Risk-stratified Approach Research Articles

Hemophagocytic lymphohistiocytosis in HIV-associated HHV8-positive multicentric castleman disease.

The clinical and laboratory characteristics of HHV8-associated Multicentric Castleman Disease (MCD) in people living with HIV (PLWH) overlap with those of Hemophagocytic Lymphohistiocytosis (HLH) disease and indeed the two diagnoses may co-exist. A risk-stratified treatment approach to MCD based on Rituximab immunotherapy for mild cases and chemo-immunotherapy for severe cases has been shown to yield excellent outcomes in PLWH. In contrast, HLH disease, previously known as secondary HLH, has a dismal prognosis even when promptly treated according to guidelines. A retrospective multicentre cohort study. Retrospective analysis of prospectively collected clinical and pathological data on patients with biopsy proven HIV-associated MCD at the National Centre for HIV Malignancy at Chelsea and Westminster Hospital, London between 2008 and 2024 and at the Department of Infectious Diseases at St. Joseph Hospital Berlin-Tempelhof, Germany between 2020 and 2024. In our UK-German cohort including 113 PWLH with MCD, we confirmed that HLH disease secondary to MCD is common (30%) and we demonstrated that HLH disease in this context does not adversely influence survival or risk of MCD relapse. We suggest that a high HScore in MCD should not lead to a change in the treatment in this specific setting.

Echocardiography in acute pulmonary embolism – what do we have?

Pulmonary thromboembolism (PE) related mortality worldwide is decreasing due to current therapeutic advances. However, PE remains the third leading cause of death in developed countries and its incidence is increasing. Timely diagnosis and appropriate therapeutic measures are extremely important in clinical practice. Echocardiography (EchoCG) remains a preferred imaging technique at the bedside for both primary diagnosis and individual patient risk determination, and provides invaluable information regarding general hemodynamics in emergency situations. The development of the methodology in recent years adds new parameters to the classic image of the patient with PE. In this review, modern approaches for risk stratification of patients with PE by means of echocardiography and the role of echocardiography in the diagnosis of the disease are considered.

Biological Age Acceleration and Colonic Polyps in Persons under Age 50.

Epigenetic clocks can quantify DNA methylation by measuring the methylation levels at specific sites in the genome, which correlate with biological age (BA). Accelerated aging, where BA exceeds chronologic age, has been studied in relation to cancer development, but its utility in cancer prevention remains unclear. Accelerated aging holds promise as a tool to explain the increase in early-onset colorectal cancer (EOCRC). We investigate the association of accelerated aging and the presence of preneoplastic polyps (PNP) in the colon, defined as tubular adenomas and sessile serrated adenomas. In this study of persons under age 50 undergoing colonoscopy, we used peripheral blood samples to determine BA and age acceleration metrics. Age acceleration was determined by interrogating DNA methylation at specific CpG sites across the genome, which has been shown to correlate with age. We then conducted logistic regression analyses to evaluate the association between age acceleration and PNPs. In total, 51 patient samples were evaluated. We found that that the odds of harboring a PNP are 16% higher with 1 year of accelerated aging, as measured by GrimAge. However, the strongest risk factor for PNPs remained male sex. This represents one of the first studies to explore accelerated aging and PNP in patients under the age of 50. A risk-stratified approach to EOCRC screening would minimize unnecessary colonoscopies and minimize healthcare burden while addressing the increase in EOCRC. Our findings suggest that BA calculations with peripheral blood collections could be an important component of such a risk model. Prevention Relevance: Understanding the association of accelerated aging and colorectal PNPs presents an opportunity to develop a risk-stratified approach to colorectal cancer screening in young persons.

Universal genetic counseling and testing for Black women: A risk-stratified approach to addressing breast cancer disparities: Genetics, Black women & breast cancer

Black women experience disproportionate breast cancer-related mortality, with similar overall incidence to White women. Approaches to address these racial health disparities should be multifaceted. Universal genetic counseling and testing for Black women could represent one dimension of a comprehensive approach in guiding early identification of those women more likely to experience higher breast cancer-related mortality. The increased risk of triple-negative breast cancer and greater likelihood of early-onset breast cancer among Black women are two major justifications, given that these elements are already preexisting criteria for genetic counseling and testing in affected persons per the National Comprehensive Cancer Network. Increasing assessment of breast cancer-related risk in the Black community through universal genetic counseling and testing should be considered to focus enhanced screening and preventive measures in a tailored risk-appropriate context.

