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Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome‐related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome‐related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC50 of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome‐related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High‐risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti‐PD‐L1 and anti‐CTLA‐4 immunotherapy, whereas low‐risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis‐related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome‐related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to describe the characteristics of patients admitted to the intensive care unit with severe pneumonia due to SARS-CoV-2, comparing them according to successive waves, and to identify prognostic factors for morbidity and mortality. Materials and methods: This single-center retrospective observational descriptive study was conducted from March 10, 2020, to October 17, 2021. All adult patients admitted with SARS-CoV-2 pneumonia presenting acute respiratory failure were included. COVID 19 diagnosis was confirmed by RT-PCR testing of respiratory specimens. The primary endpoint was ICU mortality. Secondary endpoints were the occurrence of ventilator-associated pneumonia (VAP) or bronchopulmonary aspergillosis. Results: Over the study period, 437 patients were included of whom 282 (65%) patients were ventilated for 9 [5;20] days. Among the studied population, 38% were treated for one or more episodes of VAP, and 22 (5%) for bronchopulmonary aspergillosis. ICU mortality was 26% in the first wave, then fell and stabilized at around 10% in subsequent waves (p = 0.02). Increased age, Charlson index, SOFA score and lactatemia on admission were predictive of mortality. Survival at 90 days was 85% (95% CI 82–88) and was unaffected by the presence of VAP. However, the occurrence of bronchopulmonary aspergillosis increased mortality to 36%. Conclusion: In this study, we observed mortality in the lower range of those previously reported. Risk factors for mortality mainly included age and previous comorbidities. The prognosis of these critically ill Covid 19 patients improved over the four waves, underlining the likely beneficial effect of vaccination and dexamethasone. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is a complex renal disease with a highly variable clinical course. Identifying reliable prognostic markers is crucial for risk stratification and treatment decisions. This study aimed to understand the influence of different proportions of crescents (Cs) on the progression of IgAN. Methods: Four databases (PubMed, Web of Science, Embase, and Cochrane Library) were searched until September 25, 2023. The study encompassed IgAN patients, focusing on kidney outcomes and end-stage kidney disease (ESKD). Statistical analysis included calculating hazard ratios (HR) for binary outcomes and examining publication bias. Results: The meta-analysis involved thirteen studies comprising 11,849 patients. For kidney outcomes, crescent formation may be linked to an elevated risk (HR = 2.01, 95%CI 1.40–2.87, P < 0.001). Furthermore, significantly increased risks of kidney outcomes were observed with a crescent proportion > 10 (HR = 1.8, 95%CI 1.32–2.45, P < 0.001) and > 25%(HR = 2.11, 95% CI 1.47–3.02, P < 0.001). Regarding ESKD, a proportion > 25% also displayed an elevated risk (HR = 1.70, 95% CI 1.18–2.44, P = 0.004). However, a proportion > 10% (including > 25%) did not show a significant association with ESKD (HR = 1.12, 95% CI 0.36–3.47, P = 0.842) versus less. Conclusions: This systematic review and meta-analysis established a strong association between crescent proportions and the progression of IgAN. Higher proportions, notably exceeding 25%, were reliable prognostic markers, indicating a greater risk of adverse kidney outcomes and ESKD. These findings have significant clinical implications, offering the potential for more precise risk stratification in IgAN patients. [ABSTRACT FROM AUTHOR]

As a structural protein, keratin is mainly expressed in epithelial cells and skin appendages to provide mechanical support and external resistance. The keratin family has a total of 54 members, which are divided into type I and type II. Two types of keratins connect to each other to form keratin intermediate filaments and participate in the construction of the cytoskeleton. K18 is a non-hair keratin, which is widely expressed in simple epithelial tissues with its partner, K8. Compared with mechanical support, K8/K18 pairs play more important roles in biological regulation, such as mediating anti-apoptosis, regulating cell cycle progression, and transmitting signals. Mutations in K18 can cause a variety of non-neoplastic diseases of the visceral epithelium. In addition, the expression levels of K18 are frequently altered in various epithelial-derived tumors, especially adenocarcinomas, which suggests that K18 may be involved in tumorigenesis. Due to the specific expression pattern of K18 in tumor tissues and its serum level reflecting tumor cell death, apply K18 to diagnose tumors and predict its prognosis have the potential to be simple and effective alternative methods. However, these potential roles of K18 in tumors have not been fully summarized. In this review, we focus on the relationship between K18 and epithelial-derived tumors, discuss the value of K18 as a diagnostic and prognostic marker, and summarize the interactions of K18 with various related proteins in tumorigenesis, with examples of simple epithelial tumors such as lung, breast, liver, and gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS) is associated with a high risk of endometrial cancer (EC). However, its impact on EC progression remains unclear. This meta-analysis examined the association between MetS and survival outcomes in EC patients. Methods: A comprehensive search of PubMed, EMBASE, and Web of Science databases up to May 22, 2024, was conducted. Two independent reviewers performed study selection, data extraction, and quality assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Results: Nine studies comprising 13,579 endometrial cancer (EC) patients were included. Among these, 2,896 patients (21.3%) had MetS at the time of enrollment. The follow-up durations ranged from 3.4 to 14.2 years. The results showed that EC patients with MetS at baseline demonstrated significantly poorer overall survival (HR = 1.57, 95% CI = 1.19-2.07, p = 0.002; I² = 25%) and progression-free survival (HR = 1.33, 95% CI = 1.08-1.63, p = 0.007; I² = 16%). A similar association was observed for cancer-specific survival (HR = 1.26, 95% CI = 1.10-1.44, p = 0.001; I² = 0%). Subgroup analyses based on study characteristics showed consistent results across studies conducted in countries with different follow-up durations. Conclusion: This meta-analysis suggests that MetS is associated with poor survival outcomes in EC patients. Further prospective studies are required to validate our findings. Systematic review registration: PROSPERO, identifier CRD42024561654. [ABSTRACT FROM AUTHOR]

Objectives: This study attempted to determine potential predictors among radiomics features for poor prognosis in aneurysmal subarachnoid hemorrhage (aSAH), develop models for prediction, and verify their predictive power. Methods: In total, 252 patients with aSAH were included in this study and categorized into favorable and poor outcome groups based on the modified Rankin Scale score 3 months after event. Radiomics features of the ruptured intracranial aneurysm extracted from computed tomography angiography images were selected using least absolute shrinkage and selection operator regression and 10-fold cross-validation. A radiomics score was created by selecting the optimal features. Other risk factors for a poor prognosis were screened using multivariate regression analysis. Three models (clinical, aneurysm, and clinical-aneurysm combined models) were developed. The performance of the models was assessed using receiver operating characteristic (ROC) curves. A clinical-aneurysm combined nomogram was constructed to forecast the risk of poor prognosis in patients with aSAH. Results: A total of three clinical variables and six radiomics features were shown to have a significant association with poor prognosis in patients with aSAH. In the training cohort, the clinical, aneurysm, and clinical-aneurysm combined models had areas under the ROC curves of 0.846, 0.762, and 0.893, respectively. In the testing cohort, these models had areas under the ROC curves of 0.848, 0.753, and 0.869, respectively. Conclusion: The radiomics characteristics of ruptured intracranial aneurysms are valuable to predict prognosis after aSAH. The clinical-aneurysm combined model exhibited the best among the three models. The clinical-aneurysm combined nomogram is a reliable and effective tool for predicting poor prognosis in patients with aSAH. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. Local resection, radiation therapy, and enucleation are the current first-line, primary UM treatments. However, regardless of the treatment received, around 50% of UM patients will develop metastatic disease within five to 7 years. In the largest published series of unselected patients with metastatic UM (mUM), the median survival time after diagnosis of metastasis was 3.6 months, with less than 1% of patients surviving beyond 5 years. Approved drugs for treatment of mUM include systemic treatment with tebentafusp-tebn or isolated hepatic perfusion (IHP) with melphalan. However, these drugs are only available to a subset of patients and improve survival by only a few months, highlighting the urgent need for new mUM treatments. Accurately predicting which patients are at high risk for metastases is also crucial. Researchers are developing gene expression signatures in primary UM to create reliable prognostic models aimed at improving patient follow-up and treatment strategies. In this review we discuss the evidence supporting ferroptosis, a non-apoptotic form of cell death, as a potential novel treatment target and prognosticator for UM. [ABSTRACT FROM AUTHOR]

