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  • No evidence of stolen data in Glasgow cyber attack

    No evidence of stolen data in Glasgow cyber attack

    Glasgow City Council has found no evidence of any data being stolen in a cyber attack that took a number of services offline in June.

    The local authority also says there has been no sign of any data being leaked or misused after the incident, but advised people to remain cautious.

    Technology services supplier CGI discovered malicious activity on servers managed by a third-party supplier on 19 June.

    A number of online services, including paying penalty charges and reporting school absences, became unavailable due to the council taking servers offline.

    No financial systems were affected by the attack and no details of bank accounts or credit/debit cards processed by those systems were compromised.

    A spokesperson for the council said: “As part of our investigation, experts are monitoring online activity and, to date, there has been no evidence of any data being leaked or misused.

    “However, until forensic examinations of the affected servers are complete – and we can be confident whether any data has been stolen – we are advising anyone who has used any of the affected forms to be particularly cautious about contact claiming to be from Glasgow City Council.”

    Some services, such as public freedom of information requests, can be accessed again while workarounds are being developed for other affected systems.

    Police Scotland are involved in investigating the incident, along with the council, the Scottish Cyber Co-ordination Centre and the National Cyber Security Centre.

    A number of Scottish public bodies have been hit by cyber attacks in recent months, including a ransomware group targeting NHS Dumfries and Galloway last year which saw stolen files published online.

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  • Australian scientists develop green method to produce ammonia gas from air-Xinhua

    SYDNEY, July 4 (Xinhua) — Australian scientists have pioneered a green method to produce ammonia gas from air using artificial lightning, which is low-cost, decentralized and scalable.

    The team has created a more efficient process to produce ammonia gas directly, bypassing earlier methods that first yielded ammonium in solution and required additional steps and energy to obtain the final gas, according to University of Sydney researchers whose study was published Friday.

    Ammonia is typically produced by the energy-intensive and fossil fuel-dependent Haber-Bosch process, an invention in the 19th century, said a statement from the university.

    “In this research, we’ve successfully developed a method that allows air to be converted to ammonia in its gaseous form using electricity,” said the study’s lead researcher, University of Sydney Professor PJ Cullen.

    The plasma-based method Cullen’s team developed uses electricity to excite nitrogen and oxygen molecules in the air. The team then passes these excited molecules to the membrane-based electrolyser to convert the excited molecules to ammonia, according to the study published in Angewandte Chemie International Edition under the German Chemical Society.

    Researchers stressed the need for decentralized and low-cost green ammonia production independent of fossil fuels, noting the team’s plasma-electrolysis process is already energy efficient and scalable, with further improvements underway. ■

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  • Q2 2025 Recap: Endocrinology News and Updates

    Q2 2025 Recap: Endocrinology News and Updates

    HCPLive Endocrinology Q2 2025 Recap

    The second quarter of 2025 brought meaningful developments in endocrinology, from FDA actions to clinical breakthroughs spotlighted at major meetings. Several regulatory milestones signaled progress for patients across the spectrum of endocrine disorders, including expanded access to CGM technology, new formulations for adrenal insufficiency, and a broader treatment label for Cushing’s syndrome.

    Novo Nordisk’s NDA for 25 mg oral semaglutide also marked a potential turning point in obesity care, with the first oral GLP-1 formulation for weight management now under review. Meanwhile, June’s ADA Scientific Sessions capped the quarter with a surge of new data on incretin therapies, obesity drugs, and diabetes technology—many with practice-changing potential.

    Here’s a look back at the most impactful regulatory updates and conference highlights shaping the future of endocrine care.

    Regulatory Updates in Endocrinology

    FDA Clears Dexcom G7 15-Day CGM System

    On April 10, 2025, the FDA cleared Dexcom’s G7 15-day continuous glucose monitoring (CGM) system for adults with diabetes, making it the longest-lasting and most accurate CGM approved in the U.S. Based on clinical data showing a MARD of 8.0%, the G7 15 Day demonstrated excellent accuracy and user satisfaction. According to Dexcom, the system offers features like Apple Watch integration, waterproof sensors, and extended wear with a 12-hour grace period for sensor changes. The company plans to ensure compatibility with insulin pump systems ahead of its US launch in late 2025.

    FDA Approves Label Expansion for Osilodrostat for Cushing’s Syndrome

    On April 16, 2025, the FDA approved Recordati’s sNDA for osilodrostat (Isturisa), expanding its indication to include adults with endogenous Cushing’s syndrome who are not surgical candidates or for whom surgery was not curative. Previously approved only for Cushing’s disease, the broader label is supported by data from the LINC 3 and LINC 4 trials showing sustained cortisol reduction and clinical improvement. According to Recordati, osilodrostat offers a vital option for managing hypercortisolemia and preventing severe complications.

    FDA Accepts NDA Submission for Oral Semaglutide 25 mg

    On May 2, 2025, Novo Nordisk announced the FDA accepted its NDA for a once-daily 25 mg oral formulation of semaglutide for chronic weight management in adults with obesity or overweight and at least one comorbidity. Based on results from the 64-week OASIS 4 trial, the oral semaglutide demonstrated significant weight loss and cardiovascular risk reduction. According to Novo Nordisk, this could become the first oral GLP-1 therapy approved for obesity. If approved, it would expand individualized treatment options beyond injectable formulations. An FDA decision is expected in Q4 2025.