Comorbid anxiety, loneliness, and chronic pain as predictors of intervention outcomes for subclinical depressive symptoms in older adults: evidence from a large community-based study in Hong Kong

BackgroundDepression is among the leading causes of the global burden of disease and is associated with substantial morbidity in old age. The importance of providing timely intervention, particularly those with subclinical symptoms, has thus increasingly been emphasised. Despite their overall effectiveness, a small but notable subgroup tends to be less responsive to interventions. Identifying predictors of non-remission and non-response is critical to inform future strategies for optimising intervention outcomes.MethodsA total of 4153 older adults aged 60 years and above with subclinical depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] = 5–19) were recruited from JC JoyAge, a large-scale collaborative stepped-care intervention service across Hong Kong. A wide range of clinical and modifiable risk and protective factors at baseline were assessed, including depressive symptoms, anxiety symptoms, loneliness, suicidal ideation, cognitive capacity, multimorbidity, chronic pain, need for informal care due to mental health reasons, history of abuse, and sociodemographic characteristics. Separate multivariable logistic regression models were applied to identify predictors of non-remission (PHQ-9 ≥ 5) and non-response (< 50% reduction in PHQ-9) following intervention.ResultsThe rates of non-remission and non-response were 18.9% (n = 784) and 23.0% (n = 956), respectively. Comorbid anxiety symptoms (adjusted odds ratio [aOR] = 2.08, CI = 1.72–2.51; 1.28, 1.05–1.57), loneliness (2.00, 1.66–2.42; 1.67, 1.38–2.01), need for informal care (1.86, 1.49–2.33; 1.48, 1.18–1.85), lower cognitive capacity (0.95, 0.93–0.97; 0.94, 0.92–0.96), and absence of chronic pain (0.59, 0.48–0.72; 0.76, 0.64–0.91) predicted both non-remission and non-response. Meanwhile, moderate-to-severe depressive symptoms predicted higher odds of non-remission (1.41, 1.18–1.69) and lower odds of non-response (0.28, 0.23–0.34), respectively. Subgroup analyses conducted separately in older adults with mild and moderate-to-severe depressive symptoms at baseline revealed that comorbid anxiety, loneliness, need for informal care, and absence of chronic pain were consistent predictors of non-remission. Those with non-remission and non-response showed more depression-related functional impairments and poorer health-related quality of life post-intervention.ConclusionsOlder adults with subclinical depressive symptoms showing comorbid anxiety, higher loneliness, need for informal care, and chronic pain may be offered more targeted interventions in future services. A personalised risk-stratification approach may be helpful.Trial registrationClinicalTrials.gov identifiers: NCT03593889 (registered 29 May 2018), NCT04863300 (registered 23 April 2021).

Economic evaluation of Polygenic Risk Scores in healthcare interventions: a systematic review

Abstract Background Polygenic Risk Scores (PRS) quantify genetic susceptibility to diseases, promising personalized healthcare. This review explores current evidence regarding the economic evaluation of strategies based on PRS or other polygenic risk stratification approaches, scrutinizing their methodologies. Methods The study protocol was registered in PROSPERO (CRD42023442780). A systematic search in PubMed, Scopus, and Web of Science identified full economic evaluations of intervention based on polygenic risk stratification strategies. The quality of the included articles was assessed using the Drummond checklist. This study was supported by the EC and MUR under PNRR - M4C2-I1.3 Project PE_00000019 ‘HEAL ITALIA”. Results Nineteen articles were included in the analysis, with oncological conditions being the most frequently investigated (13), followed by cardiovascular conditions (3). In nearly 80% of the studies, PRS was employed for screening interventions, with the general population being the primary target in 14 out of the 19 studies. All the economic analysis models investigated cost-utility in terms of QALYs, with Markov models and microsimulations being the most common structures. The majority of these models were based on simulated cohorts derived mostly from North American or European data, with 9 adopting a healthcare system perspective and 6 a societal perspective. Although delivery strategies for PRS testing were rarely addressed, PRS costs were included in nearly all studies. Indirect costs were examined in fewer than half of the studies. In 12 out of 19 studies, the conclusions claimed the cost utility of PRS involving strategies. Conclusions Despite the technique’s potential, evaluations of various strategies based on PRS approaches yield heterogeneous conclusions regarding cost-utility. Our study highlights the factors contributing to this heterogeneity and underscores the need for further exploration, ideally prioritizing real-world data. Key messages • PRS strategies evaluations vary in cost-utility conclusions, highlighting the need for further investigation. • Real-world data and practical implications should be prioritised in PRS research.

