Digital twin technology represents a transformative approach in healthcare, creating virtual replicas of physical entities that enable real-time data integration, predictive modelling, and personalised treatment strategies. In urology, this emerging technology offers unprecedented opportunities to optimise patient care through simulation-based decision-making. This narrative review comprehensively examines current applications of digital twin technology in urology, evaluates its clinical utility across various urological conditions, and identifies key challenges limiting its widespread implementation. A comprehensive search was conducted across PubMed, Web of Science, and Scopus databases for literature published between January 2020 and January 2026. Search terms included digital twin, virtual twin, urology, uro-oncology, prostate cancer, renal surgery, and bladder dysfunction. Studies focusing on the development, validation, and clinical implementation of digital twins in urological practice were included. Digital twin technology demonstrates significant potential in uro-oncology for treatment planning, surgical navigation, and disease progression monitoring. Key applications include patient-specific tumour growth simulation in prostate cancer, three-dimensional anatomical modelling for partial nephrectomy, and bladder function prediction in outlet obstruction. Integration with artificial intelligence enhances predictive accuracy and enables real-time surgical guidance. Digital twin technology represents a paradigm shift towards precision urology, though challenges in data integration, computational requirements, validation, and ethical considerations must be addressed before routine clinical implementation. Future developments should focus on standardisation, regulatory frameworks, and prospective clinical validation studies.
Radiotherapy has achieved substantial progress often attributed to accelerated technological innovation over decades. However, randomized controlled trials (RCTs) are costly, difficult to fund and to conduct, such that the generation of quality evidence is outpaced by changes in practice. We sought to evaluate the implementation performance of a platform approach to the conduct of pragmatic RCTs in radiation oncology. We implemented PERa, a platform consisting of a prospective registry of patients receiving standard-of-care radiation therapy, designed to support pragmatic registry-based RCT (rRCT) methods and staged informed consent. Implementation performance metrics included rate of registry enrollment, acceptability of re-contact and/or serving as controls for interventional trials, activation and recruitment of embedded comparative effectiveness rRCTs, compliance to study arms, and completeness of ePRO data acquired at scale. Between January 1, 2018 and December 31, 2023, the registry accrued 1415 participants across 5 participating institutions. At time of stage 1 consent, 93% agreed to re-contact for participation in a clinical trial, and 97% consented to serve as control. Seven embedded rRCTs were activated, and one third of participants (n = 477) were randomized. Only two study arm non-compliance events were recorded. Although 97% of subjects consented to ePROs, completion rate was only 53% in those with stage 1 only consent, rising to 62% in those subjects also consented at a second stage to a companion rRCT. The PERa platform is met with high acceptance demonstrating efficient conduct of rRCTs embedded in routine radiation oncology practice. Future work to improve ePRO completions and automate harmonization with EMR data lakes have the potential to improve the quality of evidence generation and support learning health systems. NCT03378856: Registered on December 12, 2017. NCT04100174: Registered on September 20, 2019. NCT04178174: Registered on November 17, 2019. NCT05457699: Registered on July 04, 2022. NCT04405401: Registered on May 24, 2020. NCT04901234: Registered on May 17, 2021. NCT05317026: Registered on March 08, 2022.
