Category: 8. Health

Introduction

Urologic diseases represent a major public health concern for women worldwide.¹ These include both nonmalignant and malignant conditions such as urinary tract infections (UTIs), urolithiasis, kidney cancer, and bladder cancer, which are highly prevalent and associated with substantial morbidity and disability. Although urologic trauma related to obstetric complications is an important issue in some low-resource settings, data on its burden remain limited.² Accordingly, this study focuses on four major urologic diseases in women: UTIs, urolithiasis, kidney cancer, and bladder cancer. UTIs affect more than 40% of women during their lifetime, with Escherichia coli being the most common pathogen.^3,4 A prior history of urinary tract infections is one of the strongest risk factors for future UTIs.⁵ Approximately 30% of women experience recurrent infections within six months. Rising antimicrobial resistance has diminished the effectiveness of standard antibiotic treatments, prompting interest in alternative preventive strategies, such as vaginal estrogen and lactobacillus-containing probiotics in postmenopausal women.⁶ Meanwhile, the burden of urolithiasis has also increased, particularly among women.⁷ Compared to nulliparous women, pregnant women under 50 years of age face more than double the risk of stone formation.⁸ Contributing factors include metabolic syndrome, dietary habits, weight loss interventions, hypercalciuria, and environmental and socioeconomic conditions, all of which have been linked to elevated risk of stone recurrence.^9–11

Kidney and bladder cancers are two other urologic diseases with rising incidence in women. Kidney cancer is now the ninth most common cancer among women globally, with incidence rates increasing by 2–3% per year between 2015 and 2019.¹² Alarmingly, mortality rates for kidney cancer are twice as high in Native American individuals compared to individuals of White descent.¹³ Risk factors for kidney cancer include smoking, alcohol consumption, overweight or obesity, and hypertension.¹⁴ For bladder cancer, smoking remains a major modifiable risk factor, responsible for approximately 50% of cases in men and 40% in women in the United States.¹ While the overall incidence and mortality remain higher in men, women who are active or passive smokers still face significant risk.¹⁵ Additionally, emerging evidence implicates occupational exposures, specific dietary habits, microbiome dysbiosis, gene–environment interactions, diesel exhaust, and pelvic radiotherapy in bladder cancer development.¹⁶ These disparities highlight the complex interplay of biological, behavioral, and social factors in shaping disease burden.

Despite the considerable health impact of these urologic diseases, up-to-date, sex-specific epidemiological data are scarce. Regional and national differences in incidence and outcomes are influenced by healthcare access, sociodemographic development, and environmental exposures.¹⁷ To address this gap, we used data from the Global Burden of Disease Study 2021 to systematically evaluate the incidence and disability-adjusted life years (DALYs) of UTIs, urolithiasis, kidney cancer, and bladder cancer in women across 204 countries and territories from 1990 to 2021.^18–20 This analysis aims to uncover global patterns and temporal trends of four major urinary conditions in women to support evidence-based public health strategies and inform future research and clinical practice.

Patients and Methods

Data Source and Screening

This study utilized data from the Global Burden of Disease (GBD) Study 2021, which systematically estimates the incidence, mortality, DALYs, and age-standardized rates for 371 diseases and injuries across sexes, age groups, and 204 countries and territories worldwide.¹⁸ GBD 2021 employed three core analytical tools—Cause of Death Ensemble Model (CODEm), Spatiotemporal Gaussian Process Regression (ST-GPR), and DisMod-MR 2.1—to synthesize data and generate consistent estimates of disease burden.^18,20

For the present analysis, we extracted data specific to four major urologic diseases in women—urinary tract infections, urolithiasis, kidney cancer, and bladder cancer. We extracted global-level data to analyze overarching trends. For more detailed national and subregional comparisons, we selected Western Europe, China, and North Africa and the Middle East as representative regions based on their geographic diversity, data availability, and distinct epidemiological profiles of urologic diseases. “Incidence” and “DALYs” were chosen as the primary measures of disease burden. To provide a comprehensive overview, we examined age- and year-specific incidence and DALY rates for each of the four conditions across the selected regions.

The Socio-demographic Index (SDI), a composite indicator reflecting income per capita, average educational attainment, and fertility rates, was included to account for variations in development level, given its strong association with health outcomes.²¹ Using GBD 2021 data, countries and territories were categorized into five groups based on SDI: high, high-middle, middle, low-middle, and low. Additionally, the Human Development Index (HDI), a composite measure of overall human development obtained from the United Nations Development Programme, was employed.²² Correlation analyses between GBD data and HDI were conducted to examine the relationship between human development and disease burden.²³ Risk factor attribution was based on the GBD’s comparative risk assessment framework, which comprises six key steps to estimate the proportion of disease burden attributable to modifiable risk exposures.²⁴ This framework enabled further insight into the global patterns and drivers of urologic disease burden in women.

Statistical Analysis

The age-standardized rate (ASR), was used to account for differences in age structures between populations and over time. It was calculated using the following formula:

In the equation, _i represents the age-specific rate in the i^th age group, and w_i denotes the count of individuals in the same age group based on the GBD 2021 standard population.¹⁸

To evaluate temporal trends in the burden of urologic diseases in women, we calculated the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) and age-standardized DALY rate (ASDR) from 1990 to 2021.²⁵ EAPC was derived from a linear regression model fitted to the natural logarithm of the ASR, specified as:

EAPC was then defined as:

The 95% confidence interval (CI) of the EAPC was also obtained from the regression model.²⁶ We interpreted a trend as statistically significant if both the EAPC and its 95% CI were either entirely above or entirely below zero. If the 95% CI included zero, the trend was considered statistically insignificant.

Finally, to project trends through 2046, we conducted an age–period–cohort (APC) analysis using the “Nordpred” package in R. This approach considers both demographic changes and temporal trends and has been well-established in previous studies.²⁷ All statistical analyses were performed using R software (version 4.3.2), and rates were expressed per 100,000 population. Statistical significance was determined using a p value of <0.05.

Results

Global and Regional Patterns in the Burden of Urologic Diseases in Women

In 2021, the global incidence of urologic diseases in women showed a notable increase. The estimated number of new cases was 35,718.97 × 10⁵ for UTIs (95% UI: 31,808.47–39,914.82), 3,487.81 × 10⁵ for urolithiasis (95% UI: 2,913.36–4,247.25), 13.52 × 10⁵ for kidney cancer (95% UI: 12.41–14.42), and 12.26 × 10⁵ for bladder cancer (95% UI: 10.82–13.39). To better capture temporal trends while accounting for population growth and changes in age distribution, age-standardized rates (ASRs) were utilized. Analysis of the ASIR and ASDR from 1990 to 2021 revealed heterogeneous trends across different diseases.

The ASIR of UTIs remained relatively stable globally with EAPC of 0.03 (95% CI 0.02 to 0.05), whereas its ASDR generally declined with EAPC of −0.6 (95% CI: −0.76 to −0.25), except in China where a slight upward trend was observed. For urolithiasis, both the ASIR and ASDR declined steadily over the study period, with a global ASIR EAPC of −0.16 (95% CI −0.19 to −0.14) and ASDR EAPC of −0.26 (95% CI −0.35 to −0.08). In contrast, the ASIR for kidney cancer remained relatively stable with EAPC of 0.04 (95% CI −0.03 to 0.12), while its ASDR significantly decreased with EAPC −0.23 (95% CI −0.30 to −0.13). For bladder cancer, both ASIR and ASDR showed a favorable and consistent downward trend, with an ASIR EAPC of −0.15 (95% CI −0.22 to −0.07) and ASDR EAPC of −0.31 (95% CI −0.38 to −0.22). These results are detailed in Table 1.

Table 1 Global Incidence and DALYs of Four Female Genitourinary Diseases from 1990 to 2021

National and Subregional Trends in the Burden of Urologic Diseases in Women

At the national level, the ASDR for UTIs has declined in most countries or regions worldwide, with China showing the most pronounced decrease (EAPC: –0.60; 95% CI: –0.76 to –0.25). In contrast, several countries in North Africa and South America, such as Argentina, Uruguay, and Kuwait, have experienced a rapid increase in ASDR (Figure 1A). For urolithiasis, the ASDR has increased in several countries, including Libya, Brazil, and Guyana, whereas Czechia recorded the fastest decline (EAPC: –0.73; 95% CI: –0.80 to –0.65) (Figure 1B). Regarding kidney cancer, although the ASDR is generally decreasing, the rate of decline is relatively modest. Sri Lanka leads in the reduction trend with an EAPC of –0.79 (95% CI: –0.87 to –0.67) (Figure 1C). As for bladder cancer, some countries show substantially faster declines in ASDR than others, with Mongolia, Mauritius, and Egypt ranking in the top three (Figure 1D). Overall, China stands out globally for achieving substantial reductions in the ASDR across all four major urologic diseases in women, with an EAPC of –0.60 (95% CI: –0.76 to –0.25) for urinary tract infections, –0.66 (95% CI: –0.76 to –0.40) for urolithiasis, –0.52 (95% CI: –0.67 to –0.32) for kidney cancer, and –0.33 (95% CI: –0.55 to –0.05) for bladder cancer.

Figure 1 Global and regional variations in the EAPC of ASDR for urologic diseases in women. (A) Urinary tract infections. (B) Urolithiasis. (C) Kidney cancer. (D) Bladder cancer.

Correlation Among EAPC, ASR, and HDI

In the correlation analysis between the ASR and the EAPC from 1990 to 2021 for urologic diseases in women, a notable negative correlation was observed between the ASDR of UTIs and the corresponding EAPC in 1990 (cor=−0.3184, p<0.0001), while a positive correlation emerged by 2021 (cor=0.2299, p=0.0009) (Figure 2A). A similar trend was found for urolithiasis, with a negative correlation in 1990 (cor=−0.3376, p<0.0001) and a positive correlation in 2021 (cor=0.2236, p=0.0013) (Figure 2B). In contrast, for urologic cancers, including kidney and bladder cancer, significant negative correlations were noted in 1990 between ASIR/ASDR and EAPC, but no significant correlations were found in 2021 (Figure 2C and D). Regarding the association between EAPC and the Human Development Index (HDI) in 2021, a positive correlation was observed between the ASDR and EAPC for UTI (cor = 0.2546, p = 0.0013), and a negative correlation for bladder cancer (cor = –0.1810, p = 0.0233). No statistically significant associations were identified for other diseases (Figure 2E–H).

Figure 2 Correlations of EAPC with ASR and HDI for urologic diseases in women. Panels (A–D) show the correlation between EAPC and ASRs in 1990 for urinary tract infections (A), urolithiasis (B), kidney cancer (C), and bladder cancer (D). Panels (E–H) show the correlation between EAPC and HDI in 2021 for the same diseases (E–H, respectively).

Current Age-Specific Burden of Urologic Diseases in Women

Figure 3 illustrates the global age-specific distribution of incidence and DALYs for four major urologic diseases in women in 2021. Non-neoplastic diseases displayed pronounced differences in age patterns. The incidence of UTIs peaked between ages 30–34, with approximately 37 million new cases. Conversely, urolithiasis peaked later, around ages 55–59, reaching nearly 50 million cases. Regarding incidence rates, UTIs demonstrated a bimodal distribution, with the first peak in middle-aged adults (25–54 years) and a second sharp increase among individuals older than 85, exceeding 10,000 per 100,000 population. The incidence rate pattern for urolithiasis mirrored its case distribution, peaking similarly in the 55–59 age group (Figure 3A).

Figure 3 Global incidence and DALY counts and rates for urologic diseases in women by age group. (A) Incidence of non-neoplastic diseases. (B) DALYs of non-neoplastic diseases. (C) Incidence of neoplastic diseases. (D) DALYs of neoplastic diseases.

The age distribution of DALYs for UTIs followed a bimodal trend, with a pronounced peak in the 15–24 age group, followed by a decline and then a second rise, reaching the highest burden in the 70–74 age group. In contrast, the DALYs burden for urolithiasis steadily increased until 55–59 years, then gradually declined. In terms of DALY rates, both UTIs and urolithiasis showed a general increase with age, with UTIs displaying a marked surge after age 85 (Figure 3B).

Due to the life-threatening nature of kidney and bladder cancers, both diseases exhibited similar age-related patterns in incidence and DALYs. Peaks were observed in the 65–79 age range, with the burden consistently increasing with age. Notably, kidney cancer showed a minor uptick in incidence between ages 2–10, and the corresponding DALYs among individuals aged 2–19 showed a negative correlation with age (Figure 3C and D).

