Effect Profile Research Articles

Safety and Effectiveness of Oral Anticoagulants in Atrial Fibrillation: Real-World Insights Using Natural Language Processing and Machine Learning.

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan-Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70-0.94)], minor bleeding [HR 0.89 (95% CI 0.83-0.96)], and mortality [HR 0.80 (95% CI 0.69-0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs.

Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation.

Endometrial carcinoma (EC) is a type of cancer that originates in the lining of the uterus, known as the endometrium. It is associated with various treatment options such as surgery, radiation therapy, chemotherapy, and hormone therapy, each presenting unique challenges and limitations. Beta-catenin, a protein involved in the development and progression of several cancers, including EC, plays a crucial role. Abnormal beta-catenin signaling is often linked to the emergence of specific EC subtypes, affecting tumor growth and invasion. The study's objective is to identify compounds targeting the beta-catenin protein for treating endometrial cancer (EC) using in silico drug design. Our approach includes molecular docking to evaluate binding affinities, ADME profiling for pharmacokinetic properties, toxicity assessments, and molecular dynamics simulations to assess compound stability and interactions. Approximately one thousand anti-cancer phytochemicals were sourced from PubChem and subjected to molecular docking simulations against the beta-catenin protein. The compounds were evaluated based on their binding affinities, with the top five selected for further analysis. These five molecules underwent toxicity and ADME profiling. The Prediction of Activity Spectra for Substances (PASS) tool was used to identify compounds targeting CTNNB1. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to establish quantitative structure-activity relationship (QSAR) models for the five CTNNB1 antagonist molecules. The selected five compounds, namely Pazopanib, Binimetinib, Telatinib, 4-(2,3-Dihydrobenzo[ b][1,4]dioxin-6-yl)-3-((5-nitrothiazol-2-yl)thio)-1H-1,2,4-triazol-5(4H)-one, and Ribavirin, demonstrated efficacy against CTNN1. MD simulations of the docked complexes confirmed the stability of these drugs in binding to the target protein. All five molecules showed promising safety and effectiveness profiles according to their ADME and toxicity evaluations. Through a comprehensive screening process employing in silico drug design methods, this study successfully identified five potential human anticancer drug candidates targeting the beta-catenin protein. These findings offer a foundation for further experimental validation and development towards the treatment of EC.

516. HELLER MYOTOMY FOR SYMPTOMATIC ACHALASIA: TRADITIONAL LAPAROSCOPY OR ROBOTICS? A SYSTEMATIC REVIEW WITH META-ANALYSIS

Abstract Background Laparoscopic Heller myotomy (LH) has been established as the gold standard for symptomatic achalasia; robotic-assisted laparoscopic myotomy (RH) has shown promising outcomes regarding safety and effectiveness. We aim to meta-analyse data comparing LH and RH surgical outcomes and complications. Methods A systematic search was conducted in February 2024 without restrictions according to PRISMA guidelines in PubMed, Web of Science, Scopus, and Cochrane Register. Studies comparing laparoscopic and robotic approach for Heller myotomy in adults with symptomatic achalasia were included for systematic review. Meta-analysis was performed trough generalized linear mixed model in R 4.3.2. Results 16 observational studies, out of 273, were included; reporting on 15076 patients. No statistically differences in preop characteristics were noted. RH had significantly fewer intraoperative esophageal perforations (OR=7.29, p< 0.0001, 95%), fewer subsequent myotomies and endoscopic treatments for recurrence (OR= 3.64, p=0.01 and OR= 3.38, p=0.03) and better symptom score improvement (OR=0.507, p=0.04). Although not clinically significant, RH had shorter hospital stays (MD=0.45 days, p= 0.005,) and reduced intraoperative blood loss (MD=10.46 ml, p=0.0002). Although not statistically significant, RH had fewer bleeding episodes, lower conversion, reintervention and mortality rates, comparable morbidity and postoperative GERD and higher operative time. Conclusion This updated meta-analysis suggests that RH is associated with lower regarding perforations, recurrence rates and symptom improvement compared to LH, with negligible lengthening of operative times. RH for symptomatic achalasia represents a feasible treatment for symptomatic achalasia, with a satisfying safety and effectiveness profile. RCTs on the topic and about cost-effectiveness evaluations are necessary to support the reported data.

