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  • Studying chiropractic science in Australia? Here’s the reality

    Studying chiropractic science in Australia? Here’s the reality

    What’s it like, trying to cement your name in an industry that’s not being taken seriously? To prove that you’re truly standing on business despite what the media throws on the ground?

    When Chanathon Charas Virojna — 27, from Penang, a childhood gamer — first took a liking to chiropractic science in Year 12 of high school, the stakes weren’t as high. The industry had been present in Malaysia since the 1920s, but it wasn’t until the 2010s that it really started to take off. The first degree programme was established at International Medical University (IMU) in Bukit Jalil, and by 2014, the number of qualified practitioners had increased by 50%.

    “I discovered chiropractic from a bunch of friends, and even parents talked about it — it was a booming thing in Malaysia back then,” says Virojna. “I really enjoyed that, like physio, you do have a lot of hands-on [work], but instead of rehabilitating in the hospital, you spend time outside of it, which I preferred.”

    So why did its reputation take a turn for the worse?

    For starters, it’s widely viewed as a pseudoscience, drawing speculations as if it were astrology or aromatherapy. There are multiple reasons for this, from people thinking the job is as simple as cracking your back in place to the fact that practitioners aren’t required to spend 10 years of their life on a Doctor of Medicine.

    Then, there’s social media.

    Virojna finds it rewarding to be able to help people heal. Source: Chanathon Charas Virojna

    In 2020, the coronavirus pandemic spurred a new era of low back pain (LBP), with 619 million people worldwide affected by the phenomenon. As a result, chiropractors gained traction, but not exactly for the right reasons. Despite lacking scientific evidence, many individuals with a social media presence began to claim that chiropractic care could cure COVID-19, thereby spreading misinformation.

    As if that’s not enough, chiropractic influencers would resort to filming “sensationalised content,” or in other words, sexualised videos featuring half-naked models making sounds that would require parental guidance.

    One Reddit user even asked a practitioner: “Do you try to treat hot chicks to drive up views?”

    For the record, there’s so much more to chiropractic care than 30-second loops on TikTok. First off, it’s not a pseudoscience. Peer-reviewed journals back it up as an effective treatment for LBP, neck pain, headaches, and more. Chiropractors are required to attain a degree, and their profession is a regulated healthcare field that’s evidence-based — imperfect, but evolving.

    “We have so much we were taught in Macquarie University,” says Virojna. “We are taught the same units as physiotherapy throughout the whole bachelor’s degree. That means we got all the base knowledge.”

    Rather than forming an opinion based on the authority of social media, why not hear from an actual chiropractor? Someone truly passionate about helping people?

    chiropractic science

    Virojna decided to stay in Australia after graduating to gain experience. Source: Chanathon Charas Virojna

    Virojna’s shaky, uncertain beginnings in chiropractic science

    After staining its reputation, chiropractic science is losing institutional support. In Australia — where Virojna studied and is now living — only four universities offer programmes, including Macquarie University, his alma mater. The Friends of Science in Medicine (FSM) Association has heavily campaigned against the industry in the past, and the ban on spinal manipulation for infants was reinstated by the Chiropractic Board of Australia, as demanded by health ministers.

    “The medical board doesn’t trust us because they think we’re just whack jobs,” he says. “I don’t blame them, because we are seen like that. Chiropractic has been presented this way for a long time. But the more we promote ourselves like this, the more it feeds into that cycle. Trying to break that cycle is hard.”

    Despite that, after graduating with his bachelor’s and master’s at Macquarie, Virojna decided to stay in Australia anyway. He has got a rough vision of where he wants to be further out in his career, which looks like returning home to Malaysia with groundbreaking expertise — but of course, he needs experience. He interned at Marquarie’s Chiropractic Clinic as a student, then moved onto his first post-grad job at a practice in a suburb of Sydney.

    Virojna’s considering opening a practice in Malaysia, but that’s a goal for a distant future. For now, the job’s to learn. Source: Chanathon Charas Virojna

    “It was a very humble beginning, being a graduate, thinking, ‘Oh it was going to be so great,’” says Virojna. “The first two years were so bad. There was no support, and you had no mentorship. You don’t even know what you’re doing. You barely make any living…the dropout rate is crazy.”

    Still, the trials weren’t enough to break his spirit, even if it took too many cups of coffee. It wasn’t until Virojna found a job at a different clinic hosting a proper mentorship programme that he received guidance on crawling his way out of the pit. That perseverance; it felt rewarding.

    “It’s satisfying to be able to provide relief or allow people to feel better after each consultation,” he says. “It’s like a drug, in a good way. My goal is to be able to gain as much experience as I can in the years that I have to learn, which is probably the first 10 years of my career, to be able to set myself up in the right way.”

    The biggest lesson Virojna has learned over the years is managing expectations. He’s a chiropractor, not a magician. He’s trained to treat and prevent biomechanical disorders, not hand out miracles.

    “Everyone wants to hear good news, but sometimes, we can’t be the bearer of good news,” he says. “We have to be realistic, and we have to draw a fine line between reassuring and kind of lying.”

    chiropractic science

    Whether it was due to passion or not wanting to return to university, he’d make this career work. Source: Chanathon Charas Virojna

    Finding steady ground

    This year, Virojna co-founded a new practice. It’s called Wally’s Health, and offers chiropractic and physiotherapy services in the city — a pursuit he balances with a part-time job at a different clinic. He’s tracing his steps back to those humble beginnings, renting a single room in a medical centre. Still, the upside is that he’s working to collaborate with general practitioners and others in the same space.

    “My other company was trying to offload, so my mate and I found it to be the perfect gap for us to start something in a safe net environment, where they already had a reputation with the general practitioners,” he says. The name “Wally’s” was inspired by a street in Macquarie, with its upbeat vibe resonating with Virojna and his business partner, who both felt it reflected the good they were trying hard to achieve.

    It had always been Virojna’s goal to start something on his own; he was simply waiting for the right opportunity to break away and take the challenge. Years of struggle had enabled him to develop his skills as a clinician. Though he’s 99% convinced he might fail, he’s still got that 1% of hope pushing him forward.

    It’s been just over four months since he opened his practice, and progress has been smooth. By now, Virojna’s a permanent resident in Australia, which has made setting up his business easier, especially since he earned his degree from a local university. There were numerous hidden red tape fees, but working with general practitioners has gradually allowed them to build up their clientele through word of mouth.

    “I thought to myself, I’m definitely going to make this work because I don’t want to go back to studying. I don’t want to go back to university,” he says. “I had that confidence in me, that I knew I was going to make it work. It’s just a matter of when and how, but I was going to find a way.”


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  • Surfshark launches FastTrack to deliver up to 70% faster VPN connections

    Surfshark launches FastTrack to deliver up to 70% faster VPN connections

    Surfshark B.V.

    Surfshark_FastTrack_connection_1304x638

    Surfshark FastTrack
    Surfshark FastTrack

    Surfshark, a leading VPN (Virtual Private Network) provider, introduces FastTrack, an innovative technology that optimizes users’ traffic paths for improved speed and performance. Built on Nexus infrastructure, this solution routes traffic through a network of servers rather than a single VPN tunnel, boosting internet speeds by up to 70%. As a result, users can now experience enhanced VPN connectivity to Sydney, Seattle, and Vancouver.

    “We understand how VPN speed and low latency are important to our users. For this reason, we are proud to introduce a technology that can optimize network routing by finding the best data paths to increase connection speeds and reduce latency in real time. Surfshark Nexus infrastructure was designed with a goal in mind to build future improvements like FastTrack, by allowing us to connect users not just to a VPN server, but to a single, global Surfshark VPN network,” says Karolis Kaciulis, Leading System Engineer at Surfshark.

    Optimized network for better VPN speed and performance

    Many people believe their internet connection follows a direct, straightforward path, just as it appears at first glance when looking at a world map. However, this is a common misconception, similar to the belief that ISPs (Internet Service Providers) will always optimize user connectivity through the best routes.

    In reality, data often travels across a complex web of overground and submarine cables located around the globe. These cables define the actual physical routes that data packets take, which can be very different from what we might think. For example, due to the layout of global network infrastructure, a data packet traveling from one city to another may be routed through multiple cities, countries, or even across continents and oceans.

    There’s a similar misconception about ISPs. While they generally prioritize delivering acceptable speeds, they often do not focus on optimizing the actual network routes your data follows. Instead, ISPs typically choose paths based on cost, selecting the most economical routes for them rather than the fastest or most efficient ones for user data.

    “By optimizing data paths and selecting the most efficient routing, our technology substantially enhanced VPN performance, delivering high connection speeds regardless of users’ geographic location to Sydney, Seattle, and Vancouver. Notably, the most effective routes are not always the most direct, as it might seem. In some cases, longer paths with additional network hops can boost performance by using higher-capacity cables and more powerful routers. As a result, we have gained up to 70% in VPN speed,” explains K. Kaciulis.

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  • Anatomical and functional outcomes of anti-VEGF therapy in pachychoroi

    Anatomical and functional outcomes of anti-VEGF therapy in pachychoroi

    Vasilena Sitnilska,1 Johannes Maximillian Pohl,2 Yuhe Tang,1 Katrin Löw,1 Jeany Q Lammert,1 Tim U Krohne,1 Lebriz Altay1

    1Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany; 2Department of Ophthalmology, Faculty of Medicine and University Hospital of Bonn, University of Bonn, Bonn, Germany

    Correspondence: Vasilena Sitnilska, Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Kerpener Str. 62, Cologne, 50924, Germany, Tel +49 221 478 86041, Fax +49 221 478 3526, Email [email protected]

    Background: Evaluation of real-life effectiveness of anti-VEGF therapy in patients diagnosed with pachychoroid neovasculopathy (PNV).
    Methods: This retrospective analysis included central serous chorioretinopathy (CSC) patients who developed PNV and underwent anti-VEGF treatment. Individuals with concomitant retinal diseases were excluded. Key measures included best-corrected visual acuity (BCVA), spectral domain optical coherence tomography (SD-OCT) features (intra-/subretinal fluid, central retinal thickness (CRT), and choroidal thickness (CT)), and potential risk factors such as age, sex, and corticosteroid intake, baseline neovascularization area in fluorescein angiography and in OCT-angiography, and time from PNV diagnosis to treatment initiation.
    Results: The study included 40 eyes of 40 patients (24 males, 16 females), with a mean follow-up period of 38.23± 19.73 months and a mean number of anti-VEGF injections of 27.47± 16.73. BCVA, CRT and CT improved significantly at the final visit compared to baseline (BCVA p=0.019, CRT p< 0.001, CT p< 0.001). 85% of eyes achieved a “completely dry” status on SD-OCT after a mean of 10.94± 11.22 months and a mean of 8.88± 9.17 injections. However, 82.4% of these eyes had a recurrence after a mean 3.32± 4.82 months. There was no significant association of the evaluated risk factors with the treatment response. At the end of the observation period, there was no significant difference in BCVA between the “completely dry” group and the non-responders (p=0.765).
    Conclusion: A majority of PNV patients exhibit anatomical and functional improvement following anti-VEGF therapy. However, the high rate of recurrences suggests a need for long-term treatment.