Background: Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex and heterogeneous diseases driven by uncontrolled cell growth and proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them a promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value in HNSCC through comprehensive bioinformatics analysis, with a particular focus on the therapeutic potential of placental growth factor (PIGF). Methods: Transcriptome data for HNSCC were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed genes (DEGs) were identified and analyzed for their prognostic significance. Exercise-related gene sets were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, were conducted. The biological functions and clinical implications of key genes were further explored through single-gene expression analysis, immune infiltration analysis, and in vitro cellular experiments. Results: The study identified exercise-related genes associated with survival prognosis in HNSCC. GO and KEGG pathway analyses highlighted the biological functions of these genes, and Kaplan-Meier survival curves confirmed their prognostic value. PIGF expression analysis using TCGA data showed its diagnostic potential, with higher expression linked to advanced tumor stages. Single-cell sequencing revealed PIGF's role in the tumor microenvironment. In vitro experiments demonstrated that PIGF plays a pivotal role in enhancing cell proliferation and colony formation in HNSCC, with PIGF knockdown significantly impairing these functions, highlighting its importance in tumor growth regulation. Additionally, PIGF's predictive performance in drug sensitivity across cancer datasets suggests its potential as a pharmacological target, offering opportunities to modulate the immune microenvironment and improve therapeutic outcomes in cancer treatment. Conclusion: This study provides new insights into the molecular mechanisms underlying HNSCC and identifies exercise-related genes, particularly PIGF, as promising biomarkers for clinical treatment and personalized medicine. By focusing on PTMs and their role in cancer progression, our findings suggest that targeting PIGF may offer innovative therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Characterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy. Methods: A large number of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC were collected for systematic bioinformatics analysis. Characterize subtypes of TAMs at single-cell resolution and its effect on prognosis. Differential gene analysis and cell-cell communication were used to describe the effect on prognosis and validated by the TCGA dataset. Results: We used two prognosis-favorable genes, SLC12A5 and ENPP2, to identify a benign M2-like TAMs (bM2-like TAMs), which shared similarities with C1QC + TAMs, CXCL9+ TAMs and CD169+ TAMs, by analyzing scRNA-seq data and bulk RNA data of PDAC. The bM2-like TAMs were revealed to promote T cell activation and proliferation through ALCAM/CD6 interaction. Meanwhile, the bM2-like TAMs were responsible for stroma modeling by altering αSMA+/αSMA-cell ratio. On the contrast, the rest of the M2-like TAMs were defined as malignant M2-like TAMs (mM2-like TAMs), partly overlapping with SPP1+ TAMs. mM2-like TAMs were revealed to promote tumor progression by secretion of MIF and SPP1. Conclusion: Our study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC. [ABSTRACT FROM AUTHOR]

Introduction: Open reduction and fixation are the standard of care for treating mandibular fractures and usually lead to successful healing. However, complications such as delayed healing, non-union, and infection can compromise patient outcomes and increase healthcare costs. The initial inflammatory response, particularly the response involving specific CD8+ T cell subpopulations, is thought to play a critical role in healing long bone fractures. In this study, we investigated the role of these immune cell profiles in patients with impaired healing of mandibular fractures. Materials and methods: In this prospective study, we included patients with mandibular fractures surgically treated at Charité – Universitätsmedizin Berlin, Germany, between September 2020 and December 2022. We used follow-up imaging and clinical assessment to evaluate bone healing. In addition, we analyzed immune cell profiles using flow cytometry and quantified cytokine levels using electrochemiluminescence-based multiplex immunoassays in preoperative blood samples. Results: Out of the 55 patients enrolled, 38 met the inclusion criteria (30 men and 8 women; mean age 32.18 years). Radiographic evaluation revealed 31 cases of normal healing and 7 cases of incomplete consolidation, including 1 case of non-union. Patients with impaired healing exhibited increased levels of terminally differentiated effector memory CD8+ T cells (TEMRA) and a higher TEMRA to regulatory T cell (Treg) ratio, compared with those with normal healing. Conclusions: Our analysis of mandibular fracture cases confirms our initial hypothesis derived from long bone fracture healing: monitoring the TEMRA to Treg ratio in preoperative blood can be an early indicator of patients at risk of impaired bone healing. Radiologic follow-up enabled us to detect healing complications that might not be detected by clinical assessment only. This study highlights the potential of individual immune profiles to predict successful healing and may form the basis for future strategies to manage healing complications. [ABSTRACT FROM AUTHOR]

Background: The predictive accuracy of the preoperative neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with non-muscle-invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette–Guérin immunotherapy (BCG) after transurethral resection of the bladder tumor (TURBT) remains unknown. Therefore, the current study performed a systematic review and meta-analysis to examine the relationship between preoperative NLR and the prognosis of patients with NMIBC with intravesical BCG immunotherapy. Methods: For this systematic review and meta-analysis, articles were retrieved from PubMed, Cochrane Library, Web of Science, and Embase databases from their inception to 14 May 2024. The role of NLR in predicting recurrence and progression in NMIBC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Seven articles were included in this meta-analysis, involving 4,187 patients. An elevated NLR was significantly associated with recurrence (HR = 2.67, 95% CI = 1.34–5.32, P < 0.001) and progression (HR = 1.72, 95% CI = 1.13–2.60, P = 0.004) in patients with NMIBC with intravesical BCG immunotherapy. Conclusion: This meta-analysis demonstrated that elevated preoperative NLR levels were significantly associated with recurrence and disease progression in patients with NMIBC who underwent intravesical BCG immunotherapy after TURBT. Systematic review registration: https://inplasy.com/inplasy-2024-7-0058/ , identifier 202470058. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) continues to be a major health concern in today's world. Despite conflictive findings, evidence supports systemic inflammation's impact on CRC patients' survival rates. Therefore, this study aims to assess the prognostic role of the innate immune system in patients with CRC. Method: A total of 449 patients were included, with a 5-year follow-up period, and absolute neutrophil counts and their related ratios were measured. Results: The non-survival group had increased levels of white blood cells, neutrophils (both p <0.001), and monocytes (p=0.038), compared to the survival group, along with other neutrophil-related ratios. We observed increased mortality risk in patients in the highest tertile of white blood cells [HR=1.85 (1.09-3.13), p<0.05], neutrophils [HR=1.78 (95% CI: 1.07-2.96), p<0.05], and monocytes [HR=2.11 (95% CI: 1.22-3.63)], compared to the lowest tertile, after adjusting for all clinicopathological variables. Random forest analysis identified neutrophils as the most crucial variable in predicting survival rates, having an AUC of 0.712, considering all clinicopathological variables. A positive relationship between neutrophil counts and metastasis was observed when neutrophil counts are considered continuous (β=0.92 (0.41), p<0.05) and tumor size (width) when neutrophils were considered as logistic variable (T1 vs T3) [OR=1.42, (95% CI: 1.05-1.98), p<0.05]. Conclusion: This study offers comprehensive insights into the immune factors that impact the prognosis of CRC, emphasizing the need for personalized prognostic tools. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy combined with PD-1 inhibitor treatment has revolutionized the standard of care for patients with NSCLC. However, the benefit is not universal, highlighting the need for precise prediction factors. Given their relationship with the immune system and non-invasive nature, serum cytokines are potential candidates for predicting the clinical effects of chemoimmunotherapy. Our study aims to evaluate the association of serum cytokines with the prognosis of patients with NSCLC treated with chemoimmunotherapy. Methods: Levels of 10 serum cytokines were detected in 60 NSCLC patients receiving chemotherapy plus PD-1 inhibitor-based treatment. Of these, dynamic samples from 19 patients were collected at baseline and after two treatment cycles. Their association with patients' clinicopathological characteristics, PFS and OS was described and investigated using survival analysis, cox regression and time-dependent ROC analysis. Preliminary evaluation of changes in cytokine levels associated with treatment response was conducted. Results: Patients with lower baseline levels of serum IL-6, IL-5, IL-8, TNF-α and IL-10 had longer PFS, while patients with higher levels of IL-4 had longer PFS. Patients with lower levels of serum IL-6, IL-8, IL-22, TNF-α and IL-10 had longer OS, while patients with higher levels of IL-4 had longer OS. Multivariate analysis suggested that higher IL-6 and IL-5 levels were associated with poorer PFS, and higher IL-6 levels were associated with dismal OS. Additionally, changes in serum cytokine levels could be associated with treatment response. Conclusion: Our study suggests that serum cytokines, specifically IL-6, IL-5, IL-8, TNF-α, IL-10, and IL-4, are potential prognostic factors for patients with NSCLC receiving chemotherapy plus PD-1 inhibitor treatment. [ABSTRACT FROM AUTHOR]

