ABSTRACT Corruption leaves people stressed as they struggle to access services that directly affect the availability of basic necessities. The debate over administrative capital, literacy, and preparedness occupies a significant portion of the theoretical framework of the administrative burden. However, the discussion does not explain how people behave when corruption is prevalent in a sociopolitical setting, as they find it difficult to mitigate their stress related to well-being. This gap is addressed by analysing data from the World Values Survey and the Corruption Perceptions Index. Bangladesh, Pakistan, Indonesia, Malaysia, and Thailand were selected from the Asia-Pacific region to conduct population-level analyses using structural equation modelling and moderated mediation models. The results suggest that people tend to have a higher degree of trust-based, particularised social capital than trust-based, generalised social capital, which helps reduce stress when corruption is high. Additionally, the more people follow collectivist cultural values, the more they build particularised social capital rather than generalised social capital, thereby reducing stress due to corruption. Considering these findings, I argue that particularised social capital, as a safeguard against corruption, could both mitigate and exacerbate corruption in the region.

Renal nerves are critical modulators of kidney function and blood pressure (BP) control. Their influence on sodium and fluid retention, renin release and vasoconstriction rendered them a therapeutic target more than a century ago when surgical splanchnicectomy emerged as one of the first effective antihypertensive therapies. Revisiting the concept using catheter-based approaches to ablate renal afferent and efferent nerves more selectively with various energy sources demonstrated the efficacy of renal denervation in reducing sympathetic nerve activity. A series of sham-controlled randomised clinical trials in patients with uncontrolled or resistant hypertension either on or off concomitant antihypertensive drugs demonstrated procedural safety and clinically meaningful BP reduction. Durability of the BP lowering efficacy has been demonstrated out to 10 years in observational studies. Major international guidelines now recommend renal denervation as an adjunct therapy in patients with uncontrolled or resistant hypertension where other means have failed or resulted in insufficient BP control. Patient selection and patient preference are relevant aspects to be considered in a shared decision-making process leading up to the denervation procedure, which should be performed in experienced centres. While approved in the USA, most countries in Europe, Asia-Pacific and many other regions lack adequate reimbursement currently, which remains a barrier for more widespread implementation into clinical practice despite favourable cost-effectiveness analyses. While now established in the context of hypertension management, ongoing research explores its potential utility in other conditions characterised by increased sympathetic drive, with most promising results in patients with chronic kidney disease, atrial fibrillation, heart failure and others. Further refinement of procedural aspects may reduce procedure time and augment the BP lowering efficacy. Clinicians should embrace the additional options that device-based therapies offer to improve BP management, mostly in combination with pharmacologic therapies. After all, it is just another means of bringing the pressure down.

Since 2016, the Asia-Pacific Working Group (APWG) has supported the Association for Diagnostics & Laboratory Medicine's (ADLM) Global Lab Quality Initiative (GLQI) by enhancing laboratory medicine education and training in developing countries. The group has delivered programs in 10 countries across the Asia-Pacific region. To better understand the regional landscape and country-specific needs, the APWG conducted a comprehensive needs assessment through an APWG survey and virtual interviews. The findings demonstrated the complexity of the Asia-Pacific region, while also revealing a common interest in enhancing laboratory quality. Common challenges identified include limited resources, financial constraints, outdated technology, and staff shortages. The needs assessment analysis will guide the APWG to carry out further programs to enhance laboratory quality education for laboratorians across diverse geographical regions.

Purpose This study aims to evaluate adaptive hedging strategies for the oil–stock nexus in the Asia-Pacific region. This study also aims to compare management policies for risk spillover across M-GARCH models, focusing on findings from emerging and advanced nations. Design/methodology/approach The study used a novel integration of DCC-GARCH, GO-GARCH, aDCC-GARCH and EGARCH-DCC to build hedging strategies. Meanwhile, analysis of structural breaks shows that the different global crises have altered the linkages in the oil–stock nexus. Findings Outcomes revealed that GO-GARCH is suitable for conservative investors. DCC-GARCH and aDCC-GARCH are more responsive to active investors. EGARCH-DCC offers a balance between stability and sensitivity. Oil is the most effective hedging strategy for stocks in Singapore, and the least effective in the Philippines. Optimal allocations with oil reveal a preference in Vietnam and a low weight in Malaysia. Structural breakpoints analysis highlights decision-making in Singapore, India and Vietnam. Research limitations/implications Future research may be expanded to other regions and higher frequencies. This research aims to assist participants in refining risk management across both long- and short-term crises, in line with each M-GARCH model. Originality/value The study makes a novel contribution by using various multivariate GARCH volatility models to allocate oil–stock nexus volatility across the Asia-Pacific region. Certain breakpoints and specific dates across multiple indices in different countries highlight the link between financial markets’ reactions and the global crisis.