    Keywords: pachychoroid neovasculopathy, chronical central serous chorioretinopathy, anti-VEGF therapy

    Introduction

    Pachychoroidal neovasculopathy (PNV) is a novel term to describe macular neovascularization (MNV) in association with abnormally thickened and altered choroidal vessels. PNV is part of the pachychoroid spectrum, which also includes pachychoroid pigment epitheliopathy, central serous chorioretinopathy (CSC) and pachychoroid aneurysmal type 1 MNV (PAT1), formerly known as polypoidal choroidal vasculopathy.1,2 There is a pathophysiological overlap between these diseases, and in this continuum PNV is discussed as a secondary complication in the context of chronic CSC or other pachychoroidal diseases.

    Without intervention, PNV may result in a substantial decline in central vision. Recent research has demonstrated the efficacy of anti-VEGF in addressing PNV.3–10 In addition, photodynamic therapy (PDT) has been evaluated as a potential monotherapy and as an adjunct to anti-VEGF therapy.3,11–16

    The aim of this study was to examine the long-time effectiveness of anti-VEGF therapy in patients with PNV. Furthermore, we aimed to identify possible risk and protective factors for good anatomical and functional response.

    Materials and Methods

    Patients

    All available patients’ charts with a diagnosis of macular neovascularization (MNV) secondary to CSC who received anti-VEGF treatment between January 2015 and October 2023 at the Department of Ophthalmology, University Clinic of Cologne, were retrospectively reviewed. Only therapy-naïve patients without prior anti-VEGF treatment and with available multimodal imaging were included (Figure 1). Only one eye per patient was included. The diagnosis of PNV was documented by spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCT-A), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA). Patients with follow up less than 6 months and patients with signs of concomitant retinal diseases (myopia >6dpt, age-related macular degeneration, macular dystrophy, diabetic retinopathy, MNV due to other cause like trauma or tumor) were excluded.

    Figure 1 Multimodal imaging. (A) Optical coherence tomography (OCT) with flat irregular hyperreflective retinal pigment epithelium (RPE), macular subretinal fluid and thickened subfoveal choroid (B) OCT-angiography with neovascularization membrane (C) Late leakage on fluorescein angiography corresponding to the flat irregular hyperreflective retinal pigment epithelium (D) Mid-phase indocyanine green angiography with thickened choroidal vessels.

    Demographic information and medical history (corticosteroid intake, psychological stress, PDT treatment before and/or after diagnosis of PNV) were examined by reviewing patient records. Best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) was obtained at baseline and at the end of the study for all eyes. The study was conducted in accordance with the tenets of the Declaration of Helsinki and the Medical Research Involving Human Subjects Act (WMO).

    Diagnosis and Grading of PNV

    All available images were reviewed for the diagnosis of CSC and MNV. Grading was performed on FA/ICGA (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany), OCT-A, FAF and SD-OCT (scan area 20° × 15° (5.9 × 4.4 mm), 37 B-scans, distance between B-scans 123 mm) by two independent graders (VS, LA). Any discrepancies between graders were resolved through open adjudication. Morphological features for the confirmation of CSC diagnosis included presence of macular subretinal fluid (SRF) on SD-OCT, alterations in the retinal pigment epithelium (RPE), focal or diffuse leaks/hyperfluorescent areas on FA/ICG-A and thickened choroid. The presence of neovascularization was defined by a late leakage on FA, corresponding to a late staining area on ICGA and a flat irregular, hyperreflective RPE elevation on SD-OCT.17

    Central retinal thickness (CRT), choroidal thickness (CT), presence of RPE atrophy or intraretinal cysts were graded on SD-OCT at baseline and at the final visit. (Figure 1) For all measurements, automated segmentation of Heidelberg Eye Explorer software was used, and all results were corrected manually. Hereby, CRT was measured from internal limiting membrane to Bruch´s membrane (BrM), CT was measured on a subfoveal centered SD-OCT image. Neovascularization area was manually graded on FA and on OCT-A at baseline visit. In OCT-A, the neovascularization area was identified after manual correction of the segmentation in the subretinal and sub-RPE spaces.

    Patient Treatment

    All included eyes underwent anti-VEGF treatment with either Bevacizumab, Ranibizumab or Aflibercept in the Department of Ophthalmology, University of Cologne. The following treatment regimens were assigned and decided upon within routine clinical practice: 1) One single anti-VEGF followed by injections as needed, 2) Pro re nata (PRN with upload: 3 consecutive monthly injections followed by injections as needed, 3) Modified Treat & extend (T&E): one single anti-VEGF followed by T&E. In general, patients who started therapy between 2015 and 2018 were mostly assigned to one single anti-VEGF followed by monthly OCT controls and injections as needed or to PRN. Patients who started treatment in 2018 or later were assigned directly to modified T&E (without upload). Therapy success was defined as complete SRF resolution (“completely dry”). Best-corrected visual acuity (BCVA) was obtained at each visit.

    Statistical Analyses

    Descriptive statistics were used to summarize the characteristics of all patients. Results were given as mean ± standard deviation (SD), median ± interquartile range (IQR) or number of eyes and percentage. Pearson’s chi² test was used for categorical variables and t-test or Mann–Whitney U-Test for continuous variables depending on the distribution. Statistical analyses were performed using SPSS (IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corporation). P values <0.05 were considered as statistically significant.

    Results

    About, 97 patients’ charts were retrospectively reviewed. In total, 40 eyes of 40 patients fulfilled the inclusion and none of the exclusion criteria. Fifty-seven eyes were excluded due to one of the following reasons: 1) prior anti-VEGF injections (N=13), 2) follow-up less than 6 months (N=7), 3) missing retinal imaging data for the confirmation of CSC and MNV (N=9), 4) concomitant retinal diseases (N=28).

    The mean observation time was 38.23 months, during which a mean of 27.47 injections were administrated. The majority of eyes (N=30, 75%) had T&E regimen from the beginning of the treatment. Only three eyes received 3x monthly upload followed by PRN regimen: one case had a recurrence after discontinuation of the treatment and did not receive any further follow up, another case reached a completely dry status and did not receive any further follow up, the third case switched to T&E before reaching a completely dry status. Seven eyes received primary one single anti-VEGF followed by monthly OCT controls, in cases of disease activity another anti-VEGF was administrated. Over time, six of the seven patients were switched to T&E due to high disease activity. One case reached a completely dry status only after 2 injections (duration between the two injections 3 months) and did not receive any further follow up.

    Seventeen eyes received bevacizumab as an initial drug, 23 received ranibizumab as an initial drug and none of the eyes received aflibercept from the start. Twenty eyes (50%) switched the treatment to another drug during the course of observation. In general, until the last visit, each eye received a mean of 27.48±16.72 SD injections (median 25.00, range 55, min 2-max 57): bevacizumab mean 4.5±6.36 (median 0.00, range 24, min 0-max 24); ranibizumab mean 11.28±11.53 (median 9.00, range 40, min 0-max 40); aflibercept mean 11.70±13.42 (median 7.50, range 45, min 0-max 45). Further baseline characteristics are shown in Table 1.

    Table 1 Demographics

    Anatomical and Functional Outcome

    A positive effect of the treatment could be demonstrated in all eyes regarding anatomical features (presence of SRF, CRT, CT). The majority of eyes (85%) reached a completely dry status on the SD-OCT (85%) after a mean of 10.94±11.22 months and after mean of 8.88±9.17 injections. However, 82.4% of those eyes had a reactivation after a short period of time (within 3.32±4.82 months).

    Both CRT and CT were significantly reduced after treatment with anti-VEGF at the final visit, compared with baseline (mean change CRT 90.73±81.96 µm, p<0.001, mean change CT 36.76±30.00 µm p<0.001), regardless of the current activity of the neovascularization at the final visit (n=16 with dry SD-OCT, n=24 with presence of SRF).

    Additionally, a significant improvement of BCVA could be shown (mean change from baseline to final visit BCVA 0.12±0.30, p=0.019). There was no statistically significant correlation between visual outcome and age or outcome in the CRT parameters and age (Pearson test p>0.05). Interestingly, among the eyes which reached a dry status, there was a significant correlation between the baseline neovascularization area in OCT-A and time until reaching a dry status with smaller areas drying quicker (P=0.038). The baseline neovascularization area in fluorescein angiography showed a tendency regarding the velocity of reaching a dry status, but did not reach the threshold for statistical significance (P=0.057).

    PDT Treatment

    Sixteen of the examined eyes had a history of PDT treatment. About, 13 of those 16 eyes had at least one PDT treatment before developing PNV. The mean time between first PDT treatment and first intravitreal injection was 3.11±2.47 years. Only 5 eyes had PDT after diagnosis of PNV (2 of them had PDTs before and after PNV diagnosis, 3 had PDT treatment only after PNV diagnosis). Among these cases, 3 eyes successfully reached a dry status, and two eyes were complete non-responders.

    The remaining 24 eyes (60%) were never treated with PDT. 95.8% (n=23) reached a completely dry status during the anti-VEGF treatment, so no adjunctive PDT treatment was necessary.

    Almost all non-responders to anti-VEGF had at least one PDT treatment (5/6). One patient did not receive any PDT because that was the patient’s preference.

    Prognostic Factors for Complete SRF Resolution

    None of the evaluated demographic characteristics such as age, sex, time to treatment after diagnosis or corticosteroid intake could show a significant impact on reaching a completely dry status on SD-OCT. Also, none of the evaluated morphological features reached statistical significance (Table 2). History of PDT was highly significant.

    Table 2 Prognostic Factors for Reaching a Completely Dry Status

    Discussion

    In this retrospective study, we analyzed a long term treatment response of anti-VEGF therapy in cases diagnosed with PNV. The majority of eyes achieved complete resolution of SRF on SD-OCT, confirming the efficacy of anti-VEGF treatment in eyes with PNV demonstrated in previous studies (4–8, 20–22). Nevertheless, after a short period of time there was a recurrence of disease activity which required a continuation of the treatment.