Background: Heart failure with improved ejection fraction (HFimpEF) has been regarded as a new heart failure (HF) type in 2022. However, studies on the impact of left ventricular ejection fraction (LVEF) trajectories on the prognosis of patients with HFimpEF are scarce. In this study, we investigated dynamic trajectories of LVEF and different clinical outcomes in HFimpEF. Methods and results: This was a multi-center study included patients diagnosed with HF with reduced ejection fraction (HFrEF) between January 1, 2015, and October 31, 2022. Enrolled patients were divided into HFimpEF and persistent HFrEF groups. To further investigate different LVEF trajectories in HFimpEF patients, they were classified into persistent HFimpEF and transient HFimpEF subgroups. Adverse clinical outcomes encompassed all-cause death, cardiovascular death, and HF-related rehospitalization. A total of 734 patients were included (HFimpEF: n = 162; persistent HFrEF: n = 572). Cox regression analysis revealed that compared with persistent HFrEF, patients with HFimpEF experienced a lower risk of all-cause and cardiovascular death. Subgroup analysis determined that only 113 (69.75%) patients maintained an LVEF exceeding 40%. Cox regression analysis revealed that persistent HFimpEF patients had a lower risk of all-cause and cardiovascular death compared to those with transient HFimpEF. Finally, multivariate logistic analysis showed that gender and high-density lipoprotein cholesterol levels were independent predictors of persistent HFimpEF. Conclusions: HFimpEF does not accurately represent HF recovery, given that there are different trajectories of LVEF in HFimpEF. Patients with persistent HFimpEF experience better clinical outcomes, highlighting clinicians should identify clinical modifiable factors to maintain a stable HF stage for better prognosis. Trial registration: ChiCTR2400086622, 08/07/2024. [ABSTRACT FROM AUTHOR]

Background and purpose: The baseline glucose-to-potassium ratio (GPR) is associated with poor outcomes in patients with acute brain injury and intracranial hemorrhage. However, the impact of serum GPR on clinical outcomes after endovascular thrombectomy (EVT) is unclear. This study aimed to evaluate the association between the GPR at admission and functional outcomes at 90 days after EVT. Methods: We retrospectively reviewed our database for patients with acute ischemic stroke involving an anterior circulation large-vessel occlusion who received EVT between October 2019 and December 2021. The baseline serum GPR was measured after admission. The primary outcome was a 90-day poor outcome, which was defined as a modified Rankin scale score of 3–6. Results: A total of 273 patients (mean age, 70.9 ± 11.9 years; 161 men) were finally included for analyses. During the 90-day follow-up, 151 patients (55.3%) experienced an unfavorable outcome. After adjusting for demographic characteristics and other potential confounders, the increased GPR was significantly associated with a higher risk of a 90-day poor outcome (odds ratio, 1.852; 95% confidence interval, 1.276–2.688, p = 0.001). Similar results were observed when the GPR was analyzed as a categorical variable. In addition, the restricted cubic spline observed a positive and linear association between the GPR and poor outcomes at 90 days (p = 0.329 for linearity; p = 0.001 for linearity). Conclusion: Our study found that ischemic stroke patients with the higher GPR at admission were more likely to have an unfavorable prognosis at 3 months, suggesting that GPR may be a potential prognostic biomarker for ischemic stroke after EVT. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effect of fasting blood glucose levels after reperfusion of acute large vessel occlusion (ALVO) on patient functional prognosis. Methods: Retrospectively included ALVO patients from three large stroke centers in China, all of whom achieved vascular reperfusion after mechanical thrombectomy or bridging thrombolysis. The prognosis scores of all patients at 90 ± 7 days post-recanalization were categorized into a good prognosis group (mRS 0–2) and a poor prognosis group (mRS 3–6). The relationship between mean blood glucose levels at 72 h post-recanalization and prognosis was explored using multivariable logistic regression analysis. Then we measured the area under the ROC curve for all factors to assess their predictive performance. Results: (1) Totally 2,056 patients were included in the study, with 1,488 males and 568 females. There were 1,370 patients in the good prognosis group (mRS 0–2) and 686 in the poor prognosis group (mRS 3–6). (2) The two groups exhibited significant differences in terms of age, preoperative mRS score, history of diabetes, and mean fasting blood glucose (MFBG) (p < 0.001). (3) With 90-day mRS as the outcome variable, all independent variables were included in Univariate and multivariate regression analyses analysis, and the results showed that: age, preoperative mRS score, history of diabetes, and MFBG are all independent predictors of prognosis after recanalization of ALVO, with MFBG demonstrating a higher predictive power than the other factors (AUC = 0.644). Conclusion: Various factors are correlated with the prognosis in patients who have undergone ALVO recanalization. Notably, the MFBG level demonstrates a significant predictive value for outcomes within the first 72 h following the recanalization procedure. [ABSTRACT FROM AUTHOR]

Introduction: Spontaneous intracerebral hemorrhage is the second most common subtype of stroke. Therefore, this study aimed to investigate the risk factors affecting the prognosis of patients with basal ganglia cerebral hemorrhage after neuroendoscopy. Methods: Between January 2020 and January 2024, 130 patients with basal ganglia cerebral hemorrhage who underwent neuroendoscopy were recruited from two independent centers. We split this dataset into training (n = 79), internal validation (n = 22), and external validation (n = 29) sets. The least absolute shrinkage and selection operator-regression algorithm was used to select the top 10 important radiomic features of different regions (perioperative hemorrhage area [PRH], perioperative surround area [PRS], postoperative hemorrhage area [PSH], and postoperative edema area [PSE]). The black hole, island, blend, and swirl signs were evaluated. The top 10 radiomic features and 4 radiological features were combined to construct the k-nearest neighbor classification (KNN), logistic regression (LR), and support vector machine (SVM) models. Finally, the performance of the perioperative hemorrhage and postoperative edema machine learning models was validated using another independent dataset (n = 29). The primary outcome is mRS at 6 months after discharge. The mRS score greater than 3 defined as functional independence. Results: A total of 12 models were built: PRH-KNN, PRH-LR, PRH-SVM, PRS-KNN, PRS-LR, PRS-SVM, PSH-KNN, PSH-LR, PSH-SVM, PSE-KNN, PSE-LR, and PSE-SVM, with corresponding areas under the curve (AUC) values in the internal validation set of 0.95, 0.91, 0.94, 0.52, 0.91, 0.54, 0.67, 0.9, 0.72, 0.92, 0.92, and 0.95, respectively. The AUC values of the PRH-KNN, PRH-LR, PRH-SVM, PSE-KNN, PSE-LR, and PSE-SVM in the external validation were 0.9, 0.92, 0.89, 0.91, 0.92, and 0.88, respectively. Conclusion: The model built based on computed tomography images of different regions accurately predicted the prognosis of patients with basal ganglia cerebral hemorrhage treated with neuroendoscopy. The models built based on the preoperative hematoma area and postoperative edema area showed excellent predictive efficacy in external verification, which has important clinical significance. [ABSTRACT FROM AUTHOR]

Background: Early rehabilitation after acute ischemic stroke (AIS) contributes to functional recovery. However, the optimal time for starting rehabilitation remains a topic of ongoing investigation. This article aims to shed light on the safety and efficacy of very early rehabilitation (VER) initiated within 48 h of stroke onset. Methods: A systematic search in PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from inception to January 20, 2024. Relevant literature on VER in patients with AIS was reviewed and the data related to favorable and adverse clinical outcomes were collected for meta-analysis. Subgroup analysis was conducted at different time points, namely at discharge and at three and 12 months. Statistical analyses were performed with the help of the Meta Package in STATA Version 15.0. Results: A total of 14 randomized controlled trial (RCT) studies and 3,039 participants were included in the analysis. VER demonstrated a significant association with mortality [risk ratio (RR) = 1.27, 95% confidence interval (CI) (1.00, 1.61)], ability of daily living [weighted mean difference (WMD) = 6.90, 95% CI (0.22, 13.57)], and limb motor function [WMD = 5.02, 95% CI (1.63, 8.40)]. However, no significant difference was observed between the VER group and the control group in adverse events [RR = 0.89, 95% CI (0.79, 1.01)], severity of stroke [WMD = 0.52, 95% CI (−0.04, 1.08)], degree of disability [RR = 1.06, 95% CI (0.93, 1.20)], or recovery of walking [RR = 0.98, 95% CI (0.94, 1.03)] after stroke. Subgroup analysis revealed that VER reduced the risk of adverse events in the late stage (at three and 12 months) [RR = 0.86, 95% CI (0.74, 0.99)] and degree of disability at 12 months [RR = 1.28, 95% CI (1.03, 1.60)], and improved daily living ability at 3 months [WMD = 4.26, 95% CI (0.17, 8.35)], while increasing severity of stroke during hospitalization [WMD = 0.81, 95% CI (0.01, 1.61)]. Conclusion: VER improves activities of daily living (ADLs) and lowers the incidence of long-term complications in stroke survivors. However, premature or overly intense rehabilitation may increase mortality in patients with AIS during the acute phase. PROSPERO registration number: CRD42024508180. Systematic review registration: This systematic review was registered with PROSPERO (https://www.crd.york.ac.uk/PROSPERO/). PROSPERO registration number: CRD42024508180. [ABSTRACT FROM AUTHOR]

