Stratification Strategies Research Articles

The Current State of Breast Cancer Genetics in Populations of African Ancestry

Breast cancer (BC) constitutes a significant global health burden, particularly among women, with disparities observed across populations. Notably, women of African ancestry often experience BC at earlier ages and in more aggressive forms, with a higher prevalence of metastasis. Genetic studies, including those focused on BRCA1 and BRCA2 genes, have revealed population-specific variations in BC susceptibility. Despite efforts to investigate BC genetics in African and African-descendant populations, research remains limited compared to studies conducted in populations of European descent. Socioeconomic factors further compound the challenges faced by marginalized populations, influencing disease outcomes and treatment efficacy. This review explores the BC literature in African and African-descendant populations, highlighting population-specific genetic variants associated with the disease’s subtypes, treatment response, and disease evolution. Limited sample sizes and lack of data on genetic ancestry hinder the development of precise risk stratification and treatment strategies. Efforts to expand research, improve data collection, and enhance genetic analyses in diverse populations are crucial steps toward addressing racial disparities and advancing BC care on a global scale.

Clonal dynamics of chronic myelomonocytic leukemia progression: paired-sample comparison.

This study investigated the clonal evolution of chronic myelomonocytic leukemia (CMML) progression to secondary acute myeloid leukemia (sAML) by next-generation sequencing and pyrosequencing for variant allele frequency (VAF) of gene mutations and SNP microarray for copy neutral loss of heterozygosity (CN-LOH) in 38 paired samples from CMML/sAML patients of Taiwanese origin. The median interval between CMML and sAML samples collection was 14.9 months (1.0-89.6). RUNX1 (57%), TET2 (46%), SRSF2 (37%), and ASXL1 (28%) mutations were frequent at CMML diagnosis. Baseline VAF in epigenetic regulator genes was high (>35%) in 83% of mutational events at the CMML phase, remained stable in 78% (VAF changes <10%), and increased in 20% (increased VAF > 10%) during progression to sAML. Transcription factor genes showed high VAF (>35%) in 51% at the CMML phase, and stable VAF in 60% during progression. VAF of spliceosome genes was high (>35%) in 70% at CMML phase, and stable in 61% during progression. Activated signaling genes exhibited acquisition or loss during progression. TET2 mutations were often founding clones, and SRSF2, ASXL1, DNMT3A, EZH2, or spliceosome genes also acted as ancestral mutations. RUNX1 mutations were typically later events and occasionally ancestral hits or germline mutations. Acquisition of cytogenetic changes, signaling pathways genes (PTPN11, FLT3, NRAS, CBL), or AML-defined genes (NPM1, CEBPA, CBFB::MYH11) by linear or branching evolution occurred during sAML progression. CN-LOH was noted in EZH2, CBL, TET2, and DNMT3A genes. CEBPA mutation and concurrent biallelic TET2 with NRAS mutations at CMML diagnosis were risk factors for time to AML progression and overall survival. A characteristic ASXL1MT/RUNX1MT/SpliceosomeMT/signalingWT genetic profile was associated with monocyte counts of 0.5-1.0 × 109/l. This study highlights the complexity and heterogeneity of dynamic changes in clonal architecture during CMML progression, emphasizing its importance in pathogenesis, phenotype, risk stratification, and therapeutic strategy. © 2025 The Pathological Society of Great Britain and Ireland.

Pathway-dependent brain stimulation responses indicate motion processing integrity after stroke.

