Search

Higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with increased risk of thrombosis, cardiovascular mortality, but their role in myeloproliferative neoplasms (MPN) remains unclear. We analyzed NLR and PLR as prognostic markers for thrombosis and overall survival (OS) in the study that included 461 consecutive MPN patients who were diagnosed from 2018 to 2022 at University center. Twenty age-matched patients without hematological disorder were used as controls. NLR and PLR were significantly increased in whole MPN group compared to controls. NLR was highest in PV > PMF > ET (p < 0.001) while PLR was highest in ET > PMF > PV (p < 0.001). Thrombosis occurrence during follow-up correlated with NLR, NLR ≥ 4.5, presence of ≥ 2 CV factors and previous thrombosis. Arterial thrombosis was associated with previous thrombosis, NLR and NLR ≥ 4.5. Similarly in venous thrombosis previous thrombosis was risk factor, together with NLR, NLR ≥ 4.5, PLR, but also secondary malignancy and female gender. In multivariate Cox model, most important factors for thrombosis development during follow-up were previous thrombosis, NLR ≥ 4.5 and PLR ≥ 500; for arterial thrombosis, NLR ≥ 4.5 and previous thrombosis; for venous thrombosis PLR ≥ 500 and previous thrombosis. Patients with pre-PMF had significantly higher NLR than ET patients. In multivariate Cox regression model, most important factors associated with survival were NLR ≥ 4.5 and PLR ≥ 500. This study highlights strong prognostic correlation of NLR ≥ 4.5 and PLR ≥ 500 with development of thrombosis and OS in MPN. Besides previous thrombosis, most important factor associated with development of arterial thrombosis is NLR ≥ 4.5 and for venous PLR ≥ 500. Our results revealed that NLR ≥ 4.5 could be used as additional marker to distinguish ET from prePMF., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The reduction of fluoroscopic exposure during catheter ablation of supraventricular arrhythmias is widely adopted by experienced electrophysiology physicians with a relatively short learning curve and is becoming the standard of care in many parts of the world. While observational studies in the United States and some parts of Western Europe have evaluated the minimal fluoroscopic approach, there are scarce real-world data for this technique and the generalizability of outcomes in other economic regions., Method: The AALARA study is a prospective, observational, multicenter, and multinational open-label study. Patients were recruited from 13 countries across Central Eastern Europe, North and South Africa, the Middle East, and the CIS (Commonwealth of Independent States), with different levels of operator expertise using minimal fluoroscopic exposure techniques. Data on radiation exposure, procedural success, complications, recurrence, and quality of life changes were collected and analyzed., Result: A total of 680 patients were enrolled and followed for 6 months. The majority were ablation naïve with the commonest arrhythmia ablated being typical AVNRT (58%) followed by Atrial Flutter (23%). Zero fluoroscopy exposure was observed in almost 90% of the cases. Fluoroscopy was most commonly used during the ablation phase of the procedure. We observed a high acute success rate (99%), a low complication rate (0.4%), and a 6-month recurrence rate of 3.8%. There was a significant improvement in the patient's symptoms and quality of life as measured by patient global assessment., Conclusion: The routine use of a 3D mapping system during right-sided ablation was associated with low radiation exposure and associated with high acute success rate, low complications, and recurrence rate along with significant improvement in quality of life. The data confirm the reproducibility of this approach in real-world settings across different healthcare systems, and operator experience supporting this approach to minimize radiation exposure without compromising efficacy and safety., Trial Registration: NCT04716270., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

