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The transition from regulated to dysregulated parainflammation is a new concept that needs to be elucidated to clarify the pathogenesis of dry eye disease (DED). This review summarizes the recent evidence about mechanisms that could lead to dysregulated parainflammation, proposing a new hypothesis to correlate this process with the progression to chronic inflammation.
Methods
A group of European experts on DED participated in a roundtable to discuss the role of parainflammation in the most common ocular diseases with regard to DED. Starting from the roundtable contents, a narrative review was conducted through a PubMed search based on the main topics discussed, namely: parainflammation, dysfunctional parainflammation, tear film lipid and mucin alterations, and tear cortisol.
Results
Parainflammation is involved in different ocular pathologies and is characterized by the involvement of the immune system and complement factors. In DED, continuous and persistent insults are responsible for the qualitative and quantitative alteration of the lipid and mucin components of the tear film. In addition, other contributing factors have recently been described, such as the reduction of cortisol synthesis by corneal epithelial cells. This altered condition leads to excessive macrophage activity, releasing cytokines and adhesion molecules, losing tissue homeostasis, and possibly progressing to chronic inflammation.
Conclusions
Literature evidence supports the crucial role of parainflammation and its usefulness in improving the diagnosis and treatment of DED. At the same time, further investigations are necessary to better define the transition from functional to dysfunctional parainflammation, including the role of ocular surface components other than the tear film.
Key Summary Points
Parainflammation is a protective immune response maintaining ocular homeostasis, but its dysregulation leads to chronic inflammation in dry eye disease (DED), driven by tear film lipid and mucin alterations and reduced cortisol synthesis.
Tear film instability, oxidative stress, and goblet cell dysfunction disrupt ocular surface homeostasis, amplifying inflammation and epithelial damage, contributing to the progression of DED.
Current treatments target inflammation, but newer strategies, including tear substitutes, mucin secretagogues, and ocular surface modulators, show potential to restore homeostasis and prevent chronic inflammation, warranting further investigation.
Introduction
The ocular surface is a complex system in a constant dynamic equilibrium, always adapting to changes in external (e.g., environmental stress, surgery, contact lenses, topical medications) and internal (e.g., diseases, aging, drug intake, metabolic and hormonal changes) stimuli and insults [1]. Under physiological conditions, multiple components of the ocular surface, such as cornea, conjunctiva, lacrimal glands, Meibomian glands, tear film, and endocrine, immune, and nervous systems, cooperate to preserve local health and respond to an external stimulus by restoring a condition of homeostasis [2, 3]. However, after continuous overstimulation, a loss of ocular surface adaptation can reduce the threshold of sensory nerve terminations and may induce lacrimal gland dysfunction and pro-inflammatory/anti-inflammatory cytokine imbalance [4]. The loss of homeostasis is accompanied by increased osmolarity, tear film instability and evaporation, neuroinflammation, inflammation at the ocular surface, and decreased tear secretion. Taken together, this results in clinical symptoms and signs observed in dry eye disease (DED) [5, 6]. Accordingly, in 2017, the Tear Film & Ocular Surface Society (TFOS) Dry Eye Workshop II (TFOS DEWS II) defined DED as a “multifactorial ocular surface disease characterized by loss of tear film homeostasis, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play an etiological role” [7].
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The key role of the mechanisms underlying inflammatory processes of the ocular surface has been demonstrated and further explored in recent years [8‐14]. However, in some patients with initial alterations in the ocular surface, the signs and symptoms of the underlying inflammatory condition are not clearly evident and pathological. In this context, a mild and persistent process called parainflammation has been described as an intermediate, adaptive immune response that occurs when tissue experiences mild stress or damage but has not yet reached a state of full inflammation [15]. It represents a low-level, controlled immune activation that helps maintain tissue homeostasis and repair in response to stressors, such as aging, metabolic imbalance, or mild injury. Unlike acute inflammation, which is a rapid, robust immune response to injury or infection, parainflammation operates at a lower intensity and is sustained over a longer period. In a physiological condition, it serves as finely tuned protective mechanism aimed at preventing damage and maintaining tissue health and function while responding to ongoing stress [15]. However, in the presence of intense and persistent stimuli, this regulatory mechanism becomes dysfunctional and leads to chronic inflammation, contributing to the development of several inflammatory diseases. This state has been hypothesized as the denominator of various systemic conditions, such as obesity, type 2 diabetes, and other neurodevelopmental or age-related disorders [16‐19]. Metabolic factors, such as modified proteins, saturated free fatty acids, and oxidized LDL, act as key triggers, with accumulated damage to the genome, proteome, and metabolome contributing to the pro-inflammatory status and the development of dysfunctional parainflammation [20].