Figure 4 presents the EAPC in age-specific DALY rates across different regions from 1990 to 2021. For UTIs, China experienced declines in all age groups, while many other regions, particularly high-middle SDI areas, showed a pattern of decreasing burden in younger groups and increasing burden in the oldest age groups, peaking at an EAPC of 2.48 in individuals aged 95 and older (Figure 4A). Urolithiasis showed an overall decreasing trend in most age groups globally, especially in China. However, an increasing trend in DALY rates after age 35 was observed in North Africa and the Middle East (Figure 4B). For kidney cancer, most age groups in low, low-middle, and middle SDI regions demonstrated an increasing trend in DALY rates (Figure 4C). In contrast, bladder cancer presented a more favorable picture: DALY rates declined across nearly all regions and age groups, except among individuals older than 95, where a slight increase was noted (Figure 4D).

Figure 4 EAPC in DALY rates for urologic diseases in women by age group and region, 1990–2021. (A) Urinary tract infections. (B) Urolithiasis. (C) Kidney cancer. (D) Bladder cancer.

Composition of Incident Cases and Risk-Attributable DALYs for Urologic Diseases in Women

The composition of incident cases and risk-attributable DALYs for major urologic diseases in women in 1990 and 2021 was analyzed (Figure 5). In 2021, among non-neoplastic urologic diseases in women, urinary tract infections (UTIs) accounted for a significantly higher proportion of global incident cases compared to urolithiasis (91.1% vs 8.9%). However, in China, urolithiasis contributed a relatively higher proportion than the global average, with UTIs and urolithiasis accounting for 75.7% and 24.3% of cases, respectively (Figure 5A). For urologic cancers, kidney cancer represented a slightly greater share of incident cases globally than bladder cancer (52.5% vs 47.5%). This disparity was particularly pronounced in North Africa and the Middle East (60.5% vs 39.5%). In contrast, low Socio-demographic Index (SDI) regions demonstrated the opposite pattern, with bladder cancer comprising a higher proportion (59.6% vs 40.4%) (Figure 5B). Longitudinal trends from 1990 to 2021 indicate that the global proportion of UTIs among non-neoplastic urologic diseases has continued to rise. Meanwhile, the proportion of kidney cancer among urologic malignancies has increased across all SDI regions.

Figure 5 The proportion of incident cases and DALYs attributable to risk factors for urologic diseases in women, 1990–2021. (A) Proportional distribution of incident cases among non-neoplastic urologic diseases. (B) Proportional distribution of incident cases among neoplastic urologic diseases. (C) Proportion of DALYs attributable to specific risk factors for kidney cancer. (D) Proportion of DALYs attributable to specific risk factors for bladder cancer.

In 2021, the leading attributable risk factor for kidney cancer was high body mass index (BMI), accounting for 85.0% of the DALYs, followed by smoking (14.8%) and occupational carcinogens (0.2%) (Figure 5C). The contribution of smoking was highest in high-SDI and Western European countries (23.3% and 23.2%, respectively). Risk factors for bladder cancer showed marked regional variation: in low-SDI and North Africa/Middle East regions, high fasting plasma glucose was the predominant risk factor (62.8% in North Africa and the Middle East), whereas in high-SDI and Western Europe, smoking was the leading contributor (69.1% and 71.9%, respectively) (Figure 5D). Compared to 1990, the contribution of high BMI to kidney cancer burden increased in 2021, while the role of high fasting plasma glucose as a risk factor for bladder cancer also rose. Consequently, the proportion of urologic cancer-related DALYs attributable to smoking among women has declined.

Projections of Global Incidence and DALY Rates of Urologic Diseases in Women

We projected the trends in ASIR and ASDR for four major urologic diseases in women worldwide from 2021 to 2046 (Figure 6). For UTIs, both the ASIR and ASDR are expected to remain relatively stable over the next decade, with a modest upward trend anticipated after 2032 (Figure 6A). In the case of urolithiasis, projections suggest that both ASIR and ASDR will remain stable throughout the forecast period, without significant fluctuation (Figure 6B). For malignant urologic conditions, the predicted trajectories for kidney and bladder cancers show a slight initial decline in both ASIR and ASDR, followed by a mild increase in subsequent years. However, the magnitude of these changes is relatively small, indicating a generally stable burden over time (Figure 6C and D).

Figure 6 Predicted trends in incidence and DALY rates for urologic diseases in women from 2021 to 2046. (A) Projected age-standardized incidence rates for non-neoplastic urologic diseases. (B) Projected age-standardized DALY rates for non-neoplastic urologic diseases. (C) Projected age-standardized incidence rates for neoplastic urologic diseases. (D) Projected age-standardized DALY rates for neoplastic urologic diseases.

Discussion

In recent years, women’s urologic health has gained increasing global attention due to its growing prevalence and associated healthcare burden. These diseases pose substantial challenges to public health systems and call for urgent, coordinated responses.²⁸ Using data from the Global Burden of Disease Study 2021, we systematically assessed the incidence and DALYs for UTIs, urolithiasis, kidney cancer, and bladder cancer in women across global, regional, and national levels from 1990 to 2021.

These four urologic diseases display two distinct epidemiological patterns—non-malignant conditions like UTIs and urolithiasis, and malignant ones like kidney and bladder cancers. UTIs remain a major public health concern among women due to their high prevalence and potential complications.²⁹ Our findings indicate that although the ASDR for UTIs has remained stable in most regions, the absolute number of cases has risen significantly, likely driven by population growth, aging, and the heightened susceptibility of elderly women.³⁰ This is consistent with the findings of Yang et al, who reported a rising incidence of UTIs associated with aging populations.³¹ Cognitive impairment, incontinence, and diminished functional capacity—common among older women—are established risk factors for UTIs.^32,33 Notably, several South American countries experienced a marked rise in UTI-related ASDR, possibly due to the increased prevalence of multidrug-resistant infections.³⁴ Correlation analyses further revealed shifting trends in burden disparities. In 1990, a negative association was observed between baseline ASDR and EAPC, suggesting convergence across countries. However, by 2021, this relationship reversed, possibly reflecting inequities in healthcare access. A similar trend was observed in urolithiasis, whereas it is less pronounced in kidney and bladder cancers. Additionally, UTI-related ASDRs positively correlated with HDI, potentially due to the higher prevalence of resistant pathogens in high-income settings.³⁵

Although the overall burden of urolithiasis appears stable or declining, an upward trend is evident in tropical and hot-climate regions, possibly linked to dehydration, dietary factors, and environmental exposures.^36–38 This finding aligns with Wang et al’ s findings on climate-related risk for stone formation.³⁹ The highest burden was noted among women aged 50–59, suggesting a possible link to menopause, which may increase urinary calcium excretion and thereby the risk of stone formation as suggested by Prochaska et al^40,41 Future projections indicate a relatively stable burden, likely supported by advances in surgical and minimally invasive treatment options.⁴²

Urologic cancers show distinct epidemiological trajectories. Kidney cancer has surpassed bladder cancer as the leading malignant urologic disease in women in regions such as North Africa and the Middle East. ASDRs for both kidney and bladder cancers were negatively associated with HDI, underscoring the disproportionate burden in low-resource settings due to delayed diagnosis and limited treatment access.⁴³ The long-term cancer control successes observed in North America, Oceania, and parts of Europe emphasize the importance of early detection and effective treatment.⁴⁴ While these cancers primarily affect older populations, kidney cancer also contributes substantially to DALYs in children, likely due to nephroblastoma and early-onset clear cell carcinoma.⁴⁵

Among modifiable risk factors, smoking remains the predominant contributor to DALYs from female bladder and kidney cancers. Despite a global decline in smoking prevalence since 1990, it continued to account for the largest share of bladder cancer-related DALYs in women throughout the study period. This highlights the persistent need for robust tobacco control policies, especially targeting youth and secondhand smoke exposure.^46,47 Although men are generally at higher risk for bladder cancer, women tend to be diagnosed at more advanced stages.^48,49 Sex differences in tumor detection may contribute to these disparities, with men more likely to receive early diagnosis.⁵⁰ Emerging evidence also suggests that sex hormones and their receptors may influence tumorigenesis and progression.^51–53 These findings underscore the necessity of gender-specific prevention and treatment strategies to reduce sex-based disparities in cancer outcomes. In addition, obesity, particularly abdominal obesity, is a well-documented risk factor for kidney cancer, with obese individuals showing a 1.32-fold higher risk than their non-obese counterparts.^54,55 We also observed an increasing contribution of elevated fasting plasma glucose to bladder cancer DALYs, pointing to the growing global burden of metabolic syndrome.⁵⁶ Strong evidence supports the role of lifestyle interventions, such as physical activity and balanced diets, in mitigating cancer risk.^57,58 Therefore, alongside anti-smoking measures, strategies to enhance metabolic health including diabetes management and nutritional guidance should be prioritized in future cancer control efforts targeting women.

While our study offers the most recent GBD-based estimates on the global burden of four common urologic diseases in women, it is subject to several limitations. First, like all GBD studies, the quality and completeness of data vary across countries, particularly in low- and middle-income settings where robust epidemiological data are often lacking. Biases in diagnostic criteria and data reporting in primary studies also affect accuracy.^18–20,24 Second, the impact of the COVID-19 pandemic introduces uncertainty in mortality estimates, especially in heavily affected regions. Third, our focus was limited to UTIs, urolithiasis, kidney cancer, and bladder cancer, excluding other urologic conditions that may be significant. Fourth, definitional constraints in the GBD database may lead to underestimation of disease burden. Fifth, differences in diagnostic practices across countries and over time could limit comparability. These limitations necessitate a cautious interpretation of global burden trends and call for improved data collection, harmonized diagnostic criteria, and complementary analytical approaches to validate our findings. Lastly, the GBD risk analysis is literature-based and may not account for all disease-specific risk factors.

Conclusion

Urologic diseases in women pose a growing global health challenge. The burden of UTIs and kidney cancer continues to rise with aging populations, while urolithiasis and bladder cancer are declining. Disparities in healthcare access and prevention have led to a polarized disease burden across countries. The rising impact of metabolically related cancers highlights the need for better metabolic health management. Strengthening global collaboration to develop effective screening and targeted, gender-sensitive strategies is essential to reduce the burden of these diseases.

Abbreviations

DALYs, disability-adjusted life-years; ASR, age-standardized rate; ASIR, age-standardized incidence rate; ASDR, age-standardized DALYs rate; EAPC, estimated annual percentage change; UI, uncertainty interval; SDI, socio-demographic index; HDI, human development index.

Ethics Approval and Consent to Participate

The study got an exemption from the Ethical Review Committee of the Fourth Affiliated Hospital of School of Medicine, Zhejiang University, because it used publicly available and deidentified data from GBD database.

Disclosure

The authors report no conflicts of interest in this work.

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32. Chao C-T, Lee S-Y, Wang J, Chien K-L, Huang J-W. Frailty increases the risk for developing urinary tract infection among 79,887 patients with diabetic mellitus and chronic kidney disease. BMC Geriatr. 2021;21(1):349. doi:10.1186/s12877-021-02299-3

33. Tang K, Feng J, Lai H, et al. Global burden and trends of UTI in premenopausal and postmenopausal women from 1990 to 2021 and projections to 2044. Int J Women’s Health. 2025;17:1375–1392. doi:10.2147/IJWH.S517387

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39. Wang Y, Wang Q, Deng Y, et al. Assessment of the impact of geogenic and climatic factors on global risk of urinary stone disease. Sci Total Environ. 2020;721:137769. doi:10.1016/j.scitotenv.2020.137769

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A recent study demonstrated the efficacy and safety of subcutaneous venom immunotherapy (VIT) in children with a Hymenoptera venom allergy.¹

“The results showed that the cluster protocol represents a safe and effective treatment in children, with a low rate of SR (0.4% in relation to the total number of doses administered) and none requiring epinephrine,” wrote study investigator Mattia Giovannini, from the University of Florence and the allergy unit at Meyer Children’s Hospital IRCCS in Florence, Italy, and colleagues.

VIT, recommended for patients with a history of systemic reactions to stings who test positive for venom-specific allergens, remains the sole proven treatment for venom allergy.² Extensive research has examined the safety of venom immunotherapy, but data on adverse reactions and their predictive risk factors in children remain limited.¹

In this study, investigators sought to evaluate the safety of VIT, identify factors linked to adverse reactions, assess the accuracy of insect identification and its impact on VIT extract selection, and determine treatment efficacy by examining adverse reactions following re-sting. The team retrospectively analyzed the medical charts of 58 patients < 18 years followed up at the Allergy Unit of Meyer Children’s Hospital IRCCS in Florence, Italy, who received VIT between 1997 and 2021.

Participants were mostly male (87.9%) and had a median age of 9.4 years. The median VIT duration was 5.4 years, and the median number of injections per patient was 63.4 years. Nearly half (47.7%) had a positive family history of atopy, and 27.6% presented atopic manifestations, including rhinoconjunctivitis (18.9%), asthma (6.8%), food allergy (6.8%), and atopic dermatitis (5.2%).