BackgroundHand, foot, and mouth disease (HFMD), a common childhood illness caused by various enteroviruses, poses a significant public health threat in the Asia-Pacific region, where severe cases associated with enterovirus A71 (EV71) are a major concern. The EV71 vaccination program was introduced in China in late 2016. Although randomized controlled trials have established the robust efficacy and safety of these vaccines, assessing their real-world performance remains crucial. Subsequent studies have evaluated its real-world effectiveness in several provinces, including Zhejiang and Guangdong. However, evidence on its real-world impact in reducing EV71-associated HFMD in Jiangsu Province remains limited.ObjectiveThis study aimed to describe HFMD epidemiological characteristics and to evaluate the population-level effectiveness of the EV71 vaccination program in Jiangsu Province.MethodsWe characterized the temporal distribution of EV71-related HFMD cases based on longitudinal surveillance data collected through the National Notifiable Diseases Surveillance System in Jiangsu Province from 2012 to 2019 and assessed the impact of vaccination using a Bayesian structural time series model under a counterfactual framework. The intervention effect of the EV71 vaccine was estimated by comparing the observed data with predictions from a counterfactual model scenario without vaccination.ResultsA total of 932,274 HFMD cases were reported in Jiangsu from 2012 to 2019, including 5190 (0.56%) severe cases. An estimated 140,876 (15.11%) cases were attributed to EV71. EV71-associated HFMD cases showed a marked decline, with estimated numbers of 22,303, 9796, and 3900 in 2017, 2018, and 2019, respectively. We estimated that 30,117 EV71 cases (95% credible interval −1777 to 93,601) were prevented by the vaccination program from 2017 to 2019, corresponding to a reduction of 45.55% (95% credible interval −5.19% to 72.22%). The effectiveness of vaccination increased annually, with reductions of −1.03% (95% credible interval −94.85% to 48.29%) in 2017, 55.54% (95% credible interval 13.94%-77.56%) in 2018, and 82.28% (95% credible interval 65.77%-90.89%) in 2019. Furthermore, we observed that children younger than 4 years obtained greater benefits compared with those older than 4 years, with the greatest reduction of 57.68% (95% credible interval 13.04%-79.65%) in the 3- to 4-year age group, followed by a 48.09% (95% credible interval 28.00%-62.98%) reduction in the 0- to 2-year age group. In contrast, the reduction was markedly lower, at 16.75 % (95% credible interval −96.53% to 65.47%) in children older than 4 years during the 2017 to 2019 period.ConclusionsEV71 vaccination is an effective measure to prevent HFMD. The sharp decline in EV71-associated HFMD cases following the implementation of the EV71 vaccination program suggests a potential causal relationship. Therefore, strengthening vaccine coverage remains a public health priority.

Correction: Part II: consensus statements and expert recommendations for BRCA-associated breast cancer in the Asia-Pacific region: clinical management

