Author: admin

  • Comet: A New Medical Intelligence for Clinical and Operational Insights 

    Comet: A New Medical Intelligence for Clinical and Operational Insights 

    You can read more about the methods and early evaluation results in this paper on arxiv, written in collaboration with researchers from Yale and Microsoft.

    Every day, clinicians make decisions without knowing exactly what will happen next.

    • A patient presents with abdominal pain, and the clinician needs to decide whether the patient should be admitted, sent home, or referred for further imaging.  
    • A hospitalized patient is improving, but will an early discharge result in them being readmitted in the next few days?

    These kinds of questions are central to clinical workflows but can be clouded by uncertainty.

    Comet, built on Epic Cosmos, simulates likely paths in a patient’s health journey to help care teams plan accordingly. It is trained on a subset of Cosmos data, validated on key use cases, and designed to improve as more data and additional data types are included.

    What Comet Is and How It Works

    Comet models are trained on sequences of time-ordered medical events, including diagnoses, labs, medications, and encounters, spanning millions of de-identified patient records and more than 100 billion data points.

    Using the same core technology as today’s large language models, Comet learns how clinical patterns evolve over time. When given a patient’s current state, it generates a number of plausible future timelines that reflect real-world complexity: diagnoses resolving or emerging, complications arising, and care needs shifting.

    These simulations from Comet will be summarized into insights and presented to clinicians in workflows to provide a quantitative, data-driven view of what is likely to happen next, helping care teams anticipate and act.

    Designed for Security

    Comet is built entirely within Epic Cosmos, a secure, collaborative data platform designed for large-scale health research and innovation. Cosmos uses de-identified patient data and operates under rigorous privacy, security, and compliance standards. Because Cosmos is updated as care is delivered, the data powering Comet reflects evolving clinical practices and emerging trends across diverse health systems.

    Operating within this governed environment, Comet can surface insights to participating health systems without compromising patient privacy. The platform’s architecture enables shared learning across the network while preserving privacy and security. Comet will undergo case-by-case evaluation to ensure performance is appropriate for specific workflows before being integrated into daily use.

    For Patients, Clinicians, and Health Systems

    Comet will be able to simulate a patient’s likely future trajectory and summarize key insights, such as extended hospitalization, 30-day readmission, ASCVD risk, or emergence of conditions like pancreatic cancer. In 78 early evaluations, Comet outperformed the majority of single-task models, with more that had similar performance. As more data types are incorporated and the model scales, performance will continue to improve, enabling even more precise and actionable insights across care settings.

    Starting in February 2026, researchers from Cosmos participating organizations will be able to explore Comet in a virtual lab to test new use cases and help advance its clinical relevance.

    And this is only the beginning. As simulation-based insights become part of everyday healthcare, they open the door to a new kind of care planning: anticipatory rather than reactive, personalized rather than generalized, and data-informed at every level. From use in the emergency department to case management, the future of clinical decision-making is not about finding a single answer; it is about understanding the range of what is possible and being ready for all of it, allowing teams to plan with greater confidence, distribute resources more effectively, and, ultimately, improve the lives of the patients they serve.

    Read the full article from arxiv.

    Continue Reading

  • Comprehensive Care and Follow-Up for Patients Post–CAR T Infusion

    Comprehensive Care and Follow-Up for Patients Post–CAR T Infusion

    The patient demonstrated an excellent response to CAR T therapy, achieving complete remission with MRD-negative status, representing the deepest possible remission achievable. Her treatment response included normalized light chains, disappearance of the M spike, and bone marrow cleared of plasma cells. Following IVIG therapy to boost her immune system, she experienced immediate improvement with immune markers rising the very next day. Her overall quality of life has significantly improved, with better stamina, less fatigue, and the ability to engage in activities like yard work, though she humorously noted that being tired in the mornings is likely unrelated to her cancer treatment.

    When comparing CAR T therapy with her previous stem cell transplant experience, the patient found CAR T considerably more manageable and less physically demanding. The treatment required only 3 days of what she described as “light chemotherapy” compared with the intensive regimen associated with stem cell transplantation. This easier treatment experience combined with the prospect of avoiding continuous daily chemotherapy that would be required with standard care approaches made CAR T particularly appealing to her as a treatment option.

    The patient expressed profound gratitude for discovering CAR T therapy and emphasized her preference for healing over continuous treatment that could potentially harm her body. She articulated a powerful perspective about wanting to “be healed and move on with life” rather than enduring indefinite chemotherapy that might continue damaging her body even while potentially controlling the disease. Her philosophy centered on the desire for treatment that promotes healing rather than ongoing intervention, viewing CAR T as providing an opportunity to achieve lasting remission without the burden of continuous chemotherapy. This perspective highlights the transformative impact CAR T can have not only on disease control but also on patients’ overall approach to living with and beyond cancer.

    Continue Reading

  • Global Burden of Major Urologic Diseases in Women, 1990–2021: A Syst

    Global Burden of Major Urologic Diseases in Women, 1990–2021: A Syst

    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 ith age group, and wi 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 al40,41 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.

    References

    1. van Hoogstraten LM, Vrieling A, van der Heijden AG, Kogevinas M, Richters A, Kiemeney LA. Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice. Nat Rev Clin Oncol. 2023;20(5):287–304. doi:10.1038/s41571-023-00744-3

    2. Blackwell RH, Kirshenbaum EJ, Shah AS, Kuo PC, Gupta GN, Turk TM. Complications of recognized and unrecognized iatrogenic ureteral injury at time of hysterectomy: a population based analysis. J Urol. 2018;199(6):1540–1545. doi:10.1016/j.juro.2017.12.067

    3. Timm MR, Russell SK, Hultgren SJ. Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics. Nat Rev Microbiol. 2025;23(2):72–86. doi:10.1038/s41579-024-01092-4

    4. Anger JT, Bixler BR, Holmes RS, Lee UJ, Santiago-Lastra Y, Selph SS. Updates to recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline. J Urol. 2022;208(3):536–541. doi:10.1097/JU.0000000000002860

    5. Worby CJ, Schreiber IV HL, Straub TJ, et al. Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women. Nat Microbiol. 2022;7(5):630–639. doi:10.1038/s41564-022-01107-x

    6. Sihra N, Goodman A, Zakri R, Sahai A, Malde S. Nonantibiotic prevention and management of recurrent urinary tract infection. Nat Rev Urol. 2018;15(12):750–776. doi:10.1038/s41585-018-0106-x

    7. Xu J-Z, Li C, Xia Q-D, et al. Sex disparities and the risk of urolithiasis: a large cross-sectional study. Ann Med. 2022;54(1):1627–1635. doi:10.1080/07853890.2022.2085882

    8. Pedro RN, Das K, Buchholz N. Urolithiasis in pregnancy. Int J Surg. 2016;36:688–692. doi:10.1016/j.ijsu.2016.10.046

    9. Antonelli JA, Maalouf NM, Pearle MS, Lotan Y. Use of the National Health and Nutrition Examination Survey to calculate the impact of obesity and diabetes on cost and prevalence of urolithiasis in 2030. Eur Urol. 2014;66(4):724–729. doi:10.1016/j.eururo.2014.06.036

    10. Abate N, Chandalia M, Cabo-Chan Jr AV, Moe OW, Sakhaee K. The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int. 2004;65(2):386–392. doi:10.1111/j.1523-1755.2004.00386.x

    11. Monico CG, Milliner DS. Genetic determinants of urolithiasis. Nat Rev Nephrol. 2012;8(3):151–162. doi:10.1038/nrneph.2011.211

    12. Bukavina L, Bensalah K, Bray F, et al. Epidemiology of renal cell carcinoma: 2022 update. Eur Urol. 2022;82(5):529–542. doi:10.1016/j.eururo.2022.08.019

    13. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA. 2024;74(1):12–49. doi:10.3322/caac.21820

