Unfavorable Group Research Articles

Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury - a Prospective Cohort Study.

Aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) are severe conditions impacting individuals and society. Identifying reliable prognostic biomarkers for predicting survival or recovery remains a challenge. Soluble urokinase type plasminogen activator receptor (suPAR) has gained attention as a potential prognostic biomarker in acute sepsis. This study evaluates suPAR and related neuroinflammatory biomarkers in serum for brain injury prognosis. This prospective study included 31 aSAH, 30 IS, 13 TBI, and three healthy controls (n = 77). Serum samples were collected on average 5.9days post-injury, analyzing suPAR, IL-1β, cyclophilin A, and TNFα levels using ELISA. Outcomes were assessed 90days post-injury with the modified Rankin Scale (mRS), categorized as favorable (mRS 0-2) or unfavorable (mRS 3-6). Statistical analyses included 2-tailed t-tests, Pearson's correlations, and machine learning linear discriminant analysis (LDA) for biomarker combinations. Elevated suPAR levels were found in brain injury patients compared to controls (p = 0.017). Increased suPAR correlated with unfavorable outcomes (p = 0.0018) and showed prognostic value (AUC = 0.66, p = 0.03). IL-1β levels were higher in the unfavorable group (p = 0.0015). LDA combinatory analysis resulted a fair prognostic accuracy with canonical equation = 0.775[suPAR] + 0.667[IL1-β] (AUC = 0.77, OR 0.296, sensitivity 93.1%, specificity 53.1%, p = 0.0007). No correlation was found between suPAR and CRP or infection status. Elevated suPAR levels in acute brain injury patients were associated with poorer outcomes, highlighting suPAR's potential as a prognostic biomarker across different brain injury types. Combining IL-1β with suPAR improved prognostic accuracy, supporting a multimodal biomarker approach for predicting outcomes.

Tumor-intrinsic chemosensitivity assessed by KELIM and prognosis by BRCA status in patients with advanced ovarian carcinomas.

Treatment of high-grade serous ovarian carcinomas relies on surgery and chemotherapy, potentially followed by bevacizumab and/or poly (ADP-ribose) polymerase inhibitors (PARPi). The modeled CA-125 ELIMination rate constant K (KELIM) is a pragmatic indicator of tumor primary chemosensitivity. Although it is well established that BRCA mutations are associated with platinum sensitivity, the relationship between BRCA status and KELIM score has yet to be elucidated. This study aimed to evaluate the interactions between BRCA and KELIM, and their respective prognostic values. We retrospectively collected data from 743 patients with high-grade serous ovarian carcinomas included in a French nationwide registry (NCT03275298) treated with neoadjuvant platinum-based chemotherapy followed by surgery. We analyzed the interactions between BRCA and KELIM, and their impacts on progression-free survival and overall survival. BRCA-mutated (BRCAm) patients had higher standardized KELIM than BRCA-wild type (BRCAwt) tumors (median 1.16 vs 1.06, respectively; p=0.001). The prognostic value of the KELIM score was independent of BRCA in multivariate analyses. KELIM score and BRCA could be combined to define three prognostic groups: (1) an unfavorable prognostic group with both BRCAwt and unfavorable KELIM (median progression-free survival 12.0 months); (2) an intermediate prognostic group with either BRCAm and unfavorable KELIM, or BRCAwt and favorable KELIM (median progression-free survival of 16.0 and 18.8 months, respectively; HR 0.64 compared with the unfavorable group, p<0.001); and (3) a favorable prognostic group with both BRCAm and favorable KELIM (median progression-free survival 28.8 months; HR 0.37 compared with the unfavorable group, p<0.001). The KELIM score provides complementary prognostic information with respect to BRCA, and discriminates different prognoses within BRCAm or BRCAwt patients. Patients with both BRCAwt/unfavorable KELIM have a poor prognosis, underscoring the urgent need for novel therapeutic strategies.

Clinical significance of upper arm motor nerve conduction velocity in cubital tunnel syndrome.