    PNV is considered as a new disease entity that can occur directly or can develop after a long-standing chronic CSC.18–20 Most common treatment options for PNV include anti-VEGF injection or PDT, or a combination of both. Most of the previous studies documented significant anatomical and functional improvements following anti-VEGF injections in PNV patients.3,8,10,21–23 Yet, a recent retrospective study revealed that a relatively low rate of 41% of patients experienced successful treatment outcomes (characterized by complete resolution of symptoms), over a five-year period and reported no significant visual improvement.24 These observed discrepancies may be attributable to a number of factors, including the administration of only one anti-VEGF agent, patient compliance, treatment regimens (single injection, PRN or T&E) or disease recurrence. In our cohort, the anti-VEGF medication was switched in cases of non-response and most of the patients followed a T&E regime. A recent retrospective study with a small cohort over a 3-year period of treatment suggested a superior effect of aflibercept over bevacizumab und ranibizumab.25 Several studies have reported a comparable treatment effect of anti-VEGF treatment in patients with PNV and neovascular age-related macular degeneration (nAMD), with some even showing a reduced needed number of injections in PNV. (4–8, 14) Hata et al showed a significantly lower VEGF concentration in patients with treatment-naïve PNV in comparison to patients with treatment-naïve nAMD, suggesting a different influence of VEGF in PNV patients.26

    PDT is considered to be a successful potential treatment option for PNV cases as a monotherapy, with comparable results to monotherapy with anti-VEGF injections.3,20,27 Further, the efficacy of PDT in combination with anti-VEGF therapy has been evaluated for pachychoroidal neovasculopathy with or without polyps in several studies, demonstrating regression of MNV activity and a reduction in choroidal permeability.11,13,15,16,28 For instance, Lee et al showed a positive effect of adjunctive PDT treatment for patients with type 1 MNV and thickened choroid who were refractory to anti-VEGF monotherapy, with 85.7% of patients reaching a dry status.29 There are also a few long-term reports confirming the effectiveness of a combination therapy.25,30 In our cohort history of PDT showed a significant influence of the response, which is considered a bias, since only 6 eyes were non-responders and almost all of them had received previous PDT treatment, whereas a high number of eyes with completely dry results never underwent any PDT treatment.

    So far, there is no standard treatment protocol with focus on monotherapy or combination of both anti-VEGF and PDT for treatment of PNV.

    Even though 40% of our study population had a history of PDT treatment, in most cases, PDT was performed long before the development of PNV (mean 37.3±29.7 months). Only five eyes received an adjunctive PDT treatment to the anti-VEGF treatment, and three of these five (60%) achieved a completely dry status. Overall, almost all of the eyes in our study who did not have any PDT treatment still reached a completely dry status under anti-VEGF treatment (95.8%, n=23/24), showing that a good treatment outcome can also be reached without prior PDT. Nevertheless, the high recurrence rate remains an issue. There is a wide range of reported recurrence rate after successful treatment of PNV. Several studies report a positive effect of PDT treatment on recurrence rate and a possible preventive role.11,13,15,16,29 Due to the low number of non-responders in our study, no representative results of the possible positive influence of PDT on treatment response and on recurrence of MNV activity could be shown.

    In order to determine which is the best and most effective treatment regimen for PNV we need a better understanding of the pathogenesis of formation of neovascularization membranes and subretinal fluid accumulation. So far, the pathogenesis is only partly understood. There are hypotheses, that the neovascularizations in long lasting CSC occur mostly due to arteriogenesis and less or not at all due to angiogenesis process,23,31 and that the success of anti-VEGF treatment could be explained by causing a reduction of the choroidal vascular permeability followed by reduction of the CT and absorption of SRF;10 or that the presence of SRF might not always be a sign of MNV activity.23 Recent studies suggest an involvement of thickened sclera in the pathogenesis of CCS and PNV,32,33 indicating a thickened sclera in more complex CCS34 and even only a partial response to PDT treatment.35 The role of scleral thickness particularly in PNV patients and their treatment response is yet to be better understood.

    Limitations of this study include the limited sample size, the retrospective study design and lack of data to examine the role of concomitant PDT treatment. The question regarding the ideal treatment regimen for PNV remains unanswered. No comparison could be made between different anti-VEGF agents due to the low number of patients and the switch of medication over time. Also, due to the limited sample size, the statistical power of the study may be insufficient to detect small to moderate effects. Further prospective studies are needed to address this. Nevertheless, this study provides additional evidence on treatment regimens for a positive outcome for patients with PNV after a long-lasting anti-VEGF treatment.

    Conclusions

    Most PNV eyes exhibited favorable anatomical and functional improvements with anti-VEGF therapy. However, the elevated recurrence rate underscores the necessity for continuous treatment. Future studies should focus on devising approaches to reduce recurrence and improve long-term patient outcomes.

    Data Sharing Statement

    The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

    Ethics Approval and Consent to Participate

    All methods were carried out in accordance with the tenets of the Declaration of Helsinki and ethics committee of University of Cologne. This study does not include any experimental protocols. According to the local ethics committee, informed consent and extra approval is not required for retrospective analyses. All patient information is confidential and pseudonymized.

    Consent for Publication

    This study involved retrospective analysis of pseudonymized patient data. According to the requirements of the local ethics committee, formal informed consent was not necessary for the retrospective use of such data (s. above). However, as part of standard institutional procedures, patients had previously provided general informed consent allowing the use of their pseudonymized medical data for research and publication purposes. This consent was obtained independently of this specific study.

    Acknowledgments

    Preliminary results of this work have been presented as an abstract at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5–9, 2024.36

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    There is no funding to report.

    Disclosure

    Prof. Dr. Tim Krohne reports personal fees from AbbVie, personal fees from Alimera, personal fees from Astellas, personal fees from Bayer, personal fees from Novartis, personal fees from Roche, personal fees from Stada, outside the submitted work. The authors declare that they have no other conflict of interest.

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    7. Üney G, Hazırolan D, Ünlü N, Candan Ö. Pro re nata anti-VEGF treatment in pachychoroid neovasculopathy compared with age-related macular degeneration based on optical coherence tomography. Int Ophthalmol. 2024;44(1):164. doi:10.1007/s10792-024-03094-w

    8. Matsumoto H, Hiroe T, Morimoto M, Mimura K, Ito A, Akiyama H. Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and type 1 neovascular age-related macular degeneration. Jpn J Ophthalmol. 2018;62(2):144–150. doi:10.1007/s10384-018-0562-0

    9. Schworm B, Luft N, Keidel LF, et al. Response of neovascular central serous chorioretinopathy to an extended upload of anti-VEGF agents. Graefes Arch Clin Exp Ophthalmol. 2020;258(5):1013–1021. doi:10.1007/s00417-020-04623-w

    10. Padrón-Pérez N, Arias L, Rubio M, et al. Changes in choroidal thickness after intravitreal injection of anti-vascular endothelial growth factor in pachychoroid neovasculopathy. Invest Ophthalmol Vis Sci. 2018;59(2):1119–1124. doi:10.1167/iovs.17-22144

    11. Miki A, Kusuhara S, Otsuji T, et al. Photodynamic therapy combined with anti-vascular endothelial growth factor therapy for pachychoroid neovasculopathy. PLoS One. 2021;16(3):e0248760. doi:10.1371/journal.pone.0248760

    12. Wada I, Shiose S, Ishikawa K, et al. One-year efficacy of “rescue photodynamic therapy” for patients with typical age-related macular degeneration, polypoidal choroidal vasculopathy, and pachychoroid neovasculopathy refractory to anti-vascular endothelial growth factor therapy. Graefes Arch Clin Exp Ophthalmol. 2022;260(6):2029–2036. doi:10.1007/s00417-022-05553-5

    13. Matsumoto H, Mukai R, Kikuchi Y, Morimoto M, Akiyama H. One-year outcomes of half-fluence photodynamic therapy combined with intravitreal injection of aflibercept for pachychoroid neovasculopathy without polypoidal lesions. Jpn J Ophthalmol. 2020;64(2):203–209. doi:10.1007/s10384-020-00722-7

    14. Tanaka N, Azuma K, Aoki S, et al. Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes. Graefes Arch Clin Exp Ophthalmol. 2024;262(6):1811–1818. doi:10.1007/s00417-024-06387-z

    15. Sato-Akushichi M, Ono S, Taneda T, Klose G, Sasamori A, Song Y. One-year outcome of combination therapy with full or reduced photodynamic therapy and one anti-vascular endothelial growth factor in pachychoroid neovasculopathy. Pharmaceuticals. 2022;15(4). doi:10.3390/ph15040483

    16. Kitajima Y, Maruyama-Inoue M, Ito A, et al. One-year outcome of combination therapy with intravitreal anti-vascular endothelial growth factor and photodynamic therapy in patients with pachychoroid neovasculopathy. Graefes Arch Clin Exp Ophthalmol. 2020;258(6):1279–1285. doi:10.1007/s00417-020-04661-4

    17. Shiragami C, Takasago Y, Osaka R, et al. Clinical features of central serous chorioretinopathy with type 1 choroidal neovascularization. Am J Ophthalmol. 2018;193:80–86. doi:10.1016/j.ajo.2018.06.009

    18. Jung H, Suh Y, Lee J, et al. Pachychoroid spectrum disease: comparison of patients with central serous chorioretinopathy complicated with pachychoroid neovasculopathy. Korean J Ophthalmol. 2024. doi:10.3341/kjo.2024.0020

    19. Mrejen S, Balaratnasingam C, Kaden TR, et al. Long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy. Ophthalmology. 2019;126(4):576–588. doi:10.1016/j.ophtha.2018.12.048

    20. Sartini F, Figus M, Casini G, Nardi M, Posarelli C. Pachychoroid neovasculopathy: a type-1 choroidal neovascularization belonging to the pachychoroid spectrum-pathogenesis, imaging and available treatment options. Int Ophthalmol. 2020;40(12):3577–3589. doi:10.1007/s10792-020-01522-1

    21. Schworm B, Luft N, Keidel LF, et al. Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy. BMC Ophthalmol. 2021;21(1):269. doi:10.1186/s12886-021-02022-1

    22. Schworm B, Luft N, Keidel LF, et al. Ranibizumab non-response in pachychoroid neovasculopathy: effects of switching to aflibercept. Sci Rep. 2020;10(1):8439. doi:10.1038/s41598-020-65370-w