With the global introduction and widespread administration of COVID-19 vaccines, there have been emerging reports of associated vasculitis, including leukocytoclastic cutaneous vasculitis (LCV). In this paper, we present a case of a 68-year-old female patient who developed painful purpuric skin lesions on her feet 12 days after administration of the inactivated COVID-19 vaccine BBIBP Cor-V with histopathological confirmation of LCV and no signs of systemic involvement. The case is followed by a comprehensive literature review of documented LCV cases associated with COVID-19 vaccination with overall 39 articles and 48 cases of LCV found in total. In the majority of cases (56.3%) the first symptom occurred after the first dose of the COVID-19 vaccine, with symptoms manifesting within an average of seven days (6.8 ± 4.8) post-vaccination. The adenoviral vaccine Oxford-AstraZeneca (41.7%) and the mRNA vaccine Pfizer-BioNTech (27.1%) were most frequently associated with LCV occurrences. On average, LCV resolved within 2.5 (± 1.5) weeks. The preferred treatment modality were glucocorticoids, used in 70.8% of cases, resulting in a positive outcome in most cases, including our patient. While the safety of a subsequent dose appears favorable based on our review, individual risk-benefit assessment is crucial. This review emphasis the importance of considering COVID-19 vaccination as a potential trigger for the development of cutaneous vasculitis. Despite rare adverse events, the benefits of the COVID-19 vaccination outweigh the risks, highlighting the importance of immunization programs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis. This study aims to identify potential risk factors associated with high-risk carotid plaques., Methods: This is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, North American Symptomatic Carotid Endarterectomy Trial criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated., Results: A total of 62 patients (mean age: 68.7 ± 9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81% ± 13.53%. In multivariate regression analysis, C-reactive protein > 2 mg/l was strongly associated with symptomatic stenosis (odds ratio [OR] = 9.92 [1.12-88.178]; P = 0.039), and low high-density lipoprotein levels (<1200 mmol/l) were associated with lipidic/necrotic plaque core (OR = 16.88 [1.10-259.30]; P = 0.043). Low high-density lipoprotein levels (OR = 7.22 [1.00-51.95], P = 0.049) and HbA1c >7% (OR = 0.08 [0.01-0.93], P = 0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR = 14.26 [1.21-168.34], P = 0.035) was associated with type V plaques., Conclusions: This preliminary study has revealed some potential risk factors associated with unstable carotid plaques. These data could help the future development of prognostic models for early detection patients that could benefit from further intervention., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the recent years, there has been a burgeoning interest in Takotsubo syndrome (TTS), which is renowned as a specific form of reversible myocardial dysfunction. Despite the extensive literature available on TTS, clinicians still face several practical challenges associated with the diagnosis and management of this phenomenon. This potentially results in the underdiagnosis and improper management of TTS in clinical practice. The present paper, the first part (part-1) of the consensus report, aims to cover diagnostic and therapeutic challenges associated with TTS along with certain recommendations to combat these challenges., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Takotsubo syndrome (TTS) still remains as an enigmatic phenomenon. In particular, long-term challenges (including clinical recurrence and persistent symptoms) and specific entities in the setting of TTS have been the evolving areas of interest. On the other hand, a significant gap still exists regarding the proper risk-stratification of this phenomenon in the short and long terms. The present paper, the second part (part-2) of the consensus report, aims to discuss less well-known aspects of TTS including specific entities, challenges after recovery and risk-stratification., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Background: In 2020, the coronavirus disease 2019 (COVID-19) pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe., Methods: Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017-2019. Changes occurring during the first and second waves of the pandemic were also explored., Results: The incidence of KRT was 6.2% lower in 2020 compared with 2017-2019, with the lowest point (-22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (-5.2%) than in females (-8.2%) and was moderate for peritoneal dialysis (-3.7%) and haemodialysis (-5.4%) but substantial for pre-emptive kidney transplantation (-23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of -80.1% during the first wave, and was greatest for living donor kidney transplants (-30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decrease. In dialysis patients, mortality increased by 11.4% and was highest in those 65-74 years of age (16.1%), in those with diabetes as the primary renal disease (15.1%) and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N = 317 787) resembled that of 2019 (N = 317 077)., Conclusion: The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT and prevalence of KRT in Europe with variations across countries., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Competing Interests: Declaration of competing interest N.M. reports consulting fees from Bayer, Novartis, Amgen, AstraZeneca, payment or honoraria for lectures from Boehringer Ingelheim. D.N reports consulting fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gerson Lehman Group (GLG) Consulting, Novo Nordisk, Pfizer and Zoll, payment or honoraria for lectures from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Novo Nordisk, Pfizer; К.К. reports payment or honoraria for lectures from AstraZeneca K.K.,Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novartis Pharmaceuticals Co., Ltd.; A.J.D. reports grants or contracts from Pfizer and Alnylam; I.M. payment or honoraria for lectures from Boehringer Ingelheim, support for attending meetings from Boehringer Ingelheim;M.I.F.J.O reports payment or honoraria for lectures to the institution from Novartis and Pfizer; A.B. reports consulting fees, payment or honoraria for lectures from Boehringer Ingelheim, AstraZeneca (to the institution), support for attending meetings from Novartis, Bayer, Boehringer Ingelheim (to the institution), AstraZeneca (to the institution), Participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Bayer, Boehringer Ingelheim (to the institution), Member of Heart Failure Task force under the Danish Society of Cardiology; MT reports being HFA Board member; H.S. reports payment or honoraria for lectures or advisory board meetings from Boehringer Ingelheim, AstraZeneca, Novartis, Novo Nordisk, Servier, Abbott, Roche, Vifor; FR has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Amgen, Astra Zeneca, At the Limits Ltd., Bayer, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, CM Microport, Concept Medical, CTI, Daiichi Sankyo, Edwards Lifesciences, FomF GmbH, Hamilton Health Sciences, IHF, Innosuisse, IumiraDX, Kantar, LabPoint, MedAlliance, Medcon International, Medical Education Global Solutions, Medtronic, MicroPort, Monocle, Novartis, Novo Nordisk, OM Pharma, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, Terumo Deutschland, Trama Solutions, V- Wave, Vifor, ZOLL. These grants do not impact on Prof. Ruschitzka`s personal remuneration. Remuneration for the time spent in following consulting activities were made directly to the University of Zurich and do not impact on Prof. Ruschitzka`s personal remuneration:AstraZeneca (IMC), Bayer, Boehringer Ingelheim, Citi Research, Klub Class, Novo Nordisk, Radcliffe Group, Stiftung Pfizer Forschungspreis, Vifor Remuneration for following lectures were made directly to the University of Zurich and do not impact on Prof. Ruschitzka`s personal remuneration: Abbott, Amgen, AstraZeneca (A+ Science AB), Bayer (At the Limits), Boehringer Ingelheim, Boston Scientific (CCE Services), Brigham and Women's Hospital Boston, C.T.I GmbH, FomF, Hôpitaux Universitaires des Genève (GECORE), Luzerner Kantonsspital, Sanofi-Aventis, Servier, Medcon, Medscape (WebMD), Medtronic, Medworld, Novartis, Roche, Ruwag, Swiss Heart Failure Academy, The Hong Kong Heart Failure Society, Trama Solutions SL, Inselspital Bern, Charité – Universitätsmedizin Berlin (Medical Education Global Solutions), Romanian Society of Cardiology, ÖKG Österreichische Gesellschaft für Kardiologie, Zoll; reports support for attending meetings from AstraZeneca (IMC / A+ Science AB), Boehringer Ingelheim, Centro Hospitaler de Vila Nova de Gaia, C.T.I. GmbH (Universitätsklinikum Düsseldorf), European Society of Cardiology, Monocle, Novartis, Spektar Putovanja, Austrian Heart Failure Association, Heart Failure Association of the ESC. Remuneration for following Advisory Boards were made directly to the University of Zurich and do not impact on Prof. Ruschitzka`s personal remuneration: Bayer: HF Expert Summit, Advisory Board Meeting Roche: Advisory Board Meeting IMC/AstraZeneca: Advisory Board Meeting Amgen: Advisory Board Meeting; C.S. reported grants /contracts from Novartis, Merck and Bayer, payment or honoraria for lectures from Servier, Novartis, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Ely Lilly, Pfizer, Sanofi, participation in Advisory Board for Merck, Bayer and Novo Nordisk. All other authors have nothing to disclose.