Retrograde denervation occurs in severe entrapment neuropathy. This study aimed to investigate changes in motor nerve conduction velocity (MNCV) at the upper arm, specifically proximal to the elbow, in cubital tunnel syndrome (CuTS) and to correlate these changes with preoperative severity and postoperative outcomes. We retrospectively reviewed 95 elbows with 81 patients with CuTS for preoperative severity, and then 67 elbows with 60 of these patients who underwent anterior subcutaneous transposition surgery for postoperative outcome, classified into favorable and unfavorable groups according to Messina grade. The reduction of upper arm MNCV was correlated with aging, decreased compound muscle action potentials of abductor digiti minimi muscle, loss of sensory nerve action potentials, and modified McGowan grade. Postoperative assessment revealed lower MNCV values in the "unfavorable" group compared to the "favorable" group at 1 month, 6 months, and the last follow up. At each time point, the optimal cut-off value of upper arm MNCV for predicting postoperative outcomes was 54.1 m/s. Upper arm MNCV might be a useful predictor of poor surgical outcome. Ulnar nerve MNCV at the upper arm should be measured alongside routine assessment of MNCV at the elbow and forearm, especially in clinically severe cases considering surgery.

Potential Predictive Value of Platelet Distribution Width for Functional Outcome After Ischemic Stroke.

Complete blood cell count (CBC) is the most common and readily available laboratory test in clinical practice. The relationships of some CBC indices with ischemic stroke have been reported in observational studies; however, the causal direction is not specified. This study aimed to explore the causal relationships between CBC indices and the modified Rankin Scale (mRS) score at 3months after ischemic stroke. Genetic associations of 22 blood cell traits were obtained from the UK Biobank database (n = 350,475). The outcome data for ischemic stroke were obtained from the Genetic Ischemic Stroke Functional Outcome (GISCOME) network (n = 6021). We implemented two-sample Mendelian randomization (TSMR) and several complementary analyses to assess the causal association between blood traits and unfavorable outcome (3-month mRS > 2). The clinical cohort was validated based on the results of the MR analysis. TSMR result indicated causal association between genetically determined platelet distribution width (PDW) and adverse functional outcome after ischemic stroke (OR 1.48; 95% CI 1.13-1.95; p = 0.005). Complementary analyses showed negligible causal effect of genetic variants on stroke subtypes. In cohort study (n = 351), higher level of PDW was observed in the unfavorable outcome group. However, the multivariable logistic regression analysis failed to identify the improvement in predictive performance of stroke outcomes by adding PDW to the prediction model. Further correlation analysis revealed that PDW is positively correlated with serum glucose levels, and the level of PDW in the non-thrombolysed group was significantly higher than that in the thrombolysis group, indicating that PDW may be involved in stroke prognosis in an indirect way.

Successful Factors for Improving Aortic Remodeling with Thoracic Endovascular Repair and Bare Stent Extension

ObjectiveProximal ExTension to Induce COmplete ATtachment (PETTICOAT), which utilizes downstream bare metal stents for structural support, demonstrates potential, yet its adoption is limited by variable outcomes. This study elucidates the potential of PETTICOAT in aortic dissection, emphasizing the determinants that guide patient selection. MethodsA retrospective analysis of 60 patients who underwent full PETTICOAT for aortic dissections was conducted. A multivariate logistic regression model identified predictors of favorable aortic remodeling. Patients underwent standardized follow-up with CT scans to assess size, volumetric changes, and anatomical conditions. Selection criteria included full PETTICOAT application and a minimum three-month follow-up. Demographics, preoperative conditions, and procedural details were collected and analyzed. ResultsThe analysis identified predictors of favorable aortic remodeling, including age over 60, a larger downstream aorta stent graft, a smaller abdominal aorta (<450mm2), and oral angiotensin II receptor blocker (ARB) administration. Over a median 47.5-month follow-up, survival rates in the favorable remodeling (97.3%) and unfavorable groups (100%) were similar. Downstream aortic event-free survival rates did not significantly differ (89.2% vs. 73.9%), although the unfavorable group had a relatively higher incidence of distal stent-induced new entries (26.1% vs. 8.1%). ConclusionsThe PETTICOAT concept effectively enhances aortic remodeling in complex aortic dissections. Predictors for favorable remodeling, including age, stent graft sizing, aortic diameter, and ARB therapy, offer insights for optimizing patient selection. This approach improves survival outcomes, mitigates risks associated with untreated aortic segments, and provides a minimally invasive solution for aortic dissections. Despite some outcome variations, the technique holds promise for addressing the challenges of aortic dissections, with the potential for further refinement in patient selection and technique application.