Background: The clinical importance of nutrition and inflammation in patients with end-stage renal disease is well established. In this study, we investigated the role of nutritional and inflammatory indicators in the patient outcomes of living donor kidney transplant recipients. Methods: We included 204 consecutive patients who underwent kidney transplantation at our institute between 2003 and 2022. We retrospectively reviewed medical charts to obtain clinical information. Six nutritional indicators and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored. Results: The median patient age and follow-up period were 48 years and 99 months, respectively. The cohort included patients with preoperative malnutrition and microinflammation. No significant differences in graft survival were identified according to nutritional and inflammatory indicators, whereas the survival index, controlled nutritional status, and C-reactive protein levels were associated with patient survival. The survival index was an independent indicator of survival and death in patients with functioning grafts (P = 0.047 and P = 0.013, respectively). Furthermore, the C-reactive protein level could distinguish between low and high mortality risks in patients with good nutrition (P = 0.019). Conclusions: Our findings suggest that nutrition and inflammation indicators play important roles in predicting outcomes in living donor kidney transplantation recipients. Further research is warranted to establish optimal management strategies. [ABSTRACT FROM AUTHOR]

Objective To analyze levels of pan-immune-inflammation value (PIV), interleukin-6 (IL-6), heparin-binding protein (HBP) and prealbumin (PAB) in patients with severe community-acquired pneumonia (CAP), and their values in evaluating the therapeutic effect at 72 h after admission. Methods According to the initial (72 h) treatment outcome, 120 patients with severe CAP (the severe group) were divided into the effective group (n=87) and the failed group (n=33). Meanwhile, 120 patients with non-severe CAP admitted in the same period were selected as the non-severe group. PIV, IL-6, HBP and PAB levels on the day after admission were compared between the severe group, the non-severe group, the failed group and the effective group. The value of above indicators in evaluating the condition of CAP and the therapeutic effect at 72 h after admission separately and in combination were analyzed using receiver operating characteristic (ROC) curves. Results Compared with the non-severe group, there were higher PIV, IL-6 and HBP levels, and lower PAB levels in the servere grouop (P < 0.05). ROC curves indicated that for evaluating severe CAP using a single indicator, the area under the curve (AUC) of PIV was the highest [0.830 (95%CI: 0.780-0.881)]. The AUC of PIV combined with IL-6, HBP and PAB for evaluating severe CAP was 0.929 (95%CI: 0.892-0.967), which was higher than that of evaluation using a single indicator (P < 0.05). Compared with the effective group, there were higher PIV, IL-6 and HBP levels, and lower PAB level in the failed group (P < 0.05). ROC curves indicated that for evaluating the therapeutic effect on severe CAP at 72 h after admission using a single indicator the AUC of PIV was the highest [0.777 (95%CI: 0.692-0.862)]. The AUC of PIV combined with IL-6, HBP and PAB for evaluating the therapeutic effect on severe CAP at 72 h after admission was 0.916 (95%CI: 0.846-0.986), which was higher than that of evaluation using a single indicator (P < 0.05). Conclusion Detection of PIV combined with IL-6, HBP and PAB has a good value in evaluating the condition of patients with CAP and the therapeutic effect on severe CAP at 72 h after admission. [ABSTRACT FROM AUTHOR]

Objective To investigate the prognostic value of alanine aminotransferase (ALT)/alkaline phosphatase (ALP) ratio, platelet (PLT) count/lymphocyte (LYM) ratio (PLR) in elderly patients with septic shock complicated with liver injury. Methods The clinical data of 116 patients with septic shock complicated with liver injury were retrospectively analyzed. According to the degree of liver injury, patients were divided into the mild group (39 cases), the moderate group (47 cases) and the severe group (30 cases). According to the survival of patients 28 days after admission, patients were divided into the death group (69 cases) and the survival group (47 cases). Acute physiological score, chronic health II (APACHE II) score and sequential organ failure (SOFA) score were collected. PLT and LYM in peripheral blood were detected, and PLR was calculated. ALT and ALP were measured and ALT/ALP ratio was calculated. White blood cell count, blood lactic acid, C-reactive protein and other laboratory indicators were detected. Multivariate Logistic regression was used to analyze prognostic factors of patients with septic shock complicated with liver injury. The predictive values of ALT/ALP ratio and PLR on the prognosis of patients with septic shock complicated with liver injury were analyzed by receiver operating characteristic (ROC) curve. Results Serum ALT and ALP levels, ALT/ALP ratio, PLT and PLR were increased successively in the mild group, the moderate group and the severe group, while LYM was decreased successively in the three groups (P < 0.05). The age, APACHE II score, SOFA score, PLR, ALT/ALP ratio and blood lactic acid level were higher in the death group than those in the survival group (P < 0.05). There was no significant difference in liver injury degree between the two groups (P < 0.05). Multivariate Logistic regression analysis showed that high SOFA score, high PLR, high ALT/ALP ratio and moderate to severe liver injury were risk factors for death in patients with septic shock complicated with liver injury. ROC curve analysis showed that the combined ALT/ALP ratio and PLR prediction efficiency [area under the curve 0.915 (95%CI: 0.849-0.959), sensitivity and specificity 94.20% and 89.36%, respectively] was superior to single prediction (P < 0.05). Conclusion Increased ALT/ALP ratio and PLR are associated with aggravation of liver injury and poor prognosis in patients with septic shock. ALT/ALP ratio and PLR can be used as prognostic markers. [ABSTRACT FROM AUTHOR]

Summary: The immunosuppressive treatment of immune‐mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B‐cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell‐directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab. Nine episodes from seven patients were identified. Treatment was administered for A Disintegrin And Metalloproteinase with ThromboSpondin‐1 motifs, 13th member (ADAMTS13) relapses while patients were otherwise in clinical response (N = 8), or during the acute phase of the disease following rituximab intolerance (N = 1). Patients have received a median of three previous therapeutic lines. ADAMTS13 activity improved in eight cases following daratumumab administration, including three cases where ADAMTS13 normalized. ADAMTS13 relapses occurred in three patients; in two cases, retreatment with daratumumab was successful. Median ADAMTS13 relapse‐free survival was not reached; 12‐month ADAMTS13 relapse‐free survival was 56%. Daratumumab‐related adverse events occurred in five cases and were non‐severe infusion‐related reactions in all cases. These results suggest that daratumumab may be an effective treatment option for iTTP patients with intolerance or refractoriness to rituximab. [ABSTRACT FROM AUTHOR]

Summary: In this study, we used the whole‐exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty‐five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse‐free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis. [ABSTRACT FROM AUTHOR]