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Glioblastoma (GB) is a highly malignant brain tumor with poor prognosis and limited treatment options. Standard treatment, surgery followed by chemoradiation with temozolomide (TMZ), yields an average survival of 18 months. Preclinical studies indicate that perillyl alcohol (POH) is cytotoxic to TMZ-sensitive and -resistant cells and acts as a radiosensitizer. Clinical studies of intranasal POH show low toxicity and potential survival benefits in recurrent gliomas. This study aims to evaluate the effects of POH alongside standard treatment in newly diagnosed GB patients. Eligible patients at the Oncology Services of the University of Campinas General Hospital and Municipal Hospital Mário Gatti will be assigned to a control group (chemoradiation) or an intervention group (chemoradiation + POH). Follow-up will occur every 4 months for 1 year. The primary outcome is progression-free survival, with secondary outcomes including overall survival, blood levels of P-selectin and von Willebrand factor, and tumor response assessed by cranial MRI. Previous studies have reported positive effects of intranasal POH in patients with recurrent gliomas. This study evaluates an adjunct protocol combining intranasal POH with standard therapy in newly diagnosed GB patients. This randomized clinical trial aims to support future research and guide clinical practice.Clinical trial registration: RBR-4ngc9n5 (www.ensaiosclinicos.gov.br). Glioblastoma is an aggressive type of brain tumor that is very hard to treat, and people diagnosed with this tumor usually have a short-life expectancy. The standard treatment includes surgery followed by chemotherapy and radiotherapy, but this treatment only extends survival to about 18 months on average. Recent research suggests that a natural compound called perillyl alcohol may help fight glioblastoma. Studies in the lab show that perillyl alcohol can kill tumor cells and make them more sensitive to radiotherapy. Early clinical studies using perillyl alcohol through the nose have shown this is safe and may help patients with recurring tumors live longer. This study will test whether adding intranasal perillyl alcohol to the usual treatment can help patients newly diagnosed with glioblastoma. Patients at two hospitals in Campinas, Brazil, will receive either the standard treatment or standard treatment plus perillyl alcohol. This study will follow patients for a year, checking tumor growth, overall survival, and certain blood markers. The goal of this research is to see if combining perillyl alcohol with standard therapy can improve outcomes and help guide future treatments for glioblastoma.
Drug combinations, where two drugs are co-administered, are being explored widely within Phase I trials in oncology. These trials aim to identify the maximum tolerated dose combination (MTDC) by adapting the dose of both treatments based on current trial data. Various methods have been proposed to inform how escalation decisions are made within a trial. We propose a model-based design which aims to adapt the dose combination that participants receive to a level that maximises the information gained from each move across the toxicity surface, subject to admissibility and escalation constraints (penalised D-Optimality strategy). We simulated multiple different scenarios, and the penalised D-Optimality strategy is shown to have similar operating characteristics to the Interval approach, which is widely used within Phase I oncology trials. Furthermore, the penalised D-Optimality strategy shows further exploration across the toxicity surface, providing the potential to identify multiple MTDCs, further characterise the risk-benefit profile and provide flexibility for dose selection in future trials. We also show how priors of the two drugs can be specified to show a favoured escalation route if pre-clinical data suggests this.
The therapeutic efficacy of cancer therapeutics is frequently limited by poor tumour selectivity, systemic toxicity, and the emergence of drug resistance, underscoring the need for advanced nanoscale drug delivery systems (DDSs) capable of precise molecular targeting and controlled release. Molecularly imprinted polymers (MIPs) have emerged as a promising class of synthetic nanocarriers that combine highly selective and programmable molecular recognition with the robustness, tunability, and scalability of polymeric materials. This review examines recent advances in the nanoscale engineering of MIPs for receptor-guided precision cancer therapy, focusing on how imprinting strategy, polymerisation methods, and nanostructure control govern binding affinity, selectivity, and drug-release behaviour. Key advances in epitope imprinting are highlighted to overcome the size, conformational complexity, and stability challenges associated with whole-protein templates, enabling reproducible targeting of cancer-associated receptors. Emerging stimuli-responsive, hybrid, and multifunctional MIP architectures are discussed, illustrating how molecular recognition, drug loading, and triggered release can be co-engineered within a single nanoscale platform. Finally, the current challenges related to biocompatibility, reproducibility, and translation towards manufacturable and regulatory-compliant systems are critically assessed, outlining future directions for establishing MIPs as a viable class of next-generation precision DDSs in oncology.
Modern medicine, especially oncology in low- and middle-income countries (LMICs), requires clinicians to remain updated in a rapidly evolving field of medicine in the face of a high clinical load. Clinicians need to be able to critically evaluate published evidence and make informed decisions about the individual patients they treat. A clinical culture that encourages clinicians to question and think critically would produce high-quality research from parts of the world that have highest disease burden but lowest contribution to published research. A two-day research methods course was conducted jointly by the Tata Medical Center, Kolkata and the West Bengal Chapter of the Indian Psychiatric Society on 22nd-23rd August 2025. We report on our experience of organising this course and the lessons learned from interacting with the audience in an LMIC setting. Live anonymous participant responses were captured using Mentimeter software during the training, and written anonymous feedback were provided by majority of attendees. The three main barriers to conducting research that our participants reported were: 'lack of training in research', 'difficulties in writing a research paper' and the 'researcher's personal circumstances'. The participants in our course comprised both men and women clinicians, mostly in their early careers and this group of learners appreciated hands-on training on literature search, reference management and working with the SPSS statistical software to conduct standard statistical tests. To achieve this, institutions and individuals need to foster a conducive environment for research, inspiring those who will be responsible for the future health care delivery.