Background: Acute intracranial occlusion of the internal carotid artery (ICA) can be distinguished into (a) occlusion of the terminal ICA, involving the proximal segments of the middle or anterior cerebral artery (ICA-L/-T) and (b) non-terminal intracranial occlusions of the ICA with patent circle of Willis (ICA-I). While patients with ICA-L/-T occlusion were included in all randomized controlled trials on endovascular therapy (EVT) in anterior large vessel occlusion, data on EVT in ICA-I occlusion is scarce. We thus aimed to evaluate effectiveness and safety of EVT in ICA-I occlusions in comparison to ICA-L/-T occlusions., Methods: A large international multicentre cohort was searched for patients with intracranial ICA occlusion treated with EVT between 2014 and 2023. Patients were stratified by ICA occlusion pattern, differentiating ICA-I and ICA-L/-T occlusions. Baseline factors, technical (modified thrombolysis in cerebral infarction (mTICI) scale) and functional outcomes (modified Rankin scale [mRS] at 3 months) as well as rates of (symptomatic) intracranial hemorrhage ([s]ICH) were analyzed., Results: Of 13,453 patients, 1825 (13.6%) had isolated ICA occlusion. ICA-occlusion pattern was ICA-I in 559 (4.2%) and ICA-L/-T in 1266 (9.4%) patients. Age (years: 74 vs 73), sex (female: 45.8% vs 49.0%) and pre-stroke functional independency (pre-mRS ⩽ 2: 89.9% vs 92.2%) did not differ between the groups. Stroke severity was lower in ICA-I patients (NIHSS at admission: 14 [7-19] vs 17 [13-21] points). EVT was similarly successful with respect to technical (mTICI2b/3: 76.1% (ICA-I) vs 76.6% (ICA-L/-T); aOR 1.01 [0.76-1.35]) and functional outcome (mRS ordinal shift cOR 1.01 [0.83-1.23] in adjusted analyses. Rates of ICH (18.9% vs 34.5%; aOR 0.47 [0.36-0.62] and sICH (4.7% vs 7.3%; aOR 0.58 [0.35-0.97] were lower in ICA-I patients., Conclusion: EVT might be performed safely and similarly successful in patients with ICA-I occlusions as in patients with ICA-L/-T occlusions., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RRL received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic and Abott and advisory board honoraria from Jansen and Bayer.STE has received funding for travel or speaker honoraria from Bayer, Boehringer Ingelheim and Daiichi-Sankyo. He has served on scientific advisory boards for Bayer, Boehringer Ingelheim, BMS/Pfizer, and MindMaze and on the editorial board of Stroke. His institutions have received an educational grant from Pfizer, compensation from Stago for educational efforts and research support from Daiichi-Sankyo, the Science Funds [Wissenschaftsfonds] of the University Hospital Basel, the University Basel, from the “Wissenschaftsfonds Rehabilitation” of the University Hospital for Geriatric Medicine Felix Platter, the “Freiwillige Akademische Gesellschaft Basel,” the Swiss Heart Foundation, and the Swiss National Science Foundation.HG has received research support from the Swiss National Science Foundation, advisory board honoraria from Daiichi Sankyo and funding for travel from BMS/Pfizer.AZ received speaker honoraria from CSL Behring, Boehringer-Ingelheim, Alexion-Astra Zeneca and Daiichi Sankyo and advisory board honoraria from Bayer, Astra Zeneca and Daiichi Sankyo.DRJ received speaker honoraria from Medtronic and Boehringer Ingelheim.VP received speaker honoraria from Medtronic and Boehringer Ingelheim.H.J.A. reports receiving personal fees from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, and Roche that all produce products for hyperacute stroke care.MRH reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript.AS received travel grants from NovoNordiskPM received grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and Faculty of Biology and Medicine of the Lausanne UniversityCHN reports receiving speaker honoraria from Abbot, Alexion, AstraZeneca, Bristol-Meyers Squibb, Pfizer and Takeda, all outside the submitted work.All further authors declare no conflicts of interest related to the presented study.

Background: Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a collective cohort of patients with major depressive disorder (MDD) and bipolar disorder (BD), as a unified group with two distinct phenotypes., Methods: The study included 138 patients with acute mood episodes (BD = 83; MDD = 55). HTR2A rs6313 and rs6314 genotyping was performed while measuring platelet-derived indicators of inflammation (platelet count (PLT), mean platelet volume (MPV), plateletcrit, and platelet distribution width) and the MPV/PLT ratio., Results: The HTR2A rs6313 variant is a significant predictor of the polarity phenotype in mood disorders, with the MPV/PLT ratio moderating this relationship, but only under low-inflammatory conditions. In more pronounced inflammatory states, genetic influences lose their predictive role., Conclusions: To our knowledge, this is the first study to investigate the complex interplay between platelet-derived indicators of inflammation and HTR2A variants in the context of mood disorders. Without pro-inflammatory conditions, mood disorders seem to be more genetically determined. Under pro-inflammatory conditions, phenotypic presentation is less dependent on genetic factors. GxE interactions in mood disorders are multifaceted, context-dependent and relevant for assessing their clinical presentation and course., (© 2024. The Author(s).)

Background: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance., Objective: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg)., Design: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success., Results: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness., Conclusion: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness., Trial Registration Number: NCT02328131., Competing Interests: Competing interests: XC has received research grants and fees for lectures from Allergan. JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly Spindler, Allergan, Diasorin, Richen, Biocodex and Juvisé. OPN received research funding from Allergan, Mayoly Spindler, Richen, Biocodex and Juvisé. DSB served as a lecturer for Astellas, AstraZeneca, KRKA and Abbott. FM is a consultant for PHATHOM, DaVoltera and has received grants from Allergan, bioMerieux and Mobidiag. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the last few decades, we have gained insight into how researchers attempted to modify some natural molecules to be utilized as prospective agents for cancer treatment. Many scientists synthesized new natural compounds by incorporating specific functional groups and metals that improved their antitumor activity while reducing undesirable side effects. In this investigation, we synthesized four novel structurally modified enones that differ in the functional groups attached to the carbonyl group of the enone system (methyl - E1; isopropyl - E2; isobutyl - E3; and cyclopropyl - E4) and explored their anticancer potential against human carcinoma of the colon HCT-116, the cervical HeLa, and normal lung cells MRC-5. From the findings, all the newly synthesized enones exhibited potent cytotoxic activity against the cancer cells while normal cells remained unharmed, with varying potencies among the various enones. We employed the MTT assay to assess enones's (E1-E4) cytotoxic effects, IC50 values and selectivity index in tumor cells. Furthermore, the newly synthesized enones induced cell death in cancer cells through apoptosis by promoting changes in cellular morphology, activating apoptotic regulators Bax and caspase 3, and inhibiting Bcl-2. The enones induced changes in the mitochondrial membrane potential, a release of cytochrome c, and a cell cycle arrest at the G2/M phase, thus inhibiting the growth of cancer cells. In conclusion, we demonstrated the anticancer potential of newly synthesized enones as promising candidates for future cancer treatments, especially for colon cancer, due to their selective cytotoxicity against these cancer cells. Further, in vivo studies are warranted to explore their full therapeutic potential., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Atrial fibrillation (AF) is a complex disease requiring a multidomain and (usually) long-term management, thus posing a significant burden to patients with AF, practitioners, and health care system. Unlike cardiovascular conditions with a narrow referral pathway (e.g., acute coronary syndrome), AF may be first detected by a wide range of specialties (often noncardiology) or a general practitioner. Since timely initiated optimal management is essential for the prevention of AF-related complications, a concise and simple guidance is essential for practitioners managing AF patients, regardless of their specialty. Guideline-adherent management of patients with AF has been shown to translate to improved patient outcomes compared with guideline-nonadherent treatment. To facilitate guideline implementation in routine clinical practice, a good guideline document on AF should introduce only evidence-based new recommendations, while avoiding arbitrary changes, which may be confusing to practitioners. Herein, we discuss the main changes in the 2024 European Society of Cardiology (ESC) AF Guidelines relative to the previous 2020 ESC document. Whether the updates and new recommendations issued by the new guidelines will translate in high adherence in clinical practice (and hence improved prognosis of patients with AF) will need to be addressed in upcoming years., Competing Interests: T.P. declared no conflict of interest; G.F.R. reports consultancy for Boehringer Ingelheim and an educational grant from Anthos, outside the submitted work. No fees were directly received personally., (Thieme. All rights reserved.)