    FDA Approves Hydrocortisone Oral Solution for Adrenal Insufficiency

    On May 28, 2025, the FDA approved Eton Pharmaceuticals’ hydrocortisone oral solution (KHINDIVI) for pediatric patients aged 5 and older with adrenocortical insufficiency, marking the first liquid formulation approved for this use. Designed for accurate, individualized dosing, the 1 mg/mL solution helps patients who have difficulty swallowing pills. According to Eton, this ready-to-use formulation eliminates the need for pill-splitting and supports improved treatment outcomes during childhood development.

    American Diabetes Association

    June 2025 also brought several groundbreaking trials and new updates in diabetes care at the 8th American Diabetes Association Scientific Sessions, which were held in Chicago, Illinois from June 20-23, 2025. With multiple sessions dedicated to late-breaking research, the meeting featured multiple simultaneous publications, including a slew of studies related to incretin therapies. To learn more about the meeting’s top news, check out this trio of articles recapping ADA 2025.

    Diabetes Dialogue

    Diabetes Dialogue: Semaglutide for MASH in ESSENCE Trial, With Arun Sanyal, MD

    In this episode, the hosts discuss new Phase 3 data from the ESSENCE trial showing that once-weekly semaglutide 2.4 mg significantly improved liver outcomes and reduced weight in patients with MASH and stage 2 or 3 fibrosis. They speak with the trial’s lead author about semaglutide’s clinical impact, its potential as a future MASH treatment, and how it compares to the currently approved option, resmetirom.

    Diabetes Dialogue: AACE 2025 Recap

    In this episode, the hosts recap key moments from the 2025 AACE Annual Meeting, covering major plenaries, hands-on tech workshops, and the launch of a new diabetes technology certification program. They spotlight updates on GLP-1 safety, health equity, CGM innovations, and emerging trial data, while reflecting on the future of personalized diabetes care.

    Diabetes Dialogue: Real-World Impact of iLet Bionic Pancreas, With Steven Russell, MD, PhD

    In this episode, the hosts speak with the Chief Medical Officer of Beta Bionics about real-world outcomes from the iLet Bionic Pancreas, an FDA-cleared fully autonomous insulin delivery system requiring no user settings. They highlight its strong A1c-lowering effect, minimal hypoglycemia, and promise for underserved populations and primary care use, including off-label applications in type 2 diabetes.

    Diabetes Dialogue: REDEFINE 1 and REDEFINE 2, with Timothy Garvey, MD, and Melanie Davies, MD

    In this episode recorded at ADA 2025, the hosts break down results from the REDEFINE 1 and 2 trials showing that CagriSema delivered substantial weight loss and glycemic improvements in people with and without type 2 diabetes. They also discuss the drug’s safety, clinical relevance, and future in obesity care with trial investigators, highlighting upcoming studies like REDEFINE 3.

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  • Largest Mars rock could sell for a staggering $4 million |

    Largest Mars rock could sell for a staggering $4 million |

    A rare and massive meteorite from Mars, known as NWA 16788, is poised to make headlines as it heads to auction with an estimated price of up to $4 million. Weighing 54 pounds (24.5 kilograms), it is the largest known piece of the Red Planet ever discovered on Earth, making it 70% larger than any previously found Martian meteorite. First unearthed in Niger’s remote Agadez region in November 2023, this extraordinary specimen is not only scientifically significant but also visually striking, with a glassy crust and deep red hues that reflect its Martian origin.

    Martian Rock: A once-in-a-generation discovery

    According to Sotheby’s, the auction house hosting the sale on July 16 in New York, NWA 16788 is among just 400 confirmed Martian meteorites ever found. Its immense size and exceptional condition set it apart from the usual small fragments that survive Earth’s atmosphere. Cassandra Hatton, Vice Chairman of Science and Natural History at Sotheby’s, described it as “a discovery of extraordinary significance… a tangible connection to the Red Planet.” The meteorite likely arrived on Earth after a powerful asteroid impact blasted it from Mars millions of years ago.

    Scientific insights encased in glass

    Analysis reveals that parts of NWA 16788 were turned to glass during its ejection from Mars and again during its fiery descent through Earth’s atmosphere. Planetary scientist Julia Cartwright of the University of Leicester called it a “fabulous rock,” noting that a reference sample is secured at China’s Purple Mountain Observatory, ensuring future scientific study. She emphasized the balance between private collecting and academic access: “Without the market, we wouldn’t have nearly as many samples to study.”

    Public or private? Experts weigh in

    While some scientists, like Professor Steve Brusatte of the University of Edinburgh, express concern that the rock might vanish into a private vault, others recognize the role collectors play. “It would be a shame if it disappeared from public view,” said Brusatte. Cartwright, however, remains optimistic, suggesting the new owner could still collaborate with researchers. The meteorite’s fate may remain unknown after the auction, but its legacy in planetary science is already secured.


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  • Scientists just found a major flaw in a key COVID drug study

    Scientists just found a major flaw in a key COVID drug study

    The COVID pandemic illustrated how urgently we need antiviral medications capable of treating coronavirus infections. To aid this effort, researchers quickly homed in on part of SARS-Cov-2’s molecular structure known as the NiRAN domain — an enzyme region essential to viral replication that’s common to many coronaviruses. A drug targeting the NiRAN domain would likely work broadly to shut down a range of these pathogens, potentially treating known diseases like COVID as well as helping to head off future pandemics caused by related viruses,

    In 2022, scientists in China (Yan et al.) published a structural model describing exactly how this domain works. It should have been a tremendous boon for drug developers.

    But the model was wrong.

    “Their work contains critical errors,” says Gabriel Small, a graduate fellow in the laboratories of Seth A. Darst and Elizabeth Campbell at Rockefeller. “The data does not support their conclusions.”