    14. Huang J, Leung DK-W, Chan EO-T, et al. A global trend analysis of kidney cancer incidence and mortality and their associations with smoking, alcohol consumption, and metabolic syndrome. Eur Urol Focus. 2022;8(1):200–209. doi:10.1016/j.euf.2020.12.020

    15. Catto JW, Rogers Z, Downing A, et al. Lifestyle factors in patients with bladder cancer: a contemporary picture of tobacco smoking, electronic cigarette use, body mass index, and levels of physical activity. Eur Urol Focus. 2023;9(6):974–982. doi:10.1016/j.euf.2023.04.003

    16. Jubber I, Ong S, Bukavina L, et al. Epidemiology of bladder cancer in 2023: a systematic review of risk factors. Eur Urol. 2023;84(2):176–190. doi:10.1016/j.eururo.2023.03.029

    17. Mitchell R, Popham F. Effect of exposure to natural environment on health inequalities: an observational population study. Lancet. 2008;372(9650):1655–1660. doi:10.1016/S0140-6736(08)61689-X

    18. Ferrari AJ, Santomauro DF, Aali A, et al. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133–2161.

    19. Naghavi M, Ong KL, Aali A, et al. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2100–2132.

    20. Schumacher AE, Kyu HH, Aali A, et al. Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):1989–2056.

    21. Yang H, Huang X, Westervelt DM, Horowitz L, Peng W. Socio-demographic factors shaping the future global health burden from air pollution. Nat Sustainability. 2023;6(1):58–68. doi:10.1038/s41893-022-00976-8

    22. Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol. 2012;13(8):790–801. doi:10.1016/S1470-2045(12)70211-5

    23. Murray CJ. The global burden of disease study at 30 years. Nature Med. 2022;28(10):2019–2026. doi:10.1038/s41591-022-01990-1

    24. Brauer M, Roth GA, Aravkin AY, et al. Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2162–2203.

    25. Hankey BF, Ries LA, Kosary CL, et al. Partitioning linear trends in age-adjusted rates. Cancer Causes Control. 2000;11:31–35. doi:10.1023/A:1008953201688

    26. Fay MP, Feuer EJ. Confidence intervals for directly standardized rates: a method based on the gamma distribution. Stat Med. 1997;16(7):791–801.

    27. Du Z, Chen W, Xia Q, Shi O, Chen Q. Trends and projections of kidney cancer incidence at the global and national levels, 1990–2030: a Bayesian age-period-cohort modeling study. Biomarker Res. 2020;8:1–10. doi:10.1186/s40364-020-00195-3

    28. Dy GW, Gore JL, Forouzanfar MH, Naghavi M, Fitzmaurice C. Global burden of urologic cancers, 1990–2013. Eur Urol. 2017;71(3):437–446. doi:10.1016/j.eururo.2016.10.008

    29. Mancuso G, Midiri A, Gerace E, Marra M, Zummo S, Biondo C. Urinary tract infections: the current scenario and future prospects. Pathogens. 2023;12(4):623. doi:10.3390/pathogens12040623

    30. Huang AJ, Grady D, Mody L. Recurrent urinary tract infection in older outpatient women. JAMA Intern Med. 2024;184(8):971–972. doi:10.1001/jamainternmed.2024.1069

    31. Yang X, Chen H, Zheng Y, Qu S, Wang H, Yi F. Disease burden and long-term trends of urinary tract infections: a worldwide report. Front Public Health. 2022;10:888205. doi:10.3389/fpubh.2022.888205

    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

    34. Aguilar GR, Swetschinski LR, Weaver ND, et al. The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis. Lancet Regional Health–Americas. 2023;25.

    35. Balasubramanian R, Van Boeckel TP, Carmeli Y, Cosgrove S, Laxminarayan R. Global incidence in hospital-associated infections resistant to antibiotics: an analysis of point prevalence surveys from 99 countries. PLoS Med. 2023;20(6):e1004178. doi:10.1371/journal.pmed.1004178

    36. Venugopal V, Shanmugam R, Perumal Kamalakkannan L. Heat-health vulnerabilities in the climate change context—comparing risk profiles between indoor and outdoor workers in developing country settings. Environ Res Lett. 2021;16(8):085008. doi:10.1088/1748-9326/ac1469

    37. Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y. Epidemiology of stone disease across the world. World J Urol. 2017;35:1301–1320. doi:10.1007/s00345-017-2008-6

    38. Abeywickarama B, Ralapanawa U, Chandrajith R. Geoenvironmental factors related to high incidence of human urinary calculi (kidney stones) in Central Highlands of Sri Lanka. Environ Geochem Health. 2016;38:1203–1214. doi:10.1007/s10653-015-9785-x

    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

    40. Young M, Nordin B. Effects of natural and artificial menopause on plasma and urinary calcium and phosphorus. Lancet. 1967;290(7507):118–120. doi:10.1016/S0140-6736(67)92961-3

    41. Prochaska M, Taylor EN, Curhan G. Menopause and risk of kidney stones. J Urol. 2018;200(4):823–828. doi:10.1016/j.juro.2018.04.080

    42. Borofsky MS, Lingeman JE. The role of open and laparoscopic stone surgery in the modern era of endourology. Nat Rev Urol. 2015;12(7):392–400. doi:10.1038/nrurol.2015.141

    43. Lunyera J, Kilonzo K, Lewington A, Yeates K, Finkelstein FO. Acute kidney injury in low-resource settings: barriers to diagnosis, awareness, and treatment and strategies to overcome these barriers. Am J Kidney Dis. 2016;67(6):834–840. doi:10.1053/j.ajkd.2015.12.018

    44. Fitzgerald RC, Antoniou AC, Fruk L, Rosenfeld N. The future of early cancer detection. Nat Med. 2022;28(4):666–677. doi:10.1038/s41591-022-01746-x

    45. Salzillo C, Cazzato G, Serio G, Marzullo A. Paediatric renal tumors: a state-of-the-art review. Curr Oncol Rep. 2025;27(3):211–224. doi:10.1007/s11912-025-01644-8

    46. Purdue MP, Silverman DT. Clearing the air: summarizing the smoking-related relative risks of bladder and kidney cancer. Eur Urol. 2016;70(3):467–468. doi:10.1016/j.eururo.2016.04.009

    47. Cumberbatch MG, Rota M, Catto JW, La Vecchia C. The role of tobacco smoke in bladder and kidney carcinogenesis: a comparison of exposures and meta-analysis of incidence and mortality risks. Eur Urol. 2016;70(3):458–466. doi:10.1016/j.eururo.2015.06.042

    48. Dobruch J, Daneshmand S, Fisch M, et al. Gender and bladder cancer: a collaborative review of etiology, biology, and outcomes. Eur Urol. 2016;69(2):300–310. doi:10.1016/j.eururo.2015.08.037

    49. Doshi B, Athans SR, Woloszynska A. Biological differences underlying sex and gender disparities in bladder cancer: current synopsis and future directions. Oncogenesis. 2023;12(1):44. doi:10.1038/s41389-023-00489-9

    50. Pignot G, Barthélémy P, Borchiellini D. Sex disparities in bladder cancer diagnosis and treatment. Cancers. 2024;16(23):4100. doi:10.3390/cancers16234100

    51. Li D, Wang Z, Yu Q, et al. Tracing the evolution of sex hormones and receptor-mediated immune microenvironmental differences in prostate and bladder cancers: from embryonic development to disease. Adv Sci. 2025;12(13):e2407715. doi:10.1002/advs.202407715

    52. Ide H, Miyamoto H. Sex hormone receptor signaling in bladder cancer: a potential target for enhancing the efficacy of conventional non-surgical therapy. Cells. 2021;10(5):1169. doi:10.3390/cells10051169