    23. Sacconi R, Tomasso L, Corbelli E, et al. Early response to the treatment of choroidal neovascularization complicating central serous chorioretinopathy: a OCT-angiography study. Eye. 2019;33(11):1809–1817. doi:10.1038/s41433-019-0511-2

    24. Rabinovitch D, Shulman S, Goldenberg D, et al. Choroidal response to intravitreal bevacizumab injections in treatment-naïve macular neovascularization secondary to chronic central serous chorioretinopathy. Biomedicines. 2024;12(12):2760. doi:10.3390/biomedicines12122760

    25. Nomura Y, Aoki S, Kitamoto K, et al. Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy. Graefes Arch Clin Exp Ophthalmol. 2024;262(10):3191–3200. doi:10.1007/s00417-024-06499-6

    26. Hata M, Yamashiro K, Ooto S, et al. Intraocular vascular endothelial growth factor levels in pachychoroid neovasculopathy and neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2017;58(1):292–298. doi:10.1167/iovs.16-20967

    27. Tanaka K, Mori R, Wakatsuki Y, Onoe H, Kawamura A, Nakashizuka H. Two-thirds dose photodynamic therapy for pachychoroid neovasculopathy. J Clin Med. 2021;10(10):2168. doi:10.3390/jcm10102168

    28. Takeuchi J, Ota H, Nakano Y, et al. Predictive factors for outcomes of half-dose photodynamic therapy combined with aflibercept for pachychoroid neovasculopathy. Graefes Arch Clin Exp Ophthalmol. 2023;261(8):2235–2243. doi:10.1007/s00417-023-06030-3

    29. Lee JH, Lee WK. One-year results of adjunctive photodynamic therapy for type 1 neovascularization associated with thickened choroid. Retina. 2016;36(5):889–895. doi:10.1097/iae.0000000000000809

    30. Karasu B, Celebi ARC. An efficacy comparison of combination of different anti-vascular endothelial growth factors and photodynamic therapy in patients with pachychoroid neovasculopathy. Int Ophthalmol. 2021;41(6):1989–2000. doi:10.1007/s10792-021-01754-9

    31. Spaide RF. Optical coherence tomography angiography signs of vascular abnormalization with antiangiogenic therapy for choroidal neovascularization. Am J Ophthalmol. 2015;160(1):6–16. doi:10.1016/j.ajo.2015.04.012

    32. Zarnegar A, Ong J, Matsyaraja T, Arora S, Chhablani J. Pathomechanisms in central serous chorioretinopathy: a recent update. Int J Retina Vitreous. 2023;9(1):3. doi:10.1186/s40942-023-00443-2

    33. Keidel LF, Schworm B, Langer J, et al. Scleral thickness as a risk factor for central serous chorioretinopathy and pachychoroid neovasculopathy. J Clin Med. 2023;12(9):3102. doi:10.3390/jcm12093102

    34. Imanaga N, Terao N, Wakugawa S, et al. Scleral thickness in simple versus complex central serous chorioretinopathy. Am J Ophthalmol. 2024;261:103–111. doi:10.1016/j.ajo.2024.01.025

    35. Forte P, Cattaneo J, Cardillo Piccolino F, et al. Influence of scleral thickness on photodynamic therapy outcomes in central serous chorioretinopathy. Acta Ophthalmol. 2024;103(3):e165–e175. doi:10.1111/aos.16779

    36. Sitnilska V, Pohl M, Altay L. Anatomical and functional outcome after anti-VEGF therapy in patients diagnosed with pachychoroid neovasculopathy. Invest Ophthalmol Visual Sci. 2024;65(7):218.

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  • Jannik Sinner Opens Up on Arm Sleeve — It’s Not for Style

    Jannik Sinner Opens Up on Arm Sleeve — It’s Not for Style

    On Saturday, ATP World No. 1 Jannik Sinner began his defense of his Cincinnati Open title. Sinner’s second round win over Daniel Elahi Galán was his first match since winning Wimbledon on July 13.

    While tennis fans were excited to see Sinner back on the court, many have been concerned about his ongoing use of an arm sleeve. Since taking a fall during a match at Wimbledon, Sinner has worn an arm sleeve in practice and matches.

    The media has asked Sinner about this multiple times, but the issue will not go away. Before his first match in Cincinnati, Sinner assured the ATP Press that his elbow was fine.

    “The elbow is good. Today was the first time that I put a sleeve on because I liked the feeling of the sleeve,” Sinner said during his media day press conference.

    “It gives a little bit more impact with the ball, it’s slightly more stable. That’s my point of view, and I liked it in Wimbledon. I have to see how it is when it’s very hot and humid, because it’s a little bit different, so it’s going to be something that I’m going to take into consideration, but I really love the feeling it gives of pure striking.”

    The question about Sinner’s decision to wear a sleeve came back up during another interview in Cincinnati. Was the Italian superstar wearing it as a fashion statement?

    “As I said when I came here, the impact of the ball is a bit different. And I feel it better if I would not wear it. I don’t wear things just because of style, you know?” said Sinner with a laugh.

    “At the moment I feel comfortable. With the heat, it’s actually ok. It’s not too much. I tried the black sleeve, it makes a difference, with the black sleeve. But the white one under these conditions is no problem.”

    Sinner faces unseeded Gabriel Diallo in the third round of the ATP 1000 Cincinnati. He currently has a record of 26-3 with two titles (Australian Open and Wimbledon).

    The Cincinnati Open runs through August 18. Stay locked into Sports Illustrated’s Serve on SI for all the most important news from the tennis court and beyond.

    Elena Rybakina’s coach has returned after the WTA lifted his ban.

    Iga Swiatek makes history with 300th Career win in Cincinnati.

    Naomi Osaka issued a statement apologizing for her post-match speech in Montreal.

    Ben Shelton wins first ATP Masters 1000 in Toronto.

    Montreal Magic: Victoria Mboko Wins First Masters 1000.


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  • Prince Andrew makes key gesture in first pictures since book allegations | Royal | News

    Prince Andrew makes key gesture in first pictures since book allegations | Royal | News

    Prince Andrew has been pictured for the first time since the bombshell book allegations were made against him.

    The 65-year-old and his former wife, Sarah Ferguson, also 65, were the focus of Andrew Lownie’s explosive new biography, ‘Entitled: The Rise and Fall of the Yorks’. The book discusses the couple’s life behind closed doors and focuses on areas such as their alleged rampant infidelity, “secretive money-making endeavours,” and “controversial friendships.”

    Andrew was photographed behind the wheel of his Defender on Sunday as he drove to Windsor Castle for an afternoon walk. Speaking about Andrew’s look as he drove around the estate, body language expert Jennie Bond told the Mirror: “It’s less about what has changed in Andrew’s body language here and more about what’s missing.

    “Caught in this one moment he appears to have lost the rounded-eyed, haunted expression.

    “His frown has melted slightly and there are no obvious signs of muscle tension in his facial expression. The royal known for looks of haughty arrogance appears less immersed in signals of status and entitlement and perhaps more reflective here.”

    The extracts, serialised in the Daily Mail, detailed Andrew’s close friendship with disgraced financier Jeffrey Epstein, as well as making claims about his ‘bullying’ of palace staff, vulgar sense of humour and brazen sex life.

    Andrew has always strongly and vehemently denied the claims in regards the sex scandals and previously reached an out-of-court settlement for an undisclosed amount with accuser, the late Virginia Giuffre.

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  • What Happened to All the Human Bird Flu Cases?

    What Happened to All the Human Bird Flu Cases?

    From the outset of the Trump administration, bird flu, or H5N1 avian influenza, has flown rather conspicuously — and in fact quite mysteriously — under the radar. So much so that [on July 7], the Centers for Disease Control and Prevention announced the end of its emergency response to bird flu, citing the lack of reported human cases. Updates, previously issued weekly, will now arrive monthly. But something isn’t adding up.

    At the end of 2024, infections in the United States were surging. From Ohio to California, and in a swath of intervening states, diagnoses were being made in growing numbers of farmworkers who came into contact with infected cattle and poultry.

    Most suffered a mild spectrum of symptoms — low grade fevers, muscle aches, inflammation in their eyes. As cases swelled, an older man in Louisiana fell critically ill. He would eventually become the first person in the U.S. to succumb to the virus since initial human cases were reported to the World Health Organization in 1997. We seemed then, for a moment, to be at a tipping point: bound to unleash something both larger and deadlier than we could foreseeably contain, and destined to dust off the cobwebs of a life grimly lived, again, under a pandemic.

    And yet, none of that came to pass. Instead, since February, the CDC, which still monitors infections in humans, has not recorded a single new case in the U.S. The count remains the same — stuck firmly at 70.

    Rationalizing the lull in infections has been puzzling. Researchers have tied wild birds, the virus’s largest reservoir, and their spring and fall migrations to periods of greater spread of contagion. Cuts to staff who monitored the virus, at the U.S. Department of Agriculture and the Center for Veterinary Medicine, might also be playing a role.

    But these ideas dismiss the deeper and more fundamental problem around our present grasp of bird flu. As an infectious diseases physician who works primarily with immigrant populations, my perspective often sits at the nexus between the people a novel disease affects and the apparatuses that exist to control it. Lately, the actions of each arm of that equation, no longer motivated by the ethos of a collective concern, are fractured by individual ambitions and epitomize our faltering response.

     

    Cases, in all likelihood, are being missed, in part because detecting infections is simply challenging. Foremost, it requires the ability to recognize an infected person. But this, as we’ve seen, is not always achieved. A number of bovine veterinarians, for example, were found earlier this year to harbor antibodies to the virus — a signature of infection — though none had influenza-like symptoms to suggest they’d been infected.

    Surveillance, therefore, is largely — and imperfectly — built around those who are exposed and symptomatic. It’s a system that also exposes the vulnerable contexts in which a person may have gotten infected.

    In vulnerable groups, this makes a willingness to be tested all the more fraught. According to the Center for Migration Studies, 45% of the agricultural workforce in the U.S. comprised undocumented persons in 2022. And according to USDA data from 2020 to 2022, an additional 19% don’t hold U.S. citizenship. Nearly 80% of American milk is supplied from dairies that employ immigrant labor. Consider a foreign-born dairy hand perplexed by redness in his eyes and a sore throat. He faces a dilemma: After ICE raids like “Operation Return to Sender” targeted farmworkers in California this winter, is getting to the root of his symptoms worth falling into an anti-immigrant governmental maw?

    “I can’t argue with anyone who would be risking getting shipped to a Salvadoran gulag for reporting an exposure or seeking testing,” Angela Rasmussen, a virologist at the University of Saskatchewan, told the Associated Press in May.