A diagnostic workup, conducted in line with the European Academy of Allergy and Clinical Immunology guidelines and the Italian Consensus on Hymenoptera venom allergy management, guided clinicians in selecting the VIT extract. The study examined 4 extracts: Apis mellifera (28.4%; n = 17), Vespula (33.3%; n = 20), Polistes (33.3%; n = 20), and Vespa crabro (5%; n = 3). Following 3739 injections, 335 adverse reactions occurred (9.5%), classified as local reactions (8.2%; n = 306), extended local reactions (0.9%; n = 34), and systemic reactions (0.4%; n = 15).

The study included both build-up and maintenance phases. During the buildup phase, clinicians administered 1120 injections, with 194 adverse reactions reported; most were local reactions (8.2%). The maintenance phase included 2619 injections, with 161 adverse events reported; 84.5% were local reactions.

Compared to the maintenance phase, the build-up phase was associated with a greater number of adverse and local reactions during VIT (P < .0001). The study found no differences between the build-up and maintenance phases for extended local reactions (P =.5) or systemic reactions (P =.35). The study identified no other significant factors related to the risk of developing any adverse reaction.

Systemic reactions occurred the most during VIT for Polistes (0.5%). The study found no significant differences in allergic reactions across the venom extracts.

In total, 31 patients reported 51 re-stings following VIT. Among these patients, only 2 (3.9%) experienced a systemic reaction after their re-sting, and these reactions occurred from a different Hymenoptera species than the one targeted during VIT.

The study also found that males had a lower risk of adverse reactions compared with females. No statistically significant associations emerged for age at VIT initiation or family history of atopy.

Furthermore, the study demonstrated that patients could easily identify mellifera and Vespa crabro but struggled to differentiate Vespula from Polistes before and after VIT initiation. Despite this finding, VIT demonstrated efficacy for treating venom allergies.

“The present study confirmed that cluster protocol VIT is safe and effective in pediatric patients, with a low rate of [systemic reactions],” investigators concluded.¹ “The build-up phase was associated with a higher frequency of [adverse reactions], while factors such as sex, age, atopy, and type of venom extract showed no significant impact. VIT with Polistes venom had the highest [systemic reactions] rate, requiring further validation. Despite initial [systemic reactions], VIT demonstrated indisputable efficacy upon re-stinging, underscoring its value as an essential therapy for eligible patients.”

References

1. Giovannini M, Catamerò F, Masini M, et al. Efficacy and safety of subcutaneous venom immunotherapy in children: A 24-year experience in a pediatric tertiary care center. Pediatr Allergy Immunol. 2025;36(9):e70195. doi:10.1111/pai.70195

2. Dhami S, Nurmatov U, Varga EM, et al. Allergen immunotherapy for insect venom allergy: protocol for a systematic review. Clin Transl Allergy. 2016;6:6. Published 2016 Feb 16. doi:10.1186/s13601-016-0095-x

CAMBRIDGE, Mass., Sept. 3, 2025 /PRNewswire/ — Apnimed, Inc., a pharmaceutical company building the industry-leading portfolio of first-in-class oral drugs that address the root causes of obstructive sleep apnea (OSA) and other sleep-related breathing diseases, today announced multiple upcoming oral and poster presentations at the World Sleep Congress, which will take place September 5-10, 2025, in Singapore. The presentations will highlight AD109, the company’s lead investigational once-daily oral therapy for OSA, which recently reported two Phase 3 trials, LunAIRo and SynAIRgy, as well as results from the SHINE survey of US adults highlighting the significant real-world impact and burden of OSA.

Apnimed World Sleep 2025 Presentation Details:

Oral Presentations

Title: “A combination of antimuscarinic agents with selective norepinephrine reuptake inhibitors to treat OSA”
Session Title: S-01: Pharmacotherapy of obstructive sleep apnea in 2025
Session Date: Monday, September 8, 2025
Presentation Time: 9:18 AM – 9:34 AM SGT
Location: Hall 406C

Title: “Targeting upper airway muscle dysfunction in OSA: A new frontier in treatment”
Session Title: S-42: Revolutionizing personalized medicine in OSA: Exploring new treatment modalities
Session Date: Tuesday, September 9, 2025
Presentation Time: 9:50 AM – 10:06 AM SGT
Location: Hall 406C

Poster Presentations

Title: “Impact of Obstructive Sleep Apnea on Daily Life by Disease Severity Level: Analysis from the SHINE Survey”
Session Title: Poster abstract group 1
Session Date: Sunday, September 7, 2025
Presentation Time: 5:00 PM to 6:00 PM SGT
Poster Board Number: 369

Title: “Unmasking Obstructive Sleep Apnea: Estimated Prevalence and Impact in the United States“
Session Title: Poster abstract group 2
Session Date: Monday, September 8, 2025
Presentation Time: 6:30 PM to 7:30 PM SGT
Poster Board Number: 364

Title: “Demographic and Baseline Disease Characteristics of SynAIRgy: A Phase 3 Trial of Aroxybutynin and Atomoxetine (AD109) in Obstructive Sleep Apnea”
Session Title: Poster abstract group 3
Session Date: Tuesday, September 9, 2025
Presentation Time: 4:45 PM to 5:45 PM SGT
Poster Board Number: 379

Title: “The SHINE Survey: Uncovering Gender Differences in Psychosocial Burden of Obstructive Sleep Apnea”
Session Title: Poster abstract group 3
Session Date: Tuesday, September 9, 2025
Presentation Time: 4:45 PM to 5:45 PM SGT
Poster Board Number: 346

Title: “Real-world Incremental Economic Burden of Fatigue among Patients with Obstructive Sleep Apnea in the Medicare Fee-for-Service Population”
Session Title: Poster abstract group 3
Session Date: Tuesday, September 9, 2025
Presentation Time: 4:45 PM to 5:45 PM SGT
Poster Board Number: 358

About AD109
AD109 is designed to be the first pharmacological treatment to improve oxygenation during sleep by directly addressing the neuromuscular root cause of upper airway collapse in people with obstructive sleep apnea. It is a first-in-class anti-apneic neuromuscular modulator, combining aroxybutynin, a novel antimuscarinic, and atomoxetine, a selective norepinephrine reuptake inhibitor (NRI). Their combined pharmacological synergy targets the underlying neuromuscular root cause of OSA. AD109 is an investigational, once-daily pill taken at bedtime that is designed to lower the complexity of intervention and may help more people benefit from effective, restorative sleep. In a disease characterized by complex and invasive treatment options, AD109 may be a simple solution to help improve oxygenation and wellbeing for people living with OSA.

About Obstructive Sleep Apnea
Obstructive sleep apnea (OSA) is a serious, chronic sleep-related breathing disease in which the upper airway repeatedly collapses during sleep, leading to intermittent oxygen deprivation. It is caused by two overlapping mechanisms: neuromuscular dysfunction during sleep and predisposing anatomic abnormalities. OSA affects individuals across all walks of life, impacting both males and females of all age groups, ethnicities, and weight classes, including those with or without obesity. An estimated more than 80 million people in the United States and nearly one billion people worldwide suffer from OSA. Up to 80% of people living with OSA are undiagnosed and therefore untreated.

An individual with OSA can experience hundreds of sleep apnea events in a single night, each one reducing the blood oxygen levels and negatively impacting cellular functions vital to normal health and function. Failure to effectively treat OSA increases the risk of serious long-term health consequences, including cardiovascular disease, neurocognitive impairment, metabolic dysfunction, and early mortality. Yet, the majority of those diagnosed with OSA refuse, abandon, or underutilize treatment. Currently, no available pharmacological treatments directly address the underlying neuromuscular dysfunction that is present in OSA.

About Apnimed
Apnimed is a privately held, clinical-stage pharmaceutical company based in Cambridge, Massachusetts, dedicated to transforming the treatment landscape for sleep-related breathing diseases. We believe the introduction of simple, once-nightly oral drugs may dramatically expand diagnosis and the reach of treatment for people with OSA. OSA, like other common chronic diseases such as diabetes or hypertension, would benefit from having multiple drugs with differing mechanisms to more fully address the heterogeneity of disease pathophysiology. Apnimed envisions a new era where novel oral therapies simplify intervention, expand the reach of diagnosis and treatment, and help more people get the oxygen and restorative sleep needed to thrive.

Apnimed is advancing a robust pipeline of oral pharmaceutical product candidates designed to improve oxygenation in individuals living with OSA and other chronic sleep-related breathing diseases. Our lead candidate, AD109, could become the catalyst for a new oral treatment paradigm for OSA that has been historically limited to cumbersome devices or invasive surgeries. Apnimed is also developing several therapies as part of its joint venture with Shionogi & Co., Ltd., Shionogi-Apnimed Sleep Science. Learn more at apnimed.com or follow us on X and LinkedIn.

Media Contact:
[email protected]
Investor Contact:
[email protected]

SOURCE Apnimed, Inc.

Introduction

Heart failure (HF) is a significant global health problem with substantial morbidity and mortality, affecting an estimated 26 million people worldwide.¹ Due to its high readmission rates, poor prognosis, increasing frequency with an aging population and the rising prevalence of lifestyle risk factors, HF has become a major challenge in developed countries.² In Asian countries, HF prevalence ranges from 1.3% to 6.7%.³ With its unique healthcare system, China faces a comparable HF prevalence rate of 1.2%–2.2%.^4–7 The economic burden is significant, with 70–80% of HF treatment costs in wealthy nations borne by healthcare systems.⁸ In China, the average cost per capita for inpatients with HF is $4406, and 40.5% of inpatients require three hospitalisations.⁷

Despite advancements in medical tools and medications, HF management remains challenging for healthcare professionals. Among the various strategies, transitional care interventions are the most innovative programmes aimed at improving continuity of care from admission to post-discharge.^9,10 Transitional care refers to the steps taken during clinical interactions to ensure coordination and continuity of treatment for patients transitioning between facilities or care levels. However, inadequate planning, insufficient patient/family education and fragmented access to essential services contribute to disparities in the hospital-to-home transition.^11,12 These disparities are often exacerbated by limited financial resources, insurance coverage and social support.

In the transition stage from hospital to home following discharge for patients with HF, the coordination of subsequent care is crucial. This is closely related to the compliance challenges faced by patients in various aspects, such as medication treatment, diet control, exercise adherence and psychosocial adaptation. Such patients generally need to visit the emergency department more frequently and be hospitalised multiple times and for longer periods, and these situations often interact with and reinforce each other in relation to the above-mentioned compliance issues. It is worth noting that 50% of patients with HF will be readmitted within 1 year after discharge, and 20% of patients will even experience two or more readmissions. In-depth analysis of the reasons for readmission reveals that, in addition to symptom deterioration and disease progression, self-care compliance problems – such as poor medication adherence (eg missed or incorrect dosing), lax diet management (eg excessive sodium intake) and interrupted exercise plans – as well as psychosocial factors such as anxiety, depression or insufficient social support, and patients’ lack of awareness of when and how to seek help from medical staff are all important contributing factors. Imperfect discharge planning will further exacerbate these compliance problems, thereby causing pain and anxiety for patients.¹³ This will increase the risk of adverse events and medication errors, leading to a continuous decline in treatment compliance, including medication, diet and exercise, and ultimately reducing the quality of life of patients.¹⁴ Therefore, to achieve a smooth transition from hospital to home, it is necessary to specifically address the practical difficulties of patients with HF in aspects such as medication treatment norms, diet structure adjustment and exercise plan implementation while paying attention to their psychological and mental needs. Practice has shown that transitional care plans can effectively improve the quality of life of patients and reduce the readmission and all-cause mortality rates following hospitalisation of patients with HF by optimising the intervention measures related to the above aspects.⁹

The transition period is a critical phase in HF management, requiring collaboration among individuals with diverse backgrounds, experiences and abilities. While transitional nursing models have improved overseas, research in China remains fragmented, with no unified descriptions or conclusions.¹⁵ In China, hospital-to-home transitional care typically includes pre-discharge oral health education, post-discharge telephone follow-up and home visits by family physicians and transition nurses upon request. However, the lack of a unified implementation plan, evaluation standards and training for key personnel has resulted in significant variations and disparate research outcomes. Transitional care strategies are influenced by medical resources and cultural differences, necessitating localised policy formulation combined with standardisation. Prior research has not adequately described how Chinese patients with HF perceive care transitions. Understanding patients’ experiences and perceptions is essential to identifying gaps and optimising the transition process, ultimately improving patients’ quality of life.

This study examines the difficulties and obstacles patients with HF face during the transition to self-care, exploring their needs and challenges to inform the development of targeted health interventions.

Methods

This qualitative study employed a phenomenological approach to explore the transitional care experiences of patients with HF in China. The study was conducted between June 2023 and October 2023 at a tertiary hospital’s cardiology department.