In the eye, parainflammatory mechanisms and their dysregulation have been observed in age-related macular degeneration, diabetic retinopathy (DR) [21, 22] and more recently in glaucoma [22] and DED [4].
Based on this evidence, the relation between the pathophysiology of DED and the transition from regulated to dysregulated parainflammation needs to be elucidated in order to clarify the underlying pathological picture and better explain the onset of chronic inflammatory processes of DED.
Clarifying these mechanisms could aid in the identification of early markers underlying the transition from parainflammation to inflammation in DED, which, in turn, could be useful in improving diagnosis and defining therapeutic strategies to improve patient management.
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Methods
In January 2023, a group of European experts in DED participated in a roundtable to discuss the evidence on the pathophysiology of DED and the mechanisms underlying the pathological picture. Building on the roundtable contents, a PubMed search was conducted based on the main topics that emerged, namely: parainflammation, dysfunctional parainflammation, tear film lipid and mucin alterations, and tear cortisol. Different combinations of pertinent keywords were used (e.g., parainflammation AND retina; parainflammation AND DED; dysfunctional parainflammation AND DED; tear film lipid alterations and DED; mucin alterations and DED; cortisol release AND DED), focusing on papers published in English without time restriction. Additional sources were identified through manual searches of reference lists. Studies were selected based on their relevance to the pathophysiology, diagnosis, and management of parainflammation. Due to the nature of a narrative review, no formal quality assessment was performed. The findings were synthesized to provide a comprehensive overview and propose new perspectives on the topic. Accordingly, findings and opinions presented in this paper are based on a combination of expert consensus reached during the roundtable discussion and a comprehensive review of the current literature. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
Parainflammation in the Ocular System
Functional parainflammation has been described at the ocular level, typically involving the activation of molecular mechanisms and signaling pathways, such as kinases, deacetylases, and transcription factors (Nrf-2 and NF-κB), which increase the production of cytoprotective and restorative proteins (growth factors, phase 2 and antioxidant enzymes, and protein chaperones), as well as free radicals, ion fluxes, and energy demand [23, 24]. Under physiological conditions, the immune system is able to initiate a functional parainflammatory response at the ocular level and control it [25]. Thus, even at the ocular level, functional parainflammation is an active phenomenon managed simultaneously by the nervous, endocrine, immune, and vascular systems and is considered a beneficial reaction (Fig. 1).
Fig. 1
Schematic representation depicting parainflammation as an intermediate state between homeostasis and chronic inflammation
Within the ocular system, dysfunctional parainflammation plays a pivotal pathogenic role in macular degeneration and glaucoma.
Indeed, in the retina, the parainflammatory response serves to repair damage and maintain homeostasis. Retinal pigment epithelial (RPE) cells can upregulate pro-inflammatory factors, such as CCL-2, IL-6, TNF-α, and complement factor β, and downregulate other immune regulatory factors, such as complement factor H [26]. In the parainflammatory response of the retinal immune system, a low level of complement activation occurs, as well as an age-dependent increase in the number of microglial cells with a subretinal migration and accumulation [26].
In the context of age-related macular degeneration (AMD), dysfunctional parainflammation leads to chronic inflammation and tissue damage in RPE and surrounding structures [21, 22, 27]. Key contributors to this dysfunction include oxidative stress and the accumulation of cellular debris. Over time, these factors exacerbate inflammation, contributing to the degeneration of photoreceptors and the progression of AMD. Moreover, the complement alternative pathway activation in the retina has been recognized as an important part of chronic inflammation contributing to retinal pathology in these disease states [21, 22, 27].
Glaucoma, a leading cause of irreversible blindness globally, is marked by progressive retinal ganglion cell (RGC) loss and optic nerve degeneration. Although elevated intraocular pressure (IOP) is a key risk factor, growing evidence highlights the importance of neuroinflammatory processes and oxidative stress in glaucoma pathogenesis and progression [28, 29]. Signs of inflammation include more acidic pH and increased immune proteins in the aqueous humor and vitreous, along with activation of astrocytes and microglia, and immune complex and immunoglobulin deposits in the retina, as identified through histology [30, 31].