Thermal ablation offers a safer, less invasive, and more cost-effective curative-intent treatment for selected patients with primary and metastatic liver tumours than surgery; when done with appropriate technique, ablation can deliver similar oncological outcomes. However, effectiveness in routine practice varies because structured training, planning, and procedural governance remain scarce. These international multidisciplinary, multi-society guidelines-formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology-define key domains contributing to procedural difficulty and practice variation in liver tumour thermal ablation. A Delphi consensus initiative held in Innsbruck, Austria, engaged 72 experts across three iterative rounds of scoring across 135 statements grouped into five domains: credentialing, indications, approach, procedural factors, and safety measures. Consensus was achieved for 94 (70%) of 135 statements. The least invasive route-typically percutaneous-should be prioritised, and margin adequacy was reaffirmed as the principal technical goal. Procedural difficulty was considered context-dependent, shaped by tumour factors, institutional infrastructure, and operator experience. Organ displacement techniques were endorsed to maintain safety and expand treatable indications. Complex ablations should be done by experienced operators (more than 100 previous cases), with programmes underpinned by structured training, multidisciplinary team participation, and routine audit. Future efforts should develop and validate practical tools such as difficulty scoring systems, standardised procedural reporting templates, and comprehensive training curricula to improve consistency, standardisation, and clinical outcomes globally.
Clinical trials in IBD face difficulties of escalating complexity, high costs and challenges in recruitment. Digital twins are virtual, data-driven replicas of individual patients that model disease trajectories and treatment responses, which offer a potential innovative change in the conduct of clinical trials in IBD. Built from multimodal datasets integrating clinical, molecular, imaging and real-world data, digital twins can generate synthetic control arms, enable adaptive randomisation and predict disease relapse or treatment response. Early studies across oncology, cardiology and endocrinology demonstrate their feasibility and potential to improve statistical power while reducing patient burden. However, the integration of digital twins into clinical trials in IBD will require rigorous validation frameworks, transparent data governance and attention to algorithmic bias and consent. In this review, we explore how digital twins may transform IBD research-from in silico simulation to adaptive, patient-centred trial design-and outline the regulatory, ethical and logistical challenges to be considered in order to successfully integrate them into future trials.
This retrospective study aimed to identify clinical factors associated with the long-term continuation of anamorelin hydrochloride in real-world clinical practice. We analyzed 173 patients with lung, gastric, colorectal, or pancreatic cancer who received anamorelin hydrochloride between May 2021 and May 2025. Clinical variables potentially associated with long-term anamorelin continuation were extracted from medical records. Patients were categorized into three groups according to treatment duration: <3 weeks, 3 to <12 weeks, and ≥12 weeks. Univariate and multivariate ordered logistic regression analyses were performed to identify predictors of continued anamorelin use. Multivariate analysis identified the Modified Glasgow Prognostic Score (mGPS) (odds ratio [OR] = 0.659, 95% confidence interval [CI] = 0.472- 0.920; p = 0.014), gastric cancer (OR =0.333, 95% CI = 0.135- 0.821; P = 0.017), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (OR =0.616, 95% CI = 0.448- 0.847; p = 0.003) as significant predictors. Lower mGPS, and better ECOG PS were associated with longer continuation of anamorelin, whereas patients with gastric cancer showed a tendency toward shorter duration. These findings provide guidance for patient selection and tailored supportive care in clinical practice. Some people with cancer lose weight and muscle. This condition, called cancer cachexia, can make cancer treatment more difficult, reduce strength, and make daily life harder. Anamorelin is a medicine that may help by increasing appetite, encouraging food intake, increasing body weight, and preserving muscle. Some patients stop taking anamorelin soon after starting, while others continue for a long time. We studied 173 patients in Japan with lung, gastric, colorectal, or pancreatic cancer to identify factors influencing treatment duration. Key factors included daily activity ability (ECOG PS: Eastern Cooperative Oncology Group Performance Status), inflammation and nutrition (mGPS: modified Glasgow Prognostic Score), cancer type, comorbidities, laboratory test values, regimen, and concomitant medications. Overall, patients with good PS and low mGPS were more likely to continue treatment longer. Patients with gastric cancer were less likely to maintain therapy. In patients with lung cancer, PS was the most important factor. Low BMI was associated with longer treatment in univariate analysis but was less important when other factors were included. These findings suggest that better daily activity levels, lower inflammation with better nutritional status, and cancer type are key factors influencing continued anamorelin therapy and may help doctors identify patients most likely to benefit.