Biallelic variants in phosphatidylinositol glycan anchor biosynthesis, class G (PIGG) cause hypotonia, intellectual disability, seizures, and cerebellar features. We present 8 patients from 6 families with a childhood-onset motor neuropathy and neurophysiology demonstrating variable motor conduction block and temporal dispersion. All individuals had a childhood onset tremor, 5 of 8 had cerebellar involvement, and 6 of 8 had childhood febrile seizures. All individuals have biallelic PIGG variants, including the previously reported pathogenic variant Trp505*, plus 6 novel variants. Null enzyme activity is demonstrated via PIGO/PIGG double knockout system for Val339Gly and Gly19Glu, and residual activity for Trp505* due to read-through. Emm negative blood group status was confirmed in 1 family. PIGG should be considered in unsolved motor neuropathy. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Since the introduction of insulin therapy, it has become apparent that type 1 diabetes (T1D) is accompanied by long-term microvascular and macrovascular complications. In the context of the many benefits of continuous glucose monitoring (CGM), there remain opportunities to study the large amount of data now available in order to maximise its potential in the endeavour to reduce the occurrence of diabetes tissue complications in the longer term., Methods: Continuous glucose monitoring values were downloaded for 89 type 1 diabetes mellitus (T1D) individuals for up to 18 months from 2021 to 2023. Data for patient demographics was also taken from the patient record which included Sex, Date of Birth, and Date of Diagnosis. The recorded laboratory glycated haemoglobin (HbA1c) test results were also recorded. The glucose management index (GMI) was calculated from average glucose readings for 18 months using the formula GMI (%) = (0.82 - (Average glucose/100)). This was then adjusted to give GMI (mmol/mol) = 10.929 * (GMI (%) - 2.15). Average Glucose Fluctuation (AGF) was calculated by adding up the total absolute change value between all recorded results over 18 months and dividing by the number of results minus one. The % Above Critical Threshold (ACT) was calculated by summing the total number of occurrences for each result value. A cumulative 95% limit was then applied to identify the glucose value that only 5% of results exceeded in the overall population. Using this value, we estimated the percentage of total tests that were above the Critical Threshold (ACT)., Results: The mean age of the participants was 42.6 years, and the mean duration of T1D was 18.4 years. A total of 3.22 million readings were analysed, yielding an average blood glucose level of 10.3 mmol/l and a GMI of 57.2 mmol/mol. There was a strong correlation between GMI and measured HbA1c (r 2  = 0.82). However, there were patients who had an above-critical threshold (ACT) of 4-10% at a GMI of 60 mmol/mol or less. The percentage average value at the time of day (%AVTD) was applied to all blood glucose readings at each 15-min interval throughout the day, averaged over 18 months. The %AVTD of GMI (overall average 57.2 mmol/mol) increased after midday, dipped at 18:00, and peaked at 22:00. The %AVTD of AGF (overall average 0.60 mmol/l) showed higher change rates after 09:00 declining at the end of the day. The %AVTD of ACT peaked at 22:00, with those having the highest %ACT showing an additional peak at 15:00., Conclusions: We have shown here that the percentage glucose results above 18 mmol/l (top 5% of distribution) increased exponentially above 54 mmol/mol HbA1c. The %AVTD is introduced as a useful measure. Our data indicate that over the 24-h period, improvement in metabolic control could be focussed on the afternoon and evening, when there are higher-than-average levels of GMI, a higher-than-average degree of glucose change, and higher-than-average risks of being above the critical threshold. In conclusion, a measure of glycaemic variation based on the amplitude of glucose change to a population mean could be used to provide valuable clinical insights into glucose change over a 24-h period., (© 2024. The Author(s).)

Background and Purpose: This study was undertaken to examine vestibulo-ocular reflex (VOR) characteristics in myotonic dystrophy type 1 (DM1) and type 2 (DM2) using video head impulse testing (vHIT)., Methods: VOR gain, refixation saccade prevalence, first saccade amplitude, onset latency, peak velocity, and duration were compared in DM1, DM2, age-matched normal controls, and patients with peripheral and central vestibulopathies., Results: Fifty percent of DM1 and 37.5% of DM2 patients demonstrated reduced VOR gain. Refixation saccade prevalence for horizontal canal (HC) and posterior canal (PC) was significantly higher in DM1 (101 ± 42%, 82 ± 47%) and DM2 (70 ± 45%, 61 ± 38%) compared to controls (40 ± 28% and 43 ± 33%, p < 0.05). The first saccade amplitudes and peak velocities were higher in HC and PC planes in DM1 and DM2 compared to controls (p < 0.05). HC slow phase eye velocity profiles in DM1 showed delayed peaks. The asymmetry ratio, which represents the percentage difference between the first and second halves of the slow phase eye velocity response, was therefore negative (-22.5 ± 17%, -2.3 ± 16%, and - 4.7 ± 8% in DM1, DM2, and controls). HC VOR gains were lower and gain asymmetry ratio was larger and negative in patients with DM1 with moderate to severe ptosis and a history of imbalance and falls compared to the remaining DM1 patients (p < 0.05). In peripheral vestibulopathies, saccade amplitude was larger, peak velocity was higher, and onset latency was shorter (p < 0.05) than in DM1. In central vestibulopathy (posterior circulation strokes), saccade peak velocity was higher, but amplitude and onset latency were not significantly different from DM1., Conclusions: VOR impairment is common in DM1 and DM2. In DM1, refixation saccade characteristics are closer to central than peripheral vestibulopathies. Delayed peaks in the vHIT eye velocity profile observed in patients with DM1 may reflect extraocular muscle weakness. VOR impairment and VOR asymmetry in DM1 are associated with imbalance and falls., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV's lytic phase contribution to oncogenesis.