    For anyone in this situation, the personal calculus simply does not add up. And so, outreach programs and protective measures have not been sought; infections, if they happen, fester undetected. Lacking granular data from those that might be affected, we are without the empirical information we would typically use to form broader understandings, draw conclusions, and map out predictions.

    Indeed, while this political climate has caused the vulnerable to shrink from the public conscience, the dearth of cases doesn’t seem to be a concern for the government brass handling bird flu, who placed their priorities and interests above those of the widely accepted consensuses of scientists, virologists, and public health officials.

    In March, this was evident when Health and Human Services Secretary Robert F. Kennedy Jr. proposed allowing H5N1 to sweep through poultry flocks unabated, part of an unorthodox effort to gain insight into how surviving birds could become naturally immune to the virus. The scientific community balked at the danger of such an experiment, but the proposal garnered the support of Agriculture Secretary Brooke Rollins. She suggested in a February interview that farmers would be willing to try this on as a “pilot.”

    Animal studies in this realm have already been conducted in controlled settings. And our understanding of H5N1 — which has plagued humankind for almost 30 years — and the immune responses it elicits is fairly robust. But that didn’t dissuade the current administration from pressing for a redundant mandate.

    Instead, Mehmet Oz, administrator for the Centers for Medicare and Medicaid Services, went so far as to offer refuge on his personal 900-acre ranch in Okeechobee, Florida, to about 400 ostriches that the Canadian Food Inspection Agency had ordered to be culled. This was after dozens of the birds in a British Columbia farm’s flock had come into contact with and died from H5N1.

    Kennedy, in a post on X, displayed a copy of a letter to the president of the CFIA explaining that studying the ostriches would “help us understand how to better protect human and animal populations and perhaps lead to the development of new vaccines and therapeutics.”

    Soon after, likely as part of Kennedy’s vendetta against the technology, the HHS canceled a Biden-administration contract with Moderna to develop an mRNA-based vaccine (akin to the one successfully deployed against COVID-19) for bird flu.

    Bird flu is far from a passing peril. It has been detected in almost 1,100 cattle herds across the U.S. In Brazil, the world’s largest exporter of chickens, the first outbreak on a commercial poultry farm was confirmed in May while the country was also investigating about a dozen others. And in Mexico, a 3-year-old girl died from respiratory complications related to the virus. She was the country’s first confirmed human case and was infected by the same D1.1 variant that precipitated severe illnesses in the man in Louisiana and a teenager in British Columbia.

    Because infections are still largely constrained to animals and the marginalized people who work with them, bird flu has the distinction of being both omnipresent and barely visible. The way in which one country approaches it will, invariably, have rippling effects in others.

    As the focus shifts to the economics of maintaining stocks of chickens and rebalancing the price of eggs, incentives for the testing of farmworkers remain inadequate, and protections among those who are foreign-born are, at best, dubious. From bench to barn, earnest collaborations with scientists and experts are also being undermined.

    Public health is a delicate concept. To uphold it involves a complex interplay between forces large and, more importantly, small. We can predict the risk of a bird flu pandemic from a single mutation in the virus’s genetic code. An individual, we must also realize, can upend things all the same.

    Arjun Sharma is a physician specializing in infectious diseases whose writing has appeared in the Washington Post, L.A. Times, and the Boston Globe, among other outlets.

    This story was published by Undark on July 10, 2025. It is republished with permission.

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  • New insights into how keto diet can restore cognitive function following status epilepticus

    New insights into how keto diet can restore cognitive function following status epilepticus

    Epilepsy affects over 70 million people worldwide, and a significant portion of patients suffer from drug-resistant epilepsy (DRE), where standard medications fail. Beyond the seizures themselves, many patients face a hidden but devastating burden: cognitive decline, including memory loss and difficulty concentrating. These symptoms are believed to stem from underlying inflammation and structural brain damage. The ketogenic diet (KD) has long been used to manage seizures in DRE, but its potential to protect brain function remains underexplored. Due to these challenges, researchers are turning their focus toward understanding how KD might preserve cognitive abilities by addressing the root causes of neurological decline.

    A research team at the Children’s Hospital of Chongqing Medical University has published a study (DOI: 10.1002/pdi3.70013) in Pediatric Discovery (June 23, 2025), revealing how the KD can restore cognitive function following status epilepticus. The scientists used a well-established rat model to investigate changes in memory, behavior, brain structure, and inflammation. Central to their investigation was the NF-κB pathway—a master switch for inflammation in the brain—aiming to uncover whether KD’s protective effects are tied to suppression of this pathway and its downstream inflammatory responses.

    In the study, juvenile rats were induced with SE using pilocarpine and then split into groups, with some receiving a KD for either 7 or 20 days. The researchers conducted a series of behavioral tests, including the Morris water maze and Y-maze, to assess memory and spatial learning. Rats fed with KD demonstrated notable improvements in exploratory behavior and cognitive performance compared to their non-treated counterparts.

    Microscopic analysis revealed that KD-fed rats showed significantly less damage in the hippocampus—a brain region essential for memory. Neuronal density, myelin integrity, and axonal structure were all better preserved. This structural protection correlated with reduced levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α).

    Molecular studies confirmed that KD suppressed activation of the NF-κB pathway, evident through decreased nuclear translocation of NF-κB p65 and reduced phosphorylation of IκB. These changes suggest that KD not only reduces inflammation but interrupts its signaling at the source. Together, the findings illustrate a two-pronged benefit: restoring memory and repairing brain damage—both mediated by curbing inflammation at the molecular level.

    Our research highlights a critical shift in how we view the KD—not just as a seizure-control therapy, but as a powerful tool for brain repair. By dialing down inflammation at the cellular level, KD helps the brain recover from the long-term consequences of seizures. These results open up new possibilities for non-drug therapies that address both the seizures and the silent damage they leave behind. The future of epilepsy treatment may lie in the synergy of metabolic and molecular interventions.”


    Dr. Xiaojie Song, corresponding author of the study

    These findings offer exciting possibilities for expanding the role of the KD in neurological care. Beyond epilepsy, KD could emerge as a valuable intervention for other brain disorders marked by inflammation and cognitive decline, such as Alzheimer’s disease and traumatic brain injury. The ability to modulate the NF-κB pathway through dietary means opens a door to low-risk, non-invasive therapeutic strategies. Future research will need to explore how long these benefits last, the ideal duration of treatment, and whether combining KD with pharmacological agents could further amplify its effects—especially in vulnerable populations like children with DRE.

    Source:

    Chinese Academy of Sciences

    Journal reference:

    Wang, W., et al. (2025). Protective Effects of the Ketogenic Diet on Cognitive Impairment Induced by Status Epilepticus in Rats: Modulation of Neuroinflammation Through the NF‐κB Signaling Pathway. Pediatric Discovery. doi.org/10.1002/pdi3.70013.

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  • Efficacy and safety of Guben Kechuan Granules in the treatment of chro

    Efficacy and safety of Guben Kechuan Granules in the treatment of chro

    Introduction

    Chronic bronchitis (CB) is a common chronic inflammatory respiratory disease characterized by persistent cough, expectoration, or wheezing lasting for more than three months per year for at least two consecutive years.1 During acute exacerbations, excessively thick sputum becomes difficult to expectorate, leading to airflow obstruction, progressive lung function decline, and an increased risk of acute respiratory complications, ultimately contributing to a higher all-cause mortality rates.2 Several factors contribute to the onset and progression of CB, including advanced age,3 smoking,4 exposure to tobacco smoke, biomass fuel, and environmental pollutants such as dust,5,6 as well as a history of tuberculosis, allergies, or asthma.7 Globally, CB prevalence varies widely among general adult populations, ranging from 3% to 6% in Westernised countries.8 However, individuals with chronic obstructive pulmonary disease (COPD) are significantly more susceptible, with up to 74% developing CB.9 While the global incidence of CB has declined from 1990 to 2019, the absolute number of cases and CB-related deaths.10 According to the World Health Organization (WHO), approximately 3.4 million deaths occur annually due to CB-related complications.10 Therefore, effective treatment and management strategies for CB are critical for reducing mortality and alleviating the burden of COPD. Despite therapeutic advances, chronic bronchitis continues to pose significant global health and economic burdens, particularly among aging populations. As such, complementary approaches like TCM offer a valuable avenue for improving outcomes.

    Successful CB management primarily aims to alleviate symptoms, prevent complications, and slow disease progression by reducing excessive mucus production, controlling inflammation, and minimizing chronic cough.11 Current treatment approaches include pharmacological interventions such as bronchodilators, glucocorticoids, antibiotics, and phosphodiesterase-4 inhibitors, alongside nonpharmacological strategies like smoking cessation and pulmonary rehabilitation.12 However, a CHEST Expert Panel Report by Malesker et al highlighted that current CB treatment options, particularly for chronic cough, are limited in effectiveness and generally of low quality.13–15 Although emerging treatments, such as bronchial rhinoplasty, have demonstrated potential in preliminary studies, and they are still in the early research phase.14 Given these challenges, there is an urgent need to explore reliable alternative treatment strategies to enhance CB management and improve patient outcomes.

    Traditional Chinese Medicine (TCM) takes a holistic approach to treating diseases by addressing both symptoms and underlying causes at different stages, offering unique therapeutic advantages.15 Research has shown that TCM formulations can effectively alleviate symptoms of CB. For example, Dong et al demonstrated that Zhisou Powder exerted anti-inflammatory effects by reprogramming the disrupted arachidonic acid metabolic pathway, contributing to its therapeutic benefits for CB.16 Shui Man Jing, derived from the dried aerial parts of Veronica linariifolia subsp. dilatata (Nakai & Kitag). Hong, has shown promising application in CB treatment.17 In addition, Zhang et al reported that Cordyceps sinensis, a well-known TCM herb, enhances treatment efficacy and improves the quality of life in CB patients.18

    Guben Kechuan Granules is a TCM formulation commonly used to treat cough, excessive phlegm, and shortness of breath associated with spleen deficiency, and unstable kidney qi.19,20 It should be mixed with warm water before oral administration. Its key ingredients include Radix Codonopsis, Rhizoma Atractylodis Macrocephalae, Radix Glycyrrhizae Preparata, Poria cocos, Schisandra chinensis Fructus, Radix Ophiopogonis, and Fructus Psoraleae.21 Clinically, Guben Kechuan Granules is recommended for CB patients, particularly during stable periods, as it has been shown to improve clinical symptoms, lung function, and inflammatory markers. In elderly patients with stable-stage COPD, a 12-week adjunctive treatment with Guben Kechuan Granule significantly enhanced forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and FEV1/FVC (forced vital capacity), while reducing Th17 and Th17/Treg levels.19 Additionally, Guben Kechuan Granule may help alleviate CB symptoms, lower inflammatory levels, and regulate immune function.20 When combined with salbutamol aerosol, Guben Kechuan Granules have demonstrated an improved total effective rate (99.3%), increased pulmonary function parameters (FEV1, FEV1/FVC, PEF, and maximum mid-expiratory flow [MMEF)), and reduced levels of inflammatory cytokines such as TNF-α, IL-8, IL-10, and IL-15 in stable COPD patients.