    Now, in a new study published in Cell, Small and colleagues demonstrate exactly why scientists still don’t know how the NiRAN domain works. The findings could have sweeping implications for drug developers already working to design antivirals based on flawed assumptions, and underscore the importance of rigorous validation.

    “It is absolutely important that structures be accurate for medicinal chemistry, especially when we’re talking about a critical target for antivirals that is the subject of such intense interest in industry,” says Campbell, head of the Laboratory of Molecular Pathogenesis. “We hope that our work will prevent developers from futilely trying to optimize a drug around an incorrect structure.”

    A promising lead

    By the time the original paper was published in Cell, the Campbell and Darst labs were already quite familiar with the NiRAN domain and its importance as a therapeutic target. Both laboratories study gene expression in pathogens, and their work on SARS-CoV-2 focuses in part on characterizing the molecular interactions that coordinate viral replication.

    The NiRAN domain is essential for helping SARS-CoV-2 and other coronaviruses cap their RNA, a step that allows these viruses to replicate and survive. In one version of this process, the NiRAN domain uses a molecule called GDP to attach a protective cap to the beginning of the virus’s RNA. Small previously described that process in detail, and its structure is considered solved. But the NiRAN domain can also use a related molecule, GTP, to form a protective cap. Determined to develop antivirals that comprehensively shut down the NiRAN domain, scientists were keen to discover the particulars of the latter GTP-related mechanism.

    In the 2022 paper, researchers described a chain of chemical steps, beginning with a water molecule breaking a bond to release the RNA’s 5′ phosphate end. That end then attaches to the beta-phosphate end of the GTP molecule, which removes another phosphate and, with the help of a magnesium ion, transfers the remaining portion of the GTP molecule to the RNA, forming a protective cap that allows the virus to replicate and thrive.

    The team’s evidence? A cryo-electron microscopy image that showed the process caught in action. To freeze this catalytic intermediate, the team used a GTP mimic called GMPPNP.

    Small read the paper with interest. “As soon as they published, I went to download their data,” he says. It wasn’t there. This raised a red flag — data is generally available upon release of a structural biology paper. Months later, however, when Small was finally able to access the data, he began to uncover significant flaws. “I tried to make a figure using their data, and realized that there were serious issues,” he says. Small brought his concerns to Campbell and Darst.

    They agreed. “Something was clearly wrong,” Campbell says. “But we decided to give the other team the benefit of the doubt, and reprocess all of their data ourselves.”

    An uphill battle

    It was painstaking work, with Small leading the charge. Working frame by frame, he compared the published atomic model to the actual cryo-EM map and found something striking: the key molecules that Yan and colleagues claimed to have seen — specifically, the GTP mimic GMPPNP and a magnesium ion in the NiRAN domain’s active site — simply were not there.

    Not only was there no supporting image data, but the placement of these molecules in the original model also violated basic rules of chemistry, causing severe atomic clashes and unrealistic charge interactions. Small ran additional tests, but even advanced methods designed to pick out rare particles turned up empty. He could find no evidence to support the model previously produced by Yan and colleagues.

    Once the Rockefeller researchers validated their results, they submitted their findings to Cell. “It was very important that we publish our corrective manuscript in the same journal that published the original model,” Campbell says, noting that corrections to high-profile papers are often overlooked when published in lower tier journals.

    Otherwise, this confusion in the field could cause problems that reach far beyond the lab bench, Campbell adds — a costly reminder that rigorous basic biomedical research is not just academic, but essential to real-world progress. “Companies keep their cards close to their chests, but we know that several industry groups are studying this,” she says. “Efforts based on a flawed structural model could result in years of wasted time and resources.”

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  • Detection of pathogens within Ixodid ticks collected from domestic cats across the USA | Parasites & Vectors

    Detection of pathogens within Ixodid ticks collected from domestic cats across the USA | Parasites & Vectors

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  • Knowledge and practices of dog and cat owners in Mainland Portugal regarding fleas, flea-borne pathogens, and their management | Parasites & Vectors

    Knowledge and practices of dog and cat owners in Mainland Portugal regarding fleas, flea-borne pathogens, and their management | Parasites & Vectors

    Fleas are among the most important worldwide ectoparasites of dogs and cats. Besides being responsible for causing direct deleterious effects such as anaemia and dermatological problems, they are also responsible for the transmission of numerous pathogens, some of which are zoonotic [30]. In Portugal, flea-borne infections have been reported in both companion animals and humans [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28], highlighting the importance of public education regarding the measures to be taken to reduce the risk of exposure of dogs, cats, and humans to these ectoparasites and the pathogens they transmit. In the present study, a total of 550 companion animal owners in Mainland Portugal responded to a questionnaire regarding fleas, flea-borne pathogens, and their management: 38.5% were dog owners only, 28.7% were cat owners only, and 32.7% owned both animal species. Dog owners usually represent the largest percentage of participants in surveys conducted in the country [33, 34, 39], a trend that might be related to the fact that dogs are the most common pets in Portugal [9] and globally have greater access to veterinary care [41], which increases the frequency of interactions between dog owners and surveys.

    Women made up 69.9% of the participants, which aligns with findings from previous studies on pet ownership, zoonoses, and parasite control awareness [35,36,37,38,39, 42]. This trend is likely related to a higher level of concern among women for the health and well-being of their pets. The mean age of pet owners who responded to the questionnaire was 40 years, and the majority had a secondary or higher level of education, which is similar to what was observed in other studies [35, 36, 38, 39]; this trend may reflect a greater interest among middle-aged adults and individuals with higher educational qualifications to participate in this kind of KP research studies. Geographically, the majority of participants were based in the Área Metropolitana de Lisboa (AML), whereas Algarve had the lowest response rate. Although the questionnaire was distributed through several veterinary clinics across Mainland Portugal, the number of participating clinics in the Algarve was relatively low, potentially influencing respondent numbers. This distribution pattern is consistent with previous national studies [34], [42] and may reflect regional variations in interest levels or cultural differences in pet care practices and perceptions.