Psychotic and mood disorders are discussed as part of the same continuum. The potential role of immune dysregulation in defining their clinical presentations, however, remains unclear. Differences in TNF-α, IL-6 and TGF-β levels were investigated in 143 patients with schizophrenia (SCH = 63) and bipolar disorder (BD = 80), in remission. Cytokines were evaluated against the dimensional assessment of psychosis and affective symptoms using the schizo-bipolar scale, together with the severity of the same symptom domains measured by the brief psychiatric rating scale (BPRS). Lower TGF-β was associated with more lifetime episodes, family risk for psychosis, and more severe mood and psychotic symptoms in all patients. BPRS Affect symptoms domain correlated with lower TGF-β levels in BD, and higher TGF-β levels in SCH patients. Using moderated mediation analysis, TGF-β was a relevant predictor only in the setting of non-categorical symptom distribution, with familial risk for psychosis confirmed as a significant moderator. Severity of BPRS Affect symptoms domain was an independent predictor of inclination towards the psychosis spectrum. The underlying immune dysregulation may be shared by the disorders, rather than a unique characteristic of each, having significant implications for our understanding of the continuum vs. categorical approach to psychosis and mood disorders., (© 2024. The Author(s).)

Background: The inadequacy of intensive care medicine in low-resource settings (LRS) has become significantly more visible after the COVID-19 pandemic. Recommendations for establishing medical critical care are scarce and rarely include expert clinicians from LRS., Methods: In December 2023, the National Association of Intensivists from Bosnia and Herzegovina organized a hybrid international conference on the topic of organizational structure of medical critical care in LRS. The conference proceedings and literature review informed expert statements across several domains. Following the conference, the statements were distributed via an online survey to conference participants and their wider professional network using a modified Delphi methodology. An agreement of ≥ 80% was required to reach a consensus on a statement., Results: Out of the 48 invited clinicians, 43 agreed to participate. The study participants came from 20 countries and included clinician representatives from different base specialties and health authorities. After the two rounds, consensus was reached for 13 out of 16 statements across 3 domains: organizational structure, staffing, and education. The participants favored multispecialty medical intensive care units run by a medical team with formal intensive care training. Recognition and support by health care authorities was deemed critical and the panel underscored the important roles of professional organizations, clinician educators trained in high-income countries, and novel technologies such as tele-medicine and tele-education., Conclusion: Delphi process identified a set of consensus-based statements on how to create a sustainable patient-centered medical intensive care in LRS., (© 2024. The Author(s).)

Extra-skeletal Ewing sarcoma (EWS) occurs in about 12% of EWS patients; at the same time, primary involvement of the kidneys remains extremely rare. Since it was first described in 1975, only a small case series have been reported worldwide. About 95% of surgically treated patients with EWS of the kidney described in the literature underwent nephrectomy, and the remaining patients only had a tumor biopsy. Nephron-sparing surgery (NSS) has not been sufficiently investigated as an alternative in the local surgical treatment of localized disease, mostly as a result of technically unfeasible provisions of negative surgical margins. In this report, we present a unique case of primary EWS of the kidney with an asymptomatic course without radiographic signs that suggest a highly aggressive disease, successfully locally treated with robotic-assisted NSS. This report showcases that robotic-assisted NSS could be a feasible alternative in treatment of localized disease yielding equally good oncological results while, at the same time, creating better prerequisites for necessary adjuvant chemotherapy.

Background/objectives: Degenerative cerebellar ataxias (DCA) present a group of complex neurological disorders primarily affecting the cerebellum and its pathways. Classic manifestations include motor symptoms of cerebellar ataxia. However, emerging evidence suggests that the cerebellum also plays a crucial role in various cognitive and emotional processes. The objective was to assess the psychiatric profile of a heterogeneous group of patients with degenerative cerebellar ataxia., Methods: Our sample comprised 107 participants diagnosed with cerebellar degenerative ataxia. All patients were clinically evaluated using SARA, INAS, and different neuropsychiatric scales (ACE-R, HAMA, HAMD, AS, and GAF)., Results: The majority of patients had autosomal dominant ataxia (38.3%) followed by sporadic ataxia (32.7%) with an average age at the moment of diagnosis of 35.3 ± 16.23 years, while the mean duration of disease at the study beginning was 12.1 ± 9.9 years. Psychiatric disorders were present in 40 patients (37.4%), with dysthymia (14.2%), major depressive disorder (9.4%), and MDD with melancholic features (7.6%). The presence of MDD with melancholic features was statistically significantly correlated with a lower ACE-R total score (r = -0.223; p = 0.022), while dysthymia was statistically significantly associated with a shorter duration of the disease (r = -0.226; p = 0.020) and older age (r = 0.197; p = 0.043). Statistically significant differences were observed between MSA-C patients and those with sporadic ataxia (HDRS p < 0.001, HARS p < 0.001, Apathy Scale p = 0.003, and GAF p = 0.004)., Conclusions: Based on our findings, we can conclude that the degree of motor deficit has a significant impact on the development of psychiatric disorders, including depression, anxiety, and apathy. However, it is not the only factor, and the impact also depends on the type of DCA.

Background/objectives: Stomach infections by Helicobacter pylori can cause acute or chronic gastritis, peptic ulcers, and gastric cancer. The rise in antibiotic resistance is a significant health issue highlighted by the World Health Organization. The increasing number of treatment failures underscores the necessity for antibiotic susceptibility testing (AST). The study aimed to investigate the current prevalence and resistance to fluoroquinolones and clarithromycin with their detected mutations., Methods: Stomach biopsies from symptomatic patients were subjected to molecular testing by GenoType Helico DR kit (Hain Lifescience GmbH, Nehren, Germany)., Results: Positive findings on the presence of H. pylori were detected in 42.4% of symptomatic patients, with the significant majority of patients (69%) having previously failed treatments. The resistance rates to fluoroquinolones and clarithromycin were 53.9% and 58.5%, respectively, with significantly higher rates in secondary resistant strains. The main resistance markers in fluoroquinolones and clarithromycin were N87K (27.4%) and A2147G (78.6%), respectively. Hetero-resistance or mixed genotypes were detected in over 20% of tested patients. During the study period, a significant increase in trends in both fluoroquinolones and clarithromycin resistance rates was observed., Conclusions: Results indicate the need for the implementation of the latest Maastricht VI Consensus recommendations for both AST whenever possible and the use of tailored guided therapy options due to high resistance rates and possible treatment failures. The GenoType Helico DR kit is a useful tool for AST, especially in cases of mixed H. pylori genotypes.