Defining lines of therapy (LoTs) in real-world data is challenging, but it is essential for understanding the evolving treatment landscape for metastatic non-small-cell lung cancer (NSCLC). Validated algorithms are critical for determining LoTs; however, the performance of these algorithms across different data sources remains uncertain. This retrospective study aimed to optimise and evaluate the performance of several LoT algorithms for patients with metastatic NSCLC in Germany and the UK. Six LoT algorithms were assessed in two real-world data sources: Frankfurt University Hospital, Germany, and the Real World Evidence Alliance at Leeds-Oncology, UK. The algorithms used various combinations of information on treatment (dispensation time, drug type, cycle) and progression of disease. Accuracy and positive predictive value were measured for each data source. Across both data sources, all algorithms showed similar accuracy. On average, the algorithms correctly identified the full treatment pathway for >75% of patients (≥90% excluding the worst-performing algorithm). The most accurate algorithms were time- and drug based (94% accuracy), and time- and drug-cycle based (95% accuracy). Algorithms using both drug type and timing information demonstrated high accuracy and consistent performance in defining LoTs. Adding disease progression information did not improve LoT definition. This study can help guide future real-world evidence generation.
Epidemiological research studies into Long Covid, currently defined by prolonged symptoms after SARS-CoV-2 infection, have reported widely varying prevalence estimates. As well as rapidly evolving scientific knowledge of Long Covid, these differences are partly driven by substantial methodological heterogeneity between studies, including the outcome definition of Long Covid; duration of follow-up; study design, period and population; sampling frame; data source; and the statistical techniques employed. Having a robust understanding of the prevalence of and risk factors for Long Covid is essential for informing treatment pathways, service provision and policy decisions. In preparation for the public health response to future epidemics and pandemics, this review outlines key epidemiological and statistical considerations and recommendations when designing studies of emerging post-acute infection syndromes, focussing on Long Covid as a case study.
Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.
To describe (1) the proportion of deaths that were in recently hospitalised children and (2) causes of mortality among deceased children aged 0-59 months with preceding hospitalisations who enrolled in a mortality surveillance programme. Descriptive study using prospectively collected data. Eight Child Health and Mortality Prevention Surveillance (CHAMPS) community and healthcare sites in sub-Saharan Africa and South Asia. Deaths among children aged 0-59 months enrolled in CHAMPS 2016-2023. None. Deaths with antecedent hospitalisations within 180 days of death. Causes of death determined by expert panels who reviewed clinical data and histopathologic and microbiologic results from postmortem minimally invasive tissue sampling. CHAMPS enrolled 8548 deaths; we excluded 3688 neonates who died before discharge or ≤24 hours of birth and 482 with unclear information on antecedent hospitalisations. Out of the 4378 remaining deaths, 16.7% (95% CI 15.7% to 17.9%) were deaths that occurred within 180 days of a hospitalisation (n=733/4378). Of these, 55.7% (95% CI 52.0% to 59.3%) occurred outside healthcare facilities. Among included deaths with minimally invasive tissue sampling completed (n=337), lower respiratory tract infections (41.2%, 95% CI 36.0% to 46.7%), sepsis (39.8%, 95% CI 34.5% to 45.2%) and undernutrition (n=92, 27.3%, 95% CI 22.7% to 32.4%) were most common causes of death among cases with antecedent hospitalisations. The greatest proportion of deaths with antecedent hospital admissions occurred among cases aged 1-11 months (48.0%, 95% CI 44.4% to 51.7%), compared with those aged 0-1 months (21.7%, 95% CI 18.8% to 24.9%) and those aged 1-5 years (30.3%, 95% CI 27.0% to 33.8%). Moreover, the greatest proportion of deaths with antecedent hospital admissions occurred among infants/children with weight-for-age Z-score of <-3 (62.5%, 95% CI 56.5% to 68.0%) compared with those with weight-for-age Z-score of ≥-3 (37.5%, 95% CI 32.0% to 43.5%). We observed a high proportion of deaths with antecedent hospitalisations within 180 days among young children across eight sites in sub-Saharan Africa and Asia. Among those deaths, children aged 1-11 months and undernourished infants were over-represented, suggesting early follow-up as a potential point to focus targeted support and future research.