Evidence suggests that dysfunctional parainflammatory processes in the retinal ganglion cell layer and optic nerve contribute to the inflammatory reaction in glaucoma [29, 32]. Glial cells in retinal tissue and trabecular meshwork (TM) cells typically regulate tissue repair and homeostasis, but in glaucoma, this feedback is disrupted by prolonged mechanical, vascular, and oxidative stress [29, 32]. Chronic stress leads to persistent inflammation, accelerating retinal ganglion cell loss and worsening glaucoma [29]. Additionally, subclinical inflammation at the ocular surface in glaucoma patients on active therapy can cause subconjunctival fibrosis and ocular surface disease [29]. The potential effects of ocular surface inflammation on deeper structures, such as the trabecular meshwork, lens, or even the retina, remain speculative [29]. Therefore, careful assessment of the ocular surface in glaucomatous patients is suggested, especially when treated with preserved eye drops.
Parainflammation and Dry Eye
At the ocular surface level, parainflammation has been described as regulated by the immune system of the tissue and controlled by resident macrophages and possibly the complement system, which, in turn, may also release cytokines and growth factors in order to promote the recovery to homeostasis [12]. In this context, functional parainflammation plays a beneficial role in maintaining homeostasis. An example of this comes from the literature evidence related to the description of parainflammation in contact lens wearers. The parainflammatory status of the anterior eye during contact lens wear has been described as a positive, protective phenomenon, in which the up-regulation of the immune system helps keep the eye in a state of “heightened alert”, ready to ward off any extrinsic noxious challenge [24]. Increased pro-inflammatory cytokines, transient increase in corneal and conjunctival Langerhans cell density [33, 34], involvement of dendritic cells, and transient receptor potential (TRP) ion channels have been described in this mechanism [24]. However, prolonged stress can induce a chronic disease due to predisposing external risk factors, co-morbidities, high levels of oxidative stress, or pathogen/damage-associated molecular pattern signaling [35, 36]. In such cases, failure to achieve ocular surface system homeostasis can lead to dysfunctional parainflammation that can fuel the onset or progression of chronic DED. The loss of homeostasis and the transition from dysfunctional parainflammation into inflammation has been recognized as a key pathogenetic step in the evolution of tear dysfunction in this ocular condition [4, 12]. When dysfunctional parainflammation occurs at the ocular surface level, an excessive release of inflammatory mediators from the lacrimal glands or ocular surface cells occurs, leading to damage to the corneal and conjunctival epithelial cells [15] (Fig. 2).
Fig. 2
Progression of ocular para-inflammation over time. Functional para-inflammation maintains homeostasis through increased tear production, blinking rate, mucin secretion, and epithelial turnover. As compensatory mechanisms fail, dysfunctional para-inflammation leads to elevated pro-inflammatory agents, reduced mucin and tear production, and decreased cold receptor sensitivity, resulting in a progressive loss of ocular surface homeostasis
Literature evidence reports the involvement of the tear film quality and quantity in achieving ocular surface homeostasis [2]. In this context, the persistence of alterations of the outer lipid and muco-aqueous layers can be hypothesized to be involved in the early stages of the loss of homeostasis of the ocular surface system and the shift toward dysfunctional parainflammation in DED. Accordingly, several mechanisms of alteration of the two-layer structure of the tear film have been described in the context of DED and are discussed below [37‐40].
Tear film lipids contribute significantly to the maintenance of ocular surface homeostasis, optimization of tear spreading patterns, direction of aqueous flow, and prevention of film overflow during blinking. Nonpolar lipids, which comprise over 90% of the lipid film, are supposed to be the main factor responsible for controlling tear water evaporation; they provide a clear optical surface and are a barrier against foreign objects and organisms [37, 41].