Endometriosis and hyperprolactinaemia are conditions that might lead to infertility as a consequence. The aim of this article was to present the current knowledge about possible relationships between prolactin/hyperprolactinaemia and endometriosis-related infertility. Experimental studies on local prolactin acting as cytokine and relationship of prolactin and endometriotic tissue, as well as clinical studies on hyperprolactinaemia and endometriosis-related infertility suggest the possible role of prolactin in endometriosis-related infertility, but final proof is still missing and the exact pathogenesis of infertility in such cases is still under investigation. Novel strategies in the treatment of endometriosis-related infertility, based on its connection with prolactin such as the use of prolactin receptor antibodies and prolactin receptor antagonists, are under investigation, but adequate clinical studies have yet to be undertaken.

Objectives: CALGB140503/JCOG0802 RCTs comparing lobectomy with sublobar resection in stage IA NSCLC have confirmed the non-inferiority of segmentectomy. Additional insight is needed to improve preoperative work-up and intraoperative strategies to increase safety and promote the dissemination of minimally invasive segmentectomy (MIS). A Delphi panel study assessed the level of consensus among surgeons for the planning and management of MIS., Methods: Twenty-one expert lung surgeons represented academic institutions, major teaching hospitals, and community hospitals from Europe, North America, and Asia. A 3-round Delphi methodology was used to analyse the answers of each panellist. Recognizing that questions with fewer response options have a higher consensus probability due to limited variability, weighted consensus thresholds were modified based on the number of response options., Results: The 21 panellists responded to all 3 rounds of questions. Based on the most robust consensus (94.4%), 3D chest CT reconstructions are recommended only when planning complex segmentectomies. Surgeons should perform 3D reconstructions chest CT scans (consensus = 83.3%). The most effective and safest technique is image-guided VATS in a hybrid operating room (consensus = 83.3%). Dyes with intravenous administration are the safest technique for identifying the intersegmental plane during MIS (consensus = 72.2%). Augmented/mixed reality will probably not immediately help reduce perioperative complications (consensus = 72.2%)., Conclusions: This Delphi consensus supports 3D reconstructions and preoperative pulmonary nodule localization before complex MIS. These recommendations should be considered when allocating resources to improve MIS's safety and oncologic efficacy for patients with small, early-stage lung cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis. We evaluated the safety, tolerability, and efficacy of subcutaneous efgartigimod PH20 in adults with CIDP., Methods: ADHERE, a multistage, double-blind, placebo-controlled trial, enrolled participants with CIDP from 146 clinical sites from Asia-Pacific, Europe, and North America. Participants with evidence of clinically meaningful deterioration entered an open-label phase of weekly 1000 mg subcutaneous efgartigimod PH20 for no longer than 12 weeks (stage A). Those with confirmed evidence of clinical improvement (ECI; treatment responders) entered a randomised-withdrawal phase of 1000 mg subcutaneous efgartigimod PH20 weekly treatment versus placebo for a maximum of 48 weeks (stage B). Participants were randomised (1:1) through interactive response technology and stratified by their adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score change during stage A and their most recent CIDP medication within 6 months before screening. Investigators, the clinical research organisation, and participants were masked to the treatment. The primary endpoint in stage A, evaluated in the stage A safety population, was confirmed ECI (≥1 points aINCAT decrease, ≥4 points [centile metric] Inflammatory Rasch-built Overall Disability Scale increase, or ≥8 kPa grip strength increase after four injections and two consecutive visits). The primary endpoint in stage B, evaluated in the modified intention-to-treat population, was the risk of relapse (time to first aINCAT increase of ≥1 points). ADHERE is registered with ClinicalTrials.gov (NCT04281472) and EudraCT (2019-003076-39) and is completed., Findings: Between April 15, 2020, and May 11, 2023, 629 participants were screened; 322 (114 female, 208 male) entered stage A, of whom 214 (66%, 95% CI 61·0-71·6) had confirmed ECI. In stage B, 221 participants were randomised (79 female, 142 male; 111 to subcutaneous efgartigimod PH20, 110 to placebo). Subcutaneous efgartigimod PH20 significantly reduced the risk of relapse versus placebo (hazard ratio 0·39 [95% CI 0·25-0·61]; p<0·0001). 31 (27·9% [19·6-36·3]) participants given subcutaneous efgartigimod PH20 had a relapse versus 59 (53·6% [44·3-63·0]) given placebo. In stage A, treatment-emergent adverse events (TEAEs) occurred in 204 (63%) participants and serious TEAEs in 21 (7%). In stage B, TEAEs occurred in 71 (64%) participants on subcutaneous efgartigimod PH20 and 62 (56%) participants on placebo, and serious TEAEs in six (5%) on subcutaneous efgartigimod PH20 and six (5%) on placebo. Three deaths occurred: two in stage A (one non-related and one unlikely related to treatment) and one in stage B (placebo group)., Interpretation: ADHERE showed the efficacy of subcutaneous efgartigimod PH20 in reducing the risk of relapse versus placebo in people with CIDP who responded to treatment. Further studies are needed to provide data on the longer-term effects of efgartigimod alfa and how it compares with currently available treatment options., Funding: argenx., Competing Interests: Declaration of interests JAA reports consulting fees from Akcea Therapeutics, Alexion, Alnylam, Annexon Biosciences, argenx, CSL Behring, Grifols, Immunovant, ImmuPharma, Johnson & Johnson, and Takeda, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Alnylam, Annexon Biosciences, argenx, CSL Behring, and Takeda. TD reports participation on a data safety monitoring board or advisory board for Dianthus Therapeutics. CE reports grants or contracts from argenx; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from argenx; support for attending meetings and travel from argenx; and stock or stock options from argenx. AT was an employee of argenx, and reports stock or stock options at the time of the study completion. JTG is an employee of argenx; reports support for attending meetings and travel from argenx; and reports stock or stock options from argenx. BVH is an employee of argenx. PU is an employee of argenx; reports patents planned, issued, or pending from argenx; reports stock or stock options from argenx; and reports other financial or non-financial interests from argenx. EH is an employee of argenx; reports patents planned, issued, or pending from argenx; and reports stock or stock options from argenx. KGG reports consulting fees from Alexion, and UCB; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alexion, argenx, and Xeris Pharmaceuticals; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid for Myasthenia Gravis Foundation of America. FL reports grants or contracts from German Ministry of Education and Research, German Research Society DFG, HORIZON MSCA 2022 Doctoral Network, and Stiftung Pathobiochemie of the German Society for Laboratory Medicine; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Biogen, Fresenius, Grifols, Novartis, Roche, and Teva Pharmaceuticals; support for attending meetings and travel from Bayer, Grifols, and Merck; and participation on a data safety monitoring board or advisory board for argenx, Alexion, Biogen, and Roche. MLi reports grants or contracts from Kedrion Biopharma; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from CSL Behring, Kedrion Biopharma, and Takeda; support for attending meetings and travel from CSL Behring, Kedrion Biopharma, and Takeda; and other financial or non-financial interests from argenx. MLo was an employee of argenx at the time of the study completion. LQ reports grants or contracts from argenx, CIBERER, Instituto de Salud Carlos III–Ministry of Economy and Innovation (Spain), and UCB; consulting fees from Annexon Biosciences, Alnylam, argenx, Avilar Therapeutics, CSL Behring, Dianthus Therapeutics, Janssen, LFB, Novartis, Nuvig Therapeutics, Roche, Sanofi, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alnylam, argenx, CSL Behring, Novartis, Roche, and Sanofi; support for attending meetings and travel from Alnylam and Sanofi; participation on a data safety monitoring board or advisory board for argenx, CSL Behring, Sanofi, and UCB; and a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for Inflammatory Neuropathy Consortium and Peripheral Nerve Society. NS reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alnylam, and participation on a data safety monitoring board or advisory board for Takeda. RY reports consulting fees from Japan Tobacco and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Alnylam Japan, CSL Behring, FP Pharm, Kyowa Kirin, Ono Pharmaceutical, and Takeda Pharmaceutical. RAL reports royalties or licenses from UpToDate; consulting fees from Annexon Biosciences, argenx, CSL Behring, Dianthus Therapeutics, Grifols, Immunovant, Janssen, Nuvig Therapeutics, Sanofi, and Takeda; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from argenx, CSL Behring, Medscape, and Sanofi; participation on a data safety monitoring board or advisory board for Boehringer Ingelheim and Novartis; and leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, for Peripheral Nerve Society and GBS-CIDP Foundation International. PAvD reports support for attending meetings and travel from argenx and participation on a data safety monitoring board or advisory board for argenx. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aims: This systematic review was aimed to assess the association between magnitude of body weight loss (BWL) in type 2 diabetes (T2D) patients and cardiovascular (CV) risk in CV outcome trials (CVOTs)., Methods: We searched electronic databases (PubMed, Cochrane and Scopus) for available CVOTs, observational cohort studies or post hoc analyses of clinical trials of adult T2D patients investigated the association of BWL with CV outcomes and/or all-cause mortality., Results: 19 RCTs of novel glucose-lowering drugs (GLP-1RA, DPP-4i and SGLT2i) and 6 RCT or observational trial of different strategies (intensive treatment or standard care) were included (379.904 T2D patients). Higher BWL during GLP-1RA treatment, in comaprison to lower BWL, was associated with higher decrease in risk of MACE, while DPP-4i had not that effect. With SGLT2i the higher decrease in risk of MACE was associated with lower BWL. In contrast, in other different strategies, higher BWL lead to increase in risk for MACE and all-cause mortality., Conclusions: In CVOTs, treatment of T2D patients resulted in BWL, which correlated with reduction in risk for CV outcomes, particularly with GLP-1 RAs. However, interventional non-CVOTs are warning that in the absence of structured behavioral intervention and relevant medication, the large BWL might be harmful for CV outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As healthcare workers run a high and constant occupational risk of hepatitis B virus (HBV) infection through exposure to biological material, vaccination is mandatory as well as the monitoring of antibody levels one to two months after complete immunisation. The aim of this descriptive cross-sectional study was to determine HBV vaccine coverage of 200 primary and secondary healthcare workers (100 each) from Šabac, Serbia and their blood anti-HBs titre. We also wanted to identify factors that could predict the titre. Anti-HBV vaccination covered all participants, of whom 89.5 % were fully vaccinated, and 85 % had a protective antibody titre. We found a statistically significant association between antibody titre and the number of received vaccine doses, chronic jaundice, autoimmune disease, and cancer in our participants. The fact that 15 % did not achieve the protective antibody titre confirms the necessity of its control after immunisation, which is not routinely carried out in most countries, Serbia included. It is, therefore, necessary to develop a detailed strategy for monitoring vaccination and serological status of healthcare workers in order to improve their safety at work. An important role should also be given to continuous education of healthcare workers from the beginning of schooling to the end of their professional career., (© 2024 Slobodanka Bogdanović Vasić et al., published by Sciendo.)