Background: Jaundice is the commonest presenting features of hepatitis and it is a common clinical condition in Bangladesh. As a country of the Asia Pacific region Bangladesh is considered to be a high risk country for developing hepatitis by differ ent hepatotropic viruses. This study represents the patterns and types of viruses among the patients admitted in a tertiary care hospitals in Bangladesh who were presented with jaundice. Materials and methods: Present cross sectional observational study done during a one year study period from July 2022 to June 2023 in a tertiary care hospital, Chattogram, Bangladesh among 114 patients. All patients who had clinical jaundice or having serum bilirubin > 2 mg/dl were recruited in the study. Clinical data were collected from all of them and viral serology were also done by ICT or ELISA. Informed written consent were taken from all patients and permission for the study were taken from ERB of the medical college. Results: Among 114 study subjects, male were 73(64%) and female were 41(36%) and male to female ratio was 1: 0.56. Among all, maximum were in the age range of <20 years and 21- 30 years which were 46(40.4%) and 44(38.6%) respectively. Regarding clinical features, 109(95.6%) had jaundice and 89(78.1%) had fever and 74(64.9%) had nausea and these were three dominant clinical features found. Viral serology study revealed frequency of HAV, HBV, HCV and HEV infection were 43(37.7%), 9(7.9%), 1(0.9%) and 26(22.8%) respectively. There were viral coinfections with (HAV+HEV), (HAV+HBV) and (HBV + HEV) and it were 8(7.0%), 4(3.5%) and 3(2.6%) respectively. Among all 20(17.5%) cases were tested negative for hepatotropic viruses. Again 6(5.3%) had Anti HBc Positivity and 2(1.8%) cases were found coinfected with HIV. Conclusions: In a year round, HAV and HEV are two common viral infection causing jaundice among the locality. HBV had a significant level of infection with low level HCV causing jaundice. Two HIV coinfection is an alarming condition found among the jaundice patients which need further exploration and risk factor evaluations. Chatt Maa Shi Hosp Med Coll J; Vol.24 (2); July 2025; Page 72-75

Animal models of critical illness span diverse species and experimental approaches, reflecting the biological complexity of severe disease states while being constrained by animal welfare requirements and country-specific regulatory, infrastructural, and workforce factors. Persistent challenges remain, including limited reproducibility, fragmented standards, and the need for ethical alignment across borders. This review examines these shared structural challenges in critical illness animal research across the Asia-Pacific region. While alternative and complementary methodologies are increasingly incorporated into preclinical research, their adoption remains uneven. We argue that alignment with globally recognized preclinical frameworks, including the 3Rs and disease-specific standards, such as MQTiPSS, is essential. This review discusses actionable strategies-centered on harmonized standards, shared resources, and international collaboration-to strengthen research rigor, support early career researchers, and enhance the translational relevance of critical illness animal research.

Abstract This study examines the combined effects of sudden stratospheric warming events (SSWs) and El Niño and Southern Oscillation (ENSO) on late winter (January–March) climate in China. It is found that SSWs significantly modulate El Niño’s impact over China. During El Niño winters with SSWs, southern China tends to experience notable warming; conversely, without SSWs, the surface air temperatures there are generally colder. However, SSWs do not effectively alter La Niña’s impact; southern China remains anomalously colder during La Niña winters even when SSWs occur. The net warming effect of SSWs over much of China during La Niña, defined as the difference between scenarios with and without SSWs, is found considerably weaker than during El Niño. These discrepancies arise from the contrasting tropospheric pathway of ENSO teleconnection over the East Asia–Pacific region. Specifically, El Niño influences the occurrence of SSWs primarily by enhancing the tropospheric planetary wave 1. This enhancement corresponds to an emergence of a dipole pattern of geopotential height anomalies, characterized by an anomalous low over northeastern Eurasia and an anomalous high over China. In contrast, La Niña contributes to SSW occurrences via an increase in the tropospheric wave 2, which corresponds to only an anomalous low over northeastern Eurasia. The consistently significant high over China both before and after SSWs during El Niño, but much weakened or even absent during La Niña, is mainly responsible for the stronger net warming in late winter over China in El Niño years.