Participants were recruited using purposive sampling to ensure diversity in age, gender and urban/rural residence. The inclusion criteria included (1) confirmed diagnosis of HF (NYHA Class II–IV); (2) discharged from the hospital within the past 3 months; and (3) ability to communicate in Mandarin. The exclusion criteria included severe cognitive impairment or terminal illness. Based on the method of “theoretical saturation”, we continuously recruited volunteers before thematic saturation was reached. When we interviewed the 15th and 16th volunteers, we found that the difficulties, ideas and needs mentioned by the newly arrived patients were essentially the same as those of the previous patients, and no new information was introduced. The final sample, therefore, comprised 18 participants.

Data were collected through semi-structured, face-to-face interviews conducted in a private hospital room. The interview guide was developed based on a literature review and pilot-tested with three patients with HF (not included in the final sample). Key topics included challenges during the hospital-to-home transition, self-care practices and knowledge gaps, and perceived support needs and barriers. The interviews lasted 30–60 minutes and were audio-recorded and transcribed verbatim within 48 hours. Field notes were taken to capture non-verbal cues and contextual details.

Transcripts were analysed using Braun and Clarke’s six-step thematic analysis framework. The process began with familiarisation through repeated reading of transcripts to identify initial patterns. Initial coding was performed line-by-line using NVivo 12 software, followed by grouping codes into potential themes based on shared meaning. Themes were refined through iterative discussions among the research team, clearly defined and named, and finally used to select illustrative quotes and draft the results.

To ensure methodological rigor, several strategies were employed. Two researchers independently coded 20% of the transcripts, achieving a kappa value of 0.82, indicating excellent inter-coder agreement. Discrepancies were resolved through discussion and consensus. Preliminary findings were shared with five participants for member checking to confirm accuracy and relevance. Data were cross-verified with field notes and hospital discharge records for triangulation. The research team maintained a reflective journal to document biases and assumptions throughout the study.

Most of the patients were taking diuretics. Some patients with other comorbidities were also taking other medications, such as antihypertensive drugs and antidiabetic drugs. All patients were treated and cared for in the same hospital ward, meaning they received the same care. No complications occurred during hospitalisation. There was no follow-up intervention following discharge.

The study was approved by the hospital’s ethics committee. Written informed consent was obtained from all participants, who were assured of confidentiality and the right to withdraw at any time.

Results

Through qualitative analysis, three themes were identified: 1) challenges faced (seeing in Table 1); 2) deficits in self-care during the transition (seeing in Table 2); and 3) the desire for help and support (seeing in Table 3).

Table 1 Post Admission Challenges

Table 2 Dilemma in Self-Care During the Transition

Table 3 Lack of Understanding Regarding Medication Regimen

Challenges Faced

Transition Difficulties

When participants discussed the impact of HF on their lives, most stated that the disease resulted in additional tasks. At the same time, significant changes emerged, both emotionally and in daily life. The sudden transition from hospital to home led to a certain amount of stress:

Actually, I didn’t exactly know about HF, I only had a cold before. After I got HF and had the symptoms, I didn’t know how to take care of myself. I really didn’t know this disease. I have no idea how to treat it. (P15)

I don’t know this disease as well. I sometimes have the impression of not being able to place the exact location of the discomfort in my body. I live in a rural area where there are few medical resources. I must go to the city to see the doctor. It’s really inconvenient for me. (P7)

Some of those interviewed stated that these new changes included the body’s current state and whether they could cope with self-care challenges. The transition from being healthy to being seriously ill had a substantial psychological impact on them:

When I got this disease, I felt really tired after I did the cleaning at home. I really hate that, it made me feel I’m useless. (P10)

Even though I did the treatment and felt better, it still cannot be compared with before. That made me feel like I’m no longer a normal person. (P4)

Overall, HF was a disease that sapped their energy. Some participants stated that they could formerly accomplish everything but now carefully manage their time and energy usage. They complete various activities with lower physical fitness, meaning the time spent with family and friends is shortened. Due to their diseases, the participants had to slow down their pace of life to adapt to new life situations:

Before, I could take a walk or dance after I finished dinner, but now these activities make me feel tired. Like before I could walk for around half an hour or an hour, now when I walk around 20 steps or less, I need to have a break and take a breath. You know… Like if you cannot walk for a long time, how do you expect you can dance like before? (P10)

After I got this disease, to be honest, I cannot walk too far away, my leg muscles became weaker than before, and they cannot support me for a longer time to do the labour on the farm. So, I have to give up my career due to that reason. (P3)

I used to be able to plant 20 acres of land by myself, but now I can’t do it anymore. Now my wife is farming. The main reason for the decrease in activity is my physical problems. (P14)

Some patients also described the hospital as a safe environment for them. Following transition, they were often unprepared for the sudden change in environment and felt insecure and overwhelmed. At home, patients engaged in self-care without supervision and managed their health status, creating anxiety and stress. Self-monitoring, especially while the patient is on medication, brings a certain amount of stress:

The main problem is my blood sugar level and blood pressure are hard to control. Also, every time I went to the hospital, the different doctors gave me different suggestions about how to use the medicines. It makes me feel confused. (P6)

Maybe… I will encounter more problems when I return to my work. The workplace is unlike home, where I can eat regularly and healthily. There may not be a canteen in the workplace, so I must go out to eat every day. I’d like to know how my blood sugar will fluctuate if my diet changes. (P5)

Monitoring New Body Signals

Several participants reported that after receiving a diagnosis of HF, they gained a deeper understanding of their bodies through treatment and daily self-care. Monitoring changes in the body becomes a new daily duty for patients. Some participants responded negatively and were unaware of the significance of the process, stating that they would only be monitored and treated when they were ill or exhibited symptoms:

I don’t monitor my blood pressure regularly. I only measure it when I feel uncomfortable (P1)

As for my intake and output, I generally don’t drink water when I’m not thirsty, and I will drink some water if I’m sweating in hot weather. I will take two pills if I feel uncomfortable and have chest tightness. (P14)

I care about only my heart rate and blood pressure. [I] measure [blood pressure] whenever I feel sick. (P2)

Some participants also stated that they will now actively monitor their body indicators regularly, and actively pay attention to their health:

I measure [blood pressure] four times daily and take a notebook to write down the number because it’s hard to remember all the data. Usually, the blood pressure is highest in the morning of the day. Moreover, I pay more attention to my input and output. For example, if I drink three cups of water all day, I know how much I can excrete. The doctor told me I must excrete as much water as I drink. So… I usually pay more attention to my intake and output. (P11)

Negative Social Status

Most participants had a negative attitude toward socialising, with HF having negatively affected their social and communication skills. Physical fatigue means they are unable to actively participate in family and friends’ gatherings as previously. The disease-related restrictions on living habits and diet also make them avoid certain occasions, meaning they spend more time at home:

I didn’t have any concerns before I got sick, but now I don’t go out frequently. I don’t go to drinking and smoking occasions anymore. (P9)

Before I got sick, I loved going out and spent most of my time outside. Now I feel tired physically, and there are fewer entertainment activities like going out. When I am at home, I like to be alone. (P5)

Some participants also mentioned social avoidance, preferring to close themselves off and resist communicating with others. The sense of inferiority and stigma brought about by the disease makes them eager to escape from their previous social circle and prefer being alone:

I used to be very social, but now I don’t like to talk. This is a big change… I don’t seem to be talkative anymore. (P4)

From the bottom of my heart, I don’t wanna go out or meet other people. It’s just annoying for me. (P14)

[I] go out less, and I prefer to stay by myself. Communication with others is less, and I also don’t want to join parties or other activities. (P7)

Coping with the Challenges

Some participants stated that the disease has allowed them to re-understand themselves, motivated them to change themselves, abandon some of their past bad living habits and better understand the importance of correct health concepts for their physical health:

I didn’t care about my body’s health before, but now I feel that my health is the most important thing. I didn’t have much motivation to quit smoking and drinking before. This time, I must quit immediately. Health is the most important, right? I have a better sense of health. (P9)

Although the participants faced the daily challenges of a HF diagnosis, they were dealing with their health issues. Although some patients had experienced the pain of the disease, they were still full of confidence and hope for the future:

As long as I am in good health, I can also take care of myself, and I can work again… I hope to work again. If I get better, I will still dance. (P15)

Deficits in Self-Care During the Transition

Lack of Knowledge and Education

During the interviews, most participants expressed a lack of knowledge and education about the disease, especially those who had been ill for a short period and often did not understand their condition. They did not know how to care for themselves. Some patients even demonstrated a negative and indifferent attitude, with some not understanding their current state of illness, not wanting to learn about the disease and not caring about treatment options and self-care:

I think I’m OK, I don’t need help… and I don’t wanna know the disease and what to do for follow-up appointments. (P12)

However, most patients are concerned about their bodies and are eager to understand and have this knowledge. After returning home from the hospital without professional care, learning more about HF and self-care priorities could help them better adjust to the transition and increase their confidence in self-care:

I don’t know anything about my disease. I would also like to learn [about it]… I know less about HF. (P3)

Medically, it would be wonderful to give me some information, like how to rest well and protect my body. I don’t know much about diseases. (P15)

Furthermore, participants stated that they typically used the internet to learn about related knowledge. The information on the internet is mixed; some may lack rigor or be published without any scientific basis. Patients are attempting to care for themselves after being discharged from the hospital without professional supervision. This lack of systematic and proper understanding may raise the patient’s psychological burden and have negative consequences:

The educational video… sometimes this video may cause some bad effect because there is good and bad content on the network. And I don’t know what video is suitable for me… [to] watch these contents instead has some side effects, like increasing the psychological burden. (P4)

Self-Medicating

Taking medication correctly is one of the most critical self-care tasks for Chinese patients following discharge. Many patients are often overwhelmed by abnormal conditions without complete transition care. Without the guidance of a medical professional, patients are often confused about how to administer their medications, with most wanting hospitals to provide professional assistance with medication administration:

I want to discuss issues related to my condition with a professional. For example, should I be taking a dose of the drug? (P2)

Which medications need to be adjusted? Who can I talk to about my problems? I hope to call or send a message to ask. It is more convenient to contact them through the internet, like medication guidance. (P1)

Some patients also expressed a desire for help from a specialised doctor or professional. Patients may have residences and hospitals in different cities and seek nearby medical resources when health abnormalities arise. They may receive different advice and medication regimens when visiting different hospitals and doctors. In such cases, patients often do not know whom to listen to, leading to anxiety and feeling overwhelmed:

I don’t know what I should sometimes do. Different hospitals’ doctors give different prescriptions, and I’m confused as to whom to listen to… whether there is a uniform standard. (P6)

The Desire for Help and Support

Support from Caregivers

Twelve of the 15 participants reported receiving varying degrees of care from their caregivers. Heart failure affected their physical health and made it difficult for them to participate in heavy work or daily activities. In this situation, they could not move alone or do without the help of a caregiver, meaning the caregiver has a significant role for them. The demographic characteristics of these participants, including age, gender and education, are summarised in Table 4.

I need someone to take care of me. I [can] hardly take care of myself. (P10)

My children take care of me, doing my laundry and cooking. (P4)

My mother and my husband are my caregivers. They care for my daily life, and I depend on them. (P12)

Table 4 Demographic Profile of HF Patients

Caregivers assisted in the participants’ self-care in addition to their daily routines. The patients were physically and mentally dependent on their caregivers:

I bought a blood pressure monitor, and my son helped me to measure my blood pressure. I can’t do it by myself. (P15)

In addition to taking care of the daily life of the participants, some caregivers of the participants also have to undertake the nursing tasks of the participants. They were reluctant to become more involved in self-care and were not even aware of their condition or the medications they were taking. Some patients defer to their caregivers for their daily food and medications:

[I] take my medication on time, but I don’t understand how each medication affects. My daughter knows, I listen to my daughter anyway. (P12)

Medication is on time. Then my family members are directly assigned the medication before giving it to me. (P4)

Usually, my family members remind me to take my medication, and there is no need to remember what medication to take by myself. I don’t care about the therapeutic effects of each drug. (P10)

The Need for Hospital Assistance

Most participants indicated that they often had many problems and disturbances in their daily life during the transition period due to their illness, and the lack of professional knowledge in coping left them feeling overwhelmed. Therefore, some participants wanted more support and help from the hospital, as well as professional guidance to help them transition smoothly from hospital to home and increase their self-care skills:

I think it’s better to talk with doctors about my problems face to face. I would like to learn more about my disease. (P15)

For example, why is my pulse suddenly low? What is causing my high blood pressure? How to deal with low blood pressure? Anyway, I hope the doctor can explain all of this, and I can take better care of myself after the explanation. I want to know what to do if I encounter different symptoms or situations. (P11)

Some participants indicated that the doctor who treated them in the hospital was the professional they trusted the most. They were also eager for their doctor to provide them with regular help and support long after they were discharged from the hospital:

It just feels like I want to go to a professional to talk about these things. Like, what to do if my heart rate is high? Should I increase or decrease the dosage of my medication? I want long-term regular professional guidance for my disease. I hope the hospital will take the initiative to provide a follow-up consultation. (P2)

Anyway, I will ask the attending doctor when I feel uncomfortable I must go to the hospital if I feel unwell. (P11)

Social and Government Support

Some participants mentioned the lack of caregiving staff when they described their difficulties during the transition. With the care of doctors and nurses during hospitalisation, family members were less involved. However, the caregiving responsibility shifts to family members after the patient returns home. Most patients need the assistance of caregivers, but caregivers have multiple identities and jobs simultaneously, meaning they are sometimes overwhelmed when it comes to caring for patients. Patients, therefore, prefer to have a community or other support to assist with self-directed daily caregiving:

The problem I am facing now is that there are not enough people to care for me. I have a son and a daughter-in-law, but they also need to care for two children. If I am hospitalised, my son and daughter-in-law will take care of me, and there will be no one to take care of the children. And I don’t have enough money to hire someone to care for me. (P10)

In addition to the lack of manpower, some families also have financial problems. Due to the disease, patients often lose their ability to work, and the cost of treatment and medication can be a significant expense for families. Some rural families in China have low total household income, which is further compounded when a family member loses the ability to work. Some participants are eager for support and help from government policies to ease their financial stress:

Medical bills are a bit unaffordable because the cost is so high. I wonder if I could apply for the serious illness subsidy in the community. I was wondering if it is possible to have something like this, and then I can apply it. (P10)

Now I can no longer farm. I’m a farmer, and no one can help me farm my land. Moreover, the subsidy given to me by the government is insufficient, and I have some financial difficulties. (P13)

Lack of Patient Education

We found that the so-called “patient education” (See Supplementary 1) often manifests itself in practice as a guidance sheet that is information-overloaded, full of jargon and requires patients to make complex self-judgments. Most of the interviewees said that they felt confused, anxious, and helpless to varying degrees after receiving such a single-page guidance.