Establishment and verification of a prognostic immune cell signature-based model for breast cancer overall survival.

Breast cancer (BRCA) is a prevalent and aggressive disease. Despite various treatments being applied, a significant number of patients continue to experience unfavorable prognoses. Accurate prognosis prediction in BRCA is crucial for tailoring individualized treatment plans and improving patient outcomes. Recent studies have highlighted the significance of immune cell infiltration in the tumor microenvironment (TME), but predicting survival remains challenging due to the heterogeneity of BRCA. The aim of this study was thus to produce an immune cell signature-based framework capable of predicting the prognosis of patients with BRCA. The GSE169246 dataset was from the Gene Expression Omnibus (GEO) database, comprising single-cell RNA sequencing (scRNA-seq) data from 95 individuals with BRCA. Seurat, principal component analysis (PCA), the unified matrix polynomial approach (UMAP) algorithm, and linear dimensionality reduction were used to determine the heterogeneity of T cells. Overlapping analysis of differentially expressed genes (DEGs), genes associated with prognosis, and T-cell pharmacodynamics-related genes were used to obtain the T-cell core pharmacodynamics-related genes. The dimensionality of the T-cell core pharmacodynamics-related genes was reduced employing the least absolute shrinkage and selection operator (LASSO) Cox regression model and the LASSO model. The prognostic model was built via a Cox analysis of the overall survival (OS) information. The clinical sample included 95 patients with BRCA who underwent surgical treatment from October 2018 to October 2021 at the Second Affiliated Hospital of Qiqihar Medical University. Patients were divided into a good prognosis group and a poor prognosis group based on their prognostic outcomes. The predictive value of tumor characteristics and immune responses was validated through correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) analysis. A group of 95 genes was used to establish a prognostic model. In the GEO clinical sample, with a high-risk group demonstrating shorter median survival times (2,447 vs. 6,498 days, P=4.733e-12). Area under the curve (AUC) values of 0.75, 0.75, and 0.72 were obtained for 2-, 4-, and 6-year OS predictions, respectively. Clinical validation found that the 6-year OS of the favorable prognosis group was significantly higher than that of the unfavorable prognosis group (92.06% vs. 65.62%; P=0.005). Poor prognosis was positively correlated with age, tumor size, B-cell level, and CTLA4 level and negatively correlated with tumor stage (T1/T2), lymph node metastasis stage (N0), clinical stage I-II, CD3+T-cell, CD4+T-cell, CD8+T-cell, neutrophil, lymphocyte, natural kill cell, TIGIT expression and OS. The combined model of clinical parameters had an AUC value of 0.898. This study established a prognostic model that demonstrated excellent predictive value for OS of BRCA. The predictive model developed offers valuable insights into prognosis and treatment planning, emphasizing the importance of tumor characteristics and immune cell infiltration.

Systemic immune-inflammatory markers and long-term prognosis after revascularization in Moyamoya disease: a retrospective study.

Systemic immune-inflammatory markers combine various individual inflammatory cell parameters to comprehensively explore their relationship with the development and long-term outcomes of cardiovascular, cerebrovascular, and oncological disorders. The systemic immune-inflammatory marker index has not been extensively studied in terms of its impact on the long-term prognosis following cerebral revascularization in MMD patients. Our research aims to address this gap and improve the prediction of long-term outcomes for these patients. We included 851 patients with Moyamoya disease who underwent cerebral revascularization at our medical center from 2009 to 2021. Systemic immune-inflammatory markers were calculated based on routine blood test results at admission, and follow-up was conducted for over 6 months after surgery. During monitoring and upon release, we evaluated patient neurological condition by utilizing the modified Rankin Scale (mRS). We examined the correlation between alterations in mRS ratings and systemic immune-inflammatory markers. Comparing the unfavorable long-term prognosis group to the favorable long-term prognosis group, it was found that the NLR level was markedly higher (p = 0.037), while the LMR was lower in the unfavorable long-term prognosis group (p = 0.004). Results from logistic regression analysis revealed that the high-level LMR group had a lower risk of unfavorable long-term prognosis compared to the low-level group (T3: OR = 0.433, 95% CI [0.204-0.859], p = 0.026). The AUC of the model was 0.750 (95% CI [0.693-0.806]). Lymphocyte-to-monocyte ratio levels are independently linked to an increased risk of unfavorable long-term prognosis, highlighting LMR as a new and effective predictor for postoperative Moyamoya patients.