    Few studies have assessed companion animal owners’ level of knowledge regarding fleas and flea-borne pathogens [32, 35]. In a study from Hungary [32], most dog and cat owners were unaware that fleas can harm both animals and humans or that the environment can be a source of infestation, while in a study from Malaysia [35] about 40% of cat owners recognised fleas as pathogen vectors and were aware that infestations can originate from the environment. In addition, more than half of the Malaysian cat owners were also able to identify the size, food source, and movement of the fleas, which could be because most of the responders had previously experienced flea infestations in cats. In this study, over 70% of participants correctly identified the flea’s body colour and movement, while more than half recognised its size and diet, demonstrating a reasonable understanding of flea biology. Companion animal owners also recognised the environment, mainly outdoor spaces, and contact with infested animals as common sources of flea infestations, as well as the fact that fleas may remain active year-round, reflecting their awareness of the flea life cycle. Interestingly, cat-only owners were significantly more aware than the other two owner groups that fleas have a flat body shape, and that indoor environments and humans can also be a source of infestation. In contrast to previous studies [32, 35], most participants recognised fleas as vectors of pathogens affecting both animals and humans, with bites being the most commonly known transmission route. However, as in previous studies, only a few could name the specific etiological agents. Knowledge about pathogen transmission through scratches was significantly higher among cat-only owners. Although the identification of pathogens did not differ among the three groups, cat-only owners most frequently mentioned the etiological agents of cat-scratch disease and mycoplasmosis, while D. caninum was more frequently noted by dog-only and dog+cat owners, suggesting that some participants were able to correctly associate certain pathogens with the animal species they affect.

    In this study, multivariate analysis confirmed trends observed in previous CPP questionnaires regarding sex, age, and education level. Specifically, a higher awareness of fleas and flea-borne pathogens was associated with participants who had higher education, were under 50 years of age (Kf only), and were female (Kp only). Knowledge was also higher among participants living in the AML, Centro, and Algarve regions. Interestingly, despite the low number of participants from the Algarve region, their greater knowledge may be linked to the participation of individuals particularly concerned about the seriousness of these ectoparasites.

    The considerable ability of participants to recognise fleas, to associate flea presence with changes in animals’ behaviour, and to understand the role of these ectoparasites in pathogen transmission may be attributed to information provided by veterinarians or previous experiences with flea infestations in their companion animals. In fact, about two-thirds of the participants reported prior flea infestations, which may have prompted them to seek advice from veterinarians, the most common reported source of information on fleas and flea-borne pathogens, followed by social media and the internet. The acquisition of information about zoonotic infections from veterinarians emphasises their important role in raising the awareness of owners about the ways of transmission of the pathogens to their pets and themselves [35], although in some cases the proactivity of veterinarians in passing on knowledge has been considered negligible [36, 39]. Routine consultations provide an important opportunity for veterinarians to educate owners about the health risks fleas pose. To enhance the impact of these interactions, clear and simple educational materials, such as brochures, posters, and infographics, can be displayed in clinic waiting areas to reinforce key messages and support owner understanding. Curiously, and despite the fact that advertisements on TV about the application of ectoparasiticides to prevent arthropods and vector-borne infections was a common source of information identified in previous studies [36, 43], in the present study very few participants reported the use of this communication channel to obtain information about fleas and flea-borne pathogens. Similarly, the low demand for information on these topics from physicians (less than 10% of participants) suggests that healthcare professionals are not perceived as key sources of education on the risks of vector-borne zoonotic agents for pet-owning patients [44].

    To effectively avoid and eliminate fleas, prevent flea-borne infections, and manage flea allergy dermatitis, an integrated control strategy should target both immature and adult flea stages. This strategy may involve using products containing insect growth regulators or juvenile hormone analogues, formulations with repellent or fast-killing properties, or those with combined effects on both the animal and its environment. To prevent and eliminate infestations, a range of products are available in various formulations, including collars, spot-on treatments, sprays, powders, shampoos, chewable or hard tablets, and injectables [30, 45].

    ESCCAP recommends year-round flea prevention to cover the complete activity period of the ectoparasite, as exposure is difficult to avoid [31].

    Portugal has a temperate Mediterranean climate [46], which likely creates favourable conditions for flea populations to persist throughout the year. This climate, characterized by mild winters and warm to hot summers, combined with the common outdoor access granted to pets, increases the risk of flea infestation and underscores the need for continuous preventive measures. Most participants stated that their companion animals were treated against fleas as a preventive measure, aligning with previous studies on ectoparasite control practices among dog and cat owners [33, 34, 39, 47]. About half of the participants treated their pets for ectoparasites every 3 to 4 months, followed by every 6 to 8 months, and once per month. The preference for spot-on treatments among cat owners aligns with other studies, likely due to their ease of application [47]. Similarly, oral tablets were less commonly referred to as being used by this group, probably because cats are considered to be difficult to medicate orally [47]. As the questionnaire did not include the active ingredient of the products used, the accuracy of their application according to the manufacturer’s recommendations cannot be assessed. Given that spot-on treatments were the most commonly used route among cat-only owners and owners of both animal species, and with few exceptions are effective for only 3–4 weeks, it is likely that many pets were not treated at the correct frequency. The same conclusion can be drawn for the administration of ectoparasites in tablet form, the second most commonly used product by dog owners and owners of both animal species, since the treatment schedule is between 4 and 12 weeks. Reasons for non-compliance may relate to a lack of awareness about the importance of continuous prevention, the absence of infestation (thus reducing adherence to long-term prevention protocols), or financial constraints, with the latter reported by 15.4% of participants. Flea treatment rates for all animals in the household were significantly lower among dog and cat owners than among those who owned only dogs or only cats, although the overall frequency of flea treatment did not differ significantly between these groups. A survey of dog owners in Thailand found that the cost of flea and tick prevention, especially in households with multiple dogs, was linked to less frequent use of preventive treatments. Most owners tended to use products only when their dogs were infested [37]. In the present study, only a small percentage of participants claimed to treat their animals only when fleas were detected.