Homonymous Hemianopia (HH), a common visual impairment resulting from occipital lobe lesions, affects a significant number of stroke survivors. Intensive perceptual training can foster recovery, possibly by enhancing surviving visual pathways. This study employed cortico-cortical paired associative stimulation (ccPAS) to induce associative plasticity within the residual and bi-directional primary visual cortex (V1) - middle temporal area (MT) pathways in stroke patients. We used ccPAS, which is thought to tap into Hebbian-like spike-timing dependent plasticity, over a motion processing pathway in stroke patients to transiently improve visual motion discrimination in their blind field. Sixteen stroke patients participated in this double-blind, crossover study comparing the effects of bidirectional ccPAS (V1-to-MT or MT-to-V1) on motion discrimination and EEG-Granger Causality. Additionally, we explored potential multimodal sources of inter-individual variability. Results showed that MT-to-V1 ccPAS enhanced motion direction discrimination, but the expected electrophysiological increase in top-down MT-to-V1 inputs was observed only in patients who showed improvement in motion discrimination. Good responders to MT-V1 ccPAS also demonstrated improved functional coupling between the cortical motion pathway and other relevant areas in the visual network, as well as more preserved ipsilesional V1-MT structural integrity. These findings indicate that targeted ccPAS can effectively engage functionally relevant residual visual pathways in stroke-affected brains, potentially offering new avenues for patient stratification and visual recovery strategies.

Elevated Lp(a) and its association with cardiac fibrosis in group II pulmonary hypertension patients.

Group II Pulmonary Hypertension (PH) secondary to Heart Failure with preserved Ejection Fraction (HFpEF) is associated with significant morbidity and mortality. Lipoprotein(a) [Lp(a)] is a novel biomarker implicated in cardiovascular pathology, yet its role in myocardial fibrosis within this population remains underexplored. This study investigates the association between elevated Lp(a) levels and cardiac fibrosis to improve understanding of its prognostic and diagnostic utility. This retrospective cohort study included 100 patients with Group II PH secondary to HFpEF. Serum Lp(a) levels were quantified using enzymatic assays, and myocardial fibrosis was assessed using Cardiac Magnetic Resonance Imaging (CMR) techniques, including T1 mapping and late gadolinium enhancement (LGE). Statistical models adjusted for confounding factors. Elevated Lp(a) levels were significantly associated with increased myocardial extracellular volume (31% vs. 27%, p < 0.01), prolonged native T1 times, and increased odds of myocardial scar formation. Structural cardiac changes correlated with Lp(a) concentrations. Elevated Lp(a) is a key marker of myocardial fibrosis and structural remodeling in Group II PH secondary to HFpEF. Routine Lp(a) measurement may enhance risk stratification and inform therapeutic strategies.

Serum Type I Interferon Score predicts clinically meaningful disease progression in limited cutaneous Systemic Sclerosis.

To assess the value of serum Type I Interferon (IFN) score in predicting clinically meaningful progression in limited cutaneous systemic sclerosis (lcSSc) using a novel composite endpoint adopted from the MINIMISE clinical trial. A retrospective, longitudinal lcSSc cohort was identified within a national, multicentre observational cohort. The MINIMISE combined Morbi-mortality endpoint was used as clinical outcome for a time to clinical worsening (TTCW) design. IFN score was calculated from the serum concentration of CCL2, CCL8, CCL19, CXCL9, CXCL10, and CXCL11 on patients and age- and sex-matched healthy controls (HC). "High" IFN score was defined as two standard deviations above HC mean. The association of the IFN score with TTCW was assessed using Cox Proportional Hazard regressions and Kaplan-Meier curves. The potential improvement in risk stratification when combining IFN score with lcSSc clinical features was explored. A total of 149 patients were included in the analysis, 67 "High" IFN and 82 "Low". "High" IFN patients presented a shorter TTCW (74.7 months [95% C.I. 70.1-79.3] vs 110.6 [95% C.I. 107.2-114.0], p<0.001) and met the endpoint in higher proportion compared to "Low" IFN (55% vs 12%, p<0.001). "High" IFN score conferred 5.5 (95% C.I. 2.7-11.3) Hazard Ratio (HR) for TTCW compared to "Low" IFN and IFN score as a continuous variable conferred 2.38 (95% C.I. 1.4-4.0) HR for TTCW independently of clinical variables. Pulmonary Arterial Hypertension, Interstitial Lung Disease, Digital Ulcers, and modified Rodnan Skin Score were associated to TTCW. An exploratory analysis showed that these clinical features improve risk stratification over time in combination with IFN score. Serum assessment of Type I IFN activity is a valuable predictor of clinically meaningful outcomes in lcSSc. The combination of serum IFN score with sentinel clinical features can improve stratification strategies in clinical trials and patient management.