Factors associated with unfavorable outcome of anterior circulation ischemic stroke following emergency endovascular therapy after complete recanalization

Objective: Endovascular thrombectomy (EVT) improves long-term patients outcomes and decreases mortality among ischemic stroke patients. However, not all patients can benefit from EVT recanalization. The present study aims to evaluate the predictors of unfavorable outcomes associated with emergency endovascular therapy despite complete recanalization. Methods: We investigated 74 eligible patients receiving EVT from January 2019 to January 2022 at a comprehensive stroke center. Demographics, clinical, radiological and treatment characteristics, safety, and functional outcomes were collected. Modified Rankin scale (mRS) score ≤ 2 at 90 days was defined as a good functional outcome. Results: A total of 111 patients were initially eligible for the study, of which 37 were excluded, resulting in 74 patients in the final study. The mean age was 69.08±12.12 years old, 67.57% patients were male, 44.59% patients with atrial fibrillation, 64.86% with hypertension, 21.62% patients with diabetes mellitus, 16.22% patients with coronary artery diseases, 6.76% with parenchymal hematoma. Median pre-EVT NIHSS (IQR) was 15.5 (12.0, 19.25). Median door-to-recanalization time (DRT) (IQR) was 208.0 (160.0,278.5) minutes and median last known norma to puncture time (LKNPT) (IQR), was 362.0 (280, 452.5) minutes. Individuals with a poorer outcome were older [73.56±9.29 vs. 65.28±13.02 years old, P=0.002], had a higher prevalence of atrial fibrillation (AF) [58.82 vs. 13%, P=0.023] and a higher National Institute of Health Stroke Scale (NIHSS) [median 16 (IQR 12.0-22.3) vs median 15 (IQR 10.0-18.0), P=0.143]. Female sex, hypertension, diabetes mellitus, coronary artery disease, and a slightly longer door-to-recanalization time were more prevalent in the unfavorable prognosis group; however, statistical analysis did not show any significant differences. Logistics binary regression model showed that older age [OR: 0.1.160 (1.011 to 1.112, P=0.031)] and AF [OR: 3.190 (1.111 to 9.164, P=0.031)] were associated with an unfavorable outcome. Conclusion: Older age, and atrial fibrillation were factors associated with the unfavorable outcome despite complete recanalization after emergency EVT of ischemic stroke.

High plasma BNP concentration associates with clinical outcome after mechanical thrombectomy: Post hoc analysis of SKIP

ObjectivesHeart failure may result in reduced brain perfusion, limiting the blood flow needed to achieve clinical recovery. We investigated whether plasma levels of brain natriuretic peptide (BNP), a biological marker of heart failure, were related to clinical outcomes after mechanical thrombectomy (MT). Materials and MethodsData were analyzed from stroke patients with internal carotid or middle cerebral artery occlusion enrolled in the SKIP trial for whom plasma level of BNP was evaluated on admission. Favorable outcome was defined as a modified Rankin scale score of 0–2 at 3 months. ResultsAmong 169 patients (median age, 74 years; 62% men, median National Institutes of Health Stroke Scale score, 18), 104 (62%) achieved favorable outcomes. Median plasma BNP level was lower in the favorable outcome group (124.1 pg/mL; interquartile range [IQR], 62.1–215.5 pg/mL) than in the unfavorable outcome group (198.0 pg/mL; IQR, 74.8–334.0 pg/mL; p=0.005). In multivariate regression analysis, the adjusted odds ratio for BNP for favorable outcomes was 0.971 (95% confidence interval, 0.993–0.999; p=0.048). At 3 months after onset, the favorable outcome rate was lower in the ≥186 pg/mL group (45%) than in the <186 pg/mL group (72%; p=0.001). This significant difference remained regardless of the presence of atrial fibrillation (AF), with rates of 47% and 76%, respectively, in AF patients (p=0.003) and 33% and 68%, respectively, in patients without AF (p=0.046). ConclusionHigh plasma BNP concentration appears associated with unfavorable outcomes after MT.