Summary: Traditionally, Sezary syndrome (SS) has been associated with few therapeutic options and poor prognosis, with 5‐year disease‐specific survival (DSS) less than one‐third in historical cohorts. However, newer therapies and combinations are associated with impressive time‐to‐next‐treatment (TTNT), particularly allogeneic stem‐cell transplantation (AlloSCT) and combination therapies notably those including extracorporeal photopheresis. In this multicentre, international study, we explored the prognostic outcomes of 178 patients exclusively managed for SS, diagnosed between 2012 and 2020, and treated in the modern therapeutic era. In this cohort, 58 different therapies were delivered, with 13.5% of patients receiving AlloSCT. Long‐term survival exceeded historical reports with 5‐year DSS and OS of 56.4% and 53.4% respectively. In those receiving AlloSCT, prognosis was excellent: 5‐year DSS and OS were 90.5% and 78.0% respectively. Confirming the results from the Cutaneous Lymphoma International Consortium (CLIC), LDH and LCT had significant prognostic impact. Unlike earlier studies, stage did not have prognostic impact; we speculate that greater relative benefit favours patients with extensive lymphomatous nodal disease (Stage IVA2) compared to historical reports. For patients ineligible for AlloSCT, the prognosis remains relatively poor (5‐year DSS 51.4% and OS 49.6%), representing ongoing unmet needs for more effective novel agents and investigation of improved therapeutic combinations. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the prognostic value of the Mayo additive staging system (MASS) and minimal residual disease (MRD) in newly diagnosed multiple myeloma (NDMM) patients. Methods: A total of 238 NDMM patients were enrolled in Beijing Chaoyang Hospital. Fluorescence in‐situ hybridization and next‐generation flow cytometry were used to examine cytogenetic abnormalities and MRD, respectively. The patients were classified into three groups to compare the effects on progression‐free survival (PFS). Univariate and multivariate analyses were applied to identify the survival‐related factors. Results: For MASS group, the PFS was significant difference in MASS I, II, and III patients (p = 0.0006); the patients with sustained MRD‐negative, non‐sustained MRD‐negative, sustained MRD‐positive, and non‐sustained MRD‐positive were divided into Groups 1, 2, 3, and 4, respectively. The Group 1 patients had superior PFS than Groups 2 and 3 patients (p < 0.05), but no difference in PFS was observed for Group 2 versus Group 3, Group 2 versus Group 4, and Group 3 versus Group 4 patients. For the MASS and MRD groups, among Groups 2, 3, and 4, MASS I patients had a superior PFS, while III patients showed the opposite result. Strikingly, no difference in PFS for Group 1 patients regardless of the MASS stage was observed. Despite being in MASS II and III, the PFS of Group 1 patients was longer than those with the other three groups. Response to treatment was an independent prognostic factor for MM patients. Conclusion: Patients with an accumulation of high‐risk factors and MRD‐positive have poor outcomes. Sustained MRD‐negative may improve high‐risk patients' prognoses. [ABSTRACT FROM AUTHOR]

Objectives: Whether to perform local radiotherapy on metastatic bone for primary bone‐only oligometastatic nasopharyngeal carcinoma (NPC) patients remains unclear. Therefore, we analyzed the treatment methods and their survival and developed a prognostic model to predict outcomes and guide personalized treatment. Materials and Methods: We studied 308 primary bone‐only oligometastatic NPC patients who were treated with either palliative chemotherapy (PCT) alone, PCT combined with locoregional radiotherapy (LRRT), or PCT, LRRT, and radiotherapy to metastatic bones (bRT). The primary endpoint was overall survival (OS). Cox regression was utilized to identify independent prognostic factors, leading to the construction of a nomogram model. Patients were stratified into two risk groups based on median prognostic scores, and treatment modalities were compared using log‐rank test while employing the inverse probability of treatment weighting (IPTW) to balance baseline characteristics and adjust for sample size differences between risk groups. Results: The best OS was observed in the group treated with PCT, LRRT, and bRT (HR = 0.60, 95% CI: 0.45–0.81, p = 0.002). Multivariable analysis revealed that age, N stage, pre‐treatment levels of LDH, and EBV DNA were independent prognostic factors for OS. In total, 155 patients were in low‐risk group while 153 were in high‐risk group. Before and after IPTW, the high‐risk group benefited from the PCT, LRRT, and bRT regimen (adjusted HR = 0.53, 95% CI: 0.42–0.67, p < 0.001; unadjusted HR = 0.59, 95% CI: 0.42–0.83, p = 0.007), while the low‐risk group did not (adjusted HR = 0.79, 95% CI: 0.56–1.11, p = 0.345; unadjusted HR = 0.65, 95% CI: 0.37–1.14, p = 0.309). Conclusion: Best outcomes of the whole cohort were seen with PCT + LRRT + bRT. Our study identified age, N stage, pre‐treatment LDH levels, and EBV DNA levels as independent prognostic factors for OS. The high‐risk group demonstrated a longer OS when treated with PCT + LRRT + bRT, whereas the low‐risk group did not benefit from the combinatorial treatment. [ABSTRACT FROM AUTHOR]

Objectives We sought to assess the expression of human leukocyte antigen (HLA) proteins and β2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC). Methods A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3). Results We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R 2 = 0.3) and significantly associated with MMR-deficient tumors (P <.001); B2M-low tumors were also associated with an "immune cold"' microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P =.018), a finding that maintained significance only for the proficient MMR cohort (P =.037). Conclusions Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemoradiotherapy (CCRT) is used as the primary treatment modality for currently limited cervical cancer and lacks non-invasive quantitative parameters to assess clinical outcomes of treatment for cervical cancer treatment. Purpose: To develop nomograms based on clinical prognostic factors and apparent diffusion coefficient (ADC) in predicting downstaging and progression-free survival (PFS) after CCRT for cervical cancer. Material and Methods: X-tile was used to calculate the optimal threshold for ΔADCmean(%) for prognostic stratification. Kaplan–Meier curves were used to calculate the difference in PFS between high- and low-risk groups. Univariate and multivariate Cox proportional risk regression models were used to identify clinical and radiological risk factors for prognosis and construct a prognostic nomogram model. Results: ΔADCmean(%) was significantly correlated with tumor downstaging; the area under the receiver operating characteristic curve (AUC) was 0.868. X-tile showed that the optimal threshold for ΔADCmean(%) to diagnose prognosis was 40.8. Kaplan–Meier curves showed that the low-risk population in the training group had significantly longer PFS within 3 years (P < 0.001). Multivariate Cox regression showed that ΔADC (%) is independent risk factor for PFS. The C-index of ΔADC(%) predicting 3-year PFS in the training set is 0.761 and the C-index of the nomogram model is 0.862. Conclusion: ΔADCmean(%) is a non-invasive biomarker for predicting tumor downstaging in cervical cancer after CCRT. The nomograms based on ΔADCmean(%) predict PFS of patients with cervical cancer with moderate accuracy. [ABSTRACT FROM AUTHOR]

Background: Elevated neurofilament light chain (NfL) levels are associated with worse prognosis in Guillain–Barré syndrome (GBS). Our objectives were to determine the utility of serum NfL (sNfL), cerebrospinal fluid (CSF)/serum NfL ratio and NfL index as prognostic and diagnostic biomarkers for GBS. Methods: We measured NfL in serum and/or CSF obtained from 96 GBS patients between 1989 and 2014 in western Sweden. The sNfL Z-scores, NfL ratios and NfL indices were calculated. Outcome was determined with the GBS disability scale (GBSDS) at 3 and 12 months. NfL parameters in GBS were compared with healthy controls (HC), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Results: The sNfL Z-score was higher for GBSDS > 2 at 3 months (median [IQR], 3.5 ng/L [3.2–4.0], vs 2.6 [1.7–3.4], p = 0.008) and at 12 months (3.6 ng/L [3.5–3.8] vs 2.6 [1.8–3.5], p = 0.049). NfL ratio and index were not associated with outcome. The area under the curve (AUC) for sNfL Z-score was 0.76 (95% CI 0.58–0.93, p < 0.0001) for GBSDS > 2 at 3 months. NfL ratio and index were lower in GBS than HC, MS, and ALS. The AUC for the NfL ratio was 0.66 (95% CI 0.55–0.78, p = 0.0018) and for the NfL index 0.86 (95% CI 0.78–0.93, p < 0.0001). Discussion: Our results confirm sNfL as prognostic biomarker for GBS and the precision was improved using the age-adjusted sNfL Z score. NfL index and Qalb are potential diagnostic biomarkers for GBS. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to evaluate the prognosis of idiopathic premature ventricular beats (PVBs) in children. Materials and Methods: We retrospectively evaluated 73 children (<18 years old) with idiopathic PVBs and structurally normal hearts. All patients were evaluated by 24-hour Holter electrocardiography (ECG) and echocardiography at the first admission and followed with a mean of 27 ± 7.6 months after diagnosis. Baseline Holter ECG and echocardiographic findings were compared to the last visit. Results: The mean age of the patients was 11.1 ± 4.8 years, and half were symptomatic at initial examination. Baseline Holter showed complex beats in 35 cases, non-sustained ventricular tachycardia in 7 cases, and frequent PVBs in 19 cases. Complete recovery (CR) of PVBs was observed in 37 cases (50.7%) at a median of 15 (minimum: 5, maximum: 33) months after diagnosis. There were no significant differences in CR rates between patient groups with left bundle branch block (LBBB) vs. right bundle branch block (RBBB) morphology of PVBs, simple vs. complex PVBs, and daytime vs. nighttime dominance of PVBs (P > .05 for all parameters). The CR rate of PVBs was different among patients with infrequent, moderate, and frequent PVBs (62.8%, 36.4%, and 31.6%, respectively). Premature ventricular beats disappeared more often during follow-up in patients with infrequent PVBs (P = .045). However, the absolute decrease and disappearance rates of PVBs were similar across all groups (72.1%, 81.8%, and 89.5%, respectively; P = .319). The resolution rates of PVBs were not statistically different between the patient group who received pharmacological treatment and the group who followed up without treatment (P = .070). No myocardial dysfunction was observed in any patient during follow-up. No cases experienced major cardiac events. Conclusion: Idiopathic PVBs usually regress in childhood regardless of frequency and complexity or receiving antiarrhythmic medication. The risk of ventricular dysfunction is low during childhood; however, they require careful evaluation and follow-up. [ABSTRACT FROM AUTHOR]

