Large pre-trained models (LPMs) have the capabilities to understand natural language, code, and diverse data including images; e.g., large language models (LLMs), code-generative models, and large vision models (LVMs) as well as combined as multi-modal models. We outlines the main applications of LPMs and multi-modal LPMs for ecology and biodiversity conservation. These applications include generating ecological data, generating code, providing insights into public opinion and sentiment. We highlighted the significant potential of LPMs and the potential use of Ecology-specialized LPMs for ecology and biodiversity conservation. They offer unprecedented opportunities for analyzing diverse data, extracting meaningful insights, and informing conservation decisions.

Objective: To evaluate whether the administration of high-volume intravenous (IV) fluids during labour (≥ 2500 mL) increases the risk of primary postpartum haemorrhage (PPH) and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labour (<2500 mL). Design: Retrospective cohort study Setting: Tertiary referral hospital in Sydney, Australia Sample: 1023 women with a live singleton fetus in a cephalic presentation; planning a vaginal birth; and admitted for labour and birth care between 37 - 42 weeks gestation. Methods: The study factor was IV fluids during labour. Birth and postnatal data were obtained from electronic medical records and paper fluid order documentation. Multivariable logistic regression and multiple imputation were used to explore the relationship between volume of IV fluids in labour and PPH. Main outcome measures: The primary outcome was primary PPH ≥ 500mL. Secondary outcomes included caesarean section and major perineal injury. Results: 1023 participants were included of which 339 had a primary PPH (33.1%). There was no association between high-volume IV fluids and PPH after adjusting for demographic and clinical factors (Adjusted odds ratio [OR adj]1.02 95% confidence interval [95%CI] 0.72, 1.44). However, there was a positive association between high-volume IV fluids and caesarean section (OR adj 1.99; 95%CI 1.4, 2.8). Conclusion: These findings are important to further knowledge relating to administration of IV fluids in labour and the potential impact of this common practice. It identifies future research priorities around documentation of IV fluids and their relationship with pregnancy and perinatal outcomes.

With the discovery of event-related potentials elicited by errors more than thirty years ago, a new avenue of research on performance monitoring, cognitive control, and decision making was opened. Since then, the field has developed and expanded fulminantly. After a brief overview on the EEG correlates of performance monitoring, this article reviews recent advancements in the field of performance monitoring based on single-trial analyses using independent component analysis, multiple regression, and multivariate pattern classification. Given the close interconnection between performance monitoring and reinforcement learning, computational modeling and model-based EEG analyses have made a particularly strong impact. The reviewed findings demonstrate that error- and feedback-related EEG dynamics represent variables reflecting how performance monitoring signals are weighted and transformed into an adaptation signal that guides future decisions and actions. The model-based single-trial analysis approach goes far beyond conventional peak-and-trough analyses of event-related potentials and enables testing mechanistic theories of performance monitoring, cognitive control and decision making.

Trophic change has induced substantial changes in biomass and composition of aquatic communities. Based on phytoplankton data from Lake Constance we demonstrate that community function is closely connected to community composition and responds strongly to trophic change. Community mean traits phosphate affinity and light affinity are tightly linked to trophic state during eutrophication and re-oligotrophication, suggesting reversibility of community function. Phosphate and light affinity are anti-correlated. This anti-correlation is weak in the species pool distinguished in the dataset, but strong when weighting the traits by the species biovolumes or when comparing community mean traits from different trophic states. The emergence of this tradeoff between phosphate and light affinity indicates competitive advantage of species with traits near the tradeoff line. The correlation between community mean maximum growth rate and trophic state turned out to be spurious and resulted from the development of Dinophyceae spp. which have an alternative mode of nutrition.