    53. Chaudhary P, Singha B, Abdel-Hafiz HA, et al. Sex differences in bladder cancer: understanding biological and clinical implications. Biol Sex Differences. 2025;16(1):31. doi:10.1186/s13293-025-00715-6

    54. Venkatesh N, Martini A, McQuade JL, Msaouel P, Hahn AW. Obesity and renal cell carcinoma: biological mechanisms and perspectives. Semi Cancer Biol. 2023;94:21–33. doi:10.1016/j.semcancer.2023.06.001

    55. Nam GE, Cho KH, Han K, et al. Obesity, abdominal obesity and subsequent risk of kidney cancer: a cohort study of 23.3 million East Asians. Br J Cancer. 2019;121(3):271–277. doi:10.1038/s41416-019-0500-z

    56. Fang S, Liu Y, Dai H, et al. Association of metabolic syndrome and the risk of bladder cancer: a prospective cohort study. Front Oncol. 2022;12:996440. doi:10.3389/fonc.2022.996440

    57. Byrne S, Boyle T, Ahmed M, Lee SH, Benyamin B, Hyppönen E. Lifestyle, genetic risk and incidence of cancer: a prospective cohort study of 13 cancer types. Int J Epidemiol. 2023;52(3):817–826. doi:10.1093/ije/dyac238

    58. Wang Q, Zhou W. Roles and molecular mechanisms of physical exercise in cancer prevention and treatment. J Sport Health Sci. 2021;10(2):201–210. doi:10.1016/j.jshs.2020.07.008

    Continue Reading

  • Enhancing Hearing Accessibility in One UI 8 With Samsung Supporters – Samsung Global Newsroom

    Enhancing Hearing Accessibility in One UI 8 With Samsung Supporters – Samsung Global Newsroom

    No matter how advanced a feature may be, its value is limited if it isn’t accessible to everyone. That’s why accessibility lies at the heart of true technological innovation. Guided by its vision of “Creating Better Pathways for All,” Samsung Electronics has consistently worked to deliver more inclusive products and services.

     

    This philosophy is reflected even more strongly in One UI 8, launched alongside the latest Galaxy Z series. The update enhances hearing accessibility features, enabling smoother communication even in challenging listening environments.

     

    To learn more about how these improvements came to life, Samsung Newsroom spoke with Soohyun Lee from Experience Planning Group1 of Samsung Electronics’ Mobile eXperience (MX) Business, along with Samsung Supporters Hajung Kim and Wansu Kim, who collaborated with Lee to bring more accessibility features to One UI 8.

     

    ▲ (From left) Wansu Kim and Hajung Kim with Soohyun Lee

     

     

    Real Voices, Real Change: Samsung Supporters Inspire Inclusive Features

    The hearing accessibility features in One UI 8 draw on the real-life experiences and feedback of Samsung Supporters. Currently active in Korea and the United Kingdom, the Samsung Supporters program invites users with diverse accessibility needs — including vision, hearing and mobility — to propose accessibility-related ideas directly to Samsung. It played a key role in developing the new hearing accessibility features in One UI 8, with Samsung Supporters Hajung Kim and Wansu Kim, both of whom are hard of hearing, contributing their experiences and ideas.

     

    “We listen closely to the valuable feedback from our Supporters about inconveniences and other challenges that traditional desk research might overlook,” explained Lee, who manages the Samsung Supporters program. “We then incorporate those insights to improve our products and services.”

     

    “We communicate with the Supporters in real time on a daily basis, while also conducting online surveys and in-depth offline interviews to carefully analyze issues and review solutions,” she continued. “Samsung Supporters are part of the entire process — from planning to testing and refinement.”

     

    ▲ Soohyun Lee from Experience Planning Group1 of the MX Business

     

    Features directly proposed by Samsung Supporters — such as Interpreter using keyboard and Real-Time Text calls — were brought to life in One UI 8. “After experiencing Galaxy products firsthand as a hard-of-hearing user, I suggested specific improvements regarding certain features,” said Wansu Kim, an international sign language educator. “Knowing that even a small change can make someone’s daily life much more convenient, I focused on ideas that people would truly need and be able to use with ease.”

     

    Content creator and writer Hajung Kim collaborated with Wansu Kim to produce a video introducing One UI 8’s hearing accessibility features. “We wanted the changes we suggested to seamlessly blend into the everyday lives of more people, so I planned the video from the perspective of a real user,” said Hajung Kim with pride.

     

    ▲ (From left) Samsung Supporters Hajung Kim and Wansu Kim use the new accessibility features applied to One UI 8.

     

     

    ‘Breaking Language Barriers With a Keyboard’ — Samsung Supporters’ Pick ①: Interpreter Using Keyboard

    Starting with the Galaxy S24 series, Galaxy AI’s translation capabilities have already proven to be a reliable companion for overcoming language barriers. However, its voice-based format had limitations in certain situations — for example, when the speaker’s pronunciation was unclear or when the surrounding environment was noisy.

     

    With One UI 8, Samsung enhanced Interpreter1 in a way that helps users communicate more naturally across languages through text typed on the keyboard. When a user types a sentence in their own language, the device instantly generates a real-time translation2 in both text and speech. The screen then displays two sections — one showing the user’s original text and the other the translation for their conversation partner — enabling smooth two-way communication.

     

    ▲ Soohyun Lee introduces the Interpreter using keyboard feature.

     

    “Our focus was on creating a seamless, uninterrupted conversation experience,” said Lee. “To reflect real usage patterns and refine the feature, we made typed sentences remain visible even after translation for easy editing and added an option to quickly delete the entire sentence with just one tap when users want to start a new one.”

     

    ▲ Wansu Kim demonstrates the Interpreter using keyboard feature.

     

    “I love traveling with my family, but since both my parents and I are hard of hearing, communication has always been a big challenge — especially when traveling abroad,” said Wansu Kim. “On a recent trip, Interpreter using keyboard allowed me to converse freely with people using different languages, making everything so much easier. Now, I can solely focus on the excitement of traveling without concerns about language barriers.”

     

    “Elevators were originally designed for wheelchair users, but today everyone benefits from them,” he added. “In the same way, Interpreter using keyboard can be used by anyone in situations where it’s difficult to talk. Accessibility isn’t only for people with physical limitations — it’s an opportunity for everyone.”

     

     

    ‘Don’t Miss a Word During a Call’ — Samsung Supporters’ Pick ②: Real-Time Call Captions

    For users with hearing aids or cochlear implants, phone calls can still cause anxiety. It’s easy to miss parts of the conversation and difficult to jot down important details while talking. To ease this burden, One UI 8 introduces Real-Time Call Captions.3

     

    By tapping the speech bubble icon on the right side of the call screen, the speech of both the caller and receiver are transcribed and displayed in real time. “I used to feel nervous whenever I needed to make a hospital appointment or talk with a bank representative on the phone because it was so important to understand every detail,” said Hajung Kim. “Now, with captions, I can instantly catch any words or sentences I might have missed, which makes me feel much more at ease. It’s not just a tool that converts voice into text — it’s a safety net that helps me follow the conversation and communicate more freely.”

     

    ▲ Hajung Kim uses the Real-Time Call Captions feature during a phone call.

     

    The feature assists users during everyday phone calls with friends and family as well. “Before, I often had to ask my grandparents to repeat themselves because I couldn’t clearly understand their pronunciation,” Hajung Kim said. “I often worried that going through this process again and again would tire them out, especially during longer calls. But with Real-Time Call Captions, I can now read my grandmother’s words on the screen instantly, allowing the conversation to flow without interruption.”

     

    “A short phone call can brighten an entire day, making this feature truly invaluable to my family,” she added.

     

     

    ‘Instant Conversations, No Waiting Required’ — Samsung Supporters’ Pick ③: Real-Time Text Calls

    The accessibility feature Wansu Kim uses most frequently is Real-Time Text calls,4 which allows users to communicate in text during a call, as though they’re exchanging messages. In earlier versions, the text of the other person’s speech appeared only after they finished speaking. This was particularly inconvenient during automated response system (ARS) calls with banks, telecommunications providers or credit card companies, when the input time often expired before users could read the instructions on their screens.