AbstractEndometrial cancer (EC) is a common gynecological malignancy and its mortality has been increasing in the last twenty years. A growing body of evidence suggests that circulating tumor cells (CTCs) may provide a more complete tumor profile, facilitate the understanding of the molecular mechanism and individual management of EC patients. In this review, we presented the presence and clinical applications of CTCs and disseminated tumor cells (DTCs) in EC, particularly for EC prognosis and management, also highlighted the diagnostic value of tumor cells in urine of EC patients, aim to help researchers better focus on their study in this field. [ABSTRACT FROM AUTHOR]

We recommend the stratification of high-grade (HG) non–muscle-invasive bladder cancer into HG/G2 and HG/G3, as patients with HG/G3 have worse prognosis than those with HG/G2. A Hybrid grading system (categories: low grade, HG/G2, and HG/G3) outperforms the current World Health Organization 2004/2016 system. Grade is an important determinant of progression in non–muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers. [ABSTRACT FROM AUTHOR]

Background Intraductal papillary mucinous neoplasm (IPMN)–derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared with its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)–derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. Methods Consecutive upfront surgery patients with IPMN-derived PDAC from 5 international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤0.5, T1b >0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs). Results Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1 margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95% CI = 126.0 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P  < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P  < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with T1a, nodal positivity, R1 margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P  < .001). Conclusion T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines. [ABSTRACT FROM AUTHOR]

Multiple epidermal growth factor-like domains protein 6 (MEGF6) is a high molecular weight protein with several EGF-like domains. Although it has been demonstrated to promote metastasis and chemoresistance in colon cancer cells, its specific oncogenic and immunologic functions remain largely unexplored. This study aims to comprehensively analyze publicly available datasets to define the role of MEGF6 in colon cancer development and immune response modulation. The expression of MEGF6 in colon adenocarcinoma (COAD) and normal tissues at both mRNA and protein levels was assessed using the GEPIA2 and HPA databases, respectively. The UALCAN database was employed to examine the association between MEGF6 expression and clinicopathological outcomes in COAD patients, and survival analysis was conducted using the KM plotter database. Functional enrichment analysis of MEGF6- correlated genes was performed using the ShinyGO online tool. Additionally, the correlation of MEGF6 with immune cell infiltration and immunosuppressive molecules was explored through the TIMER and TISIDB databases. Our analysis revealed significantly higher mRNA and protein expressions of MEGF6 in COAD tissues compared to normal tissues, with associations to cancer stage, nodal metastasis status, and histological subtype. High MEGF6 expression was correlated with poorer survival outcomes, and genes correlated with MEGF6 were enriched in biological processes related to cellular component organization, cell adhesion, and extracellular matrix interaction. Furthermore, MEGF6 expression demonstrated a significant correlation with immune cell infiltration and the expression of immunosuppressive molecules, particularly CTLA-4, PD-1, PD-L1, TGF-β, and IL-10. In conclusion, our findings suggest that MEGF6 may play an oncogenic role by influencing cell and extracellular matrix interactions. Its overexpression may indicate immunosuppressive properties within the cancer microenvironment. Therefore, MEGF6 holds promise as a potential biomarker for predicting both prognosis and therapeutic responses in colon cancer. [ABSTRACT FROM AUTHOR]

Background and Purpose: Paramagnetic rim lesions (PRLs) are an MRI biomarker of chronic inflammation in people with multiple sclerosis (MS). PRLs may aid in the diagnosis and prognosis of MS. However, manual identification of PRLs is time‐consuming and prone to poor interrater reliability. To address these challenges, the Automated Paramagnetic Rim Lesion (APRL) algorithm was developed to automate PRL detection. The primary objective of this study is to evaluate the accuracy of APRL for detecting PRLs in a multicenter setting. Methods: We applied APRL to a multicenter dataset, which included 3‐Tesla MRI acquired in 92 participants (43 with MS, 14 with clinically isolated syndrome [CIS]/radiologically isolated syndrome [RIS], 35 without RIS/CIS/MS). Subsequently, we assessed APRL's performance by comparing its results with manual PRL assessments carried out by a team of trained raters. Results: Among the 92 participants, expert raters identified 5637 white matter lesions and 148 PRLs. The automated segmentation method successfully captured 115 (78%) of the manually identified PRLs. Within these 115 identified lesions, APRL differentiated between manually identified PRLs and non‐PRLs with an area under the curve (AUC) of.73 (95% confidence interval [CI]: [.68,.78]). At the subject level, the count of APRL‐identified PRLs predicted MS diagnosis with an AUC of.69 (95% CI: [.57,.81]). Conclusion: Our study demonstrated APRL's capability to differentiate between PRLs and lesions without paramagnetic rims in a multicenter study. Automated identification of PRLs offers greater efficiency over manual identification and could facilitate large‐scale assessments of PRLs in clinical trials. [ABSTRACT FROM AUTHOR]