Methodical and Immunological Insights of Prime COVID-19 Vaccines

Abstract:: Vaccines' discovery, manufacturing, and distribution have been on a historic uptick in response to this worldwide COVID-19 pandemic. A handful of vaccines have been approved on an emergency basis after passing minimal clinical trials. There are voids in the existing body of research and the published body of work on phase II and III clinical trial outcomes, efficacy, and recently developed side effects of the approved COVID-19 vaccines. Furthermore, the immunological and methodological insights of successful vaccinations are still unpopular and are not publicly reported. We have attempted to review some major classes of COVID-19 vaccines, namely inactivated viral particle vaccine (BBV152 - Covaxin), mRNA vaccines (BNT162b2 - Pfizer and mRNA-1273- Moderna), viral vector vaccines (Gam-COVID-Vac-Sputnik and ChAdOx1-S-Astrazeneca) and protein subunit vaccine (NVX-CoV2373-Novavax) and discuss their methodological and immunological formulations. This review intends to address the existing literature's gaps and limitations and the vaccine’s safety, efficiency, and effectiveness profiles. This report, by accumulating and comparing the existing publicly available literature and datasheets of the vaccines, concludes that the efficacy of the vaccinations has been found to be 81% for BBV152 (COVAXIN), 94.5% for BNT162b2 (Pfizer), 94.5% for mRNA-1273 (Moderna), 91.6% for Gam-COVID-Vac (Sputnik V), 62–90% for ChAdOx1-S (AstraZeneca), and 96.4% for NVX-CoV2373 (Novavax), demonstrating their efficacy in lowering the severity and frequency of SARS-CoV-2 infection. We conclude that while the commercially approved vaccines have a few limitations regarding clinical trials and side effects, they provide immunity with efficacy ranging from 81% to 96.4% against COVID-19.

Damoctocog Alfa Pegol, a PEGylated B-domain Deleted Recombinant Extended Half-life Factor VIII for the Treatment of Hemophilia A: A Product Review.

Damoctocog alfa pegol (BAY 94-9027, Jivi®), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies. The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Damoctocog alfa pegol was generally well tolerated and none of the patients in any of the clinical trials, including the PROTECT VIII clinical program, HEM-POWR, or ongoing single-center studies, developed FVIII inhibitors. Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences.

Microparticles Made with Silk Proteins for Melanoma Adjuvant Therapy.

Melanoma is one of the most aggressive forms of skin cancer, which is characterized by metastasis and poor prognosis due to the limited effectiveness of current therapies and the toxicity of conventional drugs. For this reason and in recent years, one of the most promising strategies in the treatment of this form of cancer is the use of drug delivery systems as carriers capable of conveying the therapeutic agent into the tumor microenvironment, thus preventing its degradation and improving its safety and effectiveness profiles. In the present work, microparticles based on silk fibroin and epifibroin 0039, silk-derived proteins loaded with idebenone, were created, which act as therapeutic carriers for topical use in the treatment of melanoma. The resulting particles have a spherical shape, good loading efficiency, and release capacity of idebenone. Efficacy studies have demonstrated a reduction in the proliferation of COLO-38, melanoma tumor cells, while safety tests have demonstrated that the microparticles are not cytotoxic and do not possess prosensitizing activity. Notably, transdermal release studies revealed that all particles released idebenone over more days. The analysis of the stimulatory markers of the proinflammatory process, CD54 and CD86, did not show any increase in expression, thus confirming the absence of potential prosesensitization effects of the silk fibroin-based particles. The research, therefore, found that idebenone-loaded silk protein microparticles could effectively reduce the proliferation of melanoma cells without cytotoxicity. This indicates the promise of a safe and effective treatment of melanoma.

Implementasi Strategi Customer Relationship Management (CRM) Pada PT PLN (Persero) UP3 Surabaya Barat

Customer Relationship Management (CRM) is a crucial strategy in strengthening relationships with customers and improving service quality. This research examines the implementation of CRM at PT PLN (Persero) UP3 West Surabaya, which aims to improve the efficiency of collecting and analyzing customer data through the use of application technology and websites. By understanding customer characteristics, behavior, and needs through effective profiling, PT PLN (Persero) UP3 West Surabaya can develop a more personalized and responsive CRM strategy, and improve ongoing interaction with customers. This research uses observation method and qualitative approach with literature review method to examine CRM implementation at PT PLN (Persero) UP3 West Surabaya. The results showed that the use of a customer profiling database can help PT PLN in creating a better customer experience and increasing customer loyalty. Successful CRM implementation requires careful planning, adequate technology, and support from all parties in the organization.