TREATMENT OF PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH CONGENITAL HEART DEFECTS

Patients with pulmonary arterial hypertension, associated with congenital heart disease (PAH-CHD) are a heterogeneous population with a varied course of PH. Improvements in pediatric cardiac surgery have changed the epidemiology and survival rate of patients with CHD, of which 90% reach adulthood. Progress in terms of prognosis has also been observed among patients with PAH-CHD. Better survival was observed in ES compared with PAH after defect correction. Advances in surgical treatment of CHD and an increase in life expectancy have led to the study of PAH-CHD and the need to create recommendations for drug treatment of this category of patients. In most of studies, the evaluation of drug treatment of group 1 PAH was carried out without identifying its subgroups. And thus, according to existing recommendations, treatment algorhithms for patients with PAH-CHD are similar to approaches to other forms of PAH. However, various clinical, functional, physical and hemodynamic characteristics of patients with PAH-CHD call into question of correct risk stratification approaches development. Multicenter randomized clinical trials included predominantly a small number of patients with corrected defects, which does not allow the results to be interpreted for the entire population of patients with PAH-CHD. Data from single-center observational studies, expert opinion, and several randomized trials primarily involving patients with Eisenmenger syndrome (ES) indicate the effectiveness and safety of PAH-specific therapy in patients with PAH-CHD. In this literature review, we examined and showed the results of studies involving patients with PAH-CHD and their response to specific therapy. The results obtained significantly expanded the possibilities of using bosentan, sildenafil, epoprostenol, riociguat, ralinepag, sotatercept as they lead to improvement of functional capacity and hemodynamic parameters in patients with PAH-CHD, and only epoprostenol demonstrated an effect on prognosis. Combination PAH-specific therapy, initial or sequential administration of two or more drugs with different mechanisms of action, is an important treatment strategy for patients with PAH. The role of such therapy has increased in recent years. Based on the results of the AMBITION, SERAPHIN, GRIPHON, COMPASS-2 studies, initial or sequential oral combination PAH-specific therapy is recommended for patients with WHO FC II or III. At the same time, there is little evidence to support the effectiveness of this approach in ES patients. The use of anticoagulants in PAH-CHD remains controversial. Low-flow oxygen therapy should be considered individually and continued when there is a significant predominance of subjective or objective benefit. Iron deficiency is associated with poor survival in ES. It is important to note that microcytosis is rare in patients with iron deficiency cyanosis and a normal mean red cell volume does not indicate the absence of anemia. In cases of intolerance to oral iron, intravenous drugs should be used. Currently, based on existing guidelines, most centers follow a consistent symptom-based approach in the treatment of patients with PAH-CHD. Therapy begins with oral ERAs or PDE-5 inhibitors and is escalated if symptoms persist or clinical worsening occurs. If there is no effect of oral PAH-specific therapy, it is recommended to consider parenteral drugs.

Utilizing the glucose challenge test during pregnancy as a predictor of future diabetes risk

BackgroundGestational Diabetes Mellitus (GDM) presents a significant health concern during pregnancy, predisposing individuals to future diabetes. Despite established postpartum diabetes screening guidelines, adherence to follow-up remains inadequate.AimsThis study aimed to assess the predictive value of the 50-gram glucose challenge test (GCT) for post-pregnancy diabetes development.Materials and methodsA population-based retrospective cohort study was conducted on pregnant women aged 18–45 who underwent GCT screening between November 2007 and July 2017 in a large Israeli community medical organization. Baseline characteristics, GCT results, and diabetes development during follow-up were analyzed using univariate and multivariate Cox regression analyses.ResultsAmong 8,675 women included, 2.4% developed diabetes over a median follow-up of 73.23 months. Elevated GCT results correlated with a higher risk of future diabetes, with a 4% rise in risk per 1 mg/dL increase in glucose above 140 mg/dL. Multivariate analysis revealed a 60-fold rise in the risk of future diabetes in women with GCT results ≥ 200 mg/dL compared to those with GCT < 140 mg/dL, adjusting for age, body mass index, pre-pregnancy glucose, cholesterol, and triglycerides. A GCT result between 140 and 199 mg/dL was a predictor of future diabetes, even when adjusted for GDM based on a subsequent GTT if performed.ConclusionsGCT results during pregnancy strongly predict future diabetes development, with higher GCT values significantly increasing risk. Recognizing abnormal GCT results as indicative of a prediabetic state offers a practical approach for risk stratification, facilitating early diagnosis, and intervention in post-pregnancy care.