Medication Adherence

Analysis revealed that the discharge guidance requires patients to “gradually increase the dosage” or “slowly reduce the dosage and discontinue” multiple medications according to their blood pressure and symptoms (as shown in P1 and P2). Such complex self-regulation requirements far exceed the capabilities of ordinary elderly patients, leading them to either not dare to make adjustments or make incorrect ones, resulting in anxiety and non-compliance. This explains why some interviewees stated that “I don’t know whom to listen to” and “I want to ask a professional”.

Diet and Lifestyle Modification

The analysis indicated that the suggestion of a “low salt and low fat” diet on the guidance sheet is too general and lacks specific and feasible operation guidelines. For example, no specific recommended daily salt intake or examples of food options are provided. This can result in the patient feeling at a loss when having to consume three meals a day after returning home. This explains why some interviewees were concerned about “what will happen when eating out” and “not knowing what to eat”.

Follow-Up Plan

Analysis revealed that the patient was required to coordinate follow-ups from multiple departments on their own and remember the re-examination items at different time points over a period of 1 year (as shown in P 2). This fragmented follow-up model imposes a heavy coordination and memory burden on patients and their families. This explains why patients want “hospitals to proactively offer follow-up consultations” and believe that “it would be great if there were someone to take care of me uniformly”.

Discussion

The aim of this qualitative phenomenological study was to investigate the lived experiences of patients with HF during the transition from hospital to home. By exploring the challenges, self-care deficits and support needs of these patients, this study provides valuable insights into the complexities of transitional care in China. The findings highlight the critical need for culturally sensitive interventions and systemic improvements to address the unique challenges faced by patients with HF.

Coping Strategies and Cultural Context

The participants in this study demonstrated diverse coping strategies in response to their HF diagnosis and the challenges of transitional care. While some patients exhibited avoidance behaviours, such as denying the significance of symptoms, these responses may reflect culturally influenced coping mechanisms rather than purely negative behaviours. In Chinese culture, patients often adopt an endurance strategy, which can be misinterpreted as avoidance but is rooted in cultural norms of resilience and self-reliance.¹⁶ This finding aligns with recent studies highlighting the importance of cultural context in understanding patient behaviours.¹⁷ For example, one study found that patients with chronic illnesses often prioritise maintaining harmony within their families over expressing personal distress, leading to similar coping behaviours.¹⁸ However, prolonged reliance on such strategies can delay symptom management and exacerbate emotional distress, underscoring the need for culturally tailored psychological support. Interventions that incorporate culturally adapted cognitive-behavioral therapy have shown promise in addressing these issues.¹⁹

Communication and Care Coordination

The study revealed significant communication breakdowns between healthcare providers and patients, contributing to confusion in self-care and medication management. While systemic issues, such as fragmented care and limited provider continuity, are primary contributors, individual factors also play a role. For example, patients’ health literacy levels and cognitive impairments can hinder effective communication.²⁰ Recent research emphasises the role of health literacy interventions in improving patient–provider communication and reducing medication errors.²¹ Similar findings have been reported in other low- and middle-income countries, where limited healthcare resources exacerbate communication challenges.²² Addressing these gaps requires a dual approach: systemic reforms to enhance care coordination and targeted interventions to empower patients with the knowledge and skills needed for self-care. For example, a study in South Korea demonstrated that structured discharge education programmes significantly reduced readmission rates among patients with HF.²³

Multidimensional Support Needs

The participants emphasised the importance of diversified support systems, including caregivers, healthcare providers and social resources. The caregiver–patient relationship, particularly in the Chinese context, is crucial but often underutilised. Recent studies have shown that caregiver training programmes can significantly improve patient outcomes by enhancing caregiver competence and reducing caregiver burden.²⁴ This is consistent with findings from Australia, where caregiver support interventions have been linked to improved patient self-care and reduced hospitalisations.²⁵ Additionally, the study highlights the need for integrated care models that bridge the gap between hospital and home, such as nurse-led transitional care programmes and community-based support networks. Similar models have been successfully implemented in Europe, where nurse-led HF clinics have been associated with reduced mortality and improved quality of life.²⁶

Study Limitations

This study has several limitations. First, the small sample size (n=18) and recruitment from a single tertiary hospital may limit the generalisability of the findings. Second, the lack of diversity in the sample, particularly the underrepresentation of rural patients, restricts the applicability of the results to broader populations. Third, reliance on self-reported data may introduce recall bias, and the absence of longitudinal follow-up limits our understanding of long-term transitional care outcomes. Future studies should aim for larger, more diverse samples and incorporate mixed-methods approaches to address these limitations. Finally, this study focuses on the common difficulties that patients will encounter psychologically and in daily life after being informed that they have HF, as well as during the process of returning home from the hospital. The study does not conduct separate research according to the types of HF. Future research could focus on whether there are differences in the difficulties experienced by patients with different forms of HF during the transition period and explore practical and feasible solutions to these problems.

Implications for Research, Practice and Policy

The findings of this study have important implications for improving transitional care for patients with HF in China. First, culturally sensitive interventions should be developed to address the unique coping strategies of Chinese patients. Second, systemic reforms, such as standardised discharge protocols and enhanced care coordination, are needed to reduce communication breakdowns and medication errors. Third, caregiver training programmes and community-based support networks should be prioritised to provide holistic support for patients and their families. Finally, future research should explore the long-term impact of transitional care interventions on patient outcomes, particularly in rural and underserved populations. These efforts should be informed by successful models from other countries, such as the UK’s integrated care pathways and Australia’s nurse-led HF management programmes.^27,28

To better operationalise these recommendations, based on the research findings concerning self-care in patients with HF transitioning from the hospital to their homes, we formulated a theoretical framework (for details, refer to Supplementary 2) to simulate the predicaments faced by patients with HF and the coping mechanisms used during the transition period. We also summarised the transitional care process for patients with HF in terms of three primary themes (see Figure 1): the post-admission challenges they face; the dilemmas in self-care during the transition; and the desire for help and support. Each theme encompasses several sub-themes that collectively highlight the emotional, physical and social complexities involved in managing HF. This condensed structure provides a succinct yet profound understanding of the participants’ experiences and the universal aspects of their transitional care journey.

Figure 1 Simulacrum of the hospital to home: The labyrinth of transition in the care of heart failure (HF) patients.

Conclusion

This study identifies three core findings regarding the transitional care experiences of Chinese patients with HF: significant post-discharge challenges (eg difficult adaptation, physical limitations and social withdrawal), critical self-care deficits (eg inadequate disease knowledge and confusion over medication management); and urgent unmet support needs (encompassing family caregiving reliance, sustained professional guidance and social/government assistance). These findings highlight the uniqueness of China’s context: rural–urban disparities exacerbate access barriers; fragmented healthcare systems hinder consistent care coordination; and over-reliance on family caregivers – shaped by cultural norms – burdens both patients and their families. To address these issues, targeted interventions are needed, including standardised discharge protocols with rural-specific adjustments, hospital-led telehealth platforms for credible health information and medication guidance, caregiver training programmes and expanded government subsidies for medical costs and community-based support services. Future research should explore multi-centre implementations of these strategies to validate their effectiveness across diverse populations, ultimately improving transitional care quality and patient outcomes in China.

Data Sharing Statement

All data generated or analyzed during this study are included in this published article.

Ethics Approval and Consent to Participate

This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of School of Nursing and Health, Henan University. Written informed consent was obtained from all participants, and participant informed consent included the publication of anonymous responses/direct quotes.

Consent for Publication

The manuscript is not submitted for publication or consideration elsewhere.

Acknowledgments

This dissertation was completed with the invaluable assistance of many individuals and organizations. I extend my deepest gratitude to the President, Vice President, Nursing Director, Nursing Supervisor, Chief Nurse, and staff at my hospital employer in China for their unwavering support. I am particularly grateful to Dr. Sheilla M. Trajera for her guidance and support during the dissertation process. My heartfelt thanks also go to the panelists, Dr. Toni-An B. Lachica and F. Lachica. Lastly, I thank my spouse Ma Hongjun, my parents, and my children, Ma Haosen and Ma Ruoyu, for their unwavering love and encouragement.

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

An empirical study on the construction and health management of digital virtual wards for elderly patients with heart failure in rural areas under the perspective of rural revitalization(26B330001).

Disclosure

The authors declare that they have no competing interests in this work.

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Cancer research often reveals unexpected ways to fight disease by rethinking the cell’s environment. A new approach from the University of Cambridge suggests halting glioblastoma, the deadliest brain cancer, by freezing the very molecules that enable its spread.

Instead of killing cells outright, this strategy changes the conditions around them, turning aggressive invaders into quiet neighbors.

Glioblastoma is the most common brain cancer and one of the hardest to treat. Patients often survive less than 15 months after diagnosis, with only 15 percent living beyond five years. Surgery and radiotherapy can slow progress but rarely prevent recurrence.

Cancer cells left behind infiltrate healthy brain tissue, spreading silently through microscopic channels. Current drugs also struggle to penetrate the dense tumor mass, leaving few effective options.

Cancer uses hyaluronic acid

At the heart of this discovery is hyaluronic acid (HA), a sugar-like polymer that shapes much of the brain’s supporting structure.

Cancer cells rely on HA’s flexibility to latch onto surface receptors, especially CD44, which drives their movement. By chemically locking HA in place, scientists stripped away its flexibility. This effectively reprogrammed glioblastoma cells into dormancy, preventing them from invading new tissue.

Study co-author Melinda Duer is a professor in the Yusuf Hamied Department of Chemistry at the University of Cambridge.

“Fundamentally, hyaluronic acid molecules need to be flexible to bind to cancer cell receptors,” said Professor Duer.

“If you can stop hyaluronic acid being flexible, you can stop cancer cells from spreading. The remarkable thing is that we didn’t have to kill the cells – we simply changed their environment, and they gave up trying to escape and invade neighbouring tissue.”

Freezing flexibility stops cancer

The Cambridge study confirmed that HA’s behavior is not just about molecular size but about motion. High-molecular-weight HA, usually linked with healthy tissue, can still promote cancer invasion when diluted.

At lower concentrations, HA molecules move freely, adopting shapes that fit tightly into CD44 binding sites. This triggers powerful invasion signals.

At higher concentrations, HA molecules entangle with each other, limiting flexibility and dampening those signals.

Molecular motion and signals

Nuclear magnetic resonance spectroscopy revealed that HA’s ability to twist into specific conformations within nanoseconds determines whether it binds strongly to CD44.

When flexible, HA activates pathways that push cells to migrate. When immobilized, HA blocks these signals.

This explains why swelling in the brain after surgery, which dilutes HA, can encourage cancer to return at the surgical site.

Protein responses to hyaluronic acid

Proteomic analysis of glioblastoma cells highlighted how HA concentration reshapes their internal machinery.

In flexible environments, cells developed star-shaped structures and invasive protrusions, supported by actin-bundling proteins and enzymes that degrade tissue.

In stiffer environments, those invasive proteins disappeared. Instead, cells activated survival pathways, entered a dormant state, and upregulated proteins linked to quiescence, including Notch-2.

This switch showed how extracellular conditions can push cancer cells either into attack mode or into stillness.