Background/Objectives: Cardiac magnetic resonance (CMR) is used to diagnose and monitor the course of acute myocarditis in adults and children. This study aimed to assess the frequency of persistent inflammation at follow-up CMR and to look for predictors of ongoing active changes in CMR in children with myocarditis. Methods: This retrospective study included 31 children (median age 15 years, 68% male) with clinically and CMR-diagnosed acute myocarditis who underwent baseline and follow-up CMR at a median of 6 months. Old and new Lake Louise criteria were compared. Results: A complete resolution of changes was observed in four patients (13%) at follow-up, according to both criteria. Seven patients (23%) presented ongoing active changes, and twenty (64%) showed a persistent scar according to the old Lake Louise criteria. When the new Lake Louise criteria were used, an additional two patients (6%) were found to have persistent active changes instead of a persistent scar. Patients with persistent inflammation (nine patients, 29%) were older than those who showed recovery. None of the patients below 14 years of age presented active changes on their follow-up CMR and all the patients who showed inflammation were between 14 and 17 years old. Conclusions: Pediatric myocarditis can lead to persistent active changes in CMR beyond a 6-month follow-up in over a fifth of patients. The application of new Lake Louise criteria further increases that number compared to the old criteria. The only predictor of persistent inflammatory changes in CMR is older age. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the correlation between radiomic features extracted from contrast-enhanced mammography (CEM) tumor lesions and peritumoral background with prognostic factors in breast cancer (BC). Methods: In this retrospective, single-center study, 134 women with histologically confirmed breast cancer underwent CEM examination. Radiomic features were extracted from manually segmented lesions and lesion contours were automatically delineated using PyRadiomics. The extracted features were categorized into seven classes: First-order Features, Shape Features (2D), Gray Level Co-occurrence Matrix (GLCM), Gray Level Run Length Matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), and Neighboring Gray Tone Difference Matrix (NGTDM). Histological examination assessed tumor type, grade, receptor structure (ER, PgR, HER2), Ki67 index, and lymph node involvement. Pearson correlation and multivariate regression were applied to evaluate associations between radiomic features and prognostic factors. Results: Significant correlations were found between First-order Features and prognostic factors such as ER, PgR, and Ki67 (p < 0.05). GLCM-based texture features showed strong associations with Ki67 and HER2 (p < 0.01). Radiomic features from peritumoral regions, especially shape and GLSZM metrics, were significantly correlated with Ki67 and lymph node involvement. Conclusions: Radiomic analysis of both tumor and peritumoral regions offers significant insights into BC prognosis. These findings support the integration of radiomics into personalized diagnostic and therapeutic strategies, potentially improving clinical decision making in BC management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Atherosclerosis is a leading cause of death, especially in the developed world, and is marked by chronic arterial inflammation and lipid accumulation. As key players in its progression, monocytes contribute to plaque formation, inflammation, and tissue repair. Understanding monocyte involvement is crucial for developing better therapeutic approaches. The objective of this study is to assess the prognostic value of monocytes for limb-related outcomes following revascularization for complex aortoiliac lesions, thereby emphasizing the central role of monocytes in atherosclerosis. Methods: This prospective cohort study-enrolled patients who had undergone elective aortoiliac revascularization at two hospitals between January 2013 and December 2023. Patients with TASC II type D lesions were included, excluding those with aneurysmal disease. Demographic, clinical, and procedural data were gathered, and patients were monitored for limb-related outcomes. Preoperative complete blood counts were analyzed, and statistical analyses, including multivariable Cox regression, were conducted to identify predictors of major adverse limb events (MALE). Results: The study included 135 patients with a mean age of 62.4 ± 9.20 years and predominantly male (93%). Patients were followed for a median of 61 IQR [55.4–66.6] months. Smoking history (91%) was the most prevalent cardiovascular risk factor. Preoperative monocyte count >0.720 × 109/L was associated with worse 30-day limb-related outcomes (MALE: OR 7.138 95% CI: 1.509–33.764, p = 0.013) and long-term outcomes, including secondary patency (p = 0.03), major amputation (p = 0.04), and MALE (p = 0.039). Cox regression analysis confirmed an elevated monocyte count as an independent predictor of MALE (adjusted hazard ratio 2.149, 95% CI: 1.115–4.144, p = 0.022). Conclusions: This study demonstrated that patients with a higher absolute monocyte count may be more exposed to the risk of MALE in patients with aortoiliac TASC II type D lesions undergoing revascularization, with predictive accuracy in both the short and long term. Additionally, it was an independent predictor of major amputation. This new marker has the potential to serve as a cost-effective and easily available tool for risk stratification, helping identify patients at higher risk of MALE. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, which in 20% of cases can turn into a severe form, with mortality reaching up to 30%. One of the cornerstones of AP treatment is early nutritional treatment. Feeding intolerance (FI) occurs in up to 25% of patients with AP and is associated with a more severe disease course and poorer clinical outcome. Feeding intolerance can have a multifaceted clinical presentation. The early identification of FI risk factors and appropriately conducted nutritional treatment are critical to the course of the disease. In this review, we summarize the current knowledge of feeding intolerance in AP, its pathomechanisms and risk factors, and its impact on disease progression. We also present suggestions for the management of feeding intolerance. [ABSTRACT FROM AUTHOR]

Objectives: The role of inflammation in the pathophysiology of atherosclerosis is extensive. Our study aims to assess the predictive role of inflammatory indexes regarding in-hospital mortality in major vascular surgery of Leriche syndrome as a convenient, low-cost, and noninvasive prognostic marker to optimize the patient's perioperative course. Methods: Our retrospective single-center study enrolled consecutive patients diagnosed with aortoiliac occlusive disease, Leriche syndrome, who underwent elective major vascular surgery between 2017 and 2023 in a tertiary cardiovascular center. Preoperative, postoperative, and day-one after-surgery data, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, and monocyte–lymphocyte ratio, were studied to the endpoint, in-hospital death. We also tested the delta values of the indexes to the endpoint. The indexes were compared to the Revised Cardiac Risk Index (RCRI) and Vascular Surgery Group Cardiac Risk Index (VSG-CRI) for outcome prediction. Results: The tested inflammatory indexes significantly increased from the preoperative to postoperative and, further, to the day-one settings. Preoperative AISI (p = 0.040) emerged as the only independent risk factor regarding in-hospital death occurrence in Leriche patients who underwent major revascularization surgery. While RCRI did not significantly predict the endpoint (AUC = 0.698, p = 0.057), VSG-CRI (AUC = 0.864, p = 0.001) presented the best result in ROC analysis. Postoperative NLR (AUC = 0.758, p = 0.006) was next, followed by NLR postoperative–preoperative (_Preop-_Postop) delta value (AUC = 0.725, p = 0.004), postoperative SIRI (AUC = 0.716, p = 0.016), SIRI_Preop-_Postop delta value (AUC = 0.712, p = 0.016), postoperative SII (AUC = 0.692, p = 0.032), and SII_Preop-_Postop delta value (AUC = 0.631, p = 0.030). Conclusions: Inflammatory indexes are valuable tools for assessing perioperative risk in major vascular surgery, enhancing the value of the already validated risk scores. [ABSTRACT FROM AUTHOR]

Background/objectives: Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP). There is little information about dose tapering and sustained remission after discontinuation in ITP. In this retrospective multicenter study, we evaluated efficacy and safety of fostamatinib in adult patients with ITP before, during, and after tapering/discontinuation (T/D). Methods: T/D was performed on subjects who achieved complete platelet response (CR) with progressive, conditional dose reduction every four weeks. Results: Sixty-one patients were included from 14 reference centers between October 2021 and May 2023. In subjects that completed T/D (n = 9), the median time from treatment initiation to response was 21 days (IQR: 7.5–42), median time from treatment initiation to CR was 28 days (IQR: 28–42), median time from treatment initiation to the start of tapering was 116 days (IQR: 42–140), and duration of tapering was 112.5 days (IQR: 94.5–191). The median platelet count was 232 × 109/L (IQR: 152–345 × 109/L) at tapering and 190 × 109/L (IQR: 142.5–316.5 × 109/L) at discontinuation. With a median follow-up since discontinuation of 263 days (IQR: 247–313 days), only two patients have relapsed (at 63 and 73 days). Fostamatinib was restarted, achieving a new CR. Platelet counts higher than 100 × 109/L in week 12 were the only positive predictive factors for successful tapering and discontinuation. Conclusions: Sustained response in patient with ITP treated with fostamatinib could be developed. The prognostic factors and recommended scheme of tapering still have to be evaluated. [ABSTRACT FROM AUTHOR]

The 53rd Child Neurology Society Annual Meeting features sessions on pediatric neurology topics such as epilepsy, neurodevelopmental disorders, and gene therapy. Child neurologists emphasize the importance of early detection and intervention for improved patient outcomes. Research on various neurological conditions, including SOD, DS, and AADC deficiency, highlights the need for further studies to optimize treatment strategies. The document also includes case studies and analyses on conditions like LGI-1 autoimmune encephalitis and RAPSYN-related CMS, showcasing successful management approaches and potential therapeutic benefits. [Extracted from the article]

Prostate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-scale transcriptomic datasets. The resulting seven-gene signature (KMT5C, DPP4, TYMS, CDC25B, IRF5, MEN1, and DNMT3B) was validated across independent cohorts and patient-derived xenograft (PDX) models. This signature demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, and overall survival. Importantly, the signature not only identified specific NEPC subtypes, such as large-cell neuroendocrine carcinoma, which is associated with very poor outcomes, but also predicted a poor prognosis for PCa cases that exhibit this molecular signature, even when they were not histopathologically classified as NEPC. This dual prognostic and classifier capability makes the seven-gene signature a robust tool for personalized medicine, providing a valuable resource for predicting disease progression and guiding treatment strategies in PCa management. [ABSTRACT FROM AUTHOR]

Background: This study examines the impact of the COVID-19 pandemic on abdominal trauma management by comparing pre-pandemic (17 February 2018–26 February 2020) and pandemic periods (27 February 2020–7 March 2022). Methods: Analyzing data from 118 patients at the Emergency County Clinical Hospital of Craiova, we identified significant shifts in clinical practices affecting patient outcomes. Results: During the pandemic, a moderate increase in surgical interventions for specific abdominal traumas indicated the effective adaptation of the medical system. Prioritizing critical cases and deferring non-urgent procedures optimized limited resources. Demographic and clinical factors—including age, sex, body mass index (BMI), and red cell distribution width (RDW)—significantly influenced the hospitalization duration and recovery outcomes. Gender disparities in mortality lessened during the pandemic, possibly due to standardized interventions and the physiological effects of SARS-CoV-2. The link between occupation and obesity highlighted how work environments impact trauma severity, especially as lifestyle changes affect BMI. While age remained a major predictor of mortality, its influence slightly decreased, potentially due to improved protocols for elderly patients. RDW emerged as an important prognostic marker for disease severity and mortality risk. Conclusions: Employing advanced co-occurrence analysis enhanced with machine learning, we uncovered complex relationships between clinical and demographic variables often overlooked by traditional methods. This innovative approach provided deeper insights into the collective impact of various factors on patient outcomes. Our findings demonstrate the healthcare system's rapid adaptations during the pandemic and offer critical insights for optimizing medical strategies and developing personalized interventions in global crises. [ABSTRACT FROM AUTHOR]