Beat-to-Beat Blood Pressure Variability Within 24 Hours of Ischemic Stroke Onset: A Potential Predictor of Functional Prognosis.

Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.

Bioinformatic Exploration of Circulating microRNAs Related to Functional Outcomes in Patients With Acute Ischemic Stroke: An Exploratory Prospective Study.

Background Although epigenetic modifications have been expected to play an important role in neuroplasticity for stroke recovery, the role of dynamic microRNA (miRNA) regulation related to functional outcomes after ischemic stroke remains unclear. Therefore, the current study performed a comprehensive miRNA expression analysis in serum to identify specifically altered circulating miRNAs associated with different grades of functional outcomes in patients with acute ischemic stroke (AIS). Methods Twelve patients with AIS in the middle cerebral artery region were included in this study. Peripheral blood samples were collected from patients one or two days after hospitalization. Total RNA, including small RNAs, was extracted from 400 µL of serum, and comprehensive miRNA expression analysis was performed to identify specifically altered circulating miRNAs associated with different grades of functional outcomes. Functional outcomes were evaluated three months after stroke onset using the modified Rankin Scale (mRS), classified as favorable (mRS score of 0 or 1) or unfavorable (mRS score of 2 to 5). Differentially expressed miRNAs were analyzed using the DESeq2 package. Target genes of the miRNAs were explored using miRTargetLink 2.0. Results Acute miRNA expression dynamics were characterized by differences in the patients' functional outcomes following ischemic stroke. The favorable outcome group exhibited significantly downregulated miRNAs, including hsa-miR-218-1, hsa-miR-218-2, hsa-miR-320e, hsa-miR-320d-1, hsa-miR-320d-2, hsa-miR-326, and hsa-miR-4429. In addition, 15 miRNAs, including hsa-miR-223, hsa-miR-18a, hsa-miR-411, and hsa-miR-128-1, were significantly upregulated in the favorable outcome group compared to the unfavorable outcome group. Interesting and strong validated networks between miRNAs and their target genes were identified. Conclusion This study identified specifically altered circulating miRNAs in serum associated with varying grades of functional outcomes in AIS patients and explored miRNA-target gene networks that might contribute to these outcomes. Although further studies are needed, this study highlights their potential role as biomarkers for predicting functional outcomes in patients with AIS.

Associations of social determinants of health with life expectancy and future health risks among individuals with type 2 diabetes: two nationwide cohort studies in the UK and USA