Background: This paper compares the most recent data on the incidence and prevalence of kidney replacement therapy (KRT), kidney transplantation rates, and mortality on KRT from Europe to those from the United States (US), including comparisons of treatment modalities (haemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KTx))., Methods: Data were derived from the annual reports of the European Renal Association (ERA) Registry and the United States Renal Data System (USRDS). The European data include information from national and regional renal registries providing the ERA Registry with individual patient data. Additional analyses were performed to present results for all participating European countries together., Results: In 2021, the KRT incidence in the US (409.7 per million population (pmp)) was almost 3-fold higher than in Europe (144.4 pmp). Despite the substantial difference in KRT incidence, approximately the same proportion of patients initiated HD (Europe: 82%, US: 84%), PD (14%; 13%, respectively), or underwent pre-emptive KTx (4%; 3%, respectively). The KRT prevalence in the US (2436.1 pmp) was 2-fold higher than in Europe (1187.8 pmp). Within Europe, approximately half of all prevalent patients were living with a functioning graft (47%), while in the US, this was one third (32%). The number of kidney transplantations performed was almost twice as high in the US (77.0 pmp) compared to Europe (41.6 pmp). The mortality of patients receiving KRT was 1.6-fold higher in the US (157.3 per 1000 patient years) compared to Europe (98.7 per 1000 patient years)., Conclusions: The US had a much higher KRT incidence, prevalence, and mortality compared to Europe, and despite a higher kidney transplantation rate, a lower proportion of prevalent patients with a functioning graft., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background and Objectives : Pilocarpine is used in experimental studies for testing antiepileptic drugs, but further characterization of this model is essential for its usage in testing novel drugs. The aim of our study was to study the behavioral and EEG characteristics of acute seizures caused by different doses of pilocarpine in rats. Materials and Methods : Male Wistar rats were treated with a single intraperitoneal dose of 100 mg/kg (P100), 200 mg/kg (P200), or 300 mg/kg (P300) of pilocarpine, and epileptiform behavior and EEG changes followed within 4 h. Results : The intensity and the duration of seizures were significantly higher in P300 vs. the P200 and P100 groups, with status epilepticus dominating in P300 and self-limiting tonic-clonic seizures in the P200 group. The seizure grade was significantly higher in P200 vs. the P100 group only during the first hour after pilocarpine application. The latency of seizures was significantly shorter in P300 and P200 compared with P100 group. Conclusions : Pilocarpine (200 mg/kg) can be used as a suitable model for the initial screening of potential anti-seizure medications, while at a dose of 300 mg/kg, it can be used for study of the mechanisms of epileptogenesis.