     

    Now with One UI 8, however, Real-Time Text calls display text the moment the other person begins speaking, allowing users to follow along and prepare responses without delay. “Even during personal calls, being able to see what the other person is saying in real time makes me feel much closer to them,” said Wansu Kim.

     

    ▲ Wansu Kim uses the Real-Time Text calls feature during a phone call.

     

    “In the past, there were always slight pauses during text calls with the Supporters — it sometimes felt like playing a game of guessing each other’s timing,” Lee said. “Those experiences showed us that timing is the most crucial part of a phone call. By making text appear in real time — without waiting for the other person to finish speaking — we introduced a key improvement. Even a few seconds can make a big difference, and seamless timing helps bring people closer together.”

     

     

    Making Accessibility a Given for Everyone

    What does the future of accessibility envisioned by Samsung Electronics and Samsung Supporters look like?

     

    “Accessibility isn’t a matter of special consideration — it’s something that everyone deserves and should enjoy,” Lee said. “Our goal is to create experiences that more people, across various environments, can access and benefit from without inconvenience at any time.” She added that the journey toward greater accessibility has been a joyful one, made possible thanks to those who understand the need for change and continue to offer their encouragement and support.

     

    For Wansu Kim, accessibility means freedom. “To me, hearing accessibility is freedom,” he said. “Through my work with Samsung Supporters, I want to help ensure the voices of people like me are heard more clearly and contribute to a world where everyone can communicate freely.”

     

    “Accessibility is a bridge that not only connects people physically but also links their hearts,” Hajung Kim added. “Beyond simply reducing inconvenience, I want to help build a world where technology becomes a source of confidence and empowerment for all.”

     

    The accessibility features in One UI 8 — co-created and presented by Samsung Supporters — can be explored in detail in the video below.

     

    

     

     

    1 Interpreter requires Samsung account login. Certain languages may require language pack download. Service availability may vary by language. Accuracy of results is not guaranteed. Availability and supported features may vary by country, region or carrier. Availability of supported languages may vary. Visit Galaxy AI page at samsung.com for details.
    2 Speed may vary depending on device and network connection.
    3 Feature availability may vary by country, language and device model. Speed may vary depending on network connection. Feature and UI are subject to change without notice.
    4 Feature availability may vary by country, language and device model. Speed may vary depending on network connection. Feature and UI are subject to change without notice.

    Continue Reading

  • Safety, Efficacy of Venom Immunotherapy Confirmed for Pediatric Patients

    Safety, Efficacy of Venom Immunotherapy Confirmed for Pediatric Patients

    Credit: Adobe Stock/ Kwangmoozaa

    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

    Continue Reading

  • Dolby Atmos FlexConnect Lets You Place Speakers Anywhere

    Dolby Atmos FlexConnect Lets You Place Speakers Anywhere

    While Dolby imposes no hard limit on the number or type of speakers (or subwoofers) you can use in a single FlexConnect system, each manufacturer’s choice of processor determines what’s feasible.

    What you can’t do is use any other company’s wireless speakers—whether they’re FlexConnect-compatible or not. Naturally, this raises the question of compatibility. When other companies eventually make their own FlexConnect TVs, speakers, or soundbars, will they only work within that brand’s family of products? Dolby says this kind of brand lock-in isn’t built into Dolby Atmos FlexConnect, but neither does it require compatibility between FlexConnect products.

    TCL Exclusive (for Now)

    Photograph: Simon Cohen

    Unfortunately for now, TCL’s implementation of FlexConnect is proprietary. I’ve repeatedly asked Dolby’s reps which companies have signed up to be a part of the Atmos FlexConnect world, but they’ve steadfastly refused to comment, choosing instead to let TCL own the limelight during the initial launch.

    Each TCL Z100 is rated at 170 watts RMS, which is delivered via three front-facing drivers (woofer, midrange, and tweeter) plus an up-firing driver for height effects. TCL says it uses a 1.1.1-channel layout, which means it can receive and reproduce one front/surround/rear channel, plus height and low-frequency effects (LFE) channels.

    TCL doesn’t say how low the Z100’s woofer can go, saying only that “low frequencies are optimized and gained, lowering the extension frequency to deliver more thrilling and powerful bass performance.”

    You can’t configure the Z100 to be part of a multiroom audio setup like you can with a Sonos or Bose soundbar, but you can switch it to Bluetooth mode for direct audio streaming from a phone. Two Z100s can be stereo-paired. Unfortunately, the Bluetooth mode isn’t managed by Dolby Atmos FlexConnect, so you may want to think carefully about speaker position if you use it frequently.

    Flexin’

    Dolby Atmos FlexConnect Lets You Place Speakers Anywhere

    Photograph: Simon Cohen

    Unlike soundbars and AV receivers, which typically override a TV’s internal speakers, Dolby Atmos FlexConnect incorporates them, channeling content and frequencies in a way that works with the rest of the speakers in the system. Presumably, most of that content will be center channel (dialog, key sound effects), with the wireless speakers filling in as needed.

    Continue Reading

  • Luigi Mangione’s likeness used to model shirt on Shein

    Luigi Mangione’s likeness used to model shirt on Shein

    Fast-fashion giant Shein has launched an investigation after an image of Luigi Mangione – accused of murdering UnitedHealthcare CEO Brian Thompson in New York last year – was used to model a shirt.

    An image with his likeness, which appeared to show him wearing a white, short-sleeved shirt, appeared on the fast-fashion website until its removal.

    It is thought the product he appeared to be modelling was on sale for just under $10 (£7.50).

    A spokesperson from Shein told BBC News: “The image in question was removed immediately upon discovery.”

    “We have stringent standards for the content of listings on our platform”, the spokesperson added.

    “We are conducting a thorough review and are strengthening our monitoring processes.”

    It is not known for how long the image was used, or who the company was that was selling it on the Chinese company’s website.

    Many online have speculated the image was created using artificial intelligence (AI) – but it remains unclear how the picture was made.

    In April, Luigi Mangione pleaded not guilty to all federal charges brought over the fatal shooting of Mr Thompson.

    The 26-year-old, who was arrested in December, faces the charges of murder and stalking.

    His not guilty plea means he will face trial and prosecutors are seeking the death penalty if he is convicted.

    Public reaction to Mr Thompson’s killing has shed light on privatised healthcare, and some have celebrated Mr Mangione as a folk hero, with supporters gathering outside the courthouse during his hearings.

    But this is not the first time his name or likeness has caused controversy for a company.

    In December, the BBC complained to Apple after the tech giant’s new iPhone feature generated a false headline about the accused murderer.

    Apple Intelligence used AI to summarise and group together notifications.

    The summary falsely made it appear BBC News had published an article claiming he had shot himself – when he had not.

    A month later, Apple suspended the feature after the error and other mistakes.

    His lawyers have not commented on the use of his image on Shein.

    Additional reporting by Liv McMahon

    Continue Reading

  • The 2025 Italian Grand Prix – presented by OKX

    The 2025 Italian Grand Prix – presented by OKX

    Why we love the Italian Grand Prix

    If you were to provide a blueprint for what a Formula 1 circuit should be, the Autodromo Nazionale Monza wouldn’t be far off. It is extremely fast, pushes a car’s power and performance to the limit, is beautifully old school, and draws in some of F1’s most passionate fans.

    It is the oldest track on the F1 calendar and runs through one of the largest walled parks in Europe, the Parco di Monza, just north of Milan. Spanning 688 hectares, it uniquely connects nature, culture, and sports, with the greenery and woodlands providing quite a contrast to the roar of engines and a fanatical F1 crowd.