Although the thickness of the lipid layer is an indicator of the presence of lipids, this parameter does not fully reflect their efficiency and is not a guarantee of their ability to hinder evaporation [37]. Thinning of the tear film lipid layer may result not only from the lack of lipids but also from their inability to spread correctly in an effective elastic bilayer. In particular, the lipid-rich fraction of tears is particularly susceptible to oxidative damage that could alter the tear film quality. Under oxidative stress conditions, the tear film loses its fluidity and ability to spread quickly over the mucous-aqueous phase of the film, thus leading to tear film water evaporation [12]. Increased levels of lipid hydroperoxide are detected by two major biomarkers, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) [42]. The presence of MDA and 4-HNE has been demonstrated in the tear film and ocular surface in patients with DED [43, 44]. The increased concentration of lipid hydroperoxides seems to correlate positively with other parameters detected in DED diagnosis, such as reduced tear film break-up time and Schirmer tear values [45]. Therefore, persistent oxidative stress could play a role in altering the outer lipid layer, which in turn could lead to dysfunctional parainflammation.
Mucins are large extracellular glycoproteins that compose the mucus, an adhesive viscoelastic gel able to maintain a wet surface and protect against pathogens and other environmental toxic agents [46]. Alterations in the structure and/or expression pattern of mucins are related to the pathogenic processes of various ocular surface diseases, including DED. A common feature of all forms of DED is altered goblet cell (GC) number and function [39, 40, 47]. Specifically, when the ocular epithelium is altered due to inadequate lubrication, a condition known as squamous metaplasia, common to many pathologic processes, develops [48]. In the first phase, the GC number increases, but cells have a modified structure, appearing smaller and with increased delivery of mucus [49]. If the damaging activity is prolonged or particularly intense, the GCs tend to reduce their number. This leads to reduced conditioning of resident and recruited monocyte-derived cells, resulting in increased expression of IFN-γ, IL-12, and monocyte and Th1 chemokines by the surface epithelium and monocytes. The latter sustain the inflammatory status of the ocular surface and stimulate the expression of genes promoting cornification, inhibit cholinergic signaling and, finally, induce an unfolded protein response and apoptosis in the conjunctival GCs [48, 50]. The decrease in GC density is also responsible for the alteration of the secretory mucin layer, including decreased production of the gel-forming mucin MUC5AC, further amplifying the underlying ocular surface inflammation and epithelial disease [40].
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Decreased expression of the membrane-associated mucin (MAM) genes MUC1, MUC4, and MUC16, which are responsible for impaired ocular surface protection and less effective lubrication, has also been observed [39]. Moreover, alterations in MUC1 glycosylation have been described in DED, with an increase in MUC1 sialylation in mild-to-moderate cases and a decrease in severe cases [51]. This has been proposed as a compensatory mechanism for the decrease in MUC5AC in milder DED, which is not maintained as disease severity progresses, and this alteration could be a possible explanation for the transition from functional to dysfunctional parainflammation [39].
In maintaining ocular surface homeostasis, additional contributing factors can be identified in addition to the main components of the tear film. In particular, tear cortisol has been observed to be significantly reduced in patients with DED [52].
Cortisol is a major glucocorticoid, known as the stress hormone, involved in response to physical and/or emotional stress [53]. Cortisol also participates in various homeostatic maintenance activities: blood pressure regulating metabolism, inflammatory response, and immune function. It plays a role in the immune response through different actions related to apoptosis of pro-inflammatory T cells, suppression of B-cell antibody production, and reduction of neutrophil migration during inflammation [54].
Tissue-specific regulation of cortisol is a mechanism that is supposed to determine the length and type of inflammatory response [55]. Accordingly, protective mechanisms related to cortisol regulation have been investigated in the last decade. For example, in a wound healing model, it was observed that a simultaneous increase in steroid 11 β-hydroxylase expression (an enzyme that controls negative feedback mechanism), cortisol, and hormone-activated phosphorylated-glucocorticoid receptor (GR) occurs in epithelial cells during wound healing, both ex vivo and in vivo, using human and porcine wound models [56]. It has been proposed that this mechanism may serve as a possible feedback loop to attenuate the initial pro-inflammatory response, preventing excess inflammation and further tissue damage [56].