Analgesic and Anti-Inflammatory Activity: A Comprehensive Review on Invitro and In Vivo Screening Methods

Modern pharmacotherapy includes analgesic and anti-inflammatory medicines as essential components to relieve pain and inflammation brought on by a variety of medical diseases. Robust screening techniques are essential for the identification of possible candidates with appropriate safety and effectiveness profiles in the search and development of new analgesic and anti-inflammatory medications. This study looks at the many screening methods used in preclinical studies to assess new drugs' analgesic and anti-inflammatory quality. Conventional techniques like the tail flick, hot plate, and writhing’s tests measure analgesic activity by having animals respond to unpleasant stimuli. Comparably, anti-inflammatory activity is frequently assessed using assays like the cotton pellet granuloma test, which gauges tissue granuloma formation, and the carrageenan-induced paw edema model, which measures inflammation. These traditional techniques offer insightful information about the pharmacological effects of test substances. Despite the wide range of screening techniques available, each strategy has advantages and disadvantages. Preclinical studies are more reliable and have higher predictive value when various assays and techniques are integrated into a tiered screening strategy. Furthermore, the successful translation of preclinical findings to human applications depends on taking into account translational variables including species differences and clinical relevancies. As a result, choosing the right screening techniques is critical to the effective identification and characterization of new analgesic and anti-inflammatory drugs.

Safety and effectiveness of clofarabine in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia: a post-marketing surveillance study.

Clofarabine is used to treat acute lymphoblastic leukaemia, but evidence of its safety and effectiveness in Japanese patients is limited. We evaluated the safety and effectiveness of clofarabine in patients with relapsed/refractory acute lymphoblastic leukaemia in real-world clinical practice in Japan. An observational, multicenter, post-marketing, all-case surveillance was conducted for safety. Effectiveness analyses were conducted in patients aged ≤21years and those treated with clofarabine monotherapy and combination therapy (clofarabine plus etoposide and cyclophosphamide). In the all-case survey, 260 of 264 registered patients were eligible for safety analysis. Among the 225 patients eligible for effectiveness analysis, 139 were aged ≤21years. For monotherapy and combination therapy, 20/31 and 34/88 patients were eligible, respectively. In the all-case survey, the median age was 16.0years, and 47.7% of patients were<15years old. Adverse drug reaction incidence was 83.5% and the most common were hematologic toxicities. The best overall response rates in the population aged ≤21years were complete remission, 29.7%; complete remission without platelet recovery, 7.3% and partial remission, 10.9%. The rest (52.2%) were classified as ineffective. The sum of complete remission, complete remission without platelet recovery and partial remission rates (effectiveness rate) was 47.8% (66/138 patients). The effectiveness rates in the monotherapy and combination therapy surveys were 10.0% (2/20 patients) and 58.8% (20/34 patients), respectively. These post-marketing surveys provide real-world evidence of the safety and effectiveness of clofarabine regimens, including monotherapy and combination therapy in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia. The safety and effectiveness profiles were comparable with those of previous prospective studies.

Embolization of a pseudoaneurysm of the innominate artery with a Woven EndoBridge (WEB) device.

The Woven EndoBridge (WEB) is an intra-aneurysmal flow disruptor designed for the treatment of broad-based arterial aneurysms with a high safety and effectiveness profile.1, 2 It does not require concomitant antiplatelet therapy compared to other devices such as flow diverters or intracranial stents. Innominate artery pseudoaneurysms are a rare consequence of blunt traumatic injury, infection, or atherosclerotic disease.3, 4 We describe the case of an innominate artery pseudoaneurysm successfully treated with a WEB SL device instead of stenting, therefore alleviating the need for dual antiplatelet therapy. The treatment was successful and uneventful and postprocedural computed tomography angiography confirmed the complete occlusion of the pseudoaneurysm.

Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Real-world outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma in Japanese patients: data with a minimum of 3years of follow-up.