    Effective prophylactic treatment should be used in conjunction with environmental control to target all life stages. Mechanical environmental measures such as frequent vacuuming, washing pet bedding, and cleaning all areas that may harbour eggs can significantly reduce the household flea burden [6, 32, 50]. Interestingly, cleaning, vacuuming, and applying insecticides to the house and the animal’s resting places, along with brushing the animal, were the most frequently mentioned measures for controlling infestation, suggesting that many owners are aware of the importance of these practices in managing flea infestations. Cat-only owners were significantly more likely to choose the practice of cleaning areas with a possible higher risk of infestation and presented greater willingness to ask veterinarians for advice on preventing and controlling fleas. This, together with their greater knowledge of flea morphology and the fact that indoor environments and humans can also be sources of infestation, indicates a previous history of contact with fleas. In fact, 53.2% of the respondents of this group reported prior experience with fleas, which likely explains a greater motivation to apply preventative measures. Interestingly, a significantly higher proportion of participants in this group reported keeping their animals indoors from sunset to sunrise as a control measure. This may reflect confusion with other insects active during that time, such as mosquitoes and phlebotomine sand flies.

    As mentioned earlier, multivariate analysis indicated that higher education was associated with greater knowledge of fleas and flea-borne pathogens. However, this knowledge did not lead to a higher adoption of protective practices. This discrepancy could be related to the perception that general protective measures against arthropods and arthropod-borne infections are also effective against fleas, suggesting that specific flea control measures may be unnecessary.

    Conversely, higher practice scores were observed in owners under 60 years old, those living in the AML or Centro regions, and those owning only cats or only dogs. This may reflect a greater concern for preventive measures among middle-aged participants and individuals with higher knowledge of fleas and flea-borne pathogens. Additionally, owning a single species might lead to more focused and effective infestation prevention strategies.

    Although over 30% of Portuguese households owned at least one dog or cat in 2022, respondents in this study came from only 86 of the 278 municipalities in Mainland Portugal. This limited geographical representation may have hindered a detailed analysis of how sociodemographic differences influence knowledge about fleas, the diseases they can cause, and management measures for these ectoparasites. As a result, the study’s ability to accurately identify trends in pet owners’ KP may have been affected. Future research should address this limitation by ensuring broader geographical representation, thereby strengthening the reliability of the findings.

    Another limitation was the absence of including the residence of companion animal owners, as animals living in rural areas are more exposed to fleas, which may influence the awareness of the owners regarding these ectoparasites and their management.

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  • Prognostic Value of Spontaneous Potential in Long-Term Outcomes Follow

    Prognostic Value of Spontaneous Potential in Long-Term Outcomes Follow

    Introduction

    Pulmonary vein isolation (PVI) serves as the cornerstone of atrial fibrillation (AF) catheter ablation and remains one of the most widely used treatments for paroxysmal atrial fibrillation (PAF). Currently, PVI combined with linear ablation represents the primary surgical approach for non-paroxysmal atrial fibrillation (NPAF).1–4 In clinical practice, the long-term efficacy of standalone PVI for NPAF remains suboptimal. Advancements in cardiac electrophysiology suggest that AF development is associated with myocardial sleeves of the pulmonary veins, with the left atrial posterior wall also identified as a key abnormal site.5 Pulmonary vein isolation combined with left atrial posterior wall isolation (PVI+BOX) ablation involves linear ablation of the left atrial apex line and left atrial posterior wall line in addition to bilateral pulmonary vein isolation, thereby isolating both the pulmonary veins and the left atrial posterior wall from other atrial regions. However, data on BOX ablation remain limited, and existing conclusions are inconsistent.6–9

    Clinical findings indicate that spontaneous potential (SP) can be detected in the left atrial posterior wall of some patients with NPAF who have undergone PVI+BOX ablation. Previous studies indicated that most atrial premature beats (APBs) responsible for triggering AF originate from the pulmonary veins and induce AF through rapid discharges.4 During embryonic development, the left atrial posterior wall and pulmonary veins originate from the same site.10 However, whether the left atrial posterior wall SP is equivalent to spontaneous pulmonary vein potential and whether it can trigger AF remains unclear. Therefore, the relationship between left atrial posterior wall SP and long-term outcomes following PVI+BOX in patients with NPAF was investigated in this study.

    Data and Methods

    Objects

    The clinical data in this study were retrospectively collected from 140 patients with symptomatic NPAF who underwent radiofrequency ablation for the first time between 2022 and 2023. Based on the surgical approach, patients were categorized into the PVI group and the PVI+BOX group. The PVI+BOX group was further subdivided into the SP group and the no-SP group based on the presence of left atrial posterior wall SP following BOX. All patients provided informed consent before treatment, and the study received approval from the local ethics committee.