    Although the efficacy and safety of Guben Kechuan Granules are currently under investigation in clinical studies [ChiCTR2300078017], comprehensive data on its therapeutic effects in CB remain limited. This study aims to evaluate the efficacy and safety of Guben Kechuan Granules in CB patients through a multi-center, randomized controlled trial. To provide a comparative assessment, we include Guilong Kechuanning Capsule— a treatment with established efficacy for CB— as a positive control, while a subject education group serves as the blank control. Guilong Kechuanning Capsule was selected based on its documented effectiveness in CB treatment and widespread clinical use, serving as a credible active comparator. This study is distinguished by its 48-week duration and real-world observation of AECB episodes, providing a more comprehensive evaluation of long-term efficacy.

    Material and Methods

    Participant Recruitment and Study Design

    This multi-center, randomized, controlled trial (Chinese Clinical Trial Registry; registration number: ChiCTR2200063321) was initiated by Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd (Zhejiang, China) and conducted by China-Japan Friendship Hospital (Beijing, China). The study aimed to evaluate the efficacy and safety of Guben Kechuan Granules in improving clinical symptoms of chronic bronchitis and was carried out in compliance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, and Chinese regulatory requirements.

    Participants were recruited continuously from November 2022 to March 2023 from multiple hospitals across China, including from the China-Japan Friendship Hospital, Taiyuan Central Hospital, Ningbo Traditional Chinese Medicine Hospital, People’s Hospital of Xiangtan County, Hospital of Sanyuan County, People’s Hospital of Xindu District (Xingtai City), People’s Hospital of Yanggu County, People’s Hospital of Mengyin County, Longhua County Traditional Chinese Medicine Hospital, and Xiyang Public Hospital.

    As illustrated in Figure 1, a total of 300 participants were randomly assigned in a 2:2:1 ratio into the following groups: Experimental group (Guben Kechuan Granules, n=120), Positive drug control group (Guilong Kechuanning Capsule, n=120) and Blank control group (subject education only, n=60). Among the enrolled participants, one subject (ID: 257) in the experimental group did not take the medication. Consequently, 299 participants were included in the Full Analysis Set (FAS) analysis, 298 participants were included in the Safety Analysis Set (SS), and 278 participants were included in the Per Protocol Set (PPS). The clinical trial period comprised a 24-week treatment phase (with study visits every four weeks) followed by a 24-week follow-up phase (with study visits every four weeks).

    Figure 1 The flow chart of subject distribution.

    Inclusion Criteria

    Participants were eligible for the study if they met the following criteria:

    (1) Diagnosis of CB based on the criteria outlined in Internal Medicine (9th edition, 2018), published by the People’s Health Publishing House;

    (2) Mild symptoms (cough, expectoration, and wheezing) with symptom scores ≤ 1.

    (3) Aged 18 to 75 years, with no restriction on gender.

    (4) Voluntary participation, with signed informed consent.

    Exclusion Criteria

    Participants were excluded if they met any of the following conditions:

    (1) Recent acute bronchitis or acute exacerbation of CB (AECB) within the past month.

    (2) Presence of other respiratory diseases with similar symptoms, including pulmonary tuberculosis, eosinophilic bronchitis, bronchial lung cancer, idiopathic pulmonary fibrosis, pneumonia, bronchial asthma, bronchiectasis, and gastroesophageal reflux.

    (3) Recent use of similar medications, specifically oral drugs with comparable functions within the past two weeks.

    (4) Abnormal renal or liver function, defined as: Serum creatinine (Scr) levels exceeding the upper reference limit, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels exceeding twice the upper reference limit.

    (5) Presence of serious comorbidities, including cardiovascular, cerebrovascular, liver, kidney, digestive, or hematopoietic disorders.

    (6) History of substance abuse, including chronic alcoholism and drug addiction.

    (7) Pregnancy or lactation, or inability to adhere to strict contraceptive during the study period.

    (8) Allergy to study drug ingredients.

    (9) Cognitive or psychiatric disorders, including intellectual disability or severe mental illness.

    (10) Participating in another clinical trials within the past three months.

    (11) Any other condition deemed inappropriate for study inclusion by the investigator.

    Randomization Procedure

    This trial utilized a block randomization method to ensure balanced allocation across study groups. The appropriate block length was determined, and random sequences for 300 subjects were generated using SAS software, assigning participants to the experimental group, positive drug control group, and blank control group in a 2:2:1 ratio. Each participant was assigned a unique serial number (001–300) with a corresponding treatment allocation listed in a random coding table The study was single-blind for participants. Blinding of data analysts was also implemented. Trial medications were repackaged in identical containers to reduce perceptual bias.

    Medicine Interventions

    Participants were divided into three groups with the following intervention protocols:

    (1) Experimental group (n=120): Guben Kechuan Granules, 1 bag (2 g) three times daily

    (2) Positive drug control group (n=120): Guilong Kechuanning Capsule, 3 capsules three times daily.

    (3) Blank control group (n=60): Subject education only, in case of AECB, treatment was administered according to clinical regulations.

    During the study, additional antitussive or expectorant medications were not permitted during the non-acute attack period. However, certain concomitant treatments were allowed under the following conditions:

    (1) Management of comorbidities such as hypertension or diabetes requiring continued medication or treatment.

    (2) Intervention for adverse events occurring during the study.

    (3) When AECB occurs, antibiotics, cough relieving, expectorants, and other drugs are given according to the needs of routine diagnosis and treatment;

    (4) AECB: Standard treatment with antibiotics, cough suppressants, expectorants, or other necessary medications based on routine clinical practice. TCM decoction or Chinese patent medicine) were allowed, but their use was restricted to no more than 21 consecutive days per occurrence, a cumulative maximum of three months over the entire treatment period.

    Guben Kechuan Granules, 1 bag (2 g) three times daily (mixed with warm water before oral administration). All participants, including those in the medication groups, received standardized subject education at baseline and during follow-up.

    Compliance and Concomitant Medication Analysis

    Compliance with the treatment protocol was assessed using descriptive statistics, including: number of cases, mean, standard deviation, median, minimum and maximum values, Lower quartile (Q1), and Upper quartile (Q3).

    Treatment compliance (%) was calculated as follows.

    Treatment compliance = (actual dosage / theoretical dosage) × 100%.

    Efficacy and Safety Evaluation

    The efficacy and safety of the treatment were assessed during both the treatment period and the follow-up period using the following measures: (1) Clinical symptom evaluation: cough, expectoration and wheezing were scored on a 0–100 scale. (2) AECB assessment: AECB severity was classified based on clinical symptom criteria (see Supplementary Table 1). (3) Pulmonary function tests (PFTs): FEV1, FVC, FEV1% predicted (FEV1%pred), FEV1/FVC ratio, MMEF, and PEF via MasterScreen PFT instrument (Jaeger, Germany). (4) Immunological function assessment: CD4+, CD8+, and CD4+/CD8+ ratio (performed only at select centers with necessary facilities). (5) Quality of life assessment: Evaluated based on mobility (ability to walk), self-care, daily activities, pain/discomfort, and anxiety/depression.

    Adverse events (AEs) were recorded and classified using the System Organ Class (SOC) and Preferred Term (PT) codes from the latest edition of the Medical Dictionary for Regulatory Activities (MedDRA).22

    Statistical Analysis

    Based on prior studies, the effective rates in the experimental, positive drug control, and blank control groups were 96.15%, 95.00%, and 77.08%, respectively.20,23 Assuming a 20% dropout rate, the minimum required sample size for each group was calculated as: Experimental group: 84, Positive drug control group: 84, Blank control group: 42. The 20% dropout estimate was based on previous observational CB trials with similar duration, although the actual dropout rate was only 0.33%. The study was designed with 80% power (β = 0.20) and a two-sided α = 0.05. Statistical analyses were performed using SAS 9.4 software. Baseline characteristics, treatment compliance, and concomitant medication efficacy were analyzed using the full analysis set (FAS) and per-protocol set (PPS), while safety analyses were conducted using the safety set (SS). For measurement indices, descriptive statistics—including case numbers, cases, mean, standard deviation, median, minimum, and maximum values—were reported. Categorical variables were presented as case numbers and percentages. Variance analysis or the Kruskal–Wallis H-test was used for comparisons between groups, while paired t-tests or signed-rank tests were applied for within-group before and after treatment. All statistical tests were two-tailed, with a p<0.05 considered statistically significant.

    Results

    Demographic and Baseline Characteristics

    Table 1 summarizes the baseline demographic and clinical characteristics of participants across the three study groups: experimental group (n=119), positive drug control group (n=120), and blank control group (n=60). Key characteristics analyzed included age, gender, number of AECB episodes in the past year, hospitalizations due to AECB, past medical history, allergic history, and family history. No significant differences were observed among the three groups (p > 0.05), indicating a well-balanced randomization.

    Table 1 The Demographic Characteristics Within Three Groups

    Compliance and Concomitant Medication

    In the experimental group, the actual cumulative dosages of subjects was 496.55 ± 21.41 bags, with an average administration duration of 24.18 ± 0.90 weeks. The treatment compliance within the 80%–120% was 100%. In the positive drug control group, the actual cumulative dosages of subjects were 1475.78 ± 150.38 capsules, with an average administration duration of 23.92 ± 2.21 weeks, and a compliance rate of 99.17%.

    Regarding concomitant medication use, during the treatment period, 47 cases (92 instances, 39.50% utilization rate) were recorded in the experimental group, 61 cases (109 instances, 50.83% utilization rate) in the positive drug control group, and 37 cases (88 instances, 61.67% utilization rate) in the blank control group. During the follow-up period, 26 cases (48 instances, 21.85% utilization rate) in the experimental group, 55 cases (101 instances, 45.83% utilization rate) in the positive drug control group, and 27 cases (58 instances, 45.00% utilization rate) in the blank control group.