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Regarding the ocular surface system, the autocrine cortisol synthesis in corneal epithelial cells has been described, and a protective role for tear cortisol has been proposed in recent years [55, 57]. Under other conditions, cortisol appears to be able to control excess inflammation [58]. Since the 11ß-hydroxysteroid dehydrogenase type 1 (11 β-HSD-1) enzyme, which catalyzes the conversion of cortisone to cortisol, was found in the basal cells of the corneal epithelium, it can be hypothesized that cortisol may play a controlling role even in this district, keeping the immune response repressed and helping the system to recover its homeostasis. Under physiological conditions, the synthesis of cortisol in corneal epithelial cells is independent of Toll-like receptor (TLR) activation and contributes to the immune protection of the ocular surface mucosa [55]. In addition, synthetic glucocorticoids, such as dexamethasone, have been shown to change the global gene and miRNA profile of corneal fibroblasts, downregulating inflammatory genes and inducing the expression of anti-angiogenic and anti-inflammatory genes [59].
Further studies are necessary to understand whether there is a proportionality between the extent of DED and the reduction of cortisol levels in the tear film and whether external integration may be advantageous. Another aspect that should be studied is the possible impact of dysregulated parainflammation in initiating chronic inflammatory alterations. For example, epithelial cells are involved in the local immune-based inflammation through the independent production of interleukins 1α, 6, and 8, and tumor necrosis factor-α [60]. Furthermore, during inflammation, epithelial cells of the ocular surface or lacrimal glands may acquire antigen-presenting capability when expressing human leukocyte antigen (HLA) DR class II antigens [60]. Significantly increased expressions of HLA-DR and ICAM-1 by conjunctival epithelial cells were also reported in a flow cytometric analysis on conjunctival epithelium under chronic inflammatory conditions [61]. At the same time, studies investigating patients with DED and mouse models reported evidence of immune-based inflammation in the tears, with increased concentrations of inflammatory cytokines [62, 63].
Lastly, recent evidence has highlighted the role of microbiota in maintaining ocular surface homeostasis. Therefore, this aspect also deserves further investigation [64, 65].
Possible Strategies to Control Dysfunctional Parainflammation in Dry Eye Disease
Today, there are no specific treatments aimed at restoring a functional parainflammation on the ocular surface. Topical steroids, cyclosporine and lifitegrast, in fact, are anti-inflammatory therapies that should be used when a clinically evident chronic inflammation is responsible of symptoms and signs of DED [66]. However, tear substitutes and ocular surface modulators, if used regularly and properly, can be of help to re-equilibrate ocular surface homeostasis and improve dysregulated parainflammation [12]. In fact, tear substitutes may increase tear clearance and reduce the concentration and residence time of inflammatory cytokines on the ocular surface and can stabilize the tear film by adding either muco-mimetic substances to increase water retention or polar lipids to reduce excessive evaporation [67]. Other possible therapeutic options are the mucin secretagogues, which have proven to be an effective option for increasing mucin production and thus improving the interaction between the mucus and the aqueous part of the tear film [68], and the ocular surface modulator T-LysYal, which can interact with ocular surface epithelial cells by decreasing the expression of Aquaporin 3 and inhibiting CD14 + cells infiltration into the corneal tissue [69].
Recent studies indicate that a low concentration of hydrocortisone combined with hyaluronic acid (HY-HA) significantly improved symptoms, tear film stability, and inflammation markers in patients with DED when used for up to 6 months after a short course (7 days) of topical steroids [12]. HY-HA also showed the ability to enhance tear film stability and provide relief from DED signs and symptoms more effectively than HA or standard tear substitutes alone, especially in post-cataract surgery patients [70]. Understanding the mechanisms underlying the triggering of dysregulated parainflammation could be useful in the search for new and effective therapeutic strategies.
Conclusions
Literature evidence highlights the critical role of dysregulated parainflammatory responses in various tissues and organs as an underlying mechanism of chronic inflammation [15]. In the ocular system, parainflammation has been implicated in age-related macular degeneration, glaucoma, and, more recently, dry eye disease (DED). At the ocular surface, parainflammation plays a fundamental role in maintaining homeostasis and ensuring proper function. However, a shift toward dysregulated parainflammation and loss of homeostasis may contribute to the development of chronic inflammation.
Currently, no specific diagnostic test is available to directly detect parainflammation. As a result, an exclusion-based diagnostic approach can be applied. Lissamine Green staining, which correlates with inflammation, can help identify patients with overt inflammatory responses. Conversely, in patients presenting with decreased tear break-up time (BUT), corneal epithelial distress, or early conjunctival damage, dysfunctional parainflammation may be hypothesized. Certain biomarkers may aid in diagnosing parainflammation, particularly those associated with cytoprotective and anti-apoptotic processes. Additionally, cytokine quantification could help distinguish between parainflammation and overt inflammation [71]. Other reliable markers include those involved in cell communication and signal transduction processes, as well as matrix metalloproteinase-9 (MMP-9).