BackgroundScrub typhus is a leading cause of febrile illness across the Asia–Pacific region. Doxycycline is the first-line therapy, with azithromycin as an alternative; sequential treatment (doxycycline followed by azithromycin) is used for nonresponders. However, comparative real-world effectiveness for sequential therapy remains uncertain.MethodsWe conducted a single-center, non-interventional target-trial emulation at the 970th Hospital of the People’s Liberation Army (January 2023 – June 2025). Consecutive patients ≥12 years receiving oral doxycycline, azithromycin, or sequential doxycycline/azithromycin treatment were included. The primary outcome was 48-hour defervescence sustained ≥24 h without antipyretics. Secondary outcomes were time to defervescence, Day 5 failure, complications, length of stay, 28-day mortality, and safety. Confounding was addressed using inverse probability weighting (generalized boosted models). The confirmatory comparison (doxycycline vs azithromycin) was limited to non-pregnant initiators (pregnancy excluded due to structural non-overlap) to satisfy positivity. The sequential pathway was explored descriptively with time-varying and 48-hour landmark analyses.ResultsWe analyzed 512 patients (doxycycline 206, azithromycin 208, and sequential 98). Crude 48-hour defervescence was 82.0%, 78.8%, and 66.3%, respectively. In the confirmatory inverse probability of treatment weighting (IPTW) analysis, doxycycline vs azithromycin showed no difference (adjusted RR 1.03, 95% CI 0.95–1.12; p=0.34). Weighted time-to-event analysis was concordant (aHR 1.08, 95% CI 0.96–1.21; p=0.20). Secondary outcomes were similar between monotherapies (Day-5 failure aRR 0.83, 95% CI 0.56–1.24; complications aRR 0.94, 95% CI 0.66– 1.33; median length of stay 5 [IQR 4–7] days in both; 28-day mortality 1.6% overall). The sequential switch group had lower crude 48-hour defervescence, consistent with escalation after early non-response. Pairwise causal contrasts involving the sequential pathway were not presented due to structural bias.ConclusionsOral doxycycline and azithromycin demonstrated comparable effectiveness and safety for early defervescence in routine care. Inferior crude outcomes with sequential therapy likely reflect clinical escalation. Multi-center validation and randomized trials are warranted.

The Diversity and Equity Committee (DEC) of the Asian Pacific Society of Nephrology (APSN) conducted a regional review to characterise disparities in kidney disease burden, healthcare access and nephrology service delivery across the Asia-Pacific (AP) region. A descriptive summary was compiled using national reports, registries, and expert inputs from DEC representatives. Data included kidney disease prevalence, dialysis and transplant modalities, healthcare system characteristics and disparity-related indicators. Comparative insights were drawn across countries using structured tables and narrative synthesis. The AP region exhibits a disproportionate burden of chronic kidney disease (CKD) and kidney failure with marked heterogeneity in disease aetiology, healthcare financing, and infrastructure. High-income countries such as Japan, Korea, Taiwan and Australia demonstrate mature universal insurance systems, comprehensive dialysis networks and national CKD prevention programs. Middle- and lower-income countries-including Indonesia, Myanmar, Mongolia and parts of South and Southeast Asia-face critical challenges such as workforce shortages, limited dialysis and transplant capacity and geographic inequities. Despite these challenges, several countries have introduced exemplary models to enhance equity and sustainability in kidney care: PD-first policies (Hong Kong, Thailand), pay-for-performance CKD programs (Taiwan), Kidney Health Plan 2033 (Korea), HALT-CKD (Singapore), and ACT-KID (Malaysia), indigenous kidney health efforts in Australia and the inclusion of additional insurance points for patient education in Japan. Persistent gaps remain in early detection, transplantation access, rural care and minority equity. Kidney disease care in the Asia-Pacific region reflects both diversity and disparity. Although universal health coverage and national kidney health initiatives have improved access in many countries, substantial inequities persist across geography, income and cultural groups. The collective experiences highlight both common challenges and innovative solutions. Strengthening regional collaboration, policy-driven efforts and sustainable workforce development are essential to achieving equitable kidney health for all.