Long-acting injectable (LAI) cabotegravir and rilpivirine for HIV treatment and LAI cabotegravir for pre-exposure HIV prophylaxis are being rolled out in a multitude of countries worldwide. Due to the prolonged exposure, it can be challenging to undertake ‘traditional’ pharmacokinetic studies and current guidance is derived from their oral equivalents or physiologically-based pharmacokinetic studies. This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug-drug interactions (DDIs) with frequent concomitant medications in African settings. Relevant comedications were identified from the WHO 2021 List of Essential Medicines. All original human and physiologically-based pharmacokinetic studies published in English on PubMed, discussing DDIs with LAI cabotegravir and rilpivirine prior to April 2023, were reviewed. The Liverpool HIV interaction database was also reviewed. LAI cabotegravir and rilpivirine have half-lives of 6-12 and 13-28 weeks, respectively. Cabotegravir is primarily metabolised by UDP-glucuronyltransferase (UGT)-1A1 and rilpivirine by cytochrome P450 (CYP)-3A4. LAI cabotegravir and rilpivirine themselves exhibit low risk of perpetrating interactions with comedications as they do not induce or inhibit the major drug metabolising enzymes. However, they are victims of DDIs relating to the induction of their metabolising enzymes by concomitantly administered medication. Noteworthy contraindicated comedications include rifamycins, carbamazepine, phenytoin, flucloxacillin and griseofulvin, which induce CYP3A4 and/or UGT1A1, causing clinically-significant reduced concentrations of rilpivirine and/or cabotegravir. In addition to virologic failure, subtherapeutic concentrations resulting from DDIs can lead to emergent drug resistance. Clinicians should be aware of potential DDIs and counsel people receiving LAI cabotegravir/rilpivirine appropriately to minimise risk.

Wildlife biology is an applied discipline, where research results are to varying degree incorporated to accepted knowledge However, several factors appear to increase the divide between research results, and knowledge and implementation. First, there is an exponential increase in number of published papers, in part driven by misguided reliance on publication record for assessing scientific competence. The shear number of publications risk diluting knowledge through salami-slicing or simply making it difficult to find relevant publications. This development could be problematic for the future of wildlife biology, and it has made complex statistical analysis of already available data more profitable than the ability to generate new data in robust field studies. Research results are conceptually different from knowledge and need to be evaluated in a post-publication process to become knowledge. Secondly, the formulation of research questions has become restricted by the way research is organised and funded. A shift from a focus on individual performance to research groups could encourage the development of more complex research questions that are better suited to advance the knowledge of wildlife biology. Funding agencies and research institutions need to think beyond current norm of a three year funding package. Thirdly, defining knowledge as the result of a post-publishing evaluating of research publications would facilitate knowledge transfer between researchers and practitioners. It is well established that a two-way transfer of knowledge and experience is beneficial to both researchers and practitioners but the low return on academic recognition for such efforts is currently simply too low, which positively discourages researchers from dividing limited resources into such activities. Only academic institutions and funding agencies together can make the significant changes needed as have begun in other disciplines. However, researchers also need to embrace existing and emerging initiatives such as Open Sceince, FAIRdata, CREDIT authorship to accelerate change.

Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is this larva is being protected by the acellular laminated layer (LL), made up of mucins and calcium inositol hexakisphosphate (Ins P 6). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite’s vicinity. Although foreign particles accumulating in tissues usually cause inflammation, the LL displays adaptations for minimising various host responses, and in vivo evidence of inflammation induced by LL particles is essentially lacking. In this work, we show that LL particles injected i.p. at a dose of 225 μg dry mass per mouse cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as disappearance of resident (large peritoneal) macrophages. The calcium Ins P 6 component was dispensable for these responses. Oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils but the carbohydrate-oxidized particles caused cell influx nonetheless. The control of local granulomatous inflammation is key for survival of this larva. Therefore, our results suggest that E. granulosus must deploy mechanisms to avoid excessive local build-up of LL particles (such as targeting particles to liver Kupffer cells; Infect Immun 91:e0003123) and/or to condition the recruited cells towards immune-regulatory phenotypes.