    Efficacy Outcomes

    In the evaluation of CB symptoms, the scores for cough, expectoration, wheezing, and total symptom scores are detailed in Supplementary Table 2. As shown in Figure 2, CB symptom scores were significantly reduced after 24 weeks of treatment in both the experimental and positive drug control groups (p<0.05) compared to baseline. Throughout the treatment period, significant differences were observed among the three groups (all p<0.001), as well as in pairwise comparisons between the two treatment groups (all p<0.05). At the 24-week follow-up, significant differences in CB symptom scores remained evident both within and between groups (all p< 0.05).

    Figure 2 The relative changes of CB symptoms including cough, expectoration, wheezing in the experimental group, the positive drug control group and the blank control group. *p<0.05.

    In the assessment of AECB after treatment, the time to first AECB occurrence was 131.41±101.71 days (mean ± standard deviation) in the experimental group, 130.29±96.34 days in the positive drug control group, and 84.73±63.05 days in the blank control group (p=0.0219). The interval between AECB occurrences was longest in the experimental group (157.75±69.86 days), compared to 119.91±63.48 days in the positive drug control group and 110.43±53.13 days in the blank control group (p=0.3401). The duration of AECB was shortest in the experimental group (6.59±4.68 days), compared to 8.18±5.49 days in the positive drug control group and 12.81±8.08 days in the blank control group (p=0.0002). The average severity of AECB within the three groups was 1.25 in the experimental group, 1.33 in the positive drug control group, and 1.50 in the blank control group (p=0.0218). The frequency of AECB was also lowest in the experimental group (0.33±0.54), compared to 0.84±0.93 in the positive control group and 1.34±1.32 in the blank control group (p<0.0001). Except for AECB occurrence intervals, all other indicators in the experimental and positive drug control groups were significantly different from those in the blank control group (all p<0.05). FAS and PPS analysis further confirmed significant differences in AECB duration and frequency between groups (p<0.05, Table 2).

    Table 2 The AECB Analysis Within Three Groups After Treatment

    For the evaluation of pulmonary function, no significant changes were observed in FEV1/FVC%, FEV1%pred, PEF, MMEF, FVC, or FEV1 in any of the three groups after 24 weeks of treatment (all p>0.05, Table 3). However, no significant improvement in pulmonary function parameters (FEV1/FVC%, FEV1%pred, PEF, MMEF, FVC, or FEV1) was observed in any group after 24 weeks.

    Table 3 The Pulmonary Function and Immune Function After 24-week Treatment in Three Groups

    Regarding immune function, as presented in Table 3, there were no significant differences in CD4+ (p=0.5105), CD8+ (p=0.7045), and CD4+ / CD8+ ratio (p=0.8882) among the three groups.

    For quality of life, significant improvements were observed in Walking around, Self-care, Daily activities, and overall Health status across the three groups after 24 weeks of treatment (all p<0.05). However, no significant changes were noted in pain/discomfort or anxiety/depression, as indicated in Supplementary Table 3.

    Adverse Events

    As shown in Table 4, during the treatment period, a total of 14 cases of adverse events occurred in the experimental group (15 instances overall), resulting in an incidence rate of 11.75%. The majority of these were infectious and invasive diseases, accounting for 12 cases (12 instances) with an incidence rate of 10.08%, which may be associated with the short duration of drug use. Notably, no adverse events were reported in the experimental group during the follow-up period. These included upper respiratory tract infections, pharyngitis, and acute bronchitis.

    Table 4 The Adverse Events During the Treatment Period and Follow-up Period

    Discussion

    Chronic bronchitis (CB) is a common and increasingly prevalent condition, exacerbated by factors such as environmental pollution, smoking, and aging.3–6 In clinical practice, Chinese patent medicines offer advantages such as convenient administration, mild side effects, and distinctive therapeutic effects, making them a valuable treatment option.24

    In Traditional Chinese Medicine (TCM), CB falls under the categories of “cough”, “asthma syndrome”, and “phlegm retention”, with its pathogenesis closely linked to dysfunctions in the lung, spleen, and kidneys. The renowned physician Zhang Zhongjing recognized the essence of CB in his Synopsis of the Golden Chamber,25 where he proposed the therapeutic principle of “warming the lung and transforming phlegm”. This led to the development of several effective classical prescriptions, including Xiaoqinglong Decoction, Linggan Wuwei Jiangxin Decoction, and Shegan Mahuang Decoctionwere.25 Modern studies have further explored their mechanisms. Xiaoqinglong Decoction may exert therapeutic effects by modulating the PI3K-AKT signaling pathway,26 while Linggan Wuwei Jiangxin Decoction modulating inflammatory responses and airway fluid by reducing IL-2 and IL-4 levels and increasing aquaporin-1 expression in the lungs, thereby alleviating CB symptoms.27

    In this multi-center, randomized, and controlled trial, we assessed the efficacy and safety of Guben Kechuan Granules (experimental group, n=119) in comparison to Guilong Kechuanning Capsules (positive drug control group, n=120) and a blank control group (n=60).

    The intervention with Guben Kechuan Granules significantly improved CB symptoms—including cough, expectoration, and wheezing—during both the 24-week treatment period and the 24-week follow-up period, compared with both the positive drug control group and the blank control group (all p<0.05). As AECB represents the sudden worsening of CB symptoms, the study findings suggest that Guben Kechuan Granules effectively delayed the onset of the first AECB episode, shortened AECB duration, reduced AECB severity, and lowered AECB frequency compared to the blank control group (all p<0.05). Additionally, quality of life indicators, including walking ability, self-care, daily activities, and overall health status, showed significant improvements after 24 weeks of treatment with Guben Kechuan Granules. Despite symptom improvement, pulmonary function did not significantly change, possibly reflecting the mild baseline impairment and relatively short intervention time.

    These findings highlight the potential of Guben Kechuan Granules as an effective CB treatment. Similarly, in a Bailing capsule therapy study, patients experienced a significant reduction in CB severity and a decrease in AECB episodes following 48 weeks treatments and follow-up.18 Moreover, in CB patients, OM-85 therapy has been shown to lower the rate of acute exacerbations after 12 weeks of treatment, with a favorable safety profile.28 A combination of Hedera helix (ivy) leaf extract and Coptidis Rhizome Syrup was also found to reduce bronchitis symptoms and improve respiratory quality of life in CB patients.29

    Importantly, no overall adverse events occurred during the follow-up period in the experimental group. In terms of pulmonary function, the experimental group showed greater improvements in PEF, MMFE, FVC, and FEV1 compared to the control groups after 24 weeks of treatment; however, the differences were not statistically significant, possibly due to limited baseline severity and mild disease population rather than sample size alone. Future studies should consider expanding the sample size and extending the treatment period to further investigate the impact of Guben Kechuan Granules on lung function. Despite these promising findings, the precise mechanism of action of Guben Kechuan Granules remains unclear. Gu-Ben-Ke-Chuan decoction, recorded in the Chinese Pharmacopeia and approved by the China Food and Drug Administration,30 has been reported to treat CB via the TNF-associated anti-inflammatory pathway, as revealed by integrated systems pharmacology and surface plasmon resonance approaches.31 Another study suggests that Guben Kechuan Granules exert immunomodulatory effects by regulating T lymphocyte subsets, which influence thymus and spleen indices in experimental COPD models.32

    This study has certain limitations that should be addressed in future research. First, the use of concomitant medications may have influenced the therapeutic effects of Guben Kechuan Granules in CB patients, potentially introducing variability in outcomes. Second, the sample size was relatively small, which may have affected the statistical power of some findings, particularly regarding pulmonary function improvements. Third, this study lacked standardized mechanism research to clarify the precise biological pathways through which Guben Kechuan Granules exert their effects.

    Given the critical role of inflammatory factors in CB pathogenesis,33 future studies should investigate how Guben Kechuan Granules influence the expression levels of key inflammatory mediators such as IL-1, IL-6, and TNF-α. A deeper understanding of these mechanisms could provide stronger scientific validation for the use of Guben Kechuan Granules in CB treatment. Antibiotics and supportive treatments for AECB may have influenced symptom resolution, though their use was protocol-limited. This represents a potential confounding factor.

    Conclusion

    This study demonstrates that Guben Kechuan Granules can effectively alleviate CB symptoms, reduce AECB severity, and lower AECB frequency, making it a promising therapeutic option for CB patients. Its mechanism of action is currently being further explored at the Artemisinin Research Center of the Chinese Academy of Traditional Chinese Medicine. Moving forward, rapid patient enrollment across multiple global sites will be essential for conducting large-scale, multi-center trials. This will ensure the rapid collection of high-quality clinical data, ultimately supporting the broader application of Guben Kechuan Granules in CB management. While Guben Kechuan Granules significantly improved symptoms and reduced AECB episodes, no significant changes in pulmonary function were observed during the 24-week treatment period.

    Data Sharing Statement

    The individual deidentified participant data (including symptom scores, pulmonary function results, and adverse events) that support the findings of this study will be made available upon reasonable request. Study protocols and statistical analysis plans will also be shared. Data will be accessible via the corresponding author (Email: [email protected]) starting from the date of publication and will remain available for five years.

    Ethics Approval and Informed Consent

    This study was approved by The Ethics Committee of China-Japan Friendship Hospital (YW2022-007-02). Participants have provided their written informed consent to participate in this study.

    Funding

    This trial was funded by Traditional Chinese Medicine Inheritance and Innovation “Ten-Hundred-Thous” and Talents Program (Qihuang Program, grant No.: 2019-QTL-003).

    Disclosure

    The authors report no conflicts of interest in this work.