Development and implementation of an equitable and efficient navigation program to address supportive care needs in patients with cancer.

58 Background: Despite evidence backing the use of navigation along the cancer care trajectory, existing programs struggle to deliver services efficiently and equitably. To bridge this gap, we developed and implemented a patient-centric, data-driven navigation program that leverages a risk-stratification approach to prioritize and address unmet needs. Methods: Our program was developed with key principles to address inefficiencies in existing navigation systems. First, we embedded the program within our institution’s Epic environment, using data-driven risk calculators, dashboards, flowsheets, and templates to support the navigation curriculum. Second, the program structure aligned with the patient’s journey from initial consult through treatment, focusing on early identification of unmet needs, centralized resourcing, and remote symptom monitoring for high-risk patients. Third, we unified the workflows of navigators, intake personnel, triage nurses, and providers, fostering system-wide collaboration. Results: The program has been successfully implemented in patients with new consults in gastrointestinal, breast, and hematologic oncology. To date, 2,080 patients have had an initial assessment leading to a Navigation Assessment Score (NAS) that predicts longitudinal burden of unmet needs and directs subsequent resourcing. 226 referrals have been generated to: cancer rehabilitation (76), nutrition (60), psychosocial oncology (48), tobacco cessation (39), and palliative care (3). Remote symptom monitoring was piloted in 34 gastrointestinal oncology patients meeting the calculated highest decile risk for unplanned acute care event use. Proportions of patients with a NAS score (N=2,080): 69.3% White, 17.7% Black, 3% Latinx, 1.8% Asian, 0.9% American Indian; referrals (N=226): 61.2% White, 23.0% Black, 4.9% Latinx, 1.1% Asian, 0.5% American Indian; remote symptom monitoring (N=34): 79.4% White, 11.8% Black, 5.9% American Indian. Except for Latinx patients, these distributions align with the patient population in gastrointestinal, breast, and hematologic oncology (N=4,267; 68.0% White, 22.5% Black, 6.4% Latinx, 1.9% Asian, 0.9% American Indian). Conclusions: Development and implementation of our program is feasible, and the approach has potential to mitigate disparities in cancer service delivery and outcomes. Ongoing efforts include exploring accessibility among Latinx patients and developing the business case for sustainability and scaling.

Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning.

Hematoxylin and eosin (H&E) whole slide images provide valuable information for predicting prognostic outcomes in colorectal cancer (CRC) patients. However, extracting prognostic indicators from pathological images is challenging due to the subtle complexities of phenotypic information. We trained a weakly supervised deep learning model on data from 640 CRC patients in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial dataset and validated it using data from 522 CRC patients in the cancer genome atlas (TCGA) dataset. We created the colorectal cancer risk score (CRCRS) to assess patient prognosis, visualized the pathological phenotype of the risk score using Grad-CAM, and employed multiomics data from the TCGA CRC cohort to investigate the potential biological mechanisms underlying the risk score. The overall survival analysis revealed that the CRCRS served as an independent prognostic indicator for both the PLCO cohort (p < 0.001) and the TCGA cohort (p < 0.001), with its predictive efficacy remaining unaffected by the clinical staging system. Additionally, satisfactory chemotherapeutic benefits were observed in stage II/III CRC patients with high CRCRS but not in those with low CRCRS. A pathomics nomogram constructed by integrating the CRCRS with the tumor-node-metastasis (TNM) staging system enhanced prognostic prediction accuracy compared with using the TNM staging system alone. Noteworthy features of the risk score were identified, such as immature tumor mesenchyme, disorganized gland structures, small clusters of cancer cells associated with unfavorable prognosis, and infiltrating inflammatory cells associated with favorable prognosis. The TCGA multiomics data revealed potential correlations between the CRCRS and the activation of energy production and metabolic pathways, the tumor immune microenvironment, and genetic mutations in APC, SMAD2, EEF1AKMT4, EPG5, and TANC1. In summary, our deep learning algorithm identified the CRCRS as a prognostic indicator in CRC, providing a significant approach for prognostic risk stratification and tailoring precise treatment strategies for individual patients.