In rural Nagaland, India, where formal employment opportunities are scarce, Chakhesang women vendors find a crucial lifeline in street vending. This paper explores their socio-economic profile and livelihood activities in Phek district, focusing on their contribution to income generation, poverty alleviation, and household well-being. Selling a unique blend of fresh agricultural produce and indigenous organic forest products on highways and street pavements of nearby towns and markets, these women demonstrate immense resilience in navigating informal economies. Despite challenges like lack of access to credit, market infrastructure, and basic amenities, they persevere, securing their families' livelihoods and showcasing the potential of street vending as a sustainable livelihood option for rural women in Nagaland. A mixed-method approach was adopted to explore the socio-economic status and challenges of women vendors using a semi-structured interview and observation method. The findings reveal the crucial role of street vending in Chakhesang communities, highlighting its potential for sustainable livelihood, economic empowerment, and poverty reduction.

IntroductionPulmonary sclerosing pneumocytoma is a rare group of benign pulmonary neoplasms that usually affects older adults over 50 years of age [1].  This neoplasm is more commonly seen in women, with female to male ratio of 5:1 and is predominantly seen in Asian ethnicities [2]. These tumors originate from type II alveolar pneumocytes and are hence classified as adenoma under the 2021 World Health Organization (WHO) classification of tumors [3]. They account for 3-5 percent of total benign lung tumors [4].One of the striking aspects of PSP is its clinical presentation, or rather the lack thereof in many cases. It is often discovered incidentally during routine chest imaging, such as chest X-rays or CT scans, due to its asymptomatic nature. However, when symptoms do occur, they tend to be non-specific, including cough, chest pain, or respiratory distress. This variability in clinical manifestation further complicates the diagnosis of PSP, as these symptoms overlap with those of other pulmonary conditions. Moreover, it is essential to consider the potential for malignant transformation, as a subset of PSP cases have exhibited aggressive behavior [5].Herein, we describe a case of a 73-year-old female who was found to have an incidental lung nodule. In view of the history of interval increase in the size of the lung nodule, the patient underwent a CT-guided lung biopsy, which was characterized as sclerosing pneumocytoma, and the patient was referred to thoracic surgery for subsegmental right middle lobe resection.

A document by Husam BR Alabed. Click on the document to view its contents.

Flash droughts (FDs) have attracted increasing attention in the past decade. They are characterized by a rapid depletion of soil moisture resulting from interactions between the soil and atmospheric conditions. To date, there is a lack of consistent FD definitions and an understanding of their socioeconomic impacts. Here, we explore the relationship between biophysical FD conditions and the perceived impacts of FDs in Germany between 2000 and 2022. We measured perceived impacts by analyzing consequences reported in newspaper articles (2000-2022) and online search behavior using Google trends data (2004-2022). To characterize the physical process, we considered root zone soil moisture data. Our results show that FDs are becoming increasingly frequent in Germany, occurring once every two years on average. Despite the lack of knowledge from the general public regarding the phenomenon of FDs, the peaks of interest in drought impacts correspond to the physical occurrence of FDs across the country. We identified an average time gap of four weeks between FD onset and the reporting of perceived impacts. This gap is longer than the average duration of FDs' onset. Consequently, our findings highlight that consistent monitoring of FD conditions and drivers is necessary to guarantee effective preparedness. As impact perception is too slow to allow the adoption of mitigation measures, FDs require new schemes for response measures compared with slowly emerging (conventional) drought events. The novel method also allows the consistent and impact-based validation of flash drought identification methods.

Brugada syndrome, though rare, poses a significant risk of sudden cardiac death, particularly in young adults, and remains underdiagnosed globally. We present the case of a 22-year-old male initially presenting with a presumed seizure episode, later found to exhibit findings suggestive of type 1 Brugada pattern on his admission electrocardiogram (EKG). Differential diagnosis between seizure and syncope was challenging, compounded by the difficulty in distinguishing convulsive syncope from seizure activity. While Brugada syndrome and epilepsy are not commonly associated, there is evidence suggesting a shared genetic basis, particularly in ion channel mutations. Our case underscores the importance of considering Brugada syndrome in patients presenting with seizure-like episodes and concerning EKG findings, prompting cardiology consultation and electrophysiological studies. The absence of a Brugada pattern post-ictally should not exclude diagnosis, especially in the context of appropriate clinical suspicion. Further research is warranted to elucidate the relationship between Brugada syndrome and epilepsy, and the potential implications for diagnosis and management.

