 889 cerebral angiograms from consecutive patients with suspected cerebral aneurysms at our institution from January 2017 to October 2021. The automatic morphological analysis model was developed on the derivation cohort dataset consisting of 388 scans with 437 aneurysms, and the performance of the model was tested on the validation cohort dataset consisting of 96 scans with 124 aneurysms. Five clinically important parameters were automatically calculated by the model: aneurysm volume, maximum aneurysm size, neck size, aneurysm height, and aspect ratio. RESULTS: On the validation cohort dataset the average aneurysm size was 7.9±4.6 mm. The proposed model displayed high segmentation accuracy with a mean Dice similarity index of 0.87 (median 0.93). All the morphological parameters were significantly correlated with the reference standard (all P<0.0001; Pearson correlation analysis). The difference in the maximum aneurysm size between the model prediction and reference standard was 0.5±0.7 mm (mean±SD). The difference in neck size between the model prediction and reference standard was 0.8±1.7 mm (mean±SD). CONCLUSION: The automatic aneurysm analysis model based on angiography data exhibited high accuracy for evaluating the morphological characteristics of cerebral aneurysms.

Persistent flow inside the Woven EndoBridge at angiographic follow-up: A multicenter study.

BACKGROUND: The occurrence of persistent intra-device filling (BOSS 1, using the Bicêtre Occlusion Scale Score (BOSS)) in aneurysms treated with a Woven Endobridge (WEB) device is infrequent based on angiographic follow-up. To date, three monocentric case series were published studying BOSS 1 cases. Through a multicenter retrospective study, we aimed to report the incidence, and risk factors of intra-WEB persistent filling. METHODS: We reached out to European academic centers that treat patients using WEB devices and requested de-identified data of patients treated with a WEB device and underwent angiographic follow-up, at least 3 months after embolization, to assess the BOSS 1 occlusion score. We compared baseline characteristics, treatment modalities, and aneurysm data of the included BOSS 1 patients with those of a control group consisting of non-BOSS 1 patients (n = 116) who had an available angiographic follow-up. Univariable and multivariable models were employed for analysis. RESULTS: Among the pooled sample of 591 aneurysms treated with WEB, the rate of persistent flow (BOSS 1) at angiographic follow-up was 5.2% (n = 31 out of 591), performed after an average of 8.7 ± 6.3 months. In the multivariable-adjusted analysis, dual antiplatelet therapy in the postoperative period (adjusted odds ratio [aOR] 4.3 [95% CI 1.3-14.2]), and WEB undersizing (aOR 10.8 [95% CI 2.9-40]) were independently associated with a BOSS 1 persistent flow result. CONCLUSION: Persistent blood flow within the WEB device during angiographic follow-up (BOSS 1) is an uncommon occurrence. Our findings indicate that post-procedural dual antiplatelet therapy and undersizing of the WEB device are independently associated with the presence of BOSS 1 at follow-up.

Venous balloon test occlusion for pulsatile tinnitus assessment: A clinical feasibility study.

BACKGROUND: Pulsatile tinnitus (PT) can have huge impact on the patients' quality of life and can be associated with curable vascular anomalies. In the present study, we aim firstly to describe our protocol for venous BTO and secondly to report possible predictors for a positive BTO test. METHODS: All consecutive PT patients undergoing BTO for the purpose of determining eligibility for venous neuro-intervention were included. We recommend BTO for patients when there is uncertainty in the association of the venous pathology identified on non-invasive cross-sectional imaging (CTV or MRV) and the patient's symptoms. RESULTS: Between May 2016 and October 2022, we recorded 29 venous balloon test occlusions fulfilling our inclusions criteria. Over the 29 procedures scheduled, 8 finally did not lead to a successful balloon test occlusion. The main reason was that the patient did not hear the PT on the day the angiogram was performed. Two patients could not have the BTO due to difficulties in venous navigation. After BTO, only four patients of our cohort were scheduled for an endovascular treatment. CONCLUSION: We describe a technique and present a single cohort of venous BTO in severe PT patients with unclear anatomical cause. This angiographic test was useful to exclude patients from endovascular surgery and discuss the most probable cause of the PT. Complexity of vascular PT should support a patient-based approach when discussing interventional treatment.