Freezing molecules stops cancer

Researchers tested this idea further by creating a chemically modified HA that crosslinks tightly into the extracellular matrix. This version lost flexibility and, when added to cell cultures, completely stopped invasion.

Cells responded in the same way as in dense HA conditions, showing altered protein expression and increased dormancy signals. This provided strong evidence that flexibility itself, not size, is the decisive factor in driving cancer spread.

The findings give a new explanation for glioblastoma’s notorious tendency to regrow after surgery. Fluid build-up, or oedema, dilutes HA at the surgical site, making it more flexible and more capable of binding CD44.

This diluted environment inadvertently encourages cancer cells to invade again. By freezing HA in place, scientists hope to counteract this effect and stop recurrence before it starts.

Freezing may help treat cancer

“This could be a real opportunity to slow glioblastoma progression,” said Duer. “And because our approach doesn’t require drugs to enter every single cancer cell, it could in principle work for many solid tumours where the surrounding matrix drives invasion.

“Cancer cells behave the way they do in part because of their environment. If you change their environment, you can change the cells.”

The work now moves into animal testing before any patient trials. Still, the implications extend beyond brain cancer. Many tumors rely on signals from their surrounding environment to spread.

By targeting flexibility in key molecules like HA, researchers may uncover a new class of treatments that turn cancer’s supportive scaffolding into a trap. Instead of chasing runaway cells, this method locks the very ground beneath them.

The study is published in the journal Royal Society Open Science.

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• New research suggests not all plant-based diets are healthy.
• Some plant-based diets may be bad for heart health.
• Experts suggest focusing on certain elements when eating a plant-based diet.

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Many medical organizations recommend following a plant-forward diet, but new research points out that all plant-based foods are not created equal. In fact, some may even be bad for your heart health.

The study, which was published in the American Journal of Preventive Cardiology, found a clear link between eating an unhealthy plant-based diet and a key biomarker linked to having a heart attack. For the study, researchers analyzed data from more than 7,700 people who participated in the 1999-2004 National Health and Nutrition Examination Survey (NHANES). (Yes, that’s data from more than 20 years ago—but experts say the findings still apply.) All of the participants were at least 20 years old and had no history of heart disease at the start of the study.

During the study period, the participants reported what they ate over a 24-hour period and gave blood samples to allow the researchers to look for biomarkers of heart disease. The researchers discovered that people who followed a healthy plant-based diet had a 49% lower risk of having higher levels of cardiac troponin I. (Cardiac troponin I is a sign of cardiac muscle damage and is linked to heart attack risk.)

Meet the experts: Scott Keatley, R.D., is co-owner of Keatley Medical Nutrition Therapy; Hosam Hmoud, M.D., cardiology fellow at Northwell’s Lenox Hill Hospital; Dena Champion, R.D., a dietitian at The Ohio State University Wexner Medical Center; Jennifer Wong, M.D., a cardiologist and medical director of Non-Invasive Cardiology at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA.

But people who followed an unhealthy plant-based diet had a 65% higher risk of having elevated levels of cardiac troponin I, meaning they had a greater heart attack risk. “Supporting access to and adoption of healthy plant-based diets may be a useful strategy for promoting population-level cardiovascular health,” the researchers wrote in the conclusion.

The study raises a lot of questions about what qualifies as a “healthy” or “unhealthy” plant-based diet, plus the potential impact on your heart. Here’s what cardiologists and dietitians want you to know.

Why are certain plant-based foods bad for your heart?

It’s easy to confuse “plant-based” with “healthy,” but they’re not the same thing, points out Dena Champion, R.D., a dietitian at The Ohio State University Wexner Medical Center. “The term ‘plant-based’ lacks a universal definition, which creates confusion for consumers,” she says. “Many food manufacturers and restaurants use ‘plant-based’ simply to indicate their products contain no animal ingredients.”

Having a lack of animal products doesn’t automatically make a food healthy, Champion points out. Scott Keatley, R.D., co-owner of Keatley Medical Nutrition Therapy, agrees. “Not all plant-based foods are created equal,” he says. “A diet heavy in refined grains, fried foods, sugary beverages, and ultra-processed snacks may technically be ‘plant-based,’ but it lacks the protective compounds that whole fruits, vegetables, legumes, and intact grains provide.”

These unhealthy plant foods can spike your blood sugar, contribute to bodily inflammation, contain trans fats, and deliver excess calories without important nutrients, raising the risk of heart disease and other health issues, Keatley says.

“It’s important to point out that a vegan or vegetarian diet can absolutely be a heart-healthy diet, but eliminating animal products alone does not make a diet healthy,” Champion says.

How to tell when plant-based foods are unhealthy

There are a few different ways to tell if a plant-based food is unhealthy, according to Keatley: the level of processing and the amount of sodium and additives.

“The further a food is from its natural state, the more likely it has lost beneficial nutrients while gaining added sugars, unhealthy fats, or refined starches,” Keatley explains. “Packaged plant-based meals, snacks, or meat alternatives often carry sodium levels comparable to processed meats and may include stabilizers and oils that don’t support cardiovascular health.”

Champion also recommends being on the lookout for higher amounts of saturated fat, and making sure to read the nutrition label carefully. “The label ‘plant-based’ does not necessarily indicate anything about the healthiness of a food,” she stresses.

How to follow a heart-healthy diet

In general, whole foods—not packaged products—are best for your heart health, according to Jennifer Wong, M.D., a cardiologist and medical director of Non-Invasive Cardiology at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA. “I recommend the DASH Diet,” she says. “It’s low in salt, high in fruits and vegetables, whole grains, and legumes. It focuses on healthier fats like olive oil and avocado rather than animal fats.”

But the Mediterranean diet is also helpful for heart health, says Hosam Hmoud, M.D., cardiology fellow at Northwell’s Lenox Hill Hospital. “I encourage all of my patients to follow a Mediterranean-style diet which consists of whole grains, legumes, fruits, vegetables, and lean meats,” he says.

Ultimately, Keatley suggests filling your plate with whole foods first and building out your diet from there. “Most people already consume a plant-based diet if you look closely—grains, fruits, vegetables, and even snack foods all come from plants,” he points out. “The real distinction isn’t whether something is plant-based or not, but whether it’s minimally processed and nutrient-dense.”

C. elegans strains

C. elegans strains were cultured at 20 °C on standard Nematode Growth Medium seeded with OP50 Escherichia coli⁷⁰. On day 1 of adulthood, worms were transferred to plates containing OP50 E. coli (or HT115 E. coli for RNAi experiments) supplemented with 100 μg ml⁻¹ 5-fluoro-2′-deoxyuridine to prevent progeny development, except in lifespan assays. All experiments were conducted using hermaphrodite worms, and the age of the worms is indicated in the corresponding figures and figure legends.

WT (N2) and AM141 (rmIs133[unc-54p::Q40::YFP]) strains were obtained from the Caenorhabditis Genetics Center (CGC), supported by the National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440). RB751 (eps-8(ok539)) was generated by the C. elegans Gene Knockout Consortium and acquired from the CGC. AM23 (rmIs298[F25B3.3p::Q19::CFP]) and AM716 (rmIs284[F25B3.3p::Q67::YFP]) strains were gifted by Richard I. Morimoto²⁴. MAH602 (sqIs61[vha-6p::Q44::YFP + rol-6(su1006)]) was provided by Malene Hansen⁷¹. ZM5838 (hpIs223[rgef-1p::FUS^WT::GFP]), ZM5844 (hpIs233[rgef-1p::FUS^P525L::GFP]) and ZM5842 (hpIs228[rgef-1p::FUS^R522G::GFP]) were provided by Peter St. George-Hyslop⁴⁵. CK405(Psnb-1::TDP-43^WT,myo-2p::dsRED) and CK423 (Psnb-1::TDP-43^M337V,myo-2p::dsRED) were provided by Brian C. Kraemer³³.

From these strains, we generated NFB2862 (Psnb-1::TDP-43^WT,myo-2p::dsRED;juIs76[unc-25p::GFP + lin-15(+)]II) and NFB2863 (Psnb-1::TDP-43^M337V,myo-2p::dsRED;juIs76[unc-25p::GFP + lin-15(+)]II). NFB2858 (rmIs298[F25B3.3p::Q19::CFP];otIs549[unc-25p::unc-25(partial)::mChopti::unc-54 3′ untranslated region (UTR) + pha-1(+)];him-5(e1490)V), NFB2859 (rmIs284[F25B3.3p::Q67::YFP];otIs549[unc-25p::unc-25(partial)::mChopti::unc-54 3′ UTR + pha-1(+)];him-5(e1490)V), NFB2860 (hpIs223[rgef-1p::FUS^WT::GFP];otIs549[unc-25p::unc-25(partial)::mChopti::unc-54 3′ UTR + pha-1(+)];him-5(e1490)V) and NFB2861 (hpIs233[rgef-1p::FUS^P525L::GFP];otIs549[unc-25p::unc-25(partial)::mChopti::unc-54 3′ UTR + pha-1(+)];him-5(e1490)V) were generated by crossing the respective polyQ and FUS-expressing strains with the OH13526 strain⁷². For RNAi in the neurons of polyQ67 worms, we used the DVG196 strain (rmIs284[F25B3.3p::Q67::YFP];sid-1(pk3321)V;uIs69[pCFJ90(myo-2p::mCherry) + unc-119p::sid-1]).

Worms expressing endogenous WT EPS-8::3xHA (VDL05, eps-8(syb2901)IV) or mutant EPS-8(K524R/K583R/K621R::3×HA) (VDL06, eps-8(syb2901, syb3149)IV) were previously generated via CRISPR–Cas9 (ref. ¹⁴). The strains DVG344 (rmIs284[pF25B3.3::Q67::YFP]);eps-8(syb2901) and DVG363 (rmIs133[unc-54p::Q40::YFP]);eps-8(syb2901) were generated by crossing VDL05 with AM716 and AM141, respectively. DVG345 (rmIs284[pF25B3.3::Q67::YFP]);eps-8(syb2901, syb3149) and DVG364 (rmIs133[unc-54p::Q40::YFP]);eps-8(syb2901, syb3149) were generated by crossing VDL06 to AM716 and AM141, respectively. These strains were validated by sequencing using the following primers: eps-8(syb2901): 5′-TTTGTTCGAAGCATGAACGA-3′ and 5′-AGCAGCCCCTGAAATAGTGA-3′; eps-8(syb2901, syb3149): 5′-AACGAGCTAGCAATCCGAAA-3′ and 5′-AGTGCTCTGCCGTCATTAAT-3′. DVG365 (rmIs284[pF25B3.3::Q67::YFP];eps-8(ok539)) was generated by crossing RB751 to AM716. The strain was outcrossed two times to AM716 and validated by polymerase chain reaction with 5′-TCTCCACCACCACAACGTAA-3′ and 5′-GCGGAGCAACTCTTCCATAG-3′ primers.

RNAi constructs

Adult worms were fed HT115 E. coli carrying either an empty control vector (L4440) or vectors expressing double-stranded RNAi. The RNAi constructs targeting eps-8, ifb-2, jnk-1, kgb-1, mig-2 and otub-3 were obtained from the Vidal library. The csn-6, F07A11.4, math-33, rac-2, usp-4, usp-5 and usp-48 RNAi constructs were obtained from the Ahringer library. All RNAi constructs were sequence verified. The RNAi sequences are listed in Supplementary Table 2.

Lifespan assay

Larvae were synchronized using the egg-laying protocol and grown on OP50 E. coli at 20 °C until day 1 of adulthood. Adult hermaphrodites were then transferred to plates with HT115 E. coli carrying either an empty vector or RNAi constructs for lifespan assays. All lifespan assays were performed at 20 °C. Each condition included 96 worms, scored daily or every other day⁷³. Worms that were lost, burrowed into the medium, had a protruding vulva or underwent bagging were censored⁷³.

Nose touch assay

Age-synchronized worms were assessed for nose touch response as previously described^74,75,76. In brief, worms were placed on a thin bacterial lawn, and an eyelash pick was positioned in front of a forward-moving animal. A lack of response was recorded when the worm continued moving forward to crawl under or over the pick. For each condition, 30–40 animals were tested by monitoring the number of responses to a total of 10 gentle eyelash touches.

Chemotaxis assay

Freshly prepared agar plates (2% agar, 5 mM KPO₄ (pH 6.0), 1 mM CaCl₂, 1 mM MgSO₄) were divided into four equal quadrants, along with an inner circle measuring approximately 1 cm across diagonally. A test solution (0.5% benzaldehyde (Sigma-Aldrich, B1334) in ethanol + 0.25 M sodium azide) and a control solution (ethanol + 0.25 M sodium azide) were added to two opposing diagonal quadrants. On the indicated days of adulthood (as shown in the corresponding figures), worms were collected in S-Basal medium, washed three times to remove residual bacteria and placed at the center of the chemotaxis plate. The plates were sealed with parafilm and incubated at 20 °C for 90 minutes. The number of worms in each quadrant was counted, excluding those that did not cross the inner circle. The chemotaxis index was calculated using the following formula: chemotaxis index = ((number of animals in test quadrants) − (number of animals in control quadrants)) / total number of animals⁷⁷.