Monkeypox virus (MPXV) is a zoonotic orthopoxvirus that poses a significant threat to public health due to its potential for human-to-human transmission and the absence of a specific antiviral therapy. Monkeypox is caused by the Variola virus, which also causes smallpox, the symptoms of Monkeypox are milder but fatal. The genomic architecture of MPXV is elucidated, focusing on key genetic elements responsible for viral replication, host interaction, and immunomodulation. The poxvirus mutates much less frequently because of the stability of double-stranded DNA and the DNA polymerase’s high 3′-5′ exonuclease activity. Current treatment approaches for MPXV infection are discussed, highlighting the progress in vaccine development (JYNNEOS, ACAM2000, Aventis Pasteur smallpox vaccine (APSV)) and the efficacy of existing small-molecule antiviral agents (Tecovirimat Brincidofovir). The limitations of these treatments are acknowledged, emphasizing the need for continued research and development efforts. The potential role of herbal remedies in MPXV management is explored, drawing on traditional knowledge and recent scientific studies. Compounds with demonstrated antiviral properties are highlighted, offering a promising avenue for further investigation. An overview of ongoing clinical trials investigating novel therapeutic interventions for MPXV is presented. These include gaps in epidemiological surveillance, limited clinical data on MPXV in humans, and the necessity for targeted research on host-pathogen interactions to inform therapeutic development. This review provides a comprehensive overview of MPXV, addressing key aspects from genomics to treatment options. It underscores the urgent need for further research efforts to bridge existing knowledge gaps and develop more effective interventions against this emerging infectious disease.

Methods: In this study, the major antigen genes P1a of MP adhesion factor P1(3862-4554 bases) and P30a of P30(49-822 bases) were inserted into the nonstructural protein (NS) gene of Influenza A virus strain A/Puerto Rio/8/34(H1N1), PR8 for short, to construct the recombinant vectors NS-P1a or NS-P30a. The recombinant pHW2000 plasmids containing NS-P1a or NS-P30a were co-transfected with the rest 7 fragments of PR8 into HEK293T cells. After inoculating chicken embryos, the recombinant influenza viruses rFLU-P1a and rFLU-P30a were rescued. RT-PCR and sequencing were used to identify the recombinant viruses. The hemagglutination titers of rFLU-P1a and rFLU-P30a were determined after 5 successive generations in chicken embryos so as to indicate the genetic stability of the recombinant viruses. The morphology of recombinant influenza viruses was observed under electron microscopy. Results: P1a or P30a was designed to be inserted into the modified NS gene sequence separately and synthesized successfully. RT-PCR identification of the recombinant viruses rFLU-P1a and rFLU-P30a showed that P1a (693bp), P30a (774bp), NS-P1a (1992bp) and NS-P30a (2073bp) bands were found, and the sequencing results were correct. After 5 successive generations, each virus generation has a certain hemagglutination titer(from 1:32 to 1:64), and the band of P1a or P30a can be seen in the corresponding positions. The virus particles under the electron microscope appeared as spheres or long strips connected by several particles, revealing a complete viral membrane structure composed of virus lipid bilayer, hemagglutinin, neuraminidase, and matrix proteins. Conclusion: The recombinant viruses rFLU-P1a and rFLU-P30a which carried the advantaged immune regions of the P1 and P30 genes in MP were successfully constructed and identified. The genetic stability of rFLU-P1a or rFLU-P30a was relatively high. The typical morphology of influenza virus was observed under the electron microscope. Our research provided a foundation for the further development of MP vaccines for human.