Completed suicide accounts for over 700,000 deaths worldwide annually, while attempted suicide is 20 times more frequent. Genetic background is an important factor contributing to suicidal behavior, including candidate genes in glutamate, γ-aminobutyric acid (GABA), and polyamine systems. Our aim was to differentiate genetic predispositions underlying different types of suicidal behavior, attempted and completed suicide, in two Balkan populations. Analysis of variants in the genes GRIN2B (rs2268115 and rs220557), GABRG2 (rs424740), and ODC1 (rs1049500 and rs2302614) was performed on a study sample including 173 suicide attempters with comorbid psychiatric disorders, 216 non-suicidal psychiatric patients and 172 healthy controls from Serbia, and 333 suicide completers and 356 non-suicidal autopsy controls from Slovenia. CA genotype of rs220557 in GRIN2B gene increased the risk for completed suicide (P = 0.021), and violent suicide (P = 0.037), compared to controls. In ODC1 gene, CA genotype of rs2302614 decreased the risk for completed suicide compared to suicide attempt (P = 0.012). Marginally, AC haplotype for variants rs1049500-rs2302614 in ODC1 gene decreased the risk for completed suicide compared to suicide attempt (P = 0.052). Specific genetic variants of glutamate and polyamine systems are differently distributed among diverse suicidal phenotypes, providing further information on the implication of these systems in suicidality., (© 2024. The Author(s).)

Background and Objectives : The aim of this study was to estimate the prevalence of silent coronary artery disease (CAD) in asymptomatic patients with severe aortic stenosis (AS) and assess long-term prognosis in terms of major adverse cardiovascular event (MACE)-free survival. Materials and Methods : This was a prospective study conducted at the Clinic for Cardiac Surgery, University Clinical Center of Serbia, in asymptomatic patients with severe AS, normal LVEF and stress test without signs of myocardial ischemia. Adverse cardiovascular events (cardiac death, myocardial infarction and any hospitalization due to heart disease) was monitored during one year of follow up. Results : A total of 116 asymptomatic patients with severe AS were included in the study. The average age was 67.3 ± 9.6 years, and 56.9% of patients were men. The most common cause of AS was degenerative valvular disease (83.5%). The incidence of significant CAD was 30 out of 116 patients (25.9%). The median Society for Thoracic Surgeons (STS) predicted risk of mortality score was 1.62% (25th to 75th percentile: 1.15-2.76%). The overall mean gradient across aortic valve (Pmean) was 52.30 mmHg ± 12.16, and the mean indexed AVA (AVAi) was 0.37 ± 0.09 cm 2 /m 2 . The mean LVEF was 68.40% ± 8.01%. Early surgery for aortic valve replacement was performed in 55 patients (55.2%), while 52 (44.8%) patients received conservative treatment. Twenty-two patients (42.3%) in the conservative treatment group underwent surgery during follow up. There were a total of 44 (37.9%) patients with MACE during one year of follow up. Univariate Cox regression analyses identified the following significant risk factors for MACE-free survival: presence of CAD and early conservative treatment ( p = 0.004), age ( p = 0.003), diabetes mellitus ( p = 0.016) and STS score ( p = 0.039). According to multivariate analysis, the presence of CAD with early conservative treatment was the most important predictor of MACE-free survival in asymptomatic patients with severe aortic stenosis ( p ≤ 0.001). Conclusions : Early surgery for aortic valve replacement in asymptomatic patients with severe AS and concomitant CAD is beneficial for long-term survival.

Introduction: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results., Patients and Methods: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows., Results: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p  < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p  < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3., Discussion and Conclusion: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ivana Berisavac: speaker honoraria from Medtronic. Visnja Padjen: speaker honoraria from Medtronic and Boehringer Ingelheim. Ronen R. Leker: received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic and Abott and advisory board honoraria from Jansen and Filterlex. Andrea Zini: has received funding for speaker honoraria and consulting fees from Boehringer Ingelheim, Astra Zeneca, Daiichi Sankyo, CSL Behring, for scientific advisory board from Bayer, Astra Zeneca. Mirjam R. Heldner: reports grants from Swiss National Science Foundation, SITEM Research Support Funds and Swiss Heart Foundation, not directly related to this manuscript. Christian H Nolte: has received honoraria for lectures or speaker’s bureau from Alexion, AstraZeneca, BMS, Novartis and Pfizer. The other authors report nothing to disclose.

Background: In the post-COVID-19 era, there is growing concern regarding its impact on cardiovascular health and the following effects on the overall quality of life of affected individuals. This research seeks to investigate cardiac magnetic resonance (CMR) findings following COVID-19 and their impact on the quality of life of affected individuals., Methods: An observational, cross-sectional study was conducted in consecutive patients with persistent cardiovascular symptoms after COVID-19 who were referred to CMR due to suspected myocardial injury. In addition, patients completed a questionnaire about symptoms and the quality of life during the post-COVID-19 period., Results: In this study, 85 patients were included. The study population consisted of patients with a mean age of 42.5 ± 13.4 years, predominantly women, who made up 69.4% of the study population, while men made up 30.6%. CMR findings showed non-ischemic myocardial injury in 78.8% of patients and myocardial edema in 14.1% of patients. Late pericardial enhancement was present in 40% of patients and pericardial effusion in 51.8% of patients. Pericardial effusion ( p = 0.001) was more prevalent in patients who reported more pronounced symptoms in the post-COVID-19 period compared to the acute infection phase. Predictors of lower quality of life in the post-COVID-19 period were the presence of irregular heartbeat ( p = 0.039), cardiovascular problems that last longer than 12 weeks ( p = 0.018), and the presence of pericardial effusion ( p = 0.037)., Conclusion: Acute myocarditis was observed in a minority of patients after COVID-19, while non-ischemic LGE pattern and pericardial effusion were observed in the majority. Quality of life was worse during the post-COVID-19 period in patients with CMR abnormalities, primarily in patients with pericardial effusion. Also, irregular heartbeat, cardiovascular symptoms that last longer than 12 weeks, as well as pericardial effusion were independent predictors of lower quality of life during the post-COVID-19 period.