Cardiac ultrasomics for acute myocardial infarction risk stratification and prediction of all-cause mortality: a feasibility study

BackgroundCurrent risk stratification tools for acute myocardial infarction (AMI) have limitations, particularly in predicting mortality. This study utilizes cardiac ultrasound radiomics (i.e., ultrasomics) to risk stratify AMI patients when predicting all-cause mortality.ResultsThe study included 197 patients: (a) retrospective internal cohort (n = 155) of non-ST-elevation myocardial infarction (n = 63) and ST-elevation myocardial infarction (n = 92) patients, and (b) external cohort from the multicenter Door-To-Unload in ST-segment–elevation myocardial infarction [DTU-STEMI] Pilot Trial (n = 42). Echocardiography images of apical 2, 3, and 4-chamber were processed through an automated deep-learning pipeline to extract ultrasomic features. Unsupervised machine learning (topological data analysis) generated AMI clusters followed by a supervised classifier to generate individual predicted probabilities. Validation included assessing the incremental value of predicted probabilities over the Global Registry of Acute Coronary Events (GRACE) risk score 2.0 to predict 1-year all-cause mortality in the internal cohort and infarct size in the external cohort. Three phenogroups were identified: Cluster A (high-risk), Cluster B (intermediate-risk), and Cluster C (low-risk). Cluster A patients had decreased LV ejection fraction (P < 0.01) and global longitudinal strain (P = 0.03) and increased mortality at 1-year (log rank P = 0.05). Ultrasomics features alone (C-Index: 0.74 vs. 0.70, P = 0.04) and combined with global longitudinal strain (C-Index: 0.81 vs. 0.70, P < 0.01) increased prediction of mortality beyond the GRACE 2.0 score. In the DTU-STEMI clinical trial, Cluster A was associated with larger infarct size (> 10% LV mass, P < 0.01), compared to remaining clusters.ConclusionsUltrasomics-based phenogroup clustering, augmented by TDA and supervised machine learning, provides a novel approach for AMI risk stratification.

High-Risk HPV Detection in Paraffin-Embedded Tissue from Cervical Lesions.

Human papillomavirus (HPV), a leading cause of cervical cancer, is present in most cases of the disease and ranks as the fourth most common cancer in women globally. Among the HPV types, fourteen (HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68) are recognized as high-risk (hrHPV), each with varying levels of oncogenic potential. Detecting and genotyping these hrHPV types in cervical lesions is crucial, requiring the development of new diagnostic methods. This study focuses on a retrospective analysis conducted on 44 women from the Cova da Beira Local Health Unit. We used the Anyplex™ II hrHPV Detection kit for hrHPV genotyping from paraffin-embedded cervical tissue samples. hrHPV types were identified in 38 out of the 44 women. Genotyping revealed HPV-16 (55.3%), HPV-18/39/56/58/59 (5.3%), HPV-31 (21.1%), HPV-35 (7.9%), HPV-51/66 (2.6%), and HPV-52 (10.5%). This study demonstrates that the Anyplex™ II hrHPV Detection kit, originally designed for cervical cancer screening, is also effective for hrHPV genotyping in histological analyses. This methodology offers a simpler and more cost-effective approach for cervical cancer risk stratification. Its implementation in clinical practice could enhance the detection of hrHPV in cervical lesions, thereby contributing to more precise diagnoses and potentially more informed treatment strategies.

A novel risk stratification approach and molecular subgroup characterization based on coagulation related genes in colon adenocarcinoma

Colon adenocarcinoma (COAD) represents a significant health concern within the population. Advancing our understanding of COAD is imperative for early detection, enabling personalized treatment interventions, and facilitating the development of effective preventive measures. The coagulation system plays a role in tumor-related pathological processes; however, its specific involvement in COAD and potential contributors remain unclear. This study aimed to establish a novel risk stratification approach by analyzing coagulation related genes (CRGs) associated with COAD. Through a comprehensive bioinformatics analysis of data from public databases, we screened COAD associated CRGs and characterized the associated molecular subtypes. After a comprehensive analysis of the characteristics of each subtype, we applied differentially expressed genes in CRG subtypes to establish a new risk stratification method. Clinical subgroup analysis, immunoinfiltration analysis, therapeutic reactivity prediction and other analytical methods suggest the potential clinical value of the established risk stratification method. As one of the selected targets, the effect of MS4A4A on the proliferation and invasion of COAD was confirmed by in vitro experiments, which partially verified the reliability of bioinformatics results. Our findings delineate CRGs potentially implicated in COAD pathogenesis and offer fresh insights into the influence of the coagulation process on tumorigenesis and progression.