    Built in 1922, the circuit was only the third purpose-built race track in the world and has hosted the official Formula 1 Italian Grand Prix every year bar one since the inaugural season in 1950.

    Whether watching from the circuit or on TV, the circuit certainly holds up in the modern day. The grandstand at the Variante del Rettifilo must be considered among the best on the calendar to watch a race from, with cars slowing from 350km/h to 70km/h to tackle one of the track’s primary overtaking spots.

    Continue Reading

  • Clinical Efficacy and Safety of Omadacycline Versus Tigecycline in Tre

    Clinical Efficacy and Safety of Omadacycline Versus Tigecycline in Tre

    Introduction

    Severe pneumonia is a potentially fatal lung infection that frequently necessitates intensive care unit (ICU) hospitalization due to complications such as shock or the need for mechanical ventilation. Critically ill patients already in the ICU are also prone to developing severe pneumonia, which carries a high mortality rate.1 Pneumonia in critically ill patients includes community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP).2 Previous data indicate that inpatients with severe CAP admitted to the ICU have an in-hospital mortality rate of 17%, with a one-year mortality rate reaching almost 50%. Patients admitted to the ICU later tend to have higher mortality rates compared to those admitted earlier.3 In ICU patients, the mortality rates for VAP and mechanically ventilated HAP are as high as 28%.2 Severe pneumonia can be attributable to not only by conventional bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, but also by multidrug-resistant (MDR) bacteria.1,4 In recent years, the emergence of carbapenem-resistant gram-negative bacilli (CRGNB) has posed significant challenges for clinical treatment. It is estimated that globally, approximately 1.3 million deaths were caused by drug-resistant infections in 2019, with projections suggesting this number could surpass 10 million annually by 2050.5 The World Health Organization’s (WHO) Bacterial Priority Pathogens List (BPPL) in 2024 classifies carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) as “critical priority” pathogens.6 According to the China Antimicrobial Surveillance Network, the prevalence of CRGNB infections in China has been steadily rising. Clinically, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa consistently rank among the top five bacterial isolates recovered from hospital settings nationwide. The infection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) increased from 3% in 2005 to 23.1% in 2021, accounting for 60–90% of CRE infections. Concurrently, the prevalence of CRAB surged from 31.0% in 2005 to 71.5% in 2021.7

    Therapeutic options for CRGNB infections are currently limited, and tetracyclines have shown potential as an effective treatment. Tigecycline, a glycylcycline-class antibiotic, overcomes tetracycline resistance mediated by bacterial efflux pumps and ribosomal protection through the addition of a glycylamido side chain at the C-9 position of minocycline. It demonstrates good activity against CRE and CRAB, with lung concentrations approximately twice those in serum, but shows intrinsic resistance to CRPA. These characteristics support its recommendation for treating pulmonary infections associated with CRE and CRAB.7,8 However, the progressive increase in minimum inhibitory concentration (MIC) has led to more frequent use of double-dose tigecycline, which correlates with an increased likelihood of adverse events. Omadacycline, a novel member of the aminomethylcycline class of antibiotics, shares structural similarities with tigecycline but differs in that the glycylamido moiety at the C-9 position is replaced by an alkylaminomethyl group. Like tigecycline, omadacycline is approved for the treatment of pneumonia.9 In vitro studies have shown that omadacycline demonstrates comparable activity against CRAB to tigecycline (MIC90 4 mg/L vs 2 mg/L), and exhibits a susceptibility rate of 75% against CRKP (MIC90 = 32 mg/L).10 Currently, clinical experience with omadacycline for treating severe pneumonia caused by CRGNB remains insufficient. Moreover, due to its relatively recent introduction in China, data on its clinical efficacy and safety compared to tigecycline remain scarce and warrant further investigation. This retrospective study aims to evaluate and compare the clinical effectiveness and safety of omadacycline and tigecycline in treating severe pneumonia caused by CRGNB, and to identify predictors of 28-day mortality, thereby providing reference for therapeutic decision-making in CRGNB-associated severe pneumonia.

    Material and Methods

    Study Design

    This was a single-center, retrospective cohort study conducted at the Second Affiliated Hospital of Zhejiang Chinese Medical University in Hangzhou, China, a 1200-bed tertiary teaching hospital. Data were collected from patients admitted to four ICUs between April 1, 2023, and March 31, 2025. The inclusion criteria were as follows: age ≥ 18 years; severe pneumonia caused by CRGNB; and receipt of intravenous omadacycline or tigecycline for at least 72 hours. Exclusion criteria included pregnancy, advanced malignant tumors, and sequential use of both omadacycline and tigecycline within the 28-day period. This study adhered to the ethical standards of the Declaration of Helsinki. The study protocol underwent review and was approved by Ethics Review Committee of The Second Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. ZJTCMU2AE2025R028-IH01). Given that all data were collected retrospectively and did not include any information explicitly refused by patients for use, and considering that patient privacy and personal identifiers were fully protected with no need for follow-up or additional data collection, the Ethics Review Committee granted a waiver of informed consent.

    Eligible patients with severe pneumonia were allocated to either the omadacycline group or the tigecycline group. Patients in the omadacycline group received a loading dose of 200 mg intravenously every 24 hours, administered as a 1-hour infusion, followed by a maintenance dose of 100 mg every 24 hours, infused duration of 0.5 hour. In the tigecycline group, the treatment regimen consisted of an initial loading dose of 100 mg intravenously, followed by a maintenance dose of 50 mg every 12 hours, adjusted according to hepatic function, with an infusion time of 0.5 to 1 hour. The primary outcome was 28-day all-cause mortality following initiation of therapy. Secondary outcomes included clinical efficacy rate, microbiological clearance rate, with safety also evaluated.

    Definition and Data Collection

    Severe pneumonia was defined as the presence of either one major criterion or at least three minor criteria. Major criteria: respiratory failure requiring mechanical ventilation; septic shock with need for vasopressors. Minor criteria: core temperature < 36 °C; respiratory rate ≥ 30 breaths/min; PaO2/FiO2 ratio ≤ 250; multilobar infiltrates; confusion/disorientation; blood urea nitrogen level ≥ 20 mg/dl; infection-related white blood cell count < 4000 cells/μL; platelet count < 100,000/μL; hypotension requiring aggressive fluid resuscitation.11 Disease severity was quantified using the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score, derived from clinical parameters recorded upon admission.12,13 The observation endpoint was 28 days after the initiation of treatment. Clinical efficacy was defined as improvement or resolution of clinical symptoms during treatment, accompanied by stabilization or normalization of vital signs and inflammatory markers. Clinical failure was defined as the absence of amelioration in both clinical symptoms and inflammatory parameters.14 Microbiological clearance was defined as the absence of the initially isolated pathogen in two consecutive cultures from the infection site over the treatment period.14,15 All study data were retrospectively extracted from electronic medical records and included patient demographics, clinical diagnoses, comorbidities, APACHE II and SOFA scores, infection sources, laboratory test results, microbiological culture and antimicrobial susceptibility profiles, CRGNB treatment regimens and duration, 28-day mortality, clinical outcomes, microbiological clearance, and adverse events.

    Microbiology

    Gram-negative bacteria were identified using the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) system in China. Susceptibility to meropenem, imipenem, and tigecycline was tested using broth microdilution or disk diffusion methods. Gram-negative bacteria were classified as CRGNB if they exhibited nonsusceptibility to at least one carbapenem agent. The MIC breakpoints or zone diameters for meropenem and imipenem were interpreted in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. For tigecycline, MIC breakpoints were interpreted based on criteria from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). There are no standardized testing conditions available for omadacycline susceptibility testing.