Unveiling the role of PANoptosis-related genes in breast cancer: an integrated study by multi-omics analysis and machine learning algorithms.

The heterogeneity of breast cancer (BC) necessitates the identification of novel subtypes and prognostic models to enhance patient stratification and treatment strategies. This study aims to identify novel BC subtypes based on PANoptosis-related genes (PRGs) and construct a robust prognostic model to guide individualized treatment strategies. The transcriptome data along with clinical data of BC patients were sourced from the TCGA and GEO databases. Consensus clustering was performed on 12 PRGs to ascertain potential BC subtypes, and variances in survival, infiltration of immune cells, and functional pathways among them were examined. A prognostic model was generated through 101 combinations of machine learning algorithms and validated across multiple cohorts. The response of patients towards immunotherapy were analyzed using multiple frameworks. Consensus clustering of 12 PRGs identified two distinct BC subtypes, with subtype B exhibiting significantly lower overall survival (OS) rates compared to subtype A. Immune cell infiltration analysis revealed higher immune activity in subtype A. Functional pathway analysis revealed that subtype A exhibited a significant enrichment in immune-related pathways, while subtype B was associated with cell cycle and metabolic processes. An integrated machine learning framework integrating CoxBoost and Random Survival Forest (RSF) algorithms was developed, demonstrating high predictive performance across multiple cohorts. A nomogram combining age and risk score was constructed, showing excellent predictive performance. Immune landscape analysis revealed that the high-risk group exhibited a suppressive tumor immune microenvironment (TIME). Immunotherapy response prediction suggested that low-risk patients were more likely to benefit from PD-1 and CTLA-4 inhibitors. Our study provides a comprehensive framework for BC subtype classification and prognostic prediction, offering valuable insights for personalized treatment strategies.

Risk and protective factors of disease flare during pregnancy in systemic lupus erythematosus: a systematic review and meta-analysis.

To synthesize available evidence on predictive factors associated with systemic lupus erythematosus (SLE) flares during pregnancy, we systematically searched MEDLINE, Embase, and the Cochrane Library through January 2024 for observational studies on risk and protective factors of SLE flares during pregnancy. Odds ratios (OR) and mean differences (MD), as well as their 95% confidence intervals (CI) were used to quantify effect sizes. We employed fixed-effect or random-effect models based on heterogeneity assessments (I2 statistics). Sensitivity analyses were performed using the leave-one-out method, and publication bias was assessed through Egger's test. Thirty-two studies were included in the meta-analysis. Significant baseline SLE characteristics associated with higher risks for flares during pregnancy were identified: thrombocytopenia (with OR [95%CI], 2.29 [1.14-4.58]), hypocomplementemia (1.70 [1.28-2.27]), anti-dsDNA positivity (1.43 [1.16-1.77]), and a history of lupus nephritis (2.34 [1.70-3.21]). Protective factors included achieving remission before pregnancy (0.32 [0.20-0.49]) and antimalarial use at baseline (0.71 [0.55-0.92]) and during pregnancy (0.44 [0.33-0.58]). Additional risk factors included baseline glucocorticoid usage (1.51 [1.17-1.94]), glucocorticoid administration during pregnancy (3.39 [1.90-6.06]), use of other immunosuppressive drugs at baseline (1.46 [1.00-2.12]), and hypertension (2.16 [1.45-3.23]). Furthermore, individuals in the flare group were younger, had higher baseline disease activity, and lower C3/C4 levels compared to the non-flare group. This study highlighted the critical role of managing SLE disease activity prior to pregnancy to minimize flare risks, and identified significant risk and protective factors associated with flares. These evidences facilitate better clinical management strategies for pregnant women with SLE. Key Points • Synthesizes existing evidence on the risk and protective factors associated with SLE flares during pregnancy. • Highlights the critical importance of effectively managing disease activity prior to conception. • Provides insights to enhance risk stratification and management strategies for pregnancies in patients with SLE.