Social determinants of health (SDHs) are the primary drivers of preventable health inequities, and the associations between SDHs and health outcomes among individuals with type 2diabetes remain unclear. This study aimed to estimate the associations of combined SDHs with life expectancy and future health risks among adults with type 2diabetes from the UK and USA. In an analysis of two nationwide cohort studies, adults with type 2diabetes were identified from the UKBiobank from March 13, 2006, to Oct 1, 2010 (adults aged 37-73years) and the US National Health and Nutrition Examination Survey (NHANES) from 1999to 2018 (adults aged ≥20years). Participants with type 2diabetes at baseline were included in our analysis. Participants without information on SDHs or follow-up were excluded. TheUKBiobank assessed 17SDHs and the US NHANES assessed ten SDHs, with each SDH dichotomised into advantaged and disadvantaged levels. The combined score of SDHs were calculated as the sum of the weighted scores for each SDH. Participants were then categorised into tertiles (favourable, medium, and unfavourable SDHgroups). Primary outcomes were life expectancy and mortality in both cohorts, and incidences of cardiovascular disease, diabetes-related microvascular disease, dementia, and cancer in the UK Biobank. Outcomes were obtained from disease registries up until Dec 31, 2021, in the UK Biobank and Dec 31, 2019, in the USNHANES cohorts. We included 17 321participants from the UK Biobank cohort (median age 61·0years [IQR 56·0-65·0]; 6028[34·8%] women and 11 293 [65·2%] men) and 7885participants from the NHANES cohort (mean age 59·2years [95% CI 58·7-59·6]; 3835 [49·1%, weighted] women and 4050 [50·9%, weighted] men) in our analysis. In the UKBiobank, 3235deaths (median follow-up 12·3years [IQR 11·5-13·2]), 3010incident cardiovascular disease (12·1years [10·8-13·0]), 1997 diabetes-related microvascular disease (8·0years [7·1-8·9]), 773dementia (12·6years [11·8-13·5]), and 2259cancer cases (11·3years [10·4-12·2]) were documented; and the US NHANES documented 2278deaths during a median follow-up of 7·0years (3·7-11·2). After multivariable adjustment, compared with the favourable SDH group, the hazard ratio was 1·33 (95% CI 1·21-1·46) in the medium SDH group and 1·89(1·72-2·07) in the unfavourable SDHgroup in the UK Biobank cohort; 1·51 (1·34-1·70) in the medium SDH group and 2·02 (1·75-2·33) in theunfavourable SDH group in the US NHANES cohort for all-cause mortality; 1·13 (1·04-1·24) in the medium SDHgroup and 1·40 (1·27-1·53) in the unfavourable SDH group for incident cardiovascular disease; 1·13(1·01-1·27) in the medium SDH group and 1·41 (1·26-1·59) in the unfavourable SDHgroup for incident diabetes-related microvascular disease; 1·35 (1·11-1·64) in the medium SDH group and 1·76 (1·46-2·13) in the unfavourable SDH group for incident dementia; and 1·02 (0·92-1·13) in the medium SDHgroup and 1·17 (1·05-1·30) in the unfavourable SDH group for incident cancer in the UK Biobank cohort (ptrend<0·010for each category). At the age of 45years, the mean life expectancy of participants was 1·6years (0·6-2·3) shorter in the medium SDH group and 4·4years (3·3-5·4) shorter in the unfavourable SDH group than in the favourable SDH group in the UK Biobank. In the US NHAHES cohort, the life expectancy was 1·7years (0·6-2·7) shorter in the medium SDH group and 3·0years (1·8-4·3) shorter in the unfavourable SDHgroup, compared with the favourable group. Combined unfavourable SDHs were associated with a greater loss of life expectancy and higher risks of developing future adverse health outcomes among adults with type 2diabetes. These associations were similar across two nationwide cohorts from varied social contexts, and were largely consistent across populations with different demographic, lifestyle, and clinical features. Thus, assessing the combined SDHs of individuals with type 2diabetes might be a promising approach to incorporate into diabetes care to identify socially vulnerable groups and reduce disease burden. The National Natural Science Foundation of China, the National Key R&D Program of China, and the Fundamental Research Funds for the Central Universities.

Tumour budding, MELF-pattern and tumour-infiltrating lymphocytes as possible pathomorphological parameters of the course of endometrioid adenocarcinoma of the uterine corpus