Comparative Prognostic Value of Coronary Calcium Score and Perivascular Fat Attenuation Index in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading global cause of mortality, accounting for approximately 30% of all deaths. It is primarily characterized by the accumulation of atherosclerotic plaques within the coronary arteries, leading to reduced blood flow to the heart muscle. Early detection of atherosclerotic plaques is crucial to prevent major adverse cardiac events. Notably, recent studies have shown that 15% of myocardial infarctions occur in patients with non-obstructive CAD, underscoring the importance of comprehensive plaque assessment beyond merely identifying obstructive lesions. Cardiac Computed Tomography Angiography (CCTA) has emerged as a cost-effective and efficient technique for excluding obstructive CAD, particularly in patients with a low-to-intermediate clinical likelihood of the disease. Recent advancements in CCTA technology, such as improved resolution and reduced scan times, have mitigated many technical challenges, allowing for precise quantification and characterization of both calcified and non-calcified atherosclerotic plaques. This review focuses on two critical physiological aspects of atherosclerotic plaques: the burden of calcifications, assessed via the coronary artery calcium score (CACs), and perivascular fat attenuation index (pFAI), an emerging marker of vascular inflammation. The CACs, obtained through non-contrast CT scans, quantifies calcified plaque burden and is widely used to stratify cardiovascular risk, particularly in asymptomatic patients. Despite its prognostic value, the CACs does not provide information on non-calcified plaques or inflammatory status. In contrast, the pFAI, derived from CCTA, serves as an indirect marker of coronary inflammation and has shown potential in predicting adverse cardiac events. Combining both CACs and pFAI assessment could offer a comprehensive risk stratification approach, integrating the established calcification burden with novel inflammatory markers to enhance CAD prevention and management strategies.

Impact of a machine learning–based prediction model on annual surveillance endoscopy costs for detecting gastric cancer

Background and AimsIn this study, we assessed our machine learning (ML)-based model's impact on reducing annual surveillance endoscopy costs for detecting gastric cancer (GC). MethodsAnalyzing 1099 patients with chronic gastritis undergoing annual esophagogastroduodenoscopy (EGD), we randomly divided them into training and test sets (4:1). Using gradient boosting decision trees and incorporating patient characteristics, the ML model was developed. In the test sets, we compared the EGD number needed to screen (NNS) one GC, the cost, and the GC detection rate across different risk stratification strategies. ResultsThe ML-selected high-risk cohort demonstrated low NNS values, low total cost, low cost per one GC, and high GC detection rates compared to alternative risk stratification approaches including operative link for gastric atrophy assessment, and operative link for gastric intestinal metaplasia assessment. ConclusionOur ML model holds promise in reducing endoscopy surveillance costs while maintaining a robust gastric cancer detection rate.

Development of an Evidence-Based List of Non-Antineoplastic Vesicants: 2024 Update.

Infiltration of a vesicant, called extravasation, can result in severe patient injuries. Recognition of vesicants and their relative risk of injury is essential to extravasation prevention, early recognition, and appropriate treatment. In this article, the Vesicant Task Force (VTF) updates the previously published Infusion Nurses Society (INS) vesicant list from 2017. The 2024 INS list diverges from earlier vesicant lists, such as the 2017 VTF list, by adopting a risk stratification approach based upon documented patient outcomes, in contrast to the reliance on expert consensus or only surrogate risk indicators, such as pH and osmolarity. The methodology used to create the updated list is explained, and the criteria for high- and moderate-risk vesicants and cautionary vesicants are defined.

Comparative Analysis of AML Classification Systems: Evaluating the WHO, ICC, and ELN Frameworks and Their Distinctions.