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is one of the most prevalent liver diseases globally, contributing to both economic and health-related challenges. We aimed to evaluate the global, regional, and national burden of MASLD from 1990 to 2023, quantify the contribution of identified modifiable risk factors, and project future prevalence up to the year 2050. Estimates of MASLD prevalence and disability-adjusted life-years (DALYs) were produced by age, sex, region, Socio-demographic Index (SDI), and Healthcare Access and Quality (HAQ) index across 204 countries and territories from 1990 to 2023 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023. The MASLD burden attributable to three risk factors (smoking, high BMI, and high fasting plasma glucose) was assessed as part of the GBD comparative risk assessment. As a secondary analysis, we used these estimates to forecast MASLD prevalence up to 2050 using fasting plasma glucose and mean BMI as predictors. Furthermore, to examine the relative contributions of population ageing, population growth, and changes in MASLD prevalence rate to the forecasted changes in case counts from 2023 to 2050, we conducted a decomposition analysis. In 2023, approximately 1·3 billion (95% uncertainty interval [UI] 1·2 to 1·4) individuals were estimated to be living with MASLD (ie, 16·1% of the global population), with an age-standardised prevalence rate of 14 429·3 (95% UI 13 268·3 to 15 990·6) per 100 000 population, representing a percentage increase of 142·7% (95% UI 139·2 to 146·7) in crude numbers from 1990 (0·5 billion [0·5 to 0·6]) and of 28·6% (27·8 to 29·5) in the rate (11 217·2 [10 276·8 to 12 467·0] per 100 000 in 1990). An estimated 3·6 million (2·8 to 4·5) total DALYs were attributable to MASLD worldwide in 2023, corresponding to an age-standardised DALY rate of 39·6 (31·2 to 49·9) per 100 000 population. Despite a 116·3% (93·3 to 139·4) increase in crude DALYs (from 1·7 million [1·3 to 2·1] in 1990), its age-standardised estimate remained consistent (1·8% [-8·6 to 12·8]) from 1990 (38·9 [30·1 to 49·8] per 100 000) to 2023. There was substantial variation in age-standardised estimates across regions. North Africa and the Middle East had the highest prevalence rate (29 246·1 [26 848·3 to 32 048·7] per 100 000) and Andean Latin America showed the highest DALY rate (152·3 [114·1 to 194·7] per 100 000). By contrast, the high-income Asia Pacific region had the lowest prevalence rate (8653·5 [7923·7 to 9592·8] per 100 000) and east Asia had the lowest DALY rate (16·3 [13·5 to 19·9] per 100 000) among all GBD regions. North Africa and the Middle East showed disproportionately higher prevalence rates relative to other regions with similar SDIs. Lower SDIs and HAQs were associated with higher age-standardised DALY rates. The age-standardised prevalence rate was consistently higher in males (15 616·4 [14 349·2 to 17 263·3] per 100 000 people in 2023) than in females (13 245·2 [12 132·0 to 14 692·6] per 100 000 people), and peaked at age 80-84 years in both sexes. The number of MASLD prevalent cases was the highest in younger adults, peaking at age 35-39 years for males and age 55-59 years for females. Among the risk factors for MASLD, high fasting plasma glucose presented the largest contribution to the age-standardised DALY rate of total MASLD in 2023 (2·2 [95% UI 1·6 to 3·1] per 100 000 people), followed by high BMI (1·4 [0·6 to 2·4] per 100 000 people) and smoking (1·0 [0·3 to 1·8] per 100 000 people). Our forecasting model estimates that 1·8 billion (95% UI 1·6 to 2·0) individuals are likely to have MASLD by 2050, representing a 42·0% increase from 2023. The age-standardised prevalence rate is expected to increase to 15 774·9 (95% UI 14 613·9 to 17 336·2) per 100 000 people in 2050, representing an average annual percentage change of 0·3% (95% UI 0·3-0·3). According to our decomposition analysis, this change will be primarily due to population growth, particularly in sub-Saharan Africa and North Africa and Middle East, and less by population ageing or epidemiological change. With a global prevalence of 16·1% and approximately 1·3 billion people already living with MASLD in 2023, the condition has and will continue to have substantial health and economic impacts worldwide. An inverse association between the HAQ Index and age-standardised DALY rates suggests that countries with lower health-care access and quality might be less well positioned to manage the growing MASLD burden, underscoring the need for strengthened health-system capacity in these settings. Gates Foundation.