    References

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    13. Malesker MA, Callahan-Lyon P, Madison JM, Ireland B, Irwin RS. CHEST Expert Cough Panel. Chronic Cough Due to Stable Chronic Bronchitis: CHEST Expert Panel Report. Chest. 2020;158(2):705–718. doi:10.1016/j.chest.2020.02.015

    14. Valipour A, Fernandez-Bussy S, Ing AJ, et al. Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial. Am J Respir Crit Care Med. 2020;202(5):681–689. doi:10.1164/rccm.201908-1546OC

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    25. Xinchong P, Changxi Z, Anni Z, Wenrui Y, Jingyun L, Xue S. The Bufei Nashen pill inhibits the PI3K/AKT/HIF-1 signaling pathway to regulate extracellular matrix deposition and improve COPD progression. J Ethnopharmacol. 2024;30:118390. doi:10.1016/j.jep.2024.118390

    26. Ho TN, Wald J, Borhan S, et al. Comprehensive Care Management in Conjunction with Sputum Cytometry-Guided Pharmacotherapy in a Post-Discharge Clinic for Patients with COPD. COPD. 2021;18(4):411–416. doi:10.1080/15412555.2021.1945022

    27. Huang P, Duan B, Li D, et al. Transcriptomics and metabolomics revealed the pulmonary protective mechanism of Xixin-Ganjiang Herb Pair for warming the lungs to dissolve phlegm in COPD rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2023;1224:123665. doi:10.1016/j.jchromb.2023.123665

    28. Tang H, Fang Z, Saborío GP, Xiu Q. Efficacy and Safety of OM-85 in Patients with Chronic Bronchitis and/or Chronic Obstructive Pulmonary Disease. Lung. 2015;193(4):513–519. doi:10.1007/s00408-015-9737-3

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    31. Luo Z, Yu G, Wang W, et al. Integrated Systems Pharmacology and Surface Plasmon Resonance Approaches to Reveal the Synergistic Effect of Multiple Components of Gu-Ben-Ke-Chuan Decoction on Chronic Bronchitis. J Inflamm Res. 2021;14:1455–1471. doi:10.2147/JIR.S303530

    32. Wang W, Sun Z, Xu L, Zhu X. Effects of Guben Kechuan Granule on Pathology and T Lymphocyte Subsets in Rats with Chronic Obstructive Pulmonary Disease. China J Clin Pharmacol. 2015;10:840–842. doi:10.13699/j.cnki.1001-6821.1015

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  • Multi Cancer Early Detection Market Forecast Report

    Multi Cancer Early Detection Market Forecast Report

    Dublin, Aug. 11, 2025 (GLOBE NEWSWIRE) — The “Multi Cancer Early Detection Market and Forecasts 2025-2033” report has been added to ResearchAndMarkets.com’s offering.

    The global multi cancer early detection market size was valued at USD 1 billion in 2024 and is likely to reach USD 4.3 billion by 2033, expanding at a CAGR 16.9% during the forecast period.

    The multi cancer early detection market is experiencing significant growth as advancements in technology and changing healthcare paradigms evolve. Early detection of cancer can lead to improved treatment outcomes and potentially save lives, making this market increasingly important in the realm of healthcare.

    One of the primary drivers of the multi cancer early detection market is the rapid advancement of diagnostic technologies. Innovations in genomics, artificial intelligence, and imaging techniques are enhancing the accuracy and efficiency of cancer detection. These cutting-edge technologies allow for the identification of multiple cancer types simultaneously, which is crucial for timely intervention.

    Another key factor contributing to the market’s expansion is the growing public awareness regarding the importance of early cancer detection. More individuals are prioritizing preventive healthcare measures, leading to increased screenings and tests. Health campaigns and education initiatives are empowering patients to take charge of their health, thereby stimulating demand for multi-cancer early detection solutions.

    Multi Cancer Early Detection Market Synopsis

    This new 2025 market report presents an in-depth assessment of the global multi cancer early detection market dynamics, opportunities, future road map, competitive landscape and discusses major trends. The report offers the most up-to-date industry data on the actual market situation and future outlook in the global multi-cancer early detection market. The report also provides up-to-date historical market size data for the period 2020 – 2024 and an illustrative forecast to 2033 covering key market aspects like market value, share, analysis, and trends for the global multi cancer early detection market.

    The report provides a detailed analysis of the current industry situation and market requirements, highlighting facts about the market size, market share, revenue for global multi cancer early detection market segments, and a vivid forecast to 2033.

    It also provides a comprehensive analysis of the pricing landscape, policies and regulation, and reimbursement pattern by countries and regions. The report also offers analysis and information according to categories such as market segments, application, technology, geographies, companies and competitive landscape. The report also provides a detailed description of the porter’s five forces analysis, PESTEL analysis, SWOT analysis, funding, merger and acquisitions, pipeline, growth drivers and challenges of the global multi cancer early detection market.

    The report concludes with the profiles of major market players in the global multi cancer early detection market. The key market players are evaluated on various parameters such as company overview, product landscape, recent developments in multi cancer early detection, funding & M&A, strategic outlook, challenges and risks of the global multi cancer early detection market.

    Multi Cancer Early Detection Market by Key Players

    • GRAIL, Inc. (an Illumina Company)
    • Guardant Health
    • Exact Sciences Corporation
    • Illumina, Inc.
    • Freenome Holdings, Inc.
    • Burning Rock Biotech Limited
    • Foundation Medicine, Inc.
    • AnchorDx
    • Beijing Lyman Juntai International Medical Technology Development Co.
    • Genecast
    • Singlera Genomics Inc
    • Thrive Earlier Detection (acquired by Exact Sciences Corporation)

    Key Features of the Report

    • The global multi cancer early detection market provides granular level information about the market size, regional market share, historic market (2020-2024), and forecast (2025-2033).
    • Annualized revenues and country level analysis for each market segment.
    • Analysis of business strategies by identifying the key market segments positioned for strong growth in the future.
    • Detailed analysis of geographical landscape with country level analysis of major regions.
    • The report covers in-detail insights about the competitor’s overview, company share analysis, key market developments, and key strategies.
    • The report outlines drivers, restraints, unmet needs, and trends that are currently affecting the market.
    • The report tracks recent innovations, key developments, and start-up details that are actively working in the market.
    • The report provides a plethora of information about market entry strategies, regulatory framework, and reimbursement scenarios.
    • The report analyses the impact of the socio-political environment through SWOT analysis and competition through porter’s five force analysis and PESTEL analysis
    • Through study of the key business strategies and recommendations on future market approach.
    • Comprehensive analysis of the competitive structure of the market.
    • Demand side and supply side analysis of the market.

    Key Questions the Report Addresses

    • How big is the global multi cancer early detection market?
    • What is the current multi cancer early detection market size?
    • What is the major driving factor for the multi cancer early detection market?
    • Which factor is restraining the growth of the multi cancer early detection market?
    • Who are the key players in the multi cancer early detection market?
    • Which region has the biggest share in the multi cancer early detection market?
    • Which is the fastest growing country in the multi cancer early detection market?

    Key Attributes:

    Report Attribute Details
    No. of Pages 150
    Forecast Period 2024 – 2033
    Estimated Market Value (USD) in 2024 $1 Billion
    Forecasted Market Value (USD) by 2033 $4.3 Billion
    Compound Annual Growth Rate 16.9%
    Regions Covered Global

    Key Topics Covered:

    1. Market Definition

    2. Research and Methodology

    3. Executive Summary

    4. Global Multi Cancer Early Detection – Market Dynamics
    4.1 Growth Drivers
    4.2 Challengers
    4.3 Funding and Merger & Acquisitions

    5. Global Multi Cancer Early Detection Market – Industry Analysis
    5.1 SWOT Analysis
    5.2 Porter’s Analysis

    6. Global Multi Cancer Early Detection (MCED) Market & Forecast

    7. Global Multi Cancer Early Detection (MCED) Market Share & Forecast
    7.1 By Types
    7.2 By End Use
    7.3 By Region
    7.4 By Country

    8. By Types – Global Multi Cancer Early Detection (MCED) Market & Forecast
    8.1 Gene Panel, IDT & Others
    8.2 Liquid Biopsy

    9. By End Use – Global Multi Cancer Early Detection (MCED) Market & Forecast
    9.1 Hospitals
    9.2 Diagnostic Laboratories
    9.3 Others

    10. By Region – Global Multi Cancer Early Detection (MCED) Market & Forecast
    10.1 North America
    10.2 Europe
    10.3 Asia Pacific
    10.4 Latin America
    10.5 Middle East & Africa

    11. By Country – Global Multi Cancer Early Detection (MCED) Market & Forecast

    12. Global Multi Cancer Early Detection Market – Key Players Profiles

    • GRAIL, Inc. (an Illumina Company)
    • Guardant Health
    • Exact Sciences Corporation
    • Illumina, Inc.
    • Freenome Holdings, Inc.
    • Burning Rock Biotech Limited
    • FOUNDATION MEDICINE, INC.
    • AnchorDx
    • Beijing Lyman Juntai International Medical Technology Development Co.
    • GENECAST
    • Singlera Genomics Inc.
    • Thrive Earlier Detection (acquired by Exact Sciences Corporation)

    For more information about this report visit https://www.researchandmarkets.com/r/ovdma8

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    • Multi Cancer Early Detection Market

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  • First Complete Picture of Nighttime Clouds on Mars

    First Complete Picture of Nighttime Clouds on Mars

    Source: Journal of Geophysical Research: Planets

    Despite being thinner and drier than Earth’s atmosphere, Mars’s atmosphere contains clouds composed of tiny water ice crystals. And just as on Earth, these clouds influence the planet’s climate. However, most of what we know about clouds on Mars comes from data collected during the Martian afternoon, so there is still much to learn about how clouds tend to form and dissipate over a full day.

    Using data from the Emirates Mars Mission Hope probe, which has orbited Mars since 2021, Atwood et al. have captured the first comprehensive view of nighttime clouds on Mars.

    Hope’s high-altitude, low-inclination elliptical orbit was specifically designed to enable observation across all times of day and night and at almost all latitudes and longitudes. The researchers analyzed data collected over nearly two Martian years by the Emirates Mars Infrared Spectrometer, an instrument mounted on Hope that can detect the presence and thickness of clouds, according to how they absorb and scatter infrared light.

    The analysis revealed that for much of the Martian year, nighttime clouds are, on average, thicker than daytime clouds. Peaks in cloudiness typically occurred in the early morning and the evening, separated by a midday minimum.

    During the cold season on Mars, thick clouds tended to form in a band near the equator, becoming thickest just after sunrise. Also during the cold season, late-evening clouds typically formed in a broader distribution across low latitudes, while early-morning clouds mostly concentrated over a vast volcanic region known as Tharsis, which covers the equator and low latitudes.

    These findings shed new light on Martian atmospheric dynamics and could help scientists validate computational models of Mars’s atmosphere, the researchers say. (Journal of Geophysical Research: Planets, https://doi.org/10.1029/2025JE008961, 2025)

    —Sarah Stanley, Science Writer

    Citation: Stanley, S. (2025), First complete picture of nighttime clouds on Mars, Eos, 106, https://doi.org/10.1029/2025EO250279. Published on 11 August 2025.
    Text © 2025. AGU. CC BY-NC-ND 3.0
    Except where otherwise noted, images are subject to copyright. Any reuse without express permission from the copyright owner is prohibited.

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