Association of liver fibrosis with aneurysm size and mortality risk in patients undergoing open abdominal aortic aneurysm repair

Abdominal Aortic Aneurysm (AAA) poses a significant health risk due to its silent nature and high mortality upon rupture. The Fib-4 index, initially designed for liver fibrosis assessment, presents potential beyond its scope. This study aims to investigate the association of FIB-4 with aneurysm size and mortality risk, exploring its utility as a risk predictor for enhanced clinical management. This retrospective longitudinal research studied 141 AAA open repair surgery patients (92% male, mean age of 70 years (SD: 11.5)) from October 2016 to September 2021 for a median follow-up 35 months (IQR: 0.7 – 56.6). All-cause mortality was the primary outcome. Adjusted hazard ratios (aHR) were calculated for each Fib-4 cut-off between 1.5 and 3.25. FIB-4 cut-off range of 2.58–2.74 was associated with higher mortality risk in adjusted HR. Specifically, FIB-4 ≥ 2.67 increased mortality by 78% (aHR:1.78, 95% CI: 1.06 – 3.00). Furthermore, FIB-4 ≥ 2.67 was significantly associated with a baseline aneurysm size ≥ 8cm (aOR: 2.67, 95% CI: 1.17 – 6.09). FIB-4 was independently associated with a higher mortality risk and higher aneurysm size. These findings suggest that FIB-4 assessment in clinical practice may enhance risk profiling, aiding in more precise stratification and management strategies for AAA patients.

Analysis of postmarketing neuropsychiatric adverse events of avapritinib based on the FDA adverse event reporting system

Neuropsychiatric adverse events (AEs) significantly impact the quality of life of patients using avapritinib. However, the majority of current data comes from pre-marketing, with limited real-world studies. Our research aimed to explore post-marketing data of avapritinib. We evaluated the signals of avapritinib-related neuropsychiatric AEs by data mining using the FDA Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR) and information component (IC) were employed to quantify the signals from the first quarter of 2020 through the fourth quarter of 2023. Subsequently, stratified analyses were conducted to further explore the effect of different stratification schemes on the association between avapritinib and neuropsychiatric AEs. Finally, a combination medication analysis was conducted to explore the impact of the co-administration of neuropsychiatric AEs. A total of 2029 neuropsychiatric AEs were reported, and 49 signals were detected, of which 5 were determined to be new signals. Avapritinib was significantly associated with the occurrence of neuropsychiatric AEs (ROR: 1.52, 95% CI: 1.44–1.61; IC: 0.43, IC025: 0.35). The stratified analysis found that gender, age and eight preferred terms (PTs), including cerebral haemorrhage, may affect the severity of AEs. Combination medication analysis showed that combining avapritinib with 19 other medications, including prochlorperazine, may increase the risk of neuropsychiatric AEs. The median time-to-onset (TTO) of avapritinib-related neuropsychiatric AEs was 32 (interquartile range [IQR] 2-200) days, with about 65% of cases occurring within the first three months of treatment. An increase in the signal for neuropsychiatric AEs was identified in post-marketing studies of avapritinib. Clinicians are advised to remain vigilant for such events, particularly during the initial stages of treatment with avapritinib.

Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality

Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I–III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy. Vδ1 γδ T cells from mTNBC patients produced more IL17 than those from HDs. Chemotherapy-naïve mTNBC patients showed increased classical monocytes and neutrophils. Transcriptional, proteomic, and functional analyses revealed that neutrophils in mTNBC exhibited enhanced migratory capacity, elevated granule proteins, and higher ROS production. Some immune changes, such as reduced non-switched B cells and heightened neutrophil migration, were evident in earlier TNBC stages. This study comprehensively maps systemic immunity in TNBC, guiding future research on patient stratification and immunomodulation strategies.

Neutrophil to platelet ratio predicts in-hospital mortality in patients with acute myocardial infarction.