Background Non-melanoma skin cancer (NMSC) in Africans is less common than in Caucasians because of melanin, which plays a protective role against ultraviolet radiation and subsequent skin cancers. However, Bowen’s disease, a type of skin carcinoma-in-situ, occurs on both sun-exposed and sun-protected sites and if missed, may progress to invasive squamous cell carcinoma. In general, there is paucity of literature on NMSC occurring in skin of colour versus in white skin, and pigmented Bowen’s disease (PBD) is no exception. Clinicians should be able to recognise this type of cancer in black skin to avoid invasive malignancy. Case I A 68-year-old male presented with a 30-year-history of a pigmented plaque with cutaneous horns on the right lower trunk. The patient was unsuccessfully treated with various topical and oral medication until he was referred to a tertiary hospital. A biopsy was taken and the cutaneous horns, together with the underlying epithelium, were shaved. The histopathology confirmed PBD and invasive cancer was excluded. He was referred to the plastic surgeons for excision. Case II An 88-year-old male presented with a 30-year history of an asymptomatic pigmented 6cm x 10cm plaque on the left upper trunk, which was unresponsive to topical treatment from different healthcare facilities. The plaque was notched in one area, where there was associated hyperpigmentation. Histopathology of lesional skin confirmed PBD. Conclusion Rare in Africans though it is, skin cancer should always be suspected in a long-standing lesion that does not respond to any treatment. It is essential to biopsy such lesions for histopathological evaluation.

Cooperative spectrum sensing (CSS) has emerged as a promising strategy for identifying available spectrum resources by leveraging spatially distributed sensors in cognitive wireless sensor networks (CWSNs). Nevertheless, this open collaborative approach is susceptible to security threats posed by malicious sensors (MSs), specifically Byzantine attack, which can significantly undermine CSS accuracy. Moreover, in extensive CWSNs, the CSS process imposes substantial communication overhead on the reporting channel, thereby considerably diminishing cooperative efficiency. To tackle these challenges, this article introduces a refined CSS approach, termed weighted sequential detection (WSD). This method incorporates channel state information (CSI) to validate the global decision made by the fusion center (FC) and assess the trust value of sensors. The trust value based weight is assigned to sensing samples, which are then integrated into a sequential detection framework within a defined time window. This sequential approach prioritizes samples based on descending trust values. Numerical simulation results reveal that the proposed WSD outperforms conventional fusion rules in terms of error probability and sample size, even under varying degrees of Byzantine attack. This innovation signifies a substantial advancement in enhancing the reliability and efficiency of CSS.

Subcutaneous adipose tissue (SAT) is the deepest component of the three-layered cutaneous integument. While mesenteric adipose tissue-based immune processes have gained recognition in the context of the metabolic syndrome, SAT has been traditionally considered primarily for energy storage, with less attention to its immune functions. SAT harbors a reservoir of immune and stromal cells that significantly impact metabolic and immunologic processes not only in the skin, but even on a systemic level. These processes include wound healing, cutaneous and systemic infections, immunometabolic and autoimmune diseases, inflammatory skin diseases, as well as neoplastic conditions. A better understanding of SAT immune functions in different processes, could open avenues for novel therapeutic interventions. Targeting SAT may not only address SAT-specific diseases but also offer potential treatments for cutaneous or even systemic conditions. This review aims to provide a comprehensive overview on SAT’s structure and functions, highlight recent advancements in understanding its role in both homeostatic and pathological conditions within and beyond the skin, and discuss the main questions for future research in the field.

Antenatally detected sacrococcygeal teratoma (SCT) is a potentially life-threatening condition. Its prenatal management remains a topic of debate due to its association with fetal and maternal complications. This review delves into various fetal approaches to SCT, elucidating the roles of different procedures. Overall, fetal treatments are proposed to highly selected patients, with severe complications of SCT who carry a dismal prognosis and a high risk in utero death. No shared protocols for patient and /or procedure selection exist thus overall management of these patients is highly dependent on the team skills and facility resources. Despite the general feeling that a prenatal diagnosis of SCT involves a high mortality risk, this comprehensive review demonstrates that advancements in fetal SCT treatment positively impact both fetal and maternal outcomes.