    NPAF that can be treated with catheter ablation includes persistent AF (PerAF) and long-standing persistent AF (LSPAF), as defined by the 2020 European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) guidelines for the management of AF.11 Before catheter ablation, all patients underwent transesophageal echocardiography (TEE) or left atrial computed tomography angiography (CTA) to exclude left atrial and/or left auricular thrombosis. Additionally, pulmonary vein CTA was performed to assess the anatomical structure of the pulmonary veins. All antiarrhythmic drugs were discontinued for at least five half-life periods before the procedure.

    Patients were excluded if they met any of the following criteria: (1) age younger than 18 years or older than 80 years; (2) diagnosis of valvular AF; (3) presence of hyperthyroidism; (4) history of cerebrovascular accidents or other neurological diseases within the past three months; (5) presence of other systemic diseases or tumors; (6) left atrial and/or left auricular thrombus; (7) AF of non-pulmonary vein origin; (8) prior cardiac surgery or heart disease requiring surgical intervention; (9) incomplete clinical data or failure to complete follow-up.

    The radiofrequency ablation procedure was performed with the patient in a supine position under local anesthesia with 1% lignocaine. Bilateral femoral vein punctures were made, and a 10-pole electrode was advanced into the coronary sinus via the left femoral vein, while the interatrial septum was punctured via the right femoral vein. Two 8.5F Swartz sheaths were inserted into the left atrium for the administration of 100 μg/kg heparin. A ring electrode (Biosense-Webster, USA) and a saline-irrigated electrode catheter (Biosense-Webster, USA) were introduced into the left at rium via the Swartz sheath for modeling (CARTO 3D electroanatomic mapping system), mapping, and ablation. In the PVI group, linear ablation was performed around the circumferential bilateral pulmonary vein antrum to achieve PVI. In the PVI+BOX group, linear ablation targeted the circumferential bilateral PVI, left atrial apex line, and left atrial posterior wall line to achieve posterior wall isolation. Pulmonary vein isolation was confirmed by the absence of pulmonary vein potential or the presence of SP within the pulmonary vein, with pulmonary vein pacing unable to conduct to the left atrium. Left atrial posterior wall isolation was confirmed by the absence of atrial potential (Figure 1A) or the presence of SP (Figure 1B) in the left atrial posterior wall, with left atrial posterior wall pacing unable to conduct to other atrial sites. If AF persisted following PVI or BOX ablation, synchronized electrical cardioversion (100–150 J) was administered. Ablation parameters included power (35–45 W), saline flow rate (20–30 mL/min), and impedance (140–170 Ω).

    Figure 1 (A) Absence of spontaneous potential in the left atrial posterior wall following PVI + BOX. (B) Presence of spontaneous potential in the left atrial posterior wall following PVI + BOX.

    Follow-Up

    The clinical condition of all patients was continuously monitored through 24-hour electrocardiography (ECG), blood pressure measurement, and oxygen saturation assessment after the procedure. On the first postoperative day, patients were initiated to either warfarin or a novel oral anticoagulant based on personal preference, and were informed to use it mandatorily for at least three months. Anticoagulation therapy was then continued according to the CHA2DS2-VASc score (≥ 2 for males, ≥ 3 for females). Anti-arrhythmic medications, such as amiodarone or propafenone, with or without metoprolol, were routinely administered postoperatively and discontinued after three months. Regular follow-up was conducted through clinic visits or monthly telephone consultations to evaluate AF recurrence, assessed through symptoms including palpitations, chest discomfort, shortness of breath, and fatigue. Patients underwent routine ECG examinations at local healthcare facilities, and in cases of the aforementioned symptoms, either a standard 12-lead ECG or dynamic ECG monitoring was performed. At three and twelve months postoperatively, cardiac ultrasound and 72-hour ECG monitoring were conducted at the clinic to detect AF recurrence. Follow-up data, including recurrence occurrences within three months postoperatively, were systematically documented.

    The study’s primary endpoint was the late recurrence of AF, defined as atrial tachyarrhythmia—including AF, atrial flutter, or atrial tachycardia—lasting more than 30 seconds on either a standard or dynamic ECG after all anti-arrhythmic medications were discontinued three months postoperatively.

    Statistical Analysis

    Categorical data were presented as frequency (percentage) and analyzed using the chi-square test. The Kolmogorov–Smirnov test was used to assess the normality of baseline characteristics. An independent sample t-test was conducted to compare data between the two groups, while non-normally distributed variables were expressed as median (25th–75th percentile) and analyzed using the Mann–Whitney U-test. The recurrence rate between the two groups was assessed using Kaplan-Meier survival analysis. Logistic regression was used to evaluate correlations between variables. A two-sided P < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS 26.0 software.

    Results

    Basic Clinical Data

    Among the 140 patients, 78 received PVI+BOX treatment, while 62 underwent PVI only. No significant differences were observed in the clinical characteristics between these groups (Table 1). Of the 78 patients treated with PVI+BOX, 33 exhibited SP in the left atrial posterior wall, whereas 45 did not. Similarly, no significant differences were noted in the clinical characteristics between these subgroups (Table 2).

    Table 1 Baseline Characteristics of the PVI Group and PVI+BOX Group

    Table 2 Baseline Characteristics of the SP Group and No-SP Group

    Long-Term Effect

    Patients were monitored for 12 months postoperatively. In the PVI+BOX group, 24 patients (30.8%) experienced late recurrence, compared to 26 patients (41.9%) in the PVI group, with no statistically significant difference (p = 0.145; Figure 2A). In contrast, late recurrence occurred in 6 patients (18.2%) in the SP group and 18 patients (40%) in the no-SP group, showing a significant difference (p = 0.041; Figure 2B). Further analysis among the SP group, no-SP group, and PVI group indicated that the late recurrence rate was lower in the SP group than in the PVI group (p = 0.020), while no significant difference was found between the no-SP and PVI groups (p = 0.780; Figure 2B). Table 3 presents the late recurrence rates.