    Statistical Analysis

    Statistical analysis was conducted using IBM SPSS Statistics 27 software (IBM Corp., Armonk, N.Y., USA). Continuous variables that followed a normal distribution were presented as mean ± standard deviation (SD) and compared between groups using Student’s t-test. Non-normally distributed continuous variables were expressed as median (interquartile range, IQR) and analyzed using the Mann–Whitney U-test. Categorical variables were summarized as n (%) and compared using the chi-square test or Fisher’s exact test. Survival curves were estimated using the Kaplan-Meier method and compared by the Log rank test. Covariates with a p-value of ≤ 0.1 in univariate analysis were advanced to the logistic regression model. Multivariable logistic regression analysis was performed to identify independent factors associated with 28-day all-cause mortality. Statistical significance was defined as p < 0.05.

    Results

    Patients Enrollment

    During the study period, a total of 244 ICU patients received treatment with either omadacycline or tigecycline. Among these, 164 patients were excluded: 53 received empirical therapy, 33 did not meet the diagnostic criteria for severe pneumonia, 30 were infected with non-CRGNB pathogens, 20 had a medication duration of less than 72 hours, 19 received sequential treatment with both omadacycline and tigecycline within 28 days, and 9 had a baseline diagnosis of advanced malignant tumors. Ultimately, a total of 80 eligible patients with CRGNB-associated severe pneumonia were enrolled in the analysis. Of these, 43 patients were assigned to the omadacycline group and received intravenous omadacycline, while 37 patients were allocated to the tigecycline group and received intravenous tigecycline. The flowchart of the study is displayed in Figure 1.

    Figure 1 Patients’ flowchart.

    Abbreviation: CRGNB, carbapenem-resistant gram-negative bacilli.

    A total of 82 CRGNB isolates were identified from sputum or bronchoalveolar lavage fluid samples of 80 patients with severe pneumonia, including 44 isolates in the omadacycline group and 38 in the tigecycline group. The most commonly isolated pathogen was CRKP, followed by CRAB. Other CRE included carbapenem-resistant Escherichia coli (CREC), carbapenem-resistant Serratia marcescens, and carbapenem-resistant Enterobacter cloacae. Two patients had respiratory specimens yielding multiple CRGNB species: one patient grew both CRKP and CRAB, and another grew both CRKP and CREC. All CRGNB strains were resistant to meropenem, and the majority remained susceptible to tigecycline. Data on susceptibility to omadacycline are lacking. No statistically significant differences were revealed in the distribution of pathogens between the two groups. The distribution of Microbiology in CRGNB-associated severe pneumonia patients is summarized in Table 1.

    Table 1 Distribution of Microbiology in CRGNB-Associated Severe Pneumonia Patients

    Baseline Features

    We analyzed the demographic and clinical baseline characteristics of the enrolled patients. No statistically significant differences were observed between the omadacycline and tigecycline groups in terms of age, sex, comorbidities, medical interventions, disease severity, laboratory parameters, duration of drug administration, or concomitant medications. Both groups most commonly used β-lactams as combination therapy in managing CRGNB-associated severe pneumonia. The baseline characteristics of the enrolled patients are presented in Table 2.

    Table 2 Baseline Characteristics of Enrolled Patients

    Primary Outcome

    The primary clinical outcome was evaluated at 28 days following the initiation of omadacycline or tigecycline therapy in all patients with CRGNB-associated severe pneumonia. The 28-day mortality rates were 16.28% (7/43) in the omadacycline group and 32.43% (12/37) in the tigecycline group. Survival analysis demonstrated no statistically significant difference in 28-day mortality between the two groups (χ2 = 2.882, p = 0.090). Comparison of Kaplan-Meier survival curves is shown in Figure 2.

    Figure 2 Comparison of Kaplan-Meier survival curves.

    Secondary Outcome

    The overall clinical efficacy rate was 58.75% (47/80), and the overall microbiological clearance rate was 53.75% (43/80). As shown in Table 3, the clinical efficacy rates in the omadacycline and tigecycline groups were 72.09% and 43.24%, respectively, showing a statistically significant difference between the two groups (p = 0.012). However, no significant difference was observed in microbiological clearance rates between the groups (58.14% vs 48.65%, p = 0.501).

    Table 3 Clinical Efficacy and Microbiological Clearance Rates

    Factors Associated with 28-Day All-Cause Mortality

    We analyzed a total of 80 patients with CRGNB-associated severe pneumonia. Based on their outcomes at 28 days, these patients were categorized into the survivor group and the non-survivor group. The overall 28-day all-cause mortality rate was 23.75% (19/80). Table 4 summarizes the univariate analysis of demographic and clinical characteristics associated with 28-day all-cause mortality. Statistically significant differences between the two groups were found for the following variables: undergoing continuous renal replacement therapy (CRRT); central venous catheterization; APACHE II score; SOFA score; baseline C-reactive protein (CRP) level; combination therapy with carbapenems and combination therapy with β-lactams.

    Table 4 Univariate Analysis of Factors Associated with 28-Day All-Cause Mortality

    We further conducted logistic regression analysis on variables with p < 0.1 and present the results in Table 5. The results revealed that undergoing CRRT, presence of central venous catheter, APACHE II score, SOFA score, baseline CRP level, and combination therapy with carbapenems were linked to higher 28-day mortality. Conversely, combination therapy with β-lactams was linked to a lower risk of 28-day mortality. The multivariate regression analysis demonstrated that combination with β-lactams was a predictor of reduced 28-day mortality (OR = 0.085, 95% CI 0.008–0.946, p = 0.045), whereas central venous catheterization (OR = 14.058, 95% CI 1.493–132.326, p = 0.021) and baseline CRP levels (OR = 1.016, 95% CI 1.003–1.030, p = 0.016) were independent predictors of increased mortality. Detailed results are provided in Table 6.

    Table 5 Univariate Logistic Regression Analysis of 28-Day All-Cause Mortality

    Table 6 Multivariable Logistic Regression Analysis of 28-Day All-Cause Mortality

    Safety Assessment

    We evaluated the safety of study medications in all 80 enrolled patients. As shown in Table 7, the overall adverse events (AEs) included diarrhea, thrombocytopenia or pancytopenia, and elevated bilirubin or liver enzymes. The incidence of AEs was 4.65% (2/43) in the omadacycline group and 24.32% (9/37) in the tigecycline group, which indicates a significant intergroup difference (p = 0.020). The main difference in AEs between the two groups was gastrointestinal symptoms, particularly a significantly higher incidence of diarrhea in the tigecycline group (p = 0.008). All AEs resolved after discontinuation of the study drugs in both groups.