To improve the diagnostic approach for parainflammation and optimize therapeutic strategies, we synthesized recent evidence on tear film alterations, oxidative stress, mucin dysfunction, and tear cortisol deficiency, proposing a framework linking parainflammation to DED progression. Even if not exhaustive and conclusive on this topic, our proposal is intended to be a starting point to promote research in this area.
Several therapeutic options are currently available to manage ocular surface inflammation in chronic DED, including topical steroids and cyclosporine. However, we propose that the proper therapeutic use of tear substitutes containing low doses of steroids, mucin secretagogues, and ocular surface modulators could enhance the functional parainflammatory phase, restore ocular surface homeostasis, and potentially prevent progression to chronic inflammation.
Acknowledgements
The authors would like to thank Dr. Anna Rita Blanco (Medical Liaison, Alfa Intes) for the scientific support.
Medical Writing/Editorial Assistance.
Editorial assistance was provided by Simonetta Papa, PhD, Valentina Attanasio, and Aashni Shah (Polistudium SRL, Milan, Italy). This assistance was supported by Alfa Intes.
Declarations
Conflict of interest
Pasquale Aragona: Consultant for AbbVie, Alcon, Alfa Intes, Bausch and Lomb, DMG, FB Vision, Fidia, Santen, SIFI, Thea, TRB-Chemedica. Stefano Barabino: consultant for Fidia, TRB-Chemedica, Alfa Intes, Alcon. Christophe Baudouin: consultant for Alcon, Glaukos, Horus Pharma, Oculis, Santen, Thea. Elisabeth M. Messmer: speaker for: Alcon/Novartis, Bausch & Lomb, Dompé, Novartis, Santen GmbH, Théa Pharma GmbH, TRB-Chemedica AG, Visufarma. Consultant for: Alcon/Novartis, Alfa Intes, DMG, Dompé, Kala, Novartis, Santen GmbH, Shire, Sun, Sifi, Théa Pharma GmbH, TRB-Chemedica AG, Visufarma. José M. Benítez-del-Castillo: consultant for Brill, GSK, Santen, Sifi, Thea, Viatris. Jutta Horwath-Winter: Speaker or consultant for: Alfa Intes, Bausch & Lomb, Icom Medical, Laboratoires Thea, Mc2 Therapeutics, Santen, Shire, TRB-Chemedica, Ursapharm. Edward Wylegala: speaker for Alcon, Baush & Lomb, Thea Santen; consultant for: Optopol Technology. Kostas Boboridis, José Salgado-Borges, Adriana Stanila and Maurizio Rolando have nothing to disclose.
Ethical Approval
This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
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Parainflammation in the Ocular System: Considerations on the Underlying Mechanisms and Treatment of Dry Eye Disease
Verfasst von
Stefano Barabino
Pasquale Aragona
Christophe Baudouin
Kostas Boboridis
José Salgado-Borges
Jose M. Benitez-del-Castillo
Elisabeth M. Messmer
Adriana Stanila
Jutta Horwath-Winter
Edward Wylegala
Maurizio Rolando
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Ein Team aus Frankreich hat Fälle von plötzlichem Herzstillstand während des Paris-Marathons ausgewertet. In fast 90% waren Männer betroffen, und zwar überwiegend auf dem letzten Kilometer vor dem Ziel.
Patienten mit Adipositas weisen erniedrigte Spiegel des N-terminalen pro-B-Typ-natriuretischen Peptids (NT-ProBNP) auf. Ob sich das auf die NT-proBNP-gestützte Diagnostik von Herzinsuffizienz auswirkt, haben britische Mediziner untersucht.
Auch 2025 gab es wieder neue Studien, deren Ergebnisse zu einer Optimierung der symptomatischen und prognoseverbessernden Therapie bei Patienten mit Herzinsuffizienz in der Praxis beitragen könnten.
Laut Daten einer prospektiven britischen Studie schneidet eine Surveillance-Strategie im Vergleich mit einer risikoreduzierenden Mastektomie beim Vorliegen pathogener BRCA-Varianten in puncto Gesamtüberleben ähnlich gut ab. Im Detail sind allerdings Fragen offen.