Purpose: To explore the feasibility of minimally invasive surgery（MIS）used in the treatment of neuroblastoma. Methods: Selected NB patients were randomly assigned to the MIS group and the open surgery（OS） group. The operative details, major complications, and prognosis of the two groups were compared. Results: A total of 35 children undergoing MIS and 35 children undergoing open surgery were enrolled in this study. According to the INRGSS staging system, 30 patients were classified as stage L1, 32 as stage L2, and 8 as stage M. No statistical difference was found in the age of the children and the maximum diameter of the primary site tumor between the two groups. The bleeding volume in the OS group was significantly higher than that in the MIS group (P=0.006), The time to start postoperative feeding in the MIS group was significantly shorter than that in the OS group (P<0.001). No significant difference was found in the number of GTR between the MIS group and the OS group (P=0.246). The one-year survival rate and overall survival rate of the MIS group were 100% and 93.85%, while the OS group was 100% and 93.72%, respectively. Conclusion: MIS has more advantages than OS for suitable neuroblastoma, while the prognosis is almost the same. After gradually improving the indications for MIS, it should become the preferred surgical method for children within this range.

During induction of Acute Lymphoblastic Leukaemia (ALL) cytopenias lead to frequent toxicities, treatment interruptions, and higher mortality rates. Blood count kinetics can also be potential markers of chemotherapy efficacy and bone marrow recovery. Understanding kinetics of blood counts and their association with clinical outcomes can help in optimizing weekly chemotherapy schedule according to risk of toxicity. 243 cases were analysed and baseline data, nadir, time to recovery of counts during induction, and survival outcomes were recorded. Median age was 15 (1-62) years. Immunophenotype was B-ALL in 71%, T-ALL in 27%. Good steroid response (D8) was seen in 89%, CR in 79%, and induction mortality in 12%. Median neutrophil nadir was 0.06(0-0.49) *10 9/L and median day to nadir was D17. Median time to partial and complete platelet recovery was D18 and D25. Late neutrophil nadir (>D15) was independent predictor of refractory disease [OR=5.43; p=0.042)], late partial platelet recovery (>D22) was independent predictor of poorer EFS and OS (HR = 1.63 [p = 0.020] and HR = 1.5 [p = 0.044]. Validation of blood count kinetics as independent predictors of post-induction and survival outcomes provides neutrophil and platelet counts as a simple, easy-to-use tool for balancing treatment efficacy-toxicity during induction.

Background: Pre-eclampsia (PE) affects approximately 2-4% of pregnancies. Diagnosis involves repeated assessment of pregnant patients with risk factors. The sFlt-1/PlGF ratio test is shown to have clinical utility in ruling in and out PE among at-risk patients. By excluding the probability of PE, the addition of the sFlt-1/PlGF ratio test to antenatal care, may prevent unnecessary hospital admissions, intensive management, and premature delivery, thus reducing costs. Objectives: A systematic review to determine the cost-effectiveness of the sFlt-1/PlGF ratio test globally for pregnant patients at-risk of developing PE. Search Strategy: PubMed, Medline (OVID), National Health Service Economic Evaluation Database, Web of Science, Econlit, and Cost Effectiveness Analysis Registry searched between 2013-April 2023. Selection Criteria: Empirical studies quantifying costs of the sFlt-1/PlGF ratio test compared to other treatment options for patients with suspected PE. Data collection and Analysis: Eleven studies were included; all were cost analyses and modelled economic evaluations, and most used a health system perspective. Cost data were extracted and indexed to 2022 United States Dollars (USD). Main results: All studies reported “cost-savings” of the test in antenatal care. Studies varied with costs and assumptions included, therefore a large range of incremental cost savings per patient was reported ($15-$1,881, 2022USD). No Incremental Cost-Effectiveness Ratios or health outcomes including Quality Adjusted Life Years were reported. Conclusions: The included studies demonstrated “cost-savings” of the sFlt-1/PlGF ratio test in antenatal care for at-risk pregnant patients. However, this does not account for health outcome differences and long-term health care utilisation and expenditure. Funding: Nil