Adenoid cystic carcinoma of the anterior craniofacial region (ACF-ACC) is challenging to treat due to extensive subclinical spread and proximity to critical structures. Although surgery followed by radiotherapy (RT) is the current standard, real-world outcomes with modern photon and particle therapy remain insufficiently characterized. We retrospectively analyzed 578 patients with ACF-ACC treated at eight international centers (1984-2023). Clinicopathologic features, treatment patterns, and outcomes were assessed. Anatomical extension was classified using hierarchical clustering. Comparative analyses of gross total resection (GTR) and non-surgical treatment (NST) were adjusted using propensity score matching and multivariable Cox and Fine-Gray models. Primary endpoints were local recurrence-free survival (LRFS) and cumulative incidence of local recurrence (LRCI). Most tumors arose in the sinonasal tract (75.8%) and were low/intermediate grade (68.6%). Long-term outcomes showed high local and distant recurrence (20-year LRCI: 74.1%; cumulative incidence of distant metastasis: 55.6%). GTR followed by adjuvant RT, especially with proton therapy (PT), achieved the best local control. R2 resections provided no advantage over NST. Within the NST cohort (n = 110), PT yielded higher complete response rates than photon RT, while responders demonstrated local control comparable to surgically treated patients. Ten-year ≥G3 toxicity incidence was 36%. For ACF-ACC, GTR plus modern RT provides the strongest local control, and R2 surgery should be avoided. PT is an effective definitive option for selected patients, supporting future response-guided treatment strategies.
Myelodysplastic/myeloproliferative neoplasms (excluding CMML) are rare and heterogenous malignancies with recurrent and overlapping clinicopathological abnormalities. Classification and characterization continue to evolve, but outcomes remain unsatisfactory and allo-HCT is currently the only curative therapy. Experience with these diseases is limited by rarity, accounting for <1% of allo-HCT procedures in Europe annually. Transplant indications have recently been described by this group, however response assessment, post-transplant surveillance and management of poor graft function, splenomegaly and relapse are not well established. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization & Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) collaborated to develop a practical and expert consensus-based guideline. Criteria for remission confirmation are proposed, including timing/thresholds for morphological, molecular, cytogenetic and chimerism analysis, aiming to harmonize comparisons in registry data and between international series. Suggestions for managing poor graft function and splenomegaly are designed to broadly align with those for myelofibrosis and related disorders. Relapse post-transplant remains a frequent challenge and the lack of robust evidence, in both the pre-transplant/post-transplant setting, underpins a need for collaborative clinical trials. This document serves as a framework to model post-transplant care, guide future research and address unresolved questions.