IL-7 receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK inhibition.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted therapies. Activating mutations of interleukin-7-receptor pathway genes (IL-7Rp) play a proven leukemia-supportive role in T-ALL. JAK inhibitors, such as ruxolitinib, have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK inhibitors are still lacking. Herein, we show that IL-7R (CD127) expression is more frequent (∼70%) than IL-7Rp mutations in T-ALL (∼30%). We compared the so-called nonexpressers (no IL-7R expression/IL-7Rp mutation), expressers (IL7R expression without IL-7Rp mutation), and mutants (IL-7Rp mutations). Integrative multiomics analysis outlined IL-7R deregulation in virtually all T-ALL subtypes, at the epigenetic level in nonexpressers, genetic level in mutants, and posttranscriptional level in expressers. Ex vivo data using primary-derived xenografts support that IL-7Rp is functional whenever the IL-7R is expressed, regardless of the IL-7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL-7R expression and IL-7Rp addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, the combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting the achievement of complete remission in 2 patients with refractory/relapsed T-ALL. This provides proof of concept for translation of this strategy into clinics as a bridge-to-transplantation therapy. IL7R expression can be used as a biomarker for sensitivity to JAK inhibition, thereby expanding the fraction of patients with T-ALL eligible for ruxolitinib up to nearly ∼70% of T-ALL cases.

Short tandem repeats are important contributors to silencer elements in T cells.

The action of cis-regulatory elements with either activation or repression functions underpins the precise regulation of gene expression during normal development and cell differentiation. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts. In sharp contrast, gene repression by cis-acting silencers, defined as genetic elements that negatively regulate gene transcription in a position-independent fashion, is less well understood. Here, we repurpose the STARR-seq approach as a novel high-throughput reporter strategy to quantitatively assess silencer activity in mammals. We assessed silencer activity from DNase hypersensitive I sites in a mouse T cell line. Identified silencers were associated with either repressive or active chromatin marks and enriched for binding motifs of known transcriptional repressors. CRISPR-mediated genomic deletions validated the repressive function of distinct silencers involved in the repression of non-T cell genes and genes regulated during T cell differentiation. Finally, we unravel an association of silencer activity with short tandem repeats, highlighting the role of repetitive elements in silencer activity. Our results provide a general strategy for genome-wide identification and characterization of silencer elements.

Antithrombotic therapies for neurointerventional surgery: a 2021 French comprehensive national survey.

BACKGROUND: Neurointerventionists lack guidelines for the use of antithrombotic therapies in their clinical practice; consequently, there is likely to be significant heterogeneity in antithrombotic use between centers. Through a nationwide survey, we aimed to obtain an exhaustive cross-sectional overview of antithrombotic use in neurointerventional procedures in France. METHODS: In April 2021, French neurointerventional surgery centers were invited to participate in a nationwide 51-question survey disseminated through an active trainee-led research collaborative network (the JENI-RC). RESULTS: All 40 centers answered the survey. Fifty-one percent of centers reported using ticagrelor and 43% used clopidogrel as premedication before intracranial stenting. For flow diversion treatment, dual antiplatelet therapy was maintained for 3 or 6 months in 39% and 53% of centers, respectively, and aspirin was prescribed for 12 months or more than 12 months in 63% and 26% of centers, respectively. For unruptured aneurysms, the most common heparin bolus dose was 50 IU/kg (59%), and only 35% of centers monitored heparin activity for dose adjustment. Tirofiban was used in 64% of centers to treat thromboembolic complications. Fifteen percent of these comprehensive stroke centers reported using tenecteplase to treat acute ischemic strokes. Cangrelor appeared as an emergent drug in specific indications. CONCLUSION: This nationwide survey highlights the important heterogeneity in clinical practices across centers. There is a pressing need for trials and guidelines to further evaluate and harmonize antithrombotic regimens in the neurointerventional field.

Endosaccular flow disruption with the Contour Neurovascular System: angiographic and clinical results in a single-center study of 60 unruptured intracranial aneurysms.

BACKGROUND: The Contour Neurovascular System is a novel device designed to treat intracranial aneurysms by intrasaccular flow disruption. We report our experience and mid-term follow-up in a series of patients treated with the Contour. METHODS: The patients were divided into an intention to treat and a per protocol population, the latter defined by the successful implantation of the Contour device. The intention to treat population included 53 patients (30 women, mean age 56 years) with 60 unruptured intracranial aneurysms (53 in the anterior circulation and seven in the posterior circulation). There was clinical and angiographic follow-up immediate postoperatively and at 24 hours, 3 months and 1 year using the Raymond-Roy classification and the O'Kelly-Marotta grading scale. RESULTS: The Contour was successfully implanted in 54/60 (90%) aneurysms. With regard to the angiographic follow-up, there was adequate occlusion (defined as complete occlusion or presence of a neck remnant) in 31.5% of 54 aneurysms immediately postoperatively, 62.3% (in 53/54 aneurysms) at 24 hours, 81.4% (in 43/54 aneurysms) at 3 months, and 89.3% (in 28/54 aneurysms) at 1 year. Technical complications in 60 aneurysms of the intention to treat population included two (3.3%) inadvertent detachments of the device. Thromboembolic events were observed in four of the 60 aneurysms (6.7%), with no clinical symptoms in three patients and transient morbidity in one (1.7%). No aneurysm bleeding was observed and no patient was retreated during the 1-year follow-up period. There was no permanent morbidity or mortality. CONCLUSIONS: The Contour device is effective and safe in the treatment of intracranial aneurysms. However, more experience and long-term follow-up are needed.

Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis.

Antidepressants (ADs) are, for now, the best everyday treatment we have for moderate to severe major depressive episodes (MDEs). ADs are among the most prescribed drugs in the Western Hemisphere; however, the trial-and-error prescription strategy and side-effects leave a lot to be desired. More than 60% of patients suffering from major depression fail to respond to the first AD they are prescribed. For those who respond, full response is only observed after several weeks of treatment. In addition, there are no biomarkers that could help with therapeutic decisions; meanwhile, this is already true in cancer and other fields of medicine. For years, many investigators have been working to decipher the underlying mechanisms of AD response. Here, we provide the first systematic review of animal models. We thoroughly searched all the studies involving rodents, profiling transcriptomic alterations consecutive to AD treatment in naïve animals or in animals subjected to stress-induced models of depression. We have been confronted by an important heterogeneity regarding the drugs and the experimental settings. Thus, we perform a meta-analysis of the AD signature of fluoxetine (FLX) in the hippocampus, the most studied target. Among genes and pathways consistently modulated across species, we identify both old players of AD action and novel transcriptional biomarker candidates that warrant further investigation. We discuss the most prominent transcripts (immediate early genes and activity-dependent synaptic plasticity pathways). We also stress the need for systematic studies of AD action in animal models that span across sex, peripheral and central tissues, and pharmacological classes.

Pre-Interventional 3D-Printing-Assisted Planning of Flow Disrupter Implantation for the Treatment of an Intracranial Aneurysm.

Intrasaccular flow disrupter devices (ISFD) have opened up new ways to treat intracranial aneurysms but choosing the correct size of ISFD can be challenging. We describe the first use of 3D printing to assist in the choice of ISFD, and we report an illustrative case. We developed a technique that uses preoperative angiography to make a plastic model of the aneurysm. We tested the deployment of different sizes of intrasaccular flow disruptor on the 3D model under fluoroscopy. The best devices were then used as the first-line strategy to treat the patient. The preoperative 3D printing helped in the successful selection of a first-line ISFD, which was not the one recommended by the manufacturer. Three-dimensional printing can provide interesting information regarding the treatment of intracranial aneurysms using ISFD. Further studies are needed to fully assess its benefits.

Factors That Influence Susceptibility Vessel Sign in Patients With Acute Stroke Referred for Mechanical Thrombectomy.

Background and Purpose: The presence of a Susceptibility Vessel Sign (SVS) in the acute phase of proximal occlusion ischemic stroke indicates the presence of deoxyhemoglobin in the thrombus. Thrombi composition changes over time. The aim of this study was to investigate whether the absence of SVS is associated with a shorter symptom onset to imaging time. Methods: We retrospectively analyzed all patients referred for mechanical thrombectomy at Besançon University Hospital between 1 January 2015 and 31 December 2020 for whom readable T2*-weighted imaging was available. We compared patient characteristics according to the presence or absence of an SVS. We also studied the subgroup for whom the exact symptom onset time was known. We performed a univariate statistical analysis, then a multivariate analysis on the variables that were statistically significant in the univariate analysis. Results: Of the 389 patients included, 309 (79.4%) were SVS+. We found no significant relationship between SVS- and the time between symptom onset and imaging in the whole cohort. In the multivariate analysis, SVS- was associated with anticoagulant treatment (p < 0.01), and SVS+ with age (p = 0.023) and carotid terminus occlusion (p = 0.042). In the known symptom onset subgroup, SVS- was significantly associated with a shorter symptom onset -imaging time (p < 0.001), and this was confirmed in the multivariate analysis (p = 0.011; OR 0.911; 95% CI [0.844; 0.972]). Conclusion: In the acute phase of proximal occlusion ischemic stroke, absence of SVS was associated with a shorter symptom onset-imaging time for patients with a known symptom onset time.

Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes.

Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain-associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain-associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain-associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.

Epromoters function as a hub to recruit key transcription factors required for the inflammatory response.

Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.