    Table 3 Late Recurrence Rate

    Figure 2 (A) Late recurrence-free survival curves comparing the PVI + BOX group and the PVI group. (B) Late recurrence-free survival curves comparing the SP group, no-SP group, and PVI group.

    Complications

    In the PVI+BOX group (n = 78), postoperative complications included pneumonia in 4 patients and pericardial effusion in 2 patients. In the PVI group (n = 62), 2 patients developed pneumonia, and 1 patient experienced pericardial effusion. No statistically significant difference in complication rates was observed between the groups (p > 0.05). All affected patients recovered before discharge. Table 4 presents the details on patient complications.

    Table 4 Complication Rate

    Analysis of Risk Factors for Postoperative Recurrence

    Patients who underwent PVI+BOX treatment were categorized based on late AF recurrence. Univariate analysis results are presented in Table 5. The analysis identified AF duration (p = 0.013), total cholesterol (TC) (p = 0.038), white blood cell count (WBC) (p = 0.032), and SP (p = 0.039) as risk factors for post-ablation late recurrence of NPAF (p < 0.05).

    Table 5 Single-Factor Analysis of Postoperative Recurrence

    No statistically significant differences were observed between the two groups in gender, age, body mass index (BMI), echocardiographic parameters, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left atrial diameter (LAD), and ejection fraction (EF), as well as comorbidities and other factors.

    Multivariate logistic regression analysis (Table 6) identified the course of AF (odds ratio (OR): 1.026, 95% CI: 1.007–1.046, p =0.006) and SP (OR: 0.219, 95% CI: 0.057–0.835, p =0.026) as independent predictors of late AF recurrence.

    Table 6 Risk Factor Analysis for Late Recurrence

    Discussion

    Application of PVI+BOX in AF Ablation

    Since the identification of anomalous pulmonary venous activities as the primary trigger of AF, PVI has become the cornerstone of AF ablation. Over nearly two decades, it has been established as the standard procedure for AF catheter ablation, achieving a long-term success rate of 50% to 70% for paroxysmal AF. However, its effectiveness in NPAF remains limited, necessitating the incorporation of various linear ablation and substrate modification strategies. In recent years, growing recognition of the left atrial posterior wall’s role in AF occurrence and maintenance has led researchers to explore left atrial posterior wall isolation, with BOX being a commonly used approach. Nevertheless, available data on BOX ablation remain scarce, and study conclusions are inconsistent. Yamaji et al reported that left atrial posterior wall isolation could reduce postoperative recurrence in patients with NPAF.6,7 In contrast, Tamborero et al found no statistically significant difference between pulmonary vein isolation alone and its combination with left atrial posterior wall isolation in preventing arrhythmia recurrence.8,9

    While recent studies, such as Yan et al, have compared radiofrequency ablation (RFA) guided by ablation index (RFCA-AI) and second-generation cryoballoon ablation (CBA-2) in AF treatment, the role of spontaneous potential (SP) in the left atrial posterior wall following PVI+BOX ablation remains unexplored.12 Our study addresses this gap by evaluating SP as a novel predictor of long-term success after PVI+BOX, providing new insights into AF ablation strategies for NPAF patients.

    Analysis of Risk Factors for Postoperative Recurrence

    Several factors contribute to atrial substrate changes in patients with AF; however, the specific underlying mechanism remains unclear. Structural, electrical, and neural remodeling of the atrium are known to influence this process. Research has indicated a correlation between AF duration and post-ablation recurrence, with prolonged AF duration associated with a higher recurrence rate. The likely explanation is that an extended AF course increases the likelihood of atrial electrical and anatomical remodeling, making these changes irreversible and thereby significantly elevating the recurrence rate. In this study, univariate analysis of AF duration revealed that patients in the recurrence group had a significantly longer AF duration (30.5 [12–90] months) compared to the non-recurrence group (13 [7–36] months). Furthermore, multivariate analysis identified AF duration as an independent risk factor for post-ablation AF recurrence.

    Distribution and Generation Mechanism of SP

    Pulmonary veins exhibit distinct electrophysiological properties that contribute to the initiation and maintenance of AF. Pulmonary vein SP refers to spontaneous electrical activity generated by the pulmonary vein independent of the left atrium following PVI, with bidirectional PVI serving as a recognized endpoint of pulmonary vein ablation.13,14 Pulmonary vein SP commonly manifests in three forms: sporadic isolated ectopic beats, slow and regular ectopic rhythms, and rapid fibrillation potential activity.13,15 The primary mechanisms underlying pulmonary vein SP include (1) the focal mechanism, in which Jiang et al identified autorhythmic electrical activity as its principal cause.16 Studies have indicated the presence of P cells, transitional cells, and Purkinje cells within the myocardial sleeves of pulmonary veins, suggesting that pulmonary vein SP may result from electrical activity produced by autorhythmic cells.17 (2) The reentrant mechanism, characterized by pronounced spatial heterogeneity in atrial action potential duration and a shortened plateau phase, elevates the risk of reentrant arrhythmias. (3) The AF trigger mechanism, as described by Yves et al, suggests that an AF-triggered pulmonary vein predicts AF recurrence following pulmonary vein isolation.18 In such cases, pulmonary vein conduction is restored, leading to the occurrence of pulmonary vein SP, which has been frequently observed in AF-triggered pulmonary veins after circumferential PVI.19