Acute myocardial infarction (AMI) is a critical medical emergency worldwide and a leading cause of mortality. This study aims to investigate the predictive utility of the neutrophil-to-platelet ratio (NPR) in identifying AMI patients at an increased risk of in-hospital mortality. We enrolled 664 patients, including 421 with ST-elevation myocardial infarction (STEMI) and 243 with non-ST-elevation myocardial infarction (NSTEMI), at Zhongshan Hospital, Fudan University, from January 2020 to September 2023. NPR was calculated as the neutrophil count divided by the platelet count. The primary outcome was defined as in-hospital mortality. The overall in-hospital mortality among AMI patients was 6.78%. Mortality was notably higher in the high NPR group compared to the low NPR group. Univariate analysis identified several variables significantly associated with in-hospital mortality, including age, left ventricular ejection fraction (LVEF), neutrophil-to-lymphocyte ratio (NLR), and NPR. NPR demonstrated a strong independent association with in-hospital mortality following adjustment for potential confounders. Receiver operating characteristic (ROC) curve analyses were performed to assess the discriminative power of NPR and NLR in predicting in-hospital mortality. NPR exhibited an area under the curve (AUC) of 0.755 (95% CI, 0.682-0.829, p < 0.001), indicating good discriminative ability. Similarly, NLR showed a discriminative AUC of 0.674 (95% CI, 0.586-0.762, p < 0.001). The optimal cutoff values for predicting mortality were determined as 0.042 for NPR (sensitivity 80%, specificity 62.2%) and 8.02 for NLR (sensitivity 62.2%, specificity 67.5%). Bootstrap validation with 1000 iterations confirmed the robustness of these findings, with validated AUCs of 0.755 (95% CI, 0.681-0.826) for NPR and 0.674 (95% CI, 0.587-0.766) for NLR. This study identifies NPR as an independent and valuable predictor of in-hospital mortality among AMI patients, The findings underscore NPR's potential utility in clinical practice for risk stratification and early intervention strategies aimed at reducing mortality rates in this high-risk patient population.

Consensus molecular subtyping of colorectal carcinoma brain metastases reveals a metabolic signature associated with poor patient survival.

The transcriptomic classification of primary colorectal cancer (CRC) into distinct consensus molecular subtypes (CMSs) is a well-described strategy for patient stratification. However, the molecular nature of CRC metastases remains poorly investigated. To this end, this study aimed to identify and compare organotropic CMS frequencies in CRC liver and brain metastases. Compared to reported CMS frequencies in primary CRC, liver metastases from CRC patients were CMS4-enriched and CMS3-depleted, whereas brain metastases mainly clustered as CMS3 and rarely as CMS4. Regarding overall survival rates, CMS4 was the most favorable subtype for patients with hepatic lesions, followed by CMS1 and CMS2. The survival of patients with brain metastases did not correlate with CMS. However, we identified a CMS3-related metabolic gene signature, specifically upregulated in central nervous system (CNS)-infiltrating CRC, as a negative prognostic marker and potential tumor progressor. In summary, subtyping of CRC metastases revealed an organotropic CMS distribution in liver and brain with impact on patient survival. CNS-infiltrating CRC samples were enriched for CMS3 and predictive metabolic biomarkers, suggesting metabolic dysregulation of CRC cells as a prerequisite for metastatic colonization of the brain.

The modulating effect of circulating carbohydrate antigen 125 on ST2 and long-term recurrent morbidity burden