Motility assays

C. elegans were synchronized on OP50 E. coli using the egg-laying method and grown until day 1 of adulthood and then randomly transferred to plates with HT115 E. coli containing either empty vector or RNAi for the remainder of the experiment. For experiments with Ub-less EPS-8 mutants or DUB inhibitor treatment, worms were instead transferred to fresh plates containing OP50 E. coli. On the indicated day of adulthood (as shown in the corresponding figures), worms were randomly picked and transferred to a drop of M9 buffer, allowing 30 seconds for recovery²⁴. Body bends were then recorded for 30 seconds and analyzed using ImageJ software (version 1.53k) with the wrMTrck plugin (https://www.phage.dk/plugins/)^78,79. The locomotion velocity data were used to calculate body bends per second.

Microscopy

For imaging GABAergic neurons, fluorescent reporter worms were anesthetized with a drop of 0.5 M sodium azide (Sigma-Aldrich, 26628-22-8) on 4% agarose pads (diluted in distilled water) placed over a standard microscope glass slide (Rogo-Sampaic, 11854782). These preparations were sealed with 24 × 60-mm coverslips (RS France, BPD025). To score the number of GABAergic neurons and ventral nerve cord projections, we used a Zeiss Axio Imager.M2 microscope with a ×40 objective. Whole-body worm images were acquired using a Leica THUNDER Imager microscope with Tile Scan function and a ×40 objective.

Human cell lines

HEK293T/17 cells (American Type Culture Collection (ATCC), CRL-11268) were plated on 0.1% gelatin-coated plates and grown in DMEM (Thermo Fisher Scientific, 11966025), supplemented with 1% MEM non-essential amino acids (Thermo Fisher Scientific, 11140035), 1% GlutaMAX (Life Technologies, 35050038) and 10% FBS (Thermo Fisher Scientific, 10500064) at 37 °C with 5% CO₂. ALS-iPSCs (FUS^P525L/P525L) were kindly provided by Irene Bozzoni and Alessandro Rosa³⁷. iPSCs were cultured on Geltrex (Thermo Fisher Scientific, A1413302) using mTeSR1 medium (STEMCELL Technologies, 85850) at 37 °C with 5% CO₂. All cell lines were routinely tested for mycoplasma contamination, and no contamination was detected.

Motor neuron differentiation

Motor neurons were derived from ALS-iPSCs using a monolayer-based differentiation protocol⁸⁰. ALS-iPSCs were seeded on Geltrex-coated plates and maintained in mTeSR1 medium until confluent. Differentiation was initiated using neuron differentiation medium composed of DMEM/F12 and Neurobasal (1:1; Thermo Fisher Scientific, 11330057 and 21103049), supplemented with non-essential amino acids, GlutaMAX (Thermo Fisher Scientific, 35050038), B27 (Thermo Fisher Scientific, 12587010) and N2 (Thermo Fisher Scientific, 17502048).

From day 0 to day 6, the medium was further supplemented with 1 μM retinoic acid (Sigma-Aldrich, R2625), 1 μM smoothened agonist (SAG; Sigma-Aldrich, 566661), 0.1 μM LDN-193189 (Miltenyi Biotec, 130-103-925) and 10 μM SB-431542 (Miltenyi Biotec, 130-105-336). From day 7 to day 14, the neuron differentiation media were supplemented with 1 μM retinoic acid, 1 μM SAG, 4 μM SU-5402 (Sigma-Aldrich, SML0443) and 5 μM DAPT (Sigma-Aldrich, D5942). After day 14, differentiated motor neurons were dissociated and replated on poly-l-ornithine (Sigma-Aldrich, P3655) and laminin-coated (Thermo Fisher Scientific, 23017015) plates in Neurobasal medium, supplemented with non-essential amino acids, GlutaMAX, N2, B27 and neurotrophic factors (10 ng ml⁻¹ BDNF (BIOZOL, 450-02) and 10 ng ml⁻¹ GDNF (BIOZOL, 450-10)).

Lentiviral infection of human cells

Lentivirus (LV)-non-targeting short hairpin RNA (shRNA), LV-EPS8 shRNA 1 (TRCN0000061544), LV-EPS8 shRNA 2 (TRCN0000061545), LV-USP4 shRNA 1 (TRCN0000004039) and LV-USP4 shRNA 2 (TRCN0000004040) in the pLKO.1-puro backbone were obtained from Mission shRNA (Sigma-Aldrich). Supplementary Table 2 contains the target sequences of each shRNA construct.

To generate stable shRNA-expressing HEK293 cell lines, cells were transduced with 5 µl of concentrated lentivirus and selected with 2 µg ml⁻¹ puromycin (Thermo Fisher Scientific, A1113803). For lentiviral infection of iPSCs, cells were dissociated using Accutase (Thermo Fisher Scientific, A1110501), and 100,000 cells were seeded on Geltrex-coated plates in mTeSR1 medium supplemented with 10 μM ROCK inhibitor for 1 day. The next day, cells were infected with 5 µl of concentrated lentivirus. Medium was replaced the following day to remove residual virus. Selection for lentiviral integration was performed using 2 µg ml⁻¹ puromycin for 2 days.

Transfection of HEK293 cells

HEK293 cells (ATCC, CRL-11268) were seeded on 0.1% gelatin-coated plates. When cells reached approximately 40% confluency, they were transfected with 1 μg of one of the following plasmids using FuGENE HD (Promega), according to the manufacturer’s instructions: pARIS-mCherry-httQ23-GFP, pARIS-mCherry-httQ100-GFP, pLVX-Puro-TDP-43-WT, pLVX-Puro-TDP-43-A382T, pcDNA3.1-FUS-HA-WT or pcDNA3.1-FUS-HA-P525L. In the indicated experiments, cells were co-transfected with an additional 1 μg of the pCMV3-EPS8-HA plasmid. The cells were collected after 72 hours of incubation in standard medium. The pARIS-mCherry-httQ23-GFP and pARIS-mCherry-httQ100-GFP plasmids were generously provided by Frédéric Saudou⁸¹. The FUS-HA-WT and FUS-HA-P525L plasmids were a gift from Dorothee Dormann⁸². The pLVX-Puro-TDP-43-WT and pLVX-Puro-TDP-43-A382T plasmids were provided by Shawn Ferguson (Addgene, 133753 and 133756)⁸³. The pCMV3-EPS8-HA plasmid was obtained from Sino Biological (HG11153-CY).

Filter trap and western blot

For filter trap assays, synchronized adult C. elegans were collected and washed with M9 buffer, and worm pellets were snap frozen in liquid nitrogen. Frozen pellets were thawed on ice and lysed in non-denaturing buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 1 mM EDTA, 1% Triton X-100, 2 mM sodium orthovanadate, 1 mM PMSF, protease inhibitor cocktail (Roche)) using a Precellys 24 homogenizer. Lysates were cleared of worm debris by centrifugation (8,000g, 5 minutes, 4 °C), and protein concentrations were determined using the BCA assay (Thermo Fisher Scientific). To assess protein levels by western blot, 30 μg of total protein was separated by SDS-PAGE and transferred to polyvinylidene difluoride membranes (Millipore). To assess aggregated proteins by filter trap, 100 μg of total protein was supplemented with SDS to a final concentration of 0.5% and loaded onto a cellulose acetate membrane assembled in a slot-blot apparatus (Bio-Rad). Then, the membrane was washed with 0.2% SDS, and SDS-resistant aggregates were detected by immunoblotting.

If lysates were used solely for western blot, worms were lysed with a Precellys 24 homogenizer in buffer containing 50 mM Tris-HCl (pH 7.8), 150 mM NaCl, 1% Triton X-100, 0.25% sodium deoxycholate, 1 mM EDTA, 25 mM N-ethylmaleimide, 2 mM sodium orthovanadate, 1 mM PMSF and protease inhibitor cocktail. Lysates were cleared at 10,600g for 10 minutes at 4 °C, and 30 μg of protein was used for western blot experiments. For analysis of polyQ monomers and SDS-insoluble polyQ aggregates, age-synchronized worms were lysed by sonication in native buffer (50 mM Tris (pH 8), 150 mM NaCl, 5 mM EDTA, 1 mM PMSF, protease inhibitor cocktail). Then, 30 μg of total protein was mixed with SDS to a final concentration of 0.4% and resolved by 12.5% SDS-PAGE.

For both filter trap and western blot analyses of C. elegans, immunoblotting was performed with antibodies against GFP (AMSBIO, TP401, dilution 1:5,000), FUS (Abcam, ab154141, clone CL0190, 1:1,000) and TDP-43 (Abcam, ab225710, 1:1,000). Additionally, for western blot experiments, immunoblotting was conducted with anti-EPS8L2 (Abcam, ab85960, 1:1,000), anti-LGG-1 (ref. ⁸⁴, 1:2,000) and α-tubulin (Sigma-Aldrich, T6199, 1:5,000).

For filter trap and western blot analysis of HEK293 cell lines, the cells were collected in lysis buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 1 mM EDTA, 1% Triton X-100, 2 mM sodium orthovanadate, 1 mM PMSF, protease inhibitor cocktail), followed by homogenization through a 27-gauge syringe needle. Lysates from cells expressing pARIS-mCherry-httQ23-GFP, pARIS-mCherry-httQ100-GFP or without any overexpression were centrifuged at 8,000g for 5 minutes at 4 °C. Lysates from cells expressing FUS-HA-WT, FUS-HA-P525L, pLVX-Puro-TDP-43-WT or pLVX-Puro-TDP-43-A382T were centrifuged at 1,000g for 5 minutes at 4 °C. The supernatants were collected, and protein concentrations were measured with the BCA assay. For western blot, 30 μg of protein was analyzed as above. For filter trap analysis, 100 μg of total protein was supplemented with SDS to a final concentration of 0.5% and loaded onto a cellulose acetate membrane assembled in a slot-blot apparatus as described above. The membrane was then washed with 0.2% SDS, and SDS-resistant protein aggregates were evaluated by immunoblotting. For filter trap analysis, immunoblotting was conducted with antibodies against GFP (AMSBIO, TP401, 1:5,000), FUS (Abcam, ab154141, clone CL0190, 1:1,000) and TDP-43 (Abcam, ab225710, 1:1,000). For western blot, immunoblotting was conducted with anti-EPS8 (Proteintech, 12455-1-AP, 1:1,000), anti-β-actin (Abcam, 8226, 1:5,000), anti-HTT (Cell Signaling Technology, 5656, 1:1,000), FUS (Abcam, ab154141, clone CL0190, 1:1,000), TDP-43 (Abcam, ab225710, 1:1,000), anti-LC3B (Cell Signaling Technology, 2775, 1:1,000) and anti-USP-4 (Abcam, ab181105, 1:1,000).

For necroptosis analysis, iPSC-derived motor neurons were lysed in RIPA buffer (50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 1 mM EDTA, 1 mM PMSF, protease inhibitor cocktail). Immunoblotting was performed using anti-phospho-RIP (Ser166) (Cell Signaling Technology, 65746, clone D1L3S, 1:1,000) and anti-RIP (Cell Signaling Technology, 3493, clone D94C12, 1:1,000). Densitometry of filter trap and western blot assays was performed using ImageJ software (version 1.51).

Protein immunoprecipitation for interaction analysis

HEK293 cells were collected and lysed in a protein lysis buffer containing 50 mM Tris-HCl (pH 6.7) 150 mM NaCl, 1% NP40, 0.25% sodium deoxycholate, 1 mM EDTA, 1 mM PMSF, 1 mM sodium orthovanadate, 1 mM NaF and protease inhibitor cocktail. Lysates were homogenized through a 27-gauge syringe needle and centrifuged at 13,000g for 15 minutes at 4 °C. Supernatants were incubated on ice for 1 hour with anti-USP-4 antibody (Abcam, ab181105, 1:100). As a negative control, the same amount of protein was incubated with anti-normal rabbit IgG (Cell Signaling Technology, 2729, 1:378). Samples were then incubated with 50 µl of µMACS MicroBeads for 1 hour at 4 °C with overhead shaking. Then, the samples were loaded onto pre-cleared µMACS columns (Miltenyi Biotec, 130-042-701). The beads were washed three times with a buffer containing 50 mM Tris (pH 7.5), 150 mM NaCl, 5% glycerol and 0.05% Triton, followed by five washes with 50 mM Tris (pH 7.5) and 150 mM NaCl. The samples were eluted with 75 μl of boiled 2× Laemmli buffer, boiled for 5 minutes at 95 °C and analyzed by western blotting.