Autosomal dominant acute porphyrias are rare inherited disorders of haem biosynthesis characterised by accumulation of potentially neurotoxic porphyrin precursors and attacks of severe abdominal pain with autonomic and neuropsychiatric features. Disease severity ranges from asymptomatic individuals to those with recurrent, life-threatening attacks. The International Porphyria Network invited 34 acute porphyria specialists from 17 countries to form an expert panel. The invited group included clinicians from diverse specialities (ie, internal medicine, haematology, endocrinology, gastroenterology, hepatology, neurology, and biochemistry), together with laboratory scientists and patient representatives. The panel met online (in 2023-25) to develop 15 evidence-based recommendations with the use of the Grading of Recommendations, Assessment, Development, and Evaluations framework addressing attack prevention, management of sporadic and recurrent attacks, long-term follow-up, surveillance for primary liver cancer, and family screening. The guidelines support safe, consistent clinical care and improved outcomes, recognising global variation in resources and access to high-cost drugs, and highlighting priorities for future research.
Regulatory T cells (Tregs) form a distinct subset of CD4+ T cells essential for maintaining immune balance and preventing autoimmunity by expressing CD25 and CTLA-4. Tregs, which are defined by the expression of the transcription factor FOXP3 in mice, restrain excessive immune activation through mechanisms such as IL-10 expression, TGF-β expression, metabolic regulation, acting as an IL-2 cytokine sink, and cell-to-cell interaction through co-inhibitory receptors. Although they are indispensable for immune tolerance, Tregs can be co-opted by tumors, where their suppressive activity promotes immune escape. High Treg infiltration within the tumor microenvironment has been linked to variable prognosis depending on the tumor type, highlighting Tregs' contradictory roles as both guardians of tolerance and enablers of tumor progression. In this review, we summarize Treg biology, Tregs' contribution to cancer immunity, and emerging therapeutic strategies designed to modulate or deplete Tregs. We conducted a targeted literature review using PubMed/MEDLINE, Web of Science, ClinicalTrials.gov, and ASCO/ESMO meeting libraries, complemented by manual reference screening. We also discuss the limitations of existing therapeutic approaches and outline future directions. Efforts to therapeutically modulate Tregs have focused on three main strategies: depletion (e.g., anti-CD25, anti-CCR4, or anti-CCR8 antibodies), functional blockade (e.g., targeting CTLA-4 or TIGIT), and disruption of metabolic pathways (e.g., adenosine or PI3K signaling) that support Tregs' biological functions. Although preclinical studies have shown that targeting Tregs have antitumor effects, clinical trials have demonstrated variable efficacy and toxic effects, reflecting the fine balance between immune activation and tolerance. Newer approaches aim to selectively impair intratumoral Tregs while preserving peripheral immune control, guided by T-cell subsets such as FOXP3+Helios+CCR8+ cells, which may help predict therapeutic response. A deeper understanding of Treg regulation is needed to unlock their therapeutic potential without compromising immune equilibrium.
Feasibility of a paired-sample study comparing cervical screening and urine self-sampling at 6- and 12-weeks postnatal. Paired-sample feasibility study. Acute hospital. Females within 6 weeks of childbirth. Paired-sample study comparing cervical screening and high-risk human papillomavirus (HPV) testing from clinician-taken samples and urine self-samples at 6- and 12-weeks postnatal. Uptake rates, patient-reported outcomes, adverse events, HPV detection, relative HPV sensitivity and specificity. Of 245 potential participants, 115 (47%) consented, 102 (89%) and 96 (83%) attended their 6- and 12-week screening visits, respectively. Median pain scores for cervical screening did not differ (6-weeks = 1; 12-weeks = 1; p = 0.76). Most would be happy for future screening at 6-weeks postnatal, 97/102 (95%) and 85/95 (89%) when asked at 6- and 12-week study visits, respectively. Agreement rate of clinician-taken HPV tests between 6- and 12-weeks was 94.8% (91/96, 95% confidence interval [CI], 88.4%-97.8%), with no inadequate combination HPV/cytology tests (6 vs. 12-week: sensitivity 80% [95% CI, 44.4-97.5]; specificity 96.5% [95% CI 90.1-99.3]). Relative to 12-week clinician-taken samples, urine self-sampling may have lower sensitivity for HPV (e.g., 6-week: sensitivity 60.0% [95% CI 26.2-87.8]; specificity 96.5% [95% CI 90.1-99.3]; NPV 95.4% [95% CI 88.6-98.7]). A paired-sample study of cervical screening at 6- and 12-weeks is feasible. Inadequacy rates of cervical screening were low, with high agreement. Urine self-sampling may be less sensitive in this population.