Soluble ST2 (sST2) is released in response to vascular congestion, inflammation, and pro-fibrotic stimuli. In heart failure (HF), elevated levels of sST2 are associated with a higher risk of adverse clinical outcomes. Emerging evidence suggests that carbohydrate antigen 125 (CA125) may act as a ligand that modulates the inflammatory response. We hypothesized that CA125 might be modulating sST2 activity. In a cohort of 160 patients with acute (AHF) and renal dysfunction, we investigated whether the prognostic value of sST2 varies according to CA125 levels. The endpoints were: (a) total cardiovascular and renal hospitalizations and (b) all-cause mortality during follow-up. Cox regression analyses assessed the association between admission sST2 and endpoints across CA125 (≤ 35 vs. > 35 U/ml). This sub-study of the IMPROVE-HF trial shows that sST2 predicted the composite of cardiovascular or renal rehospitalizations when CA125 was elevated (> 35 U/ml) but not when CA125 ≤ 35 U/ml. These results highlight a potential biological interaction between sST2 and CA125, suggesting that CA125 status may refine the prognostic utility of sST2 in AHF. Clinically, these insights could guide personalized risk stratification and management strategies in this high-risk population.

Rhabdomyosarcoma Surgical Update.

Rhabdomyosarcoma (RMS) tumors arise from mesenchymal tissue and represent half of pediatric sarcomas, which in turn make up 7% of pediatric tumors. Advances in local control therapy of RMS have improved outcomes after surgical resection of the primary tumor, either before or after induction chemotherapy, even in the setting of metastatic disease. The utilization of diagnostic core needle and sentinel node biopsy techniques for lymph node staging are becoming more widely used. Over the past several years, refinement of prognostic factors with adoption of fusion status instead of histology, and optimized risk stratification schemas have been developed to assure appropriate therapy. There have been efforts between North American and European surgical oncology cooperative groups to standardize the care we provide, and yet there are still some philosophical differences to overcome.

Heart failure risk stratification using artificial intelligence applied to electrocardiogram images: a multinational study.

Current heart failure (HF) risk stratification strategies require comprehensive clinical evaluation. In this study, artificial intelligence (AI) applied to electrocardiogram (ECG) images was examined as a strategy to predict HF risk. Across multinational cohorts in the Yale New Haven Health System (YNHHS), UK Biobank (UKB), and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), individuals without baseline HF were followed for the first HF hospitalization. An AI-ECG model that defines cross-sectional left ventricular systolic dysfunction from 12-lead ECG images was used, and its association with incident HF was evaluated. Discrimination was assessed using Harrell's C-statistic. Pooled cohort equations to prevent HF (PCP-HF) were used as a comparator. Among 231 285 YNHHS patients, 4472 had primary HF hospitalizations over 4.5 years (inter-quartile range 2.5-6.6). In UKB and ELSA-Brasil, among 42 141 and 13 454 people, 46 and 31 developed HF over 3.1 (2.1-4.5) and 4.2 (3.7-4.5) years. A positive AI-ECG screen portended a 4- to 24-fold higher risk of new-onset HF [age-, sex-adjusted hazard ratio: YNHHS, 3.88 (95% confidence interval 3.63-4.14); UKB, 12.85 (6.87-24.02); ELSA-Brasil, 23.50 (11.09-49.81)]. The association was consistent after accounting for comorbidities and the competing risk of death. Higher probabilities were associated with progressively higher HF risk. Model discrimination was 0.718 in YNHHS, 0.769 in UKB, and 0.810 in ELSA-Brasil. In YNHHS and ELSA-Brasil, incorporating AI-ECG with PCP-HF yielded a significant improvement in discrimination over PCP-HF alone. An AI model applied to a single ECG image defined the risk of future HF, representing a digital biomarker for stratifying HF risk.

Investigating lung cancer microenvironment from cell segmentation of pathological image and its application in prognostic stratification