Native gels analysis

HEK293 cells expressing CMV:mRFP-Q74 (ref. ³⁰) were lysed in buffer containing 50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 0.5% NP-40, 2 mM EDTA, 1 mM EGTA, 10% glycerol, 2 mM sodium orthovanadate, 1 mM PMSF and protease inhibitor cocktail. Lysates were homogenized using a 27-gauge syringe needle and centrifuged at 12,000g for 15 minutes at 4 °C. Supernatants were collected, and protein concentrations were determined using the BCA protein assay (Thermo Fisher Scientific). Equal amounts of protein lysates were mixed 1:1 with sample buffer (50 mM Tris-HCl (pH 6.8), 10% glycerol, 0.01% bromophenol blue). Then, 20 μg of total protein was separated using 4–15% Tris-Glycine eXtended protein gels (Bio-Rad) and imaged via fluorescence using LICOR Odyssey M.

Immunocytochemistry

Cells were fixed with 4% paraformaldehyde in PBS for 20 minutes, followed by permeabilization with 0.2% Triton X-100 in PBS (10 minutes) and blocking with 3% BSA in 0.2% Triton X-100 in PBS (10 minutes). The cells were then incubated with anti-MAP2 (Sigma-Aldrich, M1406, 1:300) and rabbit anti-cleaved caspase-3 (Cell Signalling Technology, 9661S, 1:300) for 2 hours at room temperature. After washing with PBS, cells were incubated with secondary antibodies (Alexa Fluor 488 goat anti-mouse (Thermo Fisher Scientific, A-11029, 1:500) and Alexa Fluor 568 F(ab′)2 fragment of goat anti-rabbit IgG (H + L) (Thermo Fisher Scientific, A-21069, 1:500)) and Hoechst 33342 (Life Technologies, 1656104) for 1 hour at room temperature. Finally, the coverslips were rinsed in PBS, followed by a distilled water wash, and then mounted onto microscope slides with FluorSave Reagent (Merck, 345789).

CytoD, RAC activator and DUB inhibitor treatment

For CytoD treatment, worms were collected and randomly divided equally into M9 solutions containing either 10 μM CytoD (STEMCELL Technologies, 100-0557) or DMSO as a vehicle control. The worms were incubated with CytoD or DMSO for 6 hours on a shaker. For DUB inhibitor experiments, worms were collected and randomly transferred onto plates with OP50 bacteria covered with a final concentration of 13.7 μg ml⁻¹ PR-619 (Merck, 662141) or vehicle control (DMSO) for either 4 hours or 1 day as indicated in the corresponding figures.

HEK293 cells were treated with 2 μM CytoD or DMSO for 4 hours before lysis. For RAC activation, cells were treated with 2 U ml⁻¹ Rac/Cdc42 Activator II (Cytoskeleton, CN02-A) for 6 hours.

Proteasome activity

Day 5 adult worms and HEK293 cells were lysed in proteasome activity assay buffer (50 mM Tris-HCl (pH 7.5), 10% glycerol, 5 mM MgCl₂, 0.5 mM EDTA, 2 mM ATP, 1 mM DTT) using a Precellys 24 or a 27-gauge syringe, respectively. The samples were centrifuged at 10,000g for 10 minutes at 4 °C, and the supernatants were collected. Protein concentrations were determined using the BCA protein assay kit.

To measure chymotrypsin-like proteasome activity, 25 μg of total protein was incubated with the fluorogenic substrate Suc-Leu-Leu-Val-Tyr-AMC (Enzo Life Sciences, BML-P802) in 96-well plates (BD Falcon). Fluorescence was measured every 5 minutes for 2 hours at 20 °C (C. elegans) or 37 °C (human cells) using a microplate fluorometer (PerkinElmer, EnSpire) at 380-nm excitation and 460-nm emission.

Statistics and reproducibility

For quantification of filter trap and western blot data, we presented the results as relative changes compared with the corresponding control conditions. To average and statistically analyze independent experiments for these assays, we normalized test conditions to their corresponding control groups measured concurrently in each replicate experiment. Given that all the control groups were set to 100, we used a non-parametric Wilcoxon test when comparing two conditions to assess changes in protein aggregation and protein levels. For all other assays, we used parametric tests. Data distribution was assumed to be normal, but this was not formally tested. When more than two conditions or two independent variables were compared, we used one-way or two-way ANOVA followed by multiple comparisons tests. All statistical analyses were performed using GraphPad Prism (version 10.4.1).

For lifespan experiments, we used GraphPad Prism (version 10.4.1) and OASIS (version 1)⁸⁵ to determine median and mean lifespan, respectively. The P values were calculated using the log-rank (Mantel–Cox) method and refer to comparisons between experimental and control animals within a single lifespan experiment. Each lifespan graph represents a single, representative experiment. Supplementary Table 1 contains the number of total/censored worms as well as detailed statistical analyses for each replicate lifespan experiment.

No statistical methods were used to predetermine sample size, but our sample sizes are similar to, or greater than, those reported in previous publications using the same procedures^{9,14,16,26,30,33,44,46,50,73,75,76,78,86,87,88}. For motility assays, worms were excluded from analysis if they showed fewer than 0.1 body bends per second or were not recognized by the ImageJ software. No animals or data points were excluded from other analyses. For lifespan assays, worms were randomly picked and transferred from the synchronized population to the different experimental conditions. For all other experiments, worms were randomly distributed into the various experimental groups from single pulls of synchronized populations. Human cells were distributed to the various groups of all experiments from single pulls. Data collection was not randomized. Data collection and analysis were not performed blinded to the conditions of the experiments.

Reporting summary

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

A new retrospective cohort study published in The Lancet Primary Care has provided compelling real-world evidence that the MVA-BN (Modified Vaccinia Ankara-Bavarian Nordic) vaccine continues to offer substantial protection against severe monkeypox (mpox) disease more than 1.5 years after immunization. The commentary accompanying the study—written by infectious disease experts Dr. Emily Evans and Dr. Boghuma Titanji of Emory University—highlights how the findings mark a significant step forward in understanding vaccine durability and clinical protection in the face of waning antibody levels.

The original research, conducted in New South Wales (NSW), Australia, by Latham et al., represents the largest and most detailed clinical study to date on breakthrough mpox infections in fully vaccinated individuals. It is particularly significant given the limited baseline immunity in the Australian population due to the absence of historical smallpox vaccination campaigns, a contrast to settings in Europe, North America, and parts of Africa.

Durable Protection Despite Waning Antibodies

The study included 674 confirmed mpox cases between June and November 2024, during Australia’s largest recorded mpox outbreak. Of those, 251 individuals (37%) were fully vaccinated with two doses of MVA-BN. The median interval between the second dose and symptom onset was nearly 22 months.

Key outcomes demonstrate that full vaccination was associated with:

• 89% reduced risk of hospitalization compared to unvaccinated individuals (RR 0.11; 95% CI 0.03–0.43),
• 55% reduction in risk of systemic symptoms like fever, headache, and muscle pain (RR 0.72),
• Significant reduction in extragenital lesions, a potential driver of casual-contact transmission (RR 0.45).

Interestingly, fully vaccinated individuals were slightly more likely to present with anogenital lesions, though these were generally mild and did not lead to hospitalization.

Despite laboratory evidence that antibody titers wane within 5–7 months of vaccination, these clinical findings suggest meaningful protection persists well beyond serological decline. This divergence between antibody kinetics and real-world outcomes adds nuance to the discussion around correlates of protection and vaccine-induced immunity.

Implications for HIV-Positive Individuals

While the Australian cohort included people living with HIV, the study did not stratify clinical outcomes by HIV status. This is a notable omission, given that HIV-positive individuals—especially those with advanced disease—are at substantially higher risk of severe mpox, including disseminated and even fatal outcomes.

Previous research has shown that while people with HIV can mount adequate immune responses to MVA-BN, those with lower CD4 counts or poorly managed HIV may have weaker protection. In one clinical trial, antibody titers were significantly higher in people without HIV compared to those with HIV, despite both groups reaching high seropositivity rates.

The absence of outcome data stratified by HIV status represents a critical gap, especially as current mpox outbreaks in sub-Saharan Africa—where HIV prevalence is high—continue to intensify.

A Public Health Opportunity and National Imperative

The findings have important implications for both national and global health security. Infections with mpox, while relatively rare outside high-risk populations, can escalate quickly during outbreaks and impose significant strain on healthcare systems.

Preventing hospitalizations and systemic symptoms—especially in younger, unvaccinated populations—is not only a clinical goal but also a matter of public health resilience. In the Australian outbreak, the vast majority of mpox patients were men under 50, underscoring the vulnerability of generations never immunized against smallpox.

As Dr. Titanji and Dr. Evans note, leveraging sexual health clinics as vaccination hubs has proven effective, but disparities in access persist. Populations disconnected from such services may face increased risk during future outbreaks, further emphasizing the need for broader, community-engaged vaccination strategies.

Global Equity and the Next Phase: Boosters?

The NSW study’s implication that protection extends well beyond the initial year is reassuring—but it also raises new questions. Should a third (booster) dose be recommended for specific populations? Should HIV-positive individuals, or those with high behavioral exposure risk, receive tailored vaccine schedules?

The commentary urges global immunization technical advisory groups to incorporate these findings into deliberations about MVA-BN booster strategies. It also reinforces the call for equitable global access to MVA-BN, especially in lower-income settings currently grappling with resurging outbreaks.

Notably, viral sequencing in the Australian outbreak revealed no substantial genetic divergence between viruses infecting vaccinated and unvaccinated individuals. This suggests vaccine escape was not a major factor in breakthrough infections and bolsters confidence in the ongoing relevance of the MVA-BN platform.

Next Steps: Research, Policy:

This evidence base provides a firm foundation for future preparedness—but several priorities remain:

• Stratified clinical studies on vaccine efficacy in immunocompromised populations,
• Longitudinal analyses of immune response durability post-MVA-BN,
• Global coordination on vaccination campaigns in areas with rising case counts and high HIV prevalence,
• Booster dose policy frameworks informed by risk profiling, not just time since vaccination.

As mpox transitions from a global health emergency to an endemic risk, the world must shift from reactive containment to proactive, equitable protection—particularly for communities historically underserved by immunization programs.

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Sources and Further Reading

Evans EE, Titanji BK. Protection that lasts? MVA-BN against clade IIb mpox. The Lancet Primary Care, 24 July 2025.

Latham NH, Pett J, Katelaris AL, et al.  Clinical features of mpox in fully vaccinated people in New South Wales, Australia: a retrospective cohort study. The Lancet Primary Care, 24 July 2025.

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Gaithersburg, Md.-based Polaris Genomics, a mental healthcare firm eyeing physical biomarkers to aid diagnoses as well as treatments, has secured $250,000 in debt, according to a recent SEC filing. The company raised over $5.9 million from investors, according to Pitchbook.

The startup up was founded in 2017 by Yusuf Henriques, a US Army veteran, Charles Cathlin, who served in the US Air Force, Princeton graduate Tshaka Cunningham and physician Anne Naclerio, a 30-year veteran of the US Army, with Cathlin drawing on his experience treating the first responders of the 9/11 terror attacks of 2001.

Cathlin serves as the company’s CEO and Cunningham is chief science officer. Cunningham is director of R&D while Naclerio serves as chief medical officer.

According to a report in Startup Health, Cathlin — an engineer and graduate of the Air Force Academy and Stanford University — grappled with the unique clinical challenge of “diagnosing” mental health conditions, rather than relying on observation or self-reporting.

“The firefighters and police officers were traumatized by what they experienced,” Cathlin told Illumina, whose accelerator Polaris Genomics joined as an early-stage startup. “That had a large impact on me and got me interested in mental health, because no one was really addressing it.”

In his quest, Cathlin eventually tracked down the work of a psychiatric researcher in New York City that connected mental health conditions and RNS expression.

“What got me excited was that there was an actual biomarker to identify who actually had post-traumatic stress disorder,” Cathlin told Startup Health. “The fact that you can introduce an objective tool to that process was a game changer.”

Cathlin believes the company’s mission is to make “invisible wounds visible using the power of genomics.”

“We believe genomics is a driving force to connect mental illness to its biological underpinnings. By doing that, we can decrease the stigma, suffering, silence, and suicide.”

Polaris Genomics has partnered with the Illumina Accelerator, and scientists from Mount Sinai and the Max Planck Institute of Psychiatry to develop the first-to-market, patented genomic biomarker assay to identify risks of post-traumatic stress disorder (PTSD). The company was granted two patents on the blood-based biomarker model for PTSD.

Last year, the company launched a trial with Stella DC to further develop PTS-iD, called a first test of its kind to use genomics to detect the physical changes underlying PTSD. Polaris Genomics believes the Covid-19 pandemic and subsequent years of mental health repercussions has “elucidated the urgency for advances in diagnostics and treatment across a range of mental health and neuropsychiatric conditions.”