    Table 7 Incidence of Adverse Events

    Discussion

    The emergence and spread of CRGNB represent a significant public health concern. CRGNB-associated severe pneumonia presents a particularly challenging clinical problem. A study based on 94,888 clinical isolates collected between 2000 and 2017 revealed that 41% of patients from whom CRGNB was isolated were hospitalized in the ICU, with the most common source of culture specimens being the respiratory tract (53%). Importantly, both mortality and disease burden were significantly increased.16 Treatment options for CRGNB infections are extremely limited. Novel tetracyclines, which overcome the most common resistance mechanisms associated with traditional tetracyclines, have emerged as a crucial therapeutic option for managing CRGNB infections.17 Previous studies have reported that tigecycline plasma concentrations are positively correlated with the administered dose. Clinical efficacy is likely influenced by the MIC of the causative pathogen. Although increasing the dose of tigecycline may enhance clinical success rates, dose-limiting AEs can occur, leading to reduced patient tolerance and an increased likelihood of treatment discontinuation.18,19 Omadacycline and tigecycline are both third-generation novel tetracyclines with comparable and favorable tissue penetration. However, omadacycline demonstrates approximately threefold higher systemic exposure in plasma, epithelial lining fluid (ELF), and alveolar cells (AC) compared to tigecycline. Moreover, its concentration in AC is markedly higher than that in plasma or ELF.20 Omadacycline is available in both intravenous and oral formulations, whereas tigecycline is only available as an intravenous agent. A real-world study demonstrated that oral omadacycline achieved a clinical success rate of 66.7% (6/9) in treating MDR or extensively drug-resistant (XDR) gram-negative bacterial infections. Specifically, the success rates were 80.0% (4/5) for bone/joint infections, 33.3% (1/3) for intra-abdominal infections, and 100% (1/1) for VAP.21 In addition, a case report has documented the effective management of complicated acute bacterial skin and skin structure infections caused by carbapenem-resistant Enterobacter cloacae through oral administration of omadacycline.22 To date, there is a paucity of studies evaluating the efficacy of omadacycline for treating severe pneumonia caused by CRGNB. Chinese researchers have conducted studies on the efficacy and safety of omadacycline versus tigecycline for treating CRAB pneumonia in ICU patients; however, additional clinical data are still required. In our study, we enrolled 80 patients with CRGNB-associated severe pneumonia. Of these, 90.00% (72/80) were receiving mechanical ventilation, and 80.00% (64/80) had either endotracheal intubation or tracheostomy. Both drugs were administered intravenously. No significant differences were noted between the omadacycline and tigecycline groups in terms of 28-day mortality (16.28% vs 32.43%, p = 0.090) or microbial clearance rates (58.14% vs 48.65%, p = 0.501). Notably, the clinical efficacy rate was significantly higher in the omadacycline group (72.09% vs 43.24%, p = 0.012). Based on primary outcomes, we conclude that omadacycline exhibits non-inferior clinical efficacy compared to tigecycline in the treatment of CRGNB-associated severe pneumonia.

    In clinical practice, tigecycline-based combination therapy is one of the treatment options for CRGNB pulmonary infections.7 However, the majority of evidence supporting the synergistic effects of such combination therapies originates from in vitro or animal studies. One study indicated that among MDR gram-negative pathogens, the combination of tigecycline with polymyxins (colistin or polymyxin B) is the most extensively investigated and has demonstrated synergistic activity.23 Compared to monotherapy, the combination of tigecycline and aminoglycosides has shown synergistic effects in vitro against carbapenemase-producing (including KPC and NDM-1) Klebsiella pneumoniae, potentially reducing the development of tigecycline resistance.24 Studies on omadacycline have also yielded similar results. Against carbapenem-nonsusceptible Acinetobacter baumannii, omadacycline in combination with sulbactam exhibited the highest synergy rate and bactericidal activity (80%), followed by omadacycline plus amikacin or polymyxin B (both at 30%).25 Another in vitro susceptibility test indicated that the combination of omadacycline and polymyxin B exerts a robust synergistic activity against KPC-producing CRKP.26 In our study, multivariate logistic regression analysis revealed that combination therapy with β-lactams was an independent predictor of reduced 28-day mortality in patients with CRGNB-associated severe pneumonia (OR = 0.085, 95% CI 0.008–0.946, p = 0.045). Among the 33 cases treated with a combination of omadacycline or tigecycline and β-lactams, 69.70% (23/33) received cefoperazone/sulbactam, and 18.18% (6/33) received piperacillin/tazobactam. Of note, 93.94% (31/33) of the patients survived. Given that novel tetracyclines exhibit intrinsic resistance to Pseudomonas aeruginosa and are therefore not used for CRPA infections, they may be used in conjunction with β-lactams to treat severe pneumonia attributable to CRE or CRAB.

    Tigecycline treatment is frequently linked to mild to moderate gastrointestinal AEs, including diarrhea, nausea, and vomiting. At the higher dose (200 mg/day), the incidence of these AEs increases, with diarrhea, nausea, and vomiting reported at 14.3% vs 2.8%, 8.6% vs 2.8%, and 5.7% vs 2.8%, respectively.27,28 Data from a real-world cohort of 973 patients showed that 5.7% (55/973) developed tigecycline-associated liver injury, predominantly of the cholestatic type (41/55). The incidence was significantly higher with high maintenance dose regimens (100 mg) and treatment durations exceeding 14 days compared to the standard dose and conventional treatment duration.29 A retrospective study involving 373 patients revealed an incidence of thrombocytopenia at 12.3%, with tigecycline treatment for ≥7 days emerging as a significant independent risk factor.30 Another study found that patients receiving high-dose tigecycline experienced a more pronounced reduction in fibrinogen levels compared to those in the standard-dose group.19 Tetracyclines exhibit a similar pattern of AEs. Despite these commonalities, the safety profile of omadacycline has not yet been fully characterized. Clinical trials have reported gastrointestinal disturbances, as well as elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.31,32 Research data from healthy volunteers indicated a lower incidence of AEs in the omadacycline group compared to the tigecycline group. The most notable difference between the two groups was observed in the incidence of nausea, which was 2.4% versus 47.6%.20 Similar results were observed in our study. The overall incidence of AEs differed significantly between the two groups, with a lower rate observed in the omadacycline group (4.65%) compared to the tigecycline group (24.32%) (p = 0.020). Most notably, diarrhea occurred exclusively in the tigecycline group (16.22% vs 0.00%, p = 0.008). We observed that the AEs associated with omadacycline were primarily characterized by thrombocytopenia and elevated ALT. These results suggest that omadacycline may provide a safer therapeutic option than tigecycline for the management of severe pneumonia caused by CRGNB.

    This study has several limitations that should be acknowledged. Firstly, the relatively small sample size and the retrospective design of the analysis may introduce potential confounding factors, which could limit the generalizability of the findings. Secondly, tigecycline was administered at standard doses without therapeutic drug monitoring (TDM), which limits our ability to assess the relationship between dosage and efficacy. Future research should involve larger-scale, prospective, randomized controlled trials with more comprehensive clinical data to further evaluate and validate the differences in efficacy and safety between omadacycline and tigecycline, thereby providing robust evidence to guide therapeutic decisions and ultimately improve patient outcomes.

    Conclusion

    In summary, our study indicates that omadacycline provides comparable clinical efficacy to tigecycline in treating severe pneumonia caused by CRGNB, while exhibiting a more favorable safety profile. Furthermore, novel tetracyclines may be used in combination with β-lactams for the treatment of severe pneumonia caused by CRGNB. Additionally, central venous catheterization and elevated baseline CRP levels were associated with increased 28-day mortality. These findings warrant further validation through larger, well-designed randomized controlled trials.

    Data Sharing Statement

    Data will be made available on request.

    Ethical Approval

    The study protocol was approved by the Ethics Review Committee of The Second Affiliated Hospital of Zhejiang Chinese Medical University (Approval No. ZJTCMU2AE2025R028-IH01).

    Acknowledgments

    We wish to thank all the authors for completing this study in their spare time after busy work.

    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

    The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

    Disclosure

    The authors have no relevant financial or non-financial interests to disclose.