To solve the problem of negative-sequence and reactive power in electrified railway, this paper proposes a comprehensive compensation method based on V/v transformers and electromagnetic single-phase var compensator (ESVC) for co-phase power supply. First, based on the principles of static var generator (SVG) and single-phase rotary phase shifting transformer (SRPST), the topology and model of ESVC have been established, and the compensation mechanism has been analyzed. Second, the topological structure and mathematical model of co-phase power comprehensive compensation device (CPCD) are put forward based on the principles of V/v transformers and ESVC, and the operation mode of CPCD in multiple scenarios is designed. Then the strategy of CPCD with double closed loop control is analyzed: corresponding compensation mode is selected according to negative-sequence unbalance degree and expected power factor value. In this strategy, the compensated current output by ESVC is taken as the quantity of external loop control, and the rotation angle of ESVC is taken as the quantity of internal loop control to realize double-closed loop control of CPCD. Finally, the comprehensive CPCD compensation model is built on the simulation platform and validated the accuracy of the mathematical model and the effectiveness of the control strategy.

Background: A significant knowledge gap exists in the optimal anticoagulation strategy for patients with a history of left atrial appendage (LAA) closure undergoing atrial fibrillation (AF) ablation. The increasing prevalence of AF and the use of catheter-based AF ablation (CA) and left atrial appendage closure (LAAC) highlight the urgency of addressing this issue. Despite these developments, there is no consensus on anticoagulation management for this specific patient population. Non-valvular AF, the most common arrhythmia, carries a high risk of stroke, systemic embolism (SE), heart failure (HF), and mortality. Treatments like CA and LAAC are crucial in AF management. LAAC, particularly, has shown noninferiority to traditional Vitamin K antagonists (VKAs) and novel oral anticoagulants (NOACs) in stroke prevention. However, the integration of CA and LAAC, often a one-stop procedure, raises questions about optimal sequencing and anticoagulation management, especially in patients at high bleeding risk or with a history of thromboembolic or major bleeding incidents. Clinical guidelines advise against discontinuing long-term oral anticoagulation in high-stroke-risk patients post-CA. Alternative approaches, like LAAC with devices like Watchman, offer options for patients accepting procedural risks. Studies, including data from EVOLUTION and WASP registries, demonstrate the effectiveness of combining CA and LAAC in reducing stroke and late bleeding events. A retrospective observational study also highlighted the efficacy of thoracoscopic LAA occlusion in ischemic stroke prevention, with post-procedure reintroduction of OACs. However, practices vary widely, with some patients receiving warfarin or NOACs post-procedure, and others on dual antiplatelet therapy. Despite these insights, research on anticoagulation management post-AF ablation and LAA closure remains limited. This lack of comprehensive data is a significant barrier to forming evidence-based guidelines for this patient group. To address this gap, we propose a randomized controlled trial (RCT) to investigate the optimal duration of post-AF ablation anticoagulation in patients with a history of LAA closure. This RCT, utilizing the PICO framework, would explore different anticoagulant strategies versus no anticoagulation. Primary outcomes would include thromboembolic events, bleeding complications, and overall thromboembolic risk management. The RCT would involve a large cohort of patients with a history of LAA closure post-AF ablation. The intervention group would receive specific anticoagulant strategies post-combined ablation and closure procedure, compared with a control group on different anticoagulation approaches or no anticoagulation. Efficacy and safety measures would be the primary focus, offering a detailed understanding of the risks and benefits associated with each anticoagulant strategy. Conclusion: The current lack of consensus on anticoagulation strategies in patients post-LAA closure and AF ablation necessitates dedicated research. An RCT focusing on these patients could fill this critical knowledge gap, potentially leading to evidence-based guidelines for their management. We recommend the initiation of an RCT to comprehensively address this knowledge gap, aiming to establish evidence-based guidelines for the management of these patients.

A document by Francisco J. Parada. Click on the document to view its contents.