Spodoptera frugiperda (fall armyworm; FAW) is a major agricultural pest native to the Americas, with the first reported invasion of Africa in early 2016. Since then, FAW has spread rapidly across Africa and Asia before invading Australia (2020) and first being detected in Aotearoa New Zealand in February 2022. Here, we assessed the whole genomes of 34 novel FAW individuals along the invasion front (representing three new invasive populations from Cambodia, Australia, and New Zealand) with the largest publicly available global FAW genome dataset (n = 173), resulting in a dataset of 112 and 99 samples from the invasive and native range, respectively, to: (1) place the new invasive populations within the global invasion; (2) identify the potential geographic origin of the New Zealand invasion, including from a single or multiple incursion event; and (3) assess pre-existing insecticide resistance potential at the invasion front. We confirm that these new invasions conform to the broad population structure of the initial invasive populations identified in Benin (West Africa), all of which belong to the invasive corn strain, as defined through previous triosephosphate isomerase (TPI) analysis and associated isolation from specific host plants. While we could not confidently assign the source population of the New Zealand invasion, we find preliminary support for a multiple introduction hypothesis in our data, which could contribute to increased genetic diversity within the New Zealand population. Further sampling is therefore required to fully characterise the origins of the New Zealand invasion. In novel samples, we detected putative insecticide resistance alleles previously reported in other invasive populations. These resistant loci should be tracked over time to understand the mechanisms enabling the invasion success of FAW in the Asia-Pacific region. We emphasise that sharing of genomic resources between institutions and consortia is an essential first step in the control of this global invader.

Spatio-temporal dispersal patterns of SARS-CoV-2 in the Chinese mainland following the COVID-19 response adjustment.

From obstacles to opportunities: Innovations and evolution of strategies in scrub typhus vaccine research.

The multi-country epIdeMiology landscape PAtient Care paThways of Obesity (IMPACT-O) retrospective cohort study utilised existing electronic medical records to gather data on overweight and obesity. We report UK data on obesity-related complications (ORCs) and management strategies. The UK IQVIA Medical Research Database, The Health Improvement Network database, includes routine data from UK primary care. Outcomes analysed included sociodemographic and clinical characteristics, ORCs and treatments for three cohorts: adults (≥18 years) with a new record of overweight or obesity (body mass index [BMI] ≥25 kg/m2; overweight/obesity cohort) or obesity (BMI ≥30 kg/m2; obesity cohort) identified by BMI recordings and/or diagnosis codes, and adults with ≥1 recorded interventions with an effect on weight (intervention cohort) between 2018 and 2022. There were 73 279 adults in the overweight/obesity cohort, 62 226 adults in the obesity cohort and 343 755 adults in the intervention cohort. Most adults had ≥1 ORC with a numerically higher proportion of ORCs recorded in the obesity cohort (58.4%) than in the overweight/obesity cohort (48.0%). For the intervention cohort, 77.0% had ≥1 ORC. Lifestyle interventions were recorded for 96.8% of this cohort, followed by pharmacological therapies with an effect on weight (glucagon-like peptide-1 receptor agonists, 3.6%; orlistat, 2.5%), and bariatric surgery (0.3%). Results confirm the high burden of ORCs in adults at first identification of overweight or obesity in primary care and the limited use of pharmacotherapy and bariatric surgery; this suggests a need to evaluate treatment strategies and support for people with overweight and obesity in the UK. What is the context and purpose of this research study? Health-related information recorded in electronic medical records during visits to your doctor can help increase understanding of the impact of overweight and obesity in healthcare settings. What was done? The epIdeMiology landscape and PAtient Care paThways of Obesity (IMPACT-O) was a study conducted in selected countries in Europe and the Asia-Pacific region that used information from existing healthcare records to report the impact of overweight and obesity. This paper reports the results from the UK part of the study, using information provided by general practitioners. Data on social, demographic and health-related characteristics of people with overweight and obesity were collected for adults (at least 18 years of age) at the time their first record of overweight or obesity was recorded, either with a diagnosis from the doctor or a body mass index (BMI) of ≥25 kg/m2 (overweight/obesity group) or ≥30 kg/m2 (obesity group) and for adults with at least one record indicating the use of a method for weight loss (intervention cohort). What were the main results? Most adults included in the study had at least one additional condition that was related to their obesity, and more people in the obesity group than the overweight/obesity group had an additional obesity-related condition. The most commonly recorded additional obesity-related condition was high blood pressure in the obesity group and depression in the overweight/obesity group. In the group who had a method of weight loss recorded, three in every four adults had at least one additional obesity-related condition. The average BMI of adults in this group was 29.0 kg/m2. Lifestyle changes, such as diet and exercise, were recorded for nearly all adults in this group, followed by medications with an effect on weight (such as glucagon-like peptide-1 receptor agonists and orlistat), and weight-loss surgery. What is the originality and relevance of this study? The study results confirm that adults are already heavily affected by obesity-related conditions by the time of their first formal documentation of overweight or obesity in primary care. Only a small number of adults with overweight or obesity had records of medication or surgery for weight loss management. These results mean that there is a need for improved surveillance of these adults in the UK.