Long-term follow-up data regarding treatment outcomes of nivolumab plus ipilimumab combination therapy for advanced renal cell carcinoma as a first-line therapy are limited in real-world Japanese populations. We retrospectively evaluated data of 56 advanced renal cell carcinoma patients treated with nivolumab plus ipilimumab, with a follow-up of at least 3years. Survival, tumour response and adverse event profiles were assessed. A total of 41 patients (73%) were histopathologically diagnosed with clear-cell renal cell carcinoma, and 34 (61%) were categorized into the International Metastatic renal cell carcinoma Database Consortium intermediate-risk group. The median follow-up period was 34.4months. Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0months, respectively. Objective response was observed in 27 patients (48%), including eight patients with complete response (14%), and the median duration of response was 30.8months. Multivariate analyses showed that clear-cell histology was an independent factor of longer overall survival (hazard ratio: 0.23, P=0.0013). Regarding safety profiles, adverse events of any grade and those with grade≥3 developed in 40 (71%) and 25 patients (45%), respectively. Median time to adverse event development was 1.68months. Treatment was interrupted in 28 patients (50%), and corticosteroid administration was needed in 25 (45%). The 3-year follow-up data showed that nivolumab plus ipilimumab combination therapy exhibited a feasible effectiveness in real-world Japanese patients with advanced renal cell carcinoma. Accordingly, the high risk of adverse event development, which often requires treatment withdrawal and corticosteroid administration, should be considered.

Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA).

Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Desenho de Estudo de um Estudo Observacional Brasileiro sobre o uso de Edoxabana em Pacientes com Fibrilação Atrial (EdoBRA)

Abstract Background: Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. Objective: In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. Methods: The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. Conclusion: EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Direct Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: First Meta-Analysis of Prospective Studies.

Direct oral anticoagulants (DOACs) are becoming increasingly popular clinically, but their safety and effectiveness profile in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is not well-established. Literature from the PubMed and EMBASE databases was systematically screened up to February 2024 to identify relevant studies on the use of DOACs in CTEPH patients. The bias risk of RCTs was assessed using the Cochrane Risk of Bias Tool 2.0. The quality of observational prospective cohorts was assessed using the Newcastle-Ottawa Scale tool. Data pooled from different studies were analyzed. Results from 4 studies were gathered, including 2 randomized controlled trials and 2 prospective cohorts, with a total of 2038 patients, of which 751 were on DOACs and 1287 were on vitamin K antagonists (VKAs). Similar rates of all-cause mortality (3.33% vs 3.33%, RD = -0.01%, 95% CI [-0.02%, 0.00%], P = .17), VTE recurrence (1.46% vs 2.12%, RD = -0.00%, 95% CI [-0.01%, 0.01%], P = .92) were observed. DOACs were associated with a nonsignificant reduction in bleeding events including major bleeding (2.22% vs 3.71%, RD = -0.01%, 95% CI [-0.04%, 0.01%], P = .30), any bleeding (5.33% vs 9.94%, RD = -0.03%, 95% CI [-0.07%, 0.01%], P = .10), and minor bleeding (4.17% vs 13.3%, RD = -0.06%, 95% CI [-0.23%, 0.10%], P = .45). Data pooled from existing perspective trials suggests the use of DOACs in CTEPH patients as an effective and safe alternative to VKAs.

Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Amplatzer™ Vascular Plugs for Embolisation: A 10-Year Single-Centre Retrospective Study

Our objective was to investigate the indications, effectiveness, and safety of Amplatzer™ Vascular Plugs (AVPs) in clinical practice. To retrospectively identify patients managed with AVPs at the Dijon University Hospital between January 2011 and April 2021, we searched materials vigilance registries and procedure reports. The 110 identified patients underwent 111 procedures with delivery of 202 AVPs into 118 vessels; 84% of the procedures were performed by radiologists with over 10 years’ experience and 67% were scheduled. Varicocele, haemostasis, pelvic varicose veins, and arterio-venous dialysis fistulas accounted for 69% of procedures. The technical and clinical success rates were 99% and 97%, respectively. The single major complication was AVP migration in a high-flow internal iliac vein, with no residual abnormalities after successful device retrieval. Several AVPs and/or concomitant injection of coils or liquid agents were used in 80% of cases. The use of AVPs alone occurred chiefly for splenic artery embolisation in trauma patients and for collateral vein occlusion in dysfunctional arterio-venous dialysis fistulas. No cases of recanalisation occurred during the 19 ± 29 month follow-ups. Based on their good safety and effectiveness profile, AVPs deserve to be part of the therapeutic armamentarium of every interventional radiologist.

Patterns of anti-CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy.