    There are currently limited studies on left atrial posterior wall SP. The left atrial posterior wall shares an embryological origin with the pulmonary vein, and its distinct histology and anatomical structures make it a crucial substrate for sustaining AF. It serves as a trigger for AF, with its electrophysiological properties contributing to AF maintenance. Prolonged AF episodes induce both electrophysiological and structural alterations, further facilitating AF persistence.20 Embryologically, the smooth posterior wall is anatomically adjacent to the surrounding muscle trabecular tissue derived from the primitive left atrium. Due to this embryological origin, its electrophysiological characteristics more closely resemble the myocardial sleeves of pulmonary veins rather than the adjacent superior and inferior tissues.20

    Electrophysiologically, pulmonary veins and cardiomyocytes in the posterior wall exhibit distinct electrophysiological and ion channel properties, which may contribute to arrhythmogenesis.21 Anatomically, the cardiac muscle fibers of the left atrial posterior wall, particularly near the pulmonary vein junction, are oriented in varying directions. Consequently, conduction velocity and depolarization between adjacent tissues differ, and the transition between the epicardial and endocardial layers may exhibit heterogeneous anisotropy, potentially resulting in conduction delays, unidirectional blocks, and localized reentry.22 These features of the posterior wall of the left atrium may cause SP in the left atrial posterior wall to trigger reentrant mechanism or focal mechanism similar to pulmonary vein potentials. These unique characteristics of the left atrial posterior wall may contribute to AF initiation and maintenance.

    Analysis of Risk Factors for Postoperative Recurrence

    In this study, pulmonary vein isolation combined with posterior wall isolation did not show a significant difference in reducing NPAF compared to pulmonary vein isolation alone. Among patients with NPAF who underwent pulmonary vein isolation with posterior wall isolation, the recurrence rate was lower in the left atrial posterior wall SP group than in the left atrial posterior wall no-SP group. Additionally, the recurrence rate in the SP group was lower than in the simple PVI group, whereas no significant difference was observed between the no-SP group and the PVI group. This finding suggests that left atrial posterior wall SP may indicate the presence of a trigger focus outside the pulmonary vein, leading to posterior wall isolation and subsequently reducing AF recurrence. Patients without SP of the posterior left atrial wall may have other unknown lesions or triggering mechanisms, and posterior wall isolation has a relatively unsatisfactory therapeutic effect on them.

    Unlike Yan et al, which primarily focused on comparing different ablation techniques, our study introduces SP as a novel factor influencing AF recurrence after PVI+BOX ablation.12 By identifying SP as a potential predictor of improved ablation success, this study provides new mechanistic insights into the role of left atrial substrate properties in AF recurrence.

    White blood cells and neutrophils, as important indicators of the inflammatory system, their counts also reflect the degree of the inflammatory response. Previous studies have shown that patients with postoperative atrial fibrillation have significantly elevated peripheral blood white blood cells, and patients with significantly elevated white blood cells also have a longer duration of atrial fibrillation attacks. The increase of white blood cell count and neutrophil count, which are important indicators of the inflammatory system, is a risk factor for the maintenance of atrial fibrillation.

    Limitations

    In this study, SP has a certain degree of variability, the length of the recording time may affect the incidence of spontaneous potential. It is a single-center, small-sample, retrospective study, and postoperative AF recurrence was not recorded for some patients, potentially leading to discrepancies between the observed and actual long-term recurrence rates. Further multi-center studies are required to investigate the optimal degree of PVI+BOX.

    Conclusion

    SP following left atrial posterior wall isolation suggests a better long-term outcome for NPAF after PVI with BOX catheter ablation. The long-term outcome of non-paroxysmal atrial fibrillation refers to the free recurrence rate after 3 months of ablation.

    Abbreviations

    AF, Atrial Fibrillation; BMI, Body Mass Index; CAD, Coronary Artery Disease; CTA, Computerized Tomography Angiography; HCM, Hypertrophic Cardiomyopathy; HDL-C, High density lipoprotein cholesterol; LAD, Left Atrial Diameter; LDL-C, Low density lipoprotein cholesterol; LSPAF, Long-standing Persistent Atrial Fibrillation; LVEDD, Left Ventricular End-diastolic Diameter; LVEF, Left Ventricular Ejection Fraction; LVESD, Left Ventricular End-systolic Diameter; NE, Number of central granulocytes; NT-proBNP, N-terminal pro-B-type Natriuretic Peptide; PAF, Paroxysmal Atrial Fibrillation; PerAF, Persistent Atrial Fibrillation; PVI, Pulmonary Vein Isolation; Scr, Serum Creatinine; SP, Spontaneous potential; TC, Total cholesterol; TG, Triglyceride; WBC, White blood cell count.

    Data Sharing Statement

    All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

    Ethics Approval and Consent to Participate

    This study was conducted with approval from the Ethics Committee of Fujian Medical University Union Hospital (Approval Number: 2024KY085). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all participants.

    Funding

    This work was supported by the Fujian Provincial Health Technology Project (2021CXB003) and Fujian Provincial Natural Science Foundation of China (2023J01663).

    Disclosure

    The authors declare that they have no conflicts of interest in this work.

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    6. Yamaji H, Higashiya S, Murakami T, et al. Efficacy of an adjunctive electrophysiological test-guided left atrial posterior wall isolation in persistent atrial fibrillation without a left atrial low-voltage area. Circ Arrhythm Electrophysiol. 2020;13(8):e008191. doi:10.1161/CIRCEP.119.008191

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