Strengthening Oncology Data Systems for Equitable Care in Asia-Pacific: Current Practices and Future Directions.

This article provides a comparative legal analysis of the experience of various foreign countries in ensuring the protection of personal data as a fundamental human right in the context of digital transformation. The study compares the approaches to ensuring the right to privacy, the rights of the data subject, and human rights in the digital environment in the national legislative systems of the European Union, the United States of America, the Asia-Pacific region, and Central Asia. The article reveals the specific features of the models of regulation of digital rights and institutional systems of states belonging to different legal families. The author used the methodology of comparative analysis to determine the most effective ways of implementing international human rights standards into national legislation. The research results will serve to develop practical recommendations for improving the system of human rights protection in the digital environment of the Republic of Uzbekistan.

Assessing clinical utility of genome sequencing (GS) is essential for healthcare decisions. This study quantified the multidimensional utility of GS using the validated Clinician-reported Genetic testing Utility InDEx (C-GUIDE) within a diverse rare disease cohort at the Hong Kong Genome Project. Adult and paediatric patients suspected of genetic disorders were recruited from the Hong Kong Children's Hospital. Clinical geneticists evaluated GS utility based on 17 items. Total C-GUIDE utility scores and global item scores were calculated, with individual item scores ranging from -2 to 2. Between March and July 2024, three clinical geneticists completed 247 C-GUIDE ratings for 245 probands, with 25% receiving positive, 7% inconclusive, and 69% negative GS results. Total C-GUIDE scores ranges from -1 to 30, with a mean of 6.1 (SD = 10.0). Multivariate regression analysis indicates that positive GS findings are associated with a 16.9-point increase in C-GUIDE scores compared to inconclusive or negative results (p < 0.001). Notably, the highest mean scores are observed in psychosocial benefits for patients and families, regardless of GS results. The mean global item score, representing overall assessment of clinical utility, is 0.53 (SD = 0.06). Baseline patient characteristics are not independently associated with C-GUIDE scores. This study represents the first and largest of its kind in the Asia Pacific region, highlighting the multidimensional benefits of GS and the importance of nationwide Genome Projects. By highlighting that clinical utility is primarily influenced by test results rather than patient characteristics, this study underscores the importance of equitable GS implementation across populations.

Abstract Background Student achievement is shaped by family background, gender, migration status, and school context, yet little research has compared how these factors operate across distinct world regions. This study examines how parental education, educational resources, study supports, gender, and migration status predict Grade 8 mathematics and science achievement in the Gulf Cooperation Council (GCC) and Asia–Pacific regions. Methods Using TIMSS 2023 data from twelve countries—six GCC (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates) and six Asia–Pacific systems (Chinese Taipei, Hong Kong SAR, Japan, Korea, Malaysia, Singapore)—we estimated multilevel models separately for each country following a four-step specification. Models incorporated student gender, immigrant status, parental education, home educational resources, home study supports, and student-level interaction terms. Results Patterns differed across regions. In the GCC, girls consistently outperformed boys—especially in science—and immigrant students often outscored native-born peers., In Asia–Pacific countries, gender gaps were small and typically domain-specific, and immigrant performance varied. Parental education persisted as a robust predictor of higher achievement across all systems. Greater home educational resources were associated with higher achievement across countries, while study supports benefited students unevenly, with clearer advantages for girls in several GCC systems. Interaction effects indicated that students with both higher parental education and richer home resources experienced the largest achievement advantages. School-level variance was notably higher in GCC countries, reflecting greater stratification. Conclusions The findings highlight that gender, migration status, and family background do not operate uniformly but are shaped by regional opportunity structures and educational environments. GCC systems may benefit from reducing school-level disparities and strengthening supports for boys’ academic engagement, whereas Asia–Pacific systems may prioritize addressing family-level inequalities and immigrant integration. The study provides region-specific insights for promoting equity in diverse educational systems.