Lung cancer, particularly adenocarcinoma, ranks high in morbidity and mortality rates worldwide, with a relatively low five-year survival rate. To achieve precise prognostic assessment and clinical intervention for patients, thereby enhancing their survival prospects, there is an urgent need for more accurate stratification schemes. Currently, the TNM staging system is predominantly used in clinical practice for prognostic evaluation, but its accuracy is constrained by the reliance on physician experience. Although biomarker discovery based on molecular pathology offers a new perspective for prognostic assessment, its dependence on expensive gene panel testing limits its widespread clinical application. Pathological images contain abundant diagnostic information, providing a new avenue for prognostic evaluation. In this study, we employed advanced Hover-Net technology to accurately quantify the abundance of epithelial cells, lymphocytes, macrophages, and neutrophils from pathological images, and delved into the clinical and biological significance of these cellular abundances. Our research findings reveal that, in contrast to patients classified as N0 stage, those belonging to the N1 stage demonstrated a marked elevation in the infiltration of epithelial cells, lymphocytes, macrophages, and neutrophils. Notably, the infiltration patterns of lymphocytes and neutrophils exhibited an inverse relationship with the activation status of numerous pivotal gene pathways, including the HALLMARK_HEME_METABOLISM pathway. Furthermore, our analysis distinguished FABP7 as a prognostic biomarker, exhibiting pronounced differential expression between patients with high and low levels of neutrophil infiltration, indicate that cellular abundance analysis based on pathological images can provide a more accurate and cost-effective prognostic evaluation, offering new strategies for the clinical management of lung adenocarcinoma.

PET-Assessed Metabolic Tumor Volume Across the Spectrum of Solid-Organ Malignancies: A Review of the Literature.

Solid-organ malignancies represent a significant disease burden and remain one of the leading causes of death globally. In the past few decades, the rapid evolution of imaging modalities has shifted the paradigm towards image-based precision medicine, especially in the care of patients with solid-organ malignancies. Metabolic tumor volume (MTV) is one such semi-quantitative parameter obtained from positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) that has been shown to have significant implications in the clinical oncology setting. Across various solid tumor malignancies, including lung cancer, head and neck cancer, breast cancer, esophageal cancer, and colorectal cancer, the current literature has demonstrated an association between MTV and various clinical outcomes. MTV may be used in conjunction with several existing and established clinical parameters to help inform risk stratification and treatment strategies and predict outcomes in cancer. Optimizing such volumetric parameters is paramount for advancing efforts to advance cancer care for our patients. While such advancements are made, it is important to investigate and address the limitations of MTV, including variability in terms of measurement methods, a lack of standardized cut-off values, and the impact of inherent tumor heterogeneity. Despite these limitations, which can precipitate challenges in standardization, MTV as a prognostic factor has great potential and opens an avenue for the future integration of technology into an image-based precision medicine model of care for cancer patients. This article serves as a narrative review and explores the utility and limitations of PET-MTV in various settings of solid-organ malignancy.

High perioperative lactate levels as a potential predictor for severe acute kidney injury following aortic arch surgery.

Acute type A aortic dissection (ATAAD) is a life-threatening condition that often requires total aortic arch replacement (TAR) combined with frozen elephant trunk (FET) implantation. Despite advancements in surgical techniques and preoperative management, postoperative acute kidney injury (AKI) remains a prevalent complication that significantly affects patient prognosis, particularly severe AKI. The aim of this study was to investigate the predictive value of perioperative lactate levels in severe postoperative AKI after TAR. A cohort analysis of 328 patients who underwent TAR with frozen elephant trunk implantation at Xijing Hospital, Xi'an, China, between September 2019 and September 2023 was conducted. Patients were categorized according to AKI severity into non-AKI, mild-AKI, and severe-AKI cohorts, and lactate levels were measured at nine perioperative time points. The primary endpoint was severe AKI (Kidney Disease: Improving Global Outcomes stage 3). Uni-and multivariate logistic regression analyses were performed to identify risk factors for severe AKI. Subgroup analysis substantiated the robustness of lactate levels in predicting severe AKI. In total, 45.4% of patients developed mild AKI postoperatively and 20.7% developed severe AKI. Patients with severe postoperative AKI exhibited higher preoperative lactate levels. Multivariate stepwise backward logistic regression analysis identified lactate levels at 12 h postoperatively ([Lacpo12h], cutoff value: 3.3 mmol/L; sensitivity: 63.2%; specificity: 72.3%) as an independent predictor of severe AKI. The subgroup analysis underscored the consistent predictive capacity of Lacpo12h. The 30-day mortality rate was markedly elevated in the severe-AKI cohort, with deceased patients exhibiting a significantly higher Lacpo12h. Among patients with acute type A aortic dissection undergoing TAR, high perioperative lactate levels were closely associated with postoperative AKI. Lacpo12h is a reliable and effective predictor of severe postoperative AKI, highlighting its clinical utility in risk stratification and management strategies.