    References

    1. De Pascale G, Bello G, Tumbarello M, Antonelli M. Severe pneumonia in intensive care: cause, diagnosis, treatment and management: a review of the literature. Curr Opin Pulm Med. 2012;18(3):213–221. doi:10.1097/MCP.0b013e328351f9bd

    2. Cilloniz C, Torres A, Niederman MS. Management of pneumonia in critically ill patients. BMJ. 2021;375:e065871. doi:10.1136/bmj-2021-065871

    3. Liapikou A. The burden of community-acquired Pneumonia requiring admission to an ICU in the United States. Chest. 2020;158(3):841–843. doi:10.1016/j.chest.2020.06.017

    4. Ching PR, Pedersen LL. Severe Pneumonia. Med Clin North Am. 2025;109(3):705–720. doi:10.1016/j.mcna.2024.12.011

    5. Huemer M, Mairpady Shambat S, Brugger SD, Zinkernagel AS. Antibiotic resistance and persistence-Implications for human health and treatment perspectives. EMBO Rep. 2020;21(12):e51034. doi:10.15252/embr.202051034

    6. Sati H, Carrara E, Savoldi A, et al. The WHO bacterial priority pathogens list 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance. Lancet Infect Dis. 2025;25(9):1033–1043. doi:10.1016/S1473-3099(25)00118-5

    7. Zeng M, Xia J, Zong Z, et al. Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli. J Microbiol Immunol Infect. 2023;56(4):653–671. doi:10.1016/j.jmii.2023.01.017

    8. Yaghoubi S, Zekiy AO, Krutova M, et al. Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review. Eur Jo Clin Microbiol Infect Dis. 2021;41(7):1003–1022. doi:10.1007/s10096-020-04121-1

    9. Zhanel GG, Esquivel J, Zelenitsky S, et al. Omadacycline: a novel oral and intravenous aminomethylcycline antibiotic agent. Drugs. 2020;80(3):285–313. doi:10.1007/s40265-020-01257-4

    10. Dong D, Zheng Y, Chen Q, et al. In vitro activity of omadacycline against pathogens isolated from Mainland China during 2017-2018. Eur J Clin Microbiol Infect Dis. 2020;39(8):1559–1572. doi:10.1007/s10096-020-03877-w

    11. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired Pneumonia. an official clinical practice guideline of the American thoracic society and infectious diseases society of America. Am J Respir Crit Care Med. 2019;200(7):e45–e67. doi:10.1164/rccm.201908-1581ST

    12. Lambden S, Laterre PF, Levy MM, Francois B. The SOFA score-development, utility and challenges of accurate assessment in clinical trials. Crit Care. 2019;23(1):374. doi:10.1186/s13054-019-2663-7

    13. LeGall JRLP, Loirat P, Alpcrovitch A. Alpérovitch A APACHE II–a severity of disease classification system. Crit Care Med. 1986;14(8):754. doi:10.1097/00003246-198608000-00027

    14. Shi Y, Hu J, Liu P, et al. Ceftazidime-avibactam-based versus tigecycline-based regimen for the treatment of carbapenem-resistant Klebsiella Pneumoniae-induced pneumonia in critically Ill patients. Infect Dis Ther. 2021;10(4):2721–2734. doi:10.1007/s40121-021-00542-3

    15. Wang J, Shah BK, Zhao J, Xiong J, Wang C, Xie S. Comparative study of polymyxin B and colistin sulfate in the treatment of severe comorbid patients infected with CR-GNB. BMC Infect Dis. 2023;23(1):351. doi:10.1186/s12879-023-08339-0

    16. Babiker A, Clarke LG, Saul M, et al. Changing epidemiology and decreased mortality associated with carbapenem-resistant gram-negative bacteria, 2000-2017. Clin Infect Dis. 2021;73(11):e4521–e4530. doi:10.1093/cid/ciaa1464

    17. LaPlante KL, Dhand A, Wright K, Lauterio M. Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance. Ann Med. 2022;54(1):1686–1700. doi:10.1080/07853890.2022.2085881

    18. Kispal B, Walker SAN. Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults. Eur J Clin Pharmacol. 2021;77(2):197–205. doi:10.1007/s00228-020-02998-7

    19. Bai XR, Wang ZZ, Li WC, et al. Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units. BMC Infect Dis. 2023;23(1):830. doi:10.1186/s12879-023-08815-7

    20. Gotfried MHHK, Garrity-Ryan L, Villano S, et al. Comparison of omadacycline and tigecycline pharmacokinetics in the plasma, epithelial lining fluid, and alveolar cells of healthy adult subjects. antimicrob agents chemother. Antimicrob Agents Chemother. 2017;61(9):e01135–17. doi:10.1128/AAC.01135-17

    21. Morrisette T, Alosaimy S, Lagnf AM, et al. Real-world, multicenter case series of patients treated with oral omadacycline for resistant gram-negative pathogens. Infect Dis Ther. 2022. doi:10.1007/s40121-022-00645-5

    22. VanDuyn DC, Chadha S, Paul LA, Dressler AR, Beccari MV, Bajwa RPS. Omadacycline for a carbapenem-resistant enterobacter cloacae-associated wound infection. Hosp Pharm. 2022;57(6):767–770. doi:10.1177/00185787221095767

    23. Cai Y, Bai N, Liu X, Liang B, Wang J, Wang R. Tigecycline: alone or in combination? Infect Dis. 2016;48(7):491–502. doi:10.3109/23744235.2016.1155735

    24. Ni W, Yang D, Guan J, et al. In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae. J Antimicrob Chemother. 2021;76(8):2097–2105. doi:10.1093/jac/dkab122

    25. Abbey TVA, Jurkovic M, Biagi M, Wenzler E, Wenzler E. Activity of omadacycline alone and in combination against carbapenem-nonsusceptible acinetobacter baumannii with varying minocycline susceptibility. Microbiol Spectr. 2022;10(3):e0054222. doi:10.1128/spectrum.00542-22

    26. Du Y, Liu Y, Liu T, et al. The in vitro activity of omadacycline alone and in combination against carbapenem-resistant Klebsiella pneumoniae. Infect Drug Resist. 2024;17:5785–5794. doi:10.2147/IDR.S473546

    27. Zhanel GGKJ, Rubinstein E, Hoban DJ, Hoban DJ. Tigecycline: a novel glycylcycline antibiotic. Expert Rev Anti Infect Ther. 2006;4(1):9–25. doi:10.1586/14787210.4.1.9

    28. Falagas ME, Vardakas KZ, Tsiveriotis KP, Triarides NA, Tansarli GS. Effectiveness and safety of high-dose tigecycline-containing regimens for the treatment of severe bacterial infections. Int J Antimicrob Agents. 2014;44(1):1–7. doi:10.1016/j.ijantimicag.2014.01.006

    29. Shi X, Zuo C, Yu L, et al. Real-world data of tigecycline-associated drug-induced liver injury among patients in china: a 3-year retrospective study as assessed by the updated RUCAM. Front Pharmacol. 2021;12:761167. doi:10.3389/fphar.2021.761167

    30. Zhu Y, Zhao F, Jin P. Clinical manifestations and risk factors of tigecycline-associated thrombocytopenia. Infect Drug Resist. 2023;16:6225–6235. doi:10.2147/IDR.S426259

    31. Lin F, He R, Yu B, Deng B, Ling B, Yuan M. Omadacycline for treatment of acute bacterial infections: a meta-analysis of Phase II/III trials. BMC Infect Dis. 2023;23(1):232. doi:10.1186/s12879-023-08212-0

    32. Kounatidis D, Dalamaga M, Grivakou E, et al. Third-generation tetracyclines: current knowledge and therapeutic potential. Biomolecules. 2024;14(7):783. doi:10.3390/biom14070783

    Continue Reading

  • Guest curator Riz Ahmed spotlights artist Imran Perretta

    Guest curator Riz Ahmed spotlights artist Imran Perretta

    Growing up in his family, music was the thing. Perretta and his sister, along with other nineties kids from their London borough, attended a council-funded music school on weekends which gave out free instruments. He received a classical guitar. As a teenager, music videos were the thing. He’d watch Channel U, a British music television channel airing often homemade, handheld videos from the local grime scene, and then go out and make films with his friends. Art came much later, and just in time. 

    In 2008, as a 20-year-old architecture student, Perretta stopped in at Serpentine Gallery on a whim, where “Blue” by the late multidisciplinary artist and filmmaker Derek Jarman was showing. A static blue screen set to a soundscape in which Jarman speaks his lyrical thoughts aloud; musings and matter-of-facts about his deteriorating condition living with AIDS, and losing his eyesight. “It shook me to my core,” Perretta remembers, feeling especially moved as his mother was critically ill with cancer at the time. He didn’t want to be an architect anymore; “Blue” had completely broken open his definition of a creative practice. He picked up a video camera again, and eventually enrolled to do his MFA at Slade School of Fine Art. 

    Continue Reading