Comprehensive analyses of the molecular heterogeneity of acute myelogenous leukemia, AML, particularly when malignant cells retain normal karyotype, has significantly evolved. In 2022, significant revisions were introduced in the World Health Organization (WHO) classification and the European LeukemiaNet (ELN) 2022 guidelines of acute myeloid leukemia (AML). These revisions coincided with the inception of the first version of the International Consensus Classification (ICC) for AML. These modifications aim to improve diagnosis and treatment outcomes via a comprehensive incorporation of sophisticated genetic and clinical parameters as well as facilitate accruals to innovative clinical trials. Key updates include modifications to the blast count criteria for AML diagnosis, with WHO 2022 eliminating the ≥20% blast requirement in the presence of AML-defining abnormalities and ICC 2022 setting a 10% cutoff for recurrent genetic abnormalities. Additionally, new categories, such as AML with mutated TP53 and MDS/AML, were introduced. ELN 2022 guidelines retained risk stratification approach and emphasized the critical role of measurable residual disease (MRD) that increased the use of next-generation sequencing (NGS) and flow cytometry testing. These revisions underscore the importance of precise classification for targeted treatment strategies and improved patient outcomes. How much difference versus concordance these classifications present and the impact of those on clinical practice is a continuing discussion.

The medical and functional burden of surviving childhood ependymoma: A population-based study in Ontario, Canada.

Few studies have characterized the burden of late effects among childhood ependymoma survivors. To address this gap, we examined these sequelae using real-world health services data in a population-based ependymoma survivor cohort. All individuals younger than 18years diagnosed with an ependymoma in Ontario, Canada between 1987 and 2015 who had survived at least 5years from their latest pediatric cancer event (index date) were matched 1:5 with population controls. Following linkage with provincial health services data, the cumulative incidences of multiple medical and functional outcomes between survivors and controls were compared. Among 96 survivors, 77.1% had been irradiated and 9.4% had received cisplatin. At 10years post-index, survivors were at significantly higher risk of all-cause mortality (7.1%, 95% confidence interval [CI]: 1.0-13.3 vs. 0.3%, 95% CI: 0.0-1.0; p=.0002), non-obstetric hospitalization (45.1%, 95% CI: 32.6-56.7 vs. 10.6%, 95% CI: 7.6-14.1; p<.0001), stroke (6.5%, 95% CI: 2.3-13.7 vs. 0%; p<.0001), severe hearing loss requiring an amplification device (7.5%, 95% CI: 2.7-15.7 vs. 0%; p<.0001), receiving homecare service (27.6%, 95% CI: 18.5-37.5 vs. 7.7%, 95% CI: 5.3-10.7; p<.0001), and submitting a disability support prescription claim (24.0%, 95% CI: 14.8-34.3 vs. 5.4%, 95% CI: 3.5-7.8; p<.0001) compared to controls. Pediatric ependymoma survivors are highly vulnerable to severe late sequelae, including death, stroke, severe hearing loss, and disability. Urgent efforts are needed to improve risk-stratification approaches that mitigate exposure to toxic therapies for children with lower risk disease. Interventions to prevent or decrease the risk of developing late sequelae are critical to optimizing survivor long-term health.

The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines

ObjectiveDuring the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and...

Management of Acute Coronary Syndromes in Older People: Comprehensive Review and Multidisciplinary Practice-Based Recommendations.

Managing health care for older adults aged 75 years and older can pose unique challenges stemming from age-related physiological differences and comorbidities, along with elevated risk of delirium, frailty, disability, and polypharmacy. This review is aimed at providing a comprehensive analysis of the management of acute coronary syndromes (ACS) in older patients, a demographic substantially underrepresented in major clinical trials. Because older patients often exhibit atypical ACS symptoms, a nuanced diagnostic and risk stratification approach is necessary. We aim to address diagnostic challenges for older populations and highlight the diminished sensitivity of traditional symptoms with age, and the importance of biomarkers and imaging techniques tailored for older patients. Additionally, we review the efficacy and safety of pharmacological agents for ACS management in older people, emphasizing the need for a personalized and shared decision-making approach to treatment. This review also explores revascularization strategies, considering the implications of invasive procedures in older people, and weighing the potential benefits against the heightened procedural risks, particularly with surgical revascularization techniques. We explore the perioperative management of older patients experiencing myocardial infarction in the setting of noncardiac surgeries, including preoperative risk stratification and postoperative care considerations. Furthermore, we highlight the critical role of a multidisciplinary approach involving cardiologists, geriatricians, general and internal medicine physicians, primary care physicians, and allied health, to ensure a holistic care pathway in this patient cohort.