Abstract Background: Chemotherapy (CT) is the main treatment in endocrine-refractory HR+/HER2− metastatic BC but has limited efficacy and substantial toxicities. Dato-DXd is a TROP2-directed antibody-drug conjugate (ADC) that consists of a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor via a plasma-stable cleavable linker. It is approved in multiple countries for adult pts with unresectable or metastatic HR+/HER2− (IHC 0, IHC 1+, or IHC 2+/ISH−) BC who have received prior endocrine therapy and CT for advanced disease, based on the findings of the TROPION-Breast01 study (NCT05104866). In the endocrine-refractory setting, the HER2-directed ADC trastuzumab deruxtecan significantly improved outcomes vs CT in pts with HR+/HER2-low (IHC 1+ or IHC 2+/ISH−) or HER2-ultralow (IHC 0 with membrane staining) unresectable or metastatic BC who had received ≥1 line of endocrine-based therapy and no prior CT in the advanced setting (DESTINY-Breast06; NCT04494425). TROPION-Breast06 aims to assess the efficacy and safety of Dato-DXd in the pre-CT endocrine-refractory setting for pts with HR+/HER2 IHC 0 (defined as no staining or incomplete and faint/barely perceptible membrane staining in ≤10% of tumor cells) inoperable or metastatic BC. Adverse events of special interest including Dato-DXd-related oral mucositis/stomatitis (OM/S) and ocular surface events (OSE) will be assessed. Trial Design: TROPION-Breast06 (EudraCT 2025-521904-23-00) is an open-label, single-arm, phase 3b study of Dato-DXd in adults (aged ≥18 years) with locally advanced inoperable or metastatic HR+, HER2 IHC 0 (per ASCO/CAP guidelines) BC who have not received any prior ADC or CT in the inoperable/metastatic setting, with progression on and not suitable for further endocrine therapy per investigator assessment. HER2 status will be determined on the most recent biopsy (collected within 6 weeks of treatment start) by local testing, and may include central confirmation. At time of enrolment, eligible pts must have an ECOG performance status of 0 or 1 and measurable disease per RECIST v1.1 or evaluable disease. Pts with clinically stable brain metastases are permitted. Sample size estimation is based on achieving a planned precision in the 95% confidence interval for median PFS, not hypothesis testing, with 100 participants chosen. Eligible pts from approximately 35 sites in North America, Europe and the Asia Pacific region will receive Dato-DXd (6 mg/kg IV) every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or other discontinuation criteria are met. A prophylactic oral care plan will be started prior to study drug initiation and throughout treatment, including daily use of steroid-containing mouthwash and consideration of prophylactic cryotherapy; adherence to these measures and reports of mouth and throat symptoms will be captured daily in a digital tracker. Scanning/tumor assessments will be performed every 8 weeks from the first dose of study drug for 48 weeks and then every 12 weeks until RECIST v1.1-defined radiological progression by investigator assessment. Ophthalmologic assessments are mandated at regular intervals and daily use of artificial tears (4-8 times daily) and avoidance of contact lenses is recommended. The primary endpoint is investigator-assessed PFS per RECIST v1.1. Key secondary endpoints are the proportion of pts with OM/S, OSE, and treatment-related Grade ≥3 adverse events. Other secondary endpoints include clinical benefit rate, objective response rate, duration of response, overall survival, and safety/tolerability. Tumor tissue and blood samples will be collected for exploratory analyses. Citation Format: K. Jhaveri, A. C. Garrido-Castro, A. Decque, F. Lujan, M. Prahladan, R. Taylor, N. Toms, F. Bidard. TROPION-Breast06: Multicenter, multinational, open-label, single-arm, phase 3b study of datopotamab deruxtecan (Dato-DXd) in patients (pts) with locally advanced inoperable or metastatic HR+/HER2 IHC 0 breast cancer (BC) refractory to endocrine therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-21.