Background/Objective: Atrial fibrillation (AF) complicates the management of acute ischemic stroke (AIS), necessitating precise predictive models to enhance clinical outcomes. This meta-analysis evaluates the efficacy of machine learning (ML) models in three key areas: stroke prognosis in AF patients, stroke prediction in AF patients, and AF prediction in stroke patients. The study aims to assess the accuracy and variability of ML models in forecasting AIS outcomes and detecting AF in stroke patients, while exploring the clinical benefits and limitations of integrating these models into practice. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane databases up to June 2024, selecting studies that evaluated ML accuracy in stroke prognosis and prediction in AF patients and AF prediction in stroke patients. Data extraction and quality assessment were performed independently by two reviewers, with random-effects modeling applied to estimate pooled accuracy metrics. Results: The meta-analysis included twenty-four studies comprising 7,391,645 patients, categorized into groups for stroke prognosis in AF patients (eight studies), stroke prediction in AF patients (thirteen studies), and AF prediction in stroke patients (three studies). The pooled AUROC was 0.79 for stroke prognosis and 0.68 for stroke prediction in AF, with higher accuracy noted in short-term predictions. The mean AUROC across studies was 0.75, with models such as Extreme Gradient Boosting (XGB) and Random Forest (RF) showing superior performance. For stroke prognosis in AF, the mean AUROC was 0.78, whereas stroke prediction yielded a mean AUROC of 0.73. AF prediction post-stroke had an average AUROC of 0.75. These findings indicate moderate predictive capability of ML models, underscoring the need for further refinement and standardization. The absence of comprehensive sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) metrics limited the ability to conduct full meta-analytic modeling. Conclusions: While ML models demonstrate potential for enhancing stroke prognosis and AF prediction, they have yet to meet the clinical standards required for widespread adoption. Future efforts should focus on refining these models and validating them across diverse populations to improve their clinical utility. [ABSTRACT FROM AUTHOR]

Background: In recent years, liquid biopsy has emerged as a promising tool for the diagnosis and prognosis of numerous diseases, including cancer. Among the biomolecules analyzed in liquid biopsies are plasma circulating microRNAs (miRNAs), small non-coding RNAs that have proven to be crucial in the regulation of gene expression and the pathobiology of different health conditions, making them useful as biomarkers. However, variations in preanalytical conditions during biospecimen collection and processing can affect the analytical results. Objectives: Herein, we determined how the type of collection tube, the number of centrifugations, and the degree of hemolysis can affect plasma circulating miRNA levels. Methods: A cohort of 11 healthy donors was included. Whole blood was collected and handled in three different conditions, and miRNAs levels were analyzed using quantitative RT-PCR. Results: Our results show that the differences in the type of preservative tubes influence hemolysis, measured as OD at 414 nm. Moreover, the number of centrifugations performed also altered miRNAs levels, increasing or decreasing them depending on the miRNA analyzed. Hence, our study shows that alterations in preanalytical conditions affect miRNAs levels, particularly the number of centrifugations and the type of collection tubes. Conclusions: In our work, we highlight the importance of registering the preanalytical conditions in a standardized way that might be considered when analytical results are obtained. [ABSTRACT FROM AUTHOR]

Coronary artery calcium scoring (CACS), a non-invasive measure of coronary atherosclerosis, has significantly enhanced cardiovascular (CV) risk assessment and stratification in asymptomatic individuals. More recently, a higher score for CAC has been associated with an increased risk of non-CV diseases and all-cause mortality. This review consolidated evidence supporting the role of CAC in assessing non-CV diseases, emphasizing its potential in early diagnosis and prognosis. We observed a strong association between CACS and non-CV diseases, viz., chronic obstructive pulmonary disease, pulmonary embolism, pneumonia, diabetes, chronic kidney disease, osteoporosis, metabolic dysfunction-associated steatotic liver disease, nephrolithiasis, stroke, dementia, malignancies, and several autoimmune diseases. Also, CAC may aid in evaluating the risk of CV conditions developing secondary to the non-CV diseases mentioned earlier. Further evidence from prospective studies, intervention trials, and population-based behavioral studies is needed to establish CAC cutoff values and explore preventative care applications, facilitating their broader integration into healthcare practices. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) has established predictive biomarkers that enable decisions on treatment regimens for many patients. However, resistance to therapy is widespread. It is therefore essential to have a panel of molecular biomarkers that may help overcome therapy resistance and prevent adverse effects of treatment. We performed in silico analysis of NSCLC prognostic indicators, separately for adenocarcinomas and squamous carcinomas, by using The Cancer Genome Atlas (TCGA) and non-TCGA data sources in cBioPortal as well as UALCAN. This review describes lung cancer biology, elaborating on the key genetic alterations and specific genes responsible for resistance to conventional treatments. Importantly, we examined the mechanisms associated with resistance to immune checkpoint inhibitors. Our analysis indicated that a robust prognostic biomarker was lacking for NSCLC, especially for squamous cell carcinomas. In this work, our screening uncovered previously unidentified prognostic gene expression indicators, namely, MYO1E, FAM83 homologs, and DKK1 for adenocarcinoma, and FGA and TRIB1 for squamous cell carcinoma. It was further observed that overexpression of these genes was associated with poor prognosis. Additionally, FAM83 homolog and TRIB1 unexpectedly harbored copy number amplifications. In conclusion, this study elucidated novel prognostic indicators for NSCLC that may serve as targets to overcome therapy resistance toward improved patient outcomes. [ABSTRACT FROM AUTHOR]

The management of head and neck squamous cell carcinoma (HNSCC) relies heavily on TNM staging and WHO histologic grading; however, in recent years, the analysis of prognostic markers expressed in the tumor stroma has gained attention. The tumor–stroma ratio (TSR) quantifies the proportion of tumor tissue relative to the surrounding stromal tissue; it is assessed with the percentage of stromal tissue within the tumor area, with a cutoff point of 50% being widely used to discriminate high-stroma cancer. In this systematic review and meta-analysis, we investigated the potential prognostic role of the TSR in HNSCC. After a literature screening, 24 studies dealing with the TSR and survival outcomes were included. The TSR showed a significant association with overall survival (OS) in both unadjusted and adjusted measures (RR 2.04, CI 1.57–2.65, p < 0.01; HR 2.36 CI 1.89–2.94, p < 0.00001), with an even stronger prognostic potential in oral cavity/oral tongue cancers (RR 2.44 CI 1.84–3.22, p < 0.00001). The TSR also showed prognostic value when dealing with cancer-specific survival and was associated with a reduction in disease-free survival (DFS). In particular, the TSR also retained its prognostic role in terms of DFS when specifically considering early-stage cancers in both unadjusted and adjusted analyses (RR 1.81 CI 1.57–2.10, p < 0.00001; HR 2.09 CI 1.58–2.76, p < 0.00001). Therefore, we conclude that the TSR is a reliable prognostic marker that is easy to assess in routine histological slides and can be effectively implemented in the routine evaluation of HNSCC. [ABSTRACT FROM AUTHOR]

We aim to investigate cardiovascular mortality risk among diffuse large B-cell lymphoma (DLBCL) patients and explore cardiovascular mortality trends in the past decades in United States. We extracted data from the Surveillance, Epidemiology, and End Results database for adult patients diagnosed with DLBCL between 1975 and 2019. Standardized mortality ratio, joinpoint regression analysis, and competing risk model were analyzed. Overall, 49,918 patients were enrolled, of whom 4167 (8.3%) cardiovascular deaths were observed, which was 1.22 times the number expected (95%CI, 1.19–1.26). During 1985–2019, the incidence-based cardiovascular mortality rate increased by 0.98% per year (95%CI, 0.58–1.39%), with statistically significant increases in age groups younger than 75 years. The cumulative mortality from cardiovascular disease increased by age but never exceeded that from DLBCL. Older age, male sex, earlier year of diagnosis, lower tumor stage at diagnosis, chemotherapy, radiotherapy, and surgery were all poor prognostic factors for cardiovascular mortality. [ABSTRACT FROM AUTHOR]