To describe the pattern of anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) utilization in the Tuscany region, Italy, and the variation of triptan consumption after treatment initiation. Given the recent commercialization of anti-CGRP mAbs as migraine preventive medications, real-world evidence on their patterns of utilization and their impact on migraine abortive medication use is still limited. A retrospective, descriptive, cohort study on the real-world utilization of anti-CGRP mAbs was performed using the population-based regional administrative database of Tuscany. Patients with ≥1 anti-CGRP mAb dispensing (namely erenumab, galcanezumab, fremanezumab) between April 1, 2019, and September 30, 2021, were identified. The first dispensing was the cohort entry (CE). New users (NUs) were patients with no anti-CGRP mAb dispensing before CE. Kaplan-Meier (KM) curves were plotted to describe the cumulative probability of remaining with the initial anti-CGRP mAb during a 15-month follow-up period as a measure of treatment persistence. Among NUs with ≥2 triptan dispensings during the 6 months before CE (i.e., baseline), the mean monthly number of triptan dosage units dispensed was measured in five consecutive follow-up time windows (months 1-3, 4-6, 7-9, 10-12, 13-15) and the difference from the baseline was calculated. A total of 624 NUs (erenumab = 295, galcanezumab = 223, fremanezumab = 106) were identified, of whom 188 (78%) were women. Mean age was 49.2 years (standard deviation [SD] = 12.6). The survival to discontinuation at 6, 12, and 15 months was about 69%, 48%, and 6%, respectively. The survival to switch was about 6% at 15 months. The observed variation of triptan consumption at 3/6/9/12/15 months and the corresponding SD was -4.4 [8.2]/-5.2 [9.0]/-5.5 [9.2]/-5.4 [9.2]/-4.5 [10.0], respectively. Patient demographics reflect the place of these medications in therapy. Overall, findings seem to indicate a favorable tolerability and effectiveness profile. Further studies are warranted to better establish the long-term comparative effectiveness, safety, and cost effectiveness of anti-CGRP mAbs compared to other preventive medications.

Treatment of migraine in children and adolescents. The state of the art

IntroductionHeadaches and migraine are common in the pediatric population, being one of the most frequent symptoms reported in practice. Additionally, it is a considerably disabling condition, which brings significant burden and impairs several aspects of a child or adolescent's life, such as mental and physical health, executive functioning, school performance. Children and adolescents with migraine have higher risk of psychiatric comorbidities and psychosocial adjustment difficulties, which, in turn, compromise even more patient's well-functioning.ObjectiveThe present article provides the clinician with a straightforward and evidence-based approach to migraine treatment in this age group.CommentTreatment of migraine in children and adolescents requires a systematic and thorough approach. Clinicians should keep in mind the important burden migraine brings to a child's life, thus investigate, and properly manage comorbidities presented. Patient and parents' education is a meaningful part of the treatment. Moreover, non-pharmacological treatments, such as healthy lifestyle habits, behavioral interventions may also play beneficial roles. When preventive treatment is indicated, it should be tailored considering drug's profile of effectiveness and safety, as well as patient's comorbidities. Lack of evidence in this context must not translate in lack of action by the clinician, since there may be a relevant burden associated. Therefore, reasoning for the perspicacious clinician is of fundamental importance and may influence positively the outcomes.

Thromboembolic Events With the Woven Endobridge Device: Incidence, Predictive Factors, and Management.

The Woven EndoBridge (WEB) device has been increasingly used to treat wide-neck aneurysms showing a safe and effective profile, but a relatively high number of thromboembolic events (TEEs) have been reported with such treatment. We aimed to evaluate the incidence and management of TEEs and possible predictive factors related to WEB embolization of ruptured and unruptured intracranial aneurysms. A single-center database with consecutive aneurysms treated with a WEB device between July 2012 and May 2022 was reviewed for intraoperative and delayed TEEs. Univariate and multivariable analyses were used to determine factors associated with TEEs. A total of 266 independent aneurysms were treated with WEB devices in 245 patients (mean age 55.78 ± 11.64 years, 169 (63.5%) females, 80 (30%) ruptured). The overall rate of TEEs is 13% (35/266), including 8.7% intraoperative. Symptomatic TEEs with clinical sequelae at a 3-month follow-up are reported to be 2.6% (7/266) with no TEE-related mortality. Both the replacement of a WEB device during the procedure (adjusted odds ratio = 2.61, 95% CI 1.24-5.49; P = .01) and ruptured aneurysms (adjusted odds ratio = 2.74, 95% CI 1.31-5.7; P = .007) were independent predictors of TEEs. A case-by-case management of intraprocedural TEE is also presented; tirofiban was successfully used in most cases of this cohort. In this study, we demonstrated that ruptured aneurysms and WEB device replacement during the procedure were independent predictive factors for TEEs. As a result, making the correct choice of WEB is crucial for improving treatment outcomes. Moreover, with proper medical management of TEEs, minimal morbidity and no mortality could be achieved, which reinforces the safety of the technique.