Global trends and risk factors in gastric cancer: a comprehensive analysis of the Global Burden of Disease Study 2021 and multi-omics data.

Background: Gastric cancer (GC) remains a significant global health challenge. This study aimed to comprehensively analyze GC epidemiology and risk factors to inform prevention and intervention strategies. Methods: We analyzed the Global Burden of Disease Study 2021 data, conducted 16 different machine learning (ML) models of NHANES data, performed Mendelian randomization (MR) studies on disease phenotypes, dietary preferences, microbiome, blood-based markers, and integrated differential gene expression and expression quantitative trait loci (eQTL) data from multiple cohorts to identify factors associated with GC risk. Results: Global age-standardized disability-adjusted life year rates (ASDR) for GC declined from 886.24 to 358.42 per 100,000 population between 1990 and 2030, with significant regional disparities. Despite this decline, total disability-adjusted life years show a concerning upward trend from 2015, rising from approximately 22.9 million to a projected 24.3 million by 2030. The slope index of inequality shifted from 87 in 1990 to -184 in 2021, indicating a reversal in GC burden distribution, with higher ASDR now associated with lower socio-demographic index countries. The ML models analysis identified higher levels of clinical characteristics such as phosphorus, calcium, eosinophils percent, and triglycerides, as well as lower levels of iron and monocyte percent, may be associated with an increased risk of GC. MR analyses revealed causal associations between GC risk and disease phenotypes such as Helicobacter pylori infection, chronic gastritis, obesity, depression, and dietary preferences such as dairy and processed meats. Gut microbiome analysis showed associations with microbiome such as Phascolarctobacterium and Ruminococcaceae species. Blood-based markers analysis identified protective and risk effects for cortisol, glutamate, nicotinamide, Natural Killer %lymphocyte, CD4-CD8- T cell Absolute Count, Phosphatidylcholine (16:0_18:1), and Interleukin-1-alpha. Integrated genomic analysis identified 10 genes significantly associated with GC risk, with strong evidence for colocalization in genes such as CCR6 and PILRB. Conclusions: This systematic analysis reveals complex global trends in GC burden and identifies novel clinical, disease phenotypes, dietary preferences, microbial, blood-based, and genetic risk factors. These findings provide potential targets for improved risk stratification, prevention, and intervention strategies to reduce the global burden of GC.

Is Low-free Triiodothyronine (fT3) Associated with Increased Morbidity in Patients Admitted to Coronary Care Units?

The effects of thyroid hormone on patients hospitalized in coronary intensive care units are still controversial. We retrospectively examined thyroid hormone levels and their impact on cardiovascular morbidity in patients admitted to coronary intensive care units. A total of 208 (Female/Male; 47.1%/52.9%) patients without any history of thyroid disease were enrolled and screened. Patients with specific heart disease and existing thyroid hormone parameters were included in the study. Low triiodothyronine syndrome is characterized by reduced serum total or free T3 (fT3) concentrations in normal free T4 (fT4) and TSH levels. The common diagnosis of the patients in the coronary care unit is acute coronary syndrome (n=59, 28.2 %) and heart failure (n=46, 23.3%). Patients were divided into two groups according to left ventricular ejection fraction percentages (LVEF ≤39% vs LVEF ≥40%). Plasma fT3 levels were significantly correlated with low LVEF (≤39%) (p =0.002). fT3 (r=-0.183, p =0.013) and hospitalization etiology (r=-0.161, p =0.023) were also the most critical parameters affecting the length of hospitalization. Low fT3 was associated with reduced ejection fraction and prolonged hospitalization, which may lead to potential morbidities in HF patients, which may be useful in risk stratification and treatment strategies.