Aim. To evaluatethe role tumour budding (TB), MELF-pattern and tumour-infiltrating lymphocytes (TILs) as possible prognostic factors of endometrioid adenocarcinoma of the uterine corpus.Materials and methods. A single-centre, retrospective, observational study was conducted involving 188 patients with endometrioid adenocarcinoma of the uterine body. 40 patients who had disease recurrence or died directly from progression of endometrioid adenocarcinoma of the uterine body were the unfavourable outcome group, 148 patients without progression and death from this tumour were the favourable outcome group. Fisher, Yates exact two-sided criteria were used to analyze the data. Survival analysis was performed using log-rank test. The hazard ratio (HR) and its 95 % confidence interval (CI) were estimated using single-factor analysis with log-rank test and multivariate Cox proportional hazards analysis. p &lt;0.05 was considered statistically significant.Results. TB was observed predominantly in the group of patients with unfavourable outcome (р &lt;0.0001) Survival analysis revealed statistically significant decreased survival in cases with TB (HR 5.3; 95 % CI 2.2–12.7; р &lt;0.0001). MELF-pattern was statistically significantly more frequent in the group of patients with unfavourable outcome (р &lt;0.0001), a decreased survival of patients was observed in the presence of MELF-pattern (HR 5.8; 95 % CI 2.1–16.2; р &lt;0.0001). Comparison of groups according to the number of TILs revealed statistically significant differences (р = 0.0242). When analyzing survival relative to the threshold value of the number of TILs, statistically significant differences were also observed (HR 3.7; 95 % CI 1.7–7.9; р = 0.021). Multivariate Cox proportional hazards analysis revealed that only TB and MELF-pattern had prognostic significance for recurrence-free survival (HR 3.7; 95 % CI 1.8–7.4; р &lt;0.001).Conclusion. TB and MELF-pattern are specific changes in the stroma of endometrioid adenocarcinoma stroma of the uterine corpus that can be used as pathomorphological predictors of clinical outcome.

Circulating/cerebrospinal T lymphocytes as indicators of clinical prognosis in intracerebral hemorrhage: A prospective study.

Secondary injury of cerebral hemorrhage is induced by systemic inflammatory cascades, which are related to perihematomal brain edema, cellular apoptosis, and the disruption of the blood-brain barrier. This study was to specifically elaborate the relationship of circulating/cerebrospinal T lymphocytes and Glasgow Coma Scale (GCS) score at 6 months after intracerebral hemorrhage (ICH). The enrolled patients were divided into 2 groups based on GCS score: the favorable prognosis group (GCS > 12) and unfavorable prognosis group (GCS ≤ 12). T lymphocyte subpopulations were analyzed by flow cytometry. A total of 30 samples of peripheral blood and 17 samples of cerebrospinal fluid were collected and analyzed, including 19 cases and 12 cases in the favorable prognosis group (GCS > 12) respectively. Both CD3+ and CD3+CD4+ T lymphocyte counts on Day 1 after ICH were lower in the peripheral blood of patients with unfavorable prognosis (GCS ≤ 12) (P = .025 and .022, respectively). There were correlation trends between the GCS scores and CD3+ T lymphocyte count (P = .0144), and CD3+CD4+ T lymphocyte count (P = .0135). In cerebrospinal fluid, there was a close correlation between the GCS scores and CD3+CD4+ percentage, CD4+/CD8+ ratio, CD3+ and CD3+CD4+ T lymphocyte counts. The area under the curve of CD4+/CD8+ T lymphocyte ratio was the largest among them (P = .000 and area under the curve = 0.917), with a significantly high specificity and sensitivity (0.917 and 1.000). Based on cerebrospinal fluid samples, the CD4+/CD8+ T lymphocyte ratio on Day 1 after ICH may be a more significant indicator to predict the short-term prognosis at 6 months after ICH.

EEG Ictal Power Dynamics, Function-Structure Associations, and Epilepsy Surgical Outcomes.

Postoperative seizure control in drug-resistant temporal lobe epilepsy (TLE) remains variable, and the causes for this variability are not well understood. One contributing factor could be the extensive spread of synchronized ictal activity across networks. Our study used novel quantifiable assessments from intracranial EEG (iEEG) to test this hypothesis and investigated how the spread of seizures is determined by underlying structural network topological properties. We evaluated iEEG data from 157 seizures in 27 patients with TLE: 100 seizures from 17 patients with postoperative seizure control (Engel score I) vs 57 seizures from 10 patients with unfavorable surgical outcomes (Engel score II-IV). We introduced a quantifiable method to measure seizure power dynamics within anatomical regions, refining existing seizure imaging frameworks and minimizing reliance on subjective human decision-making. Time-frequency power representations were obtained in 6 frequency bands ranging from theta to gamma. Ictal power spectrums were normalized against a baseline clip taken at least 6 hours away from ictal events. Electrodes' time-frequency power spectrums were then mapped onto individual T1-weighted MRIs and grouped based on a standard brain atlas. We compared spatiotemporal dynamics for seizures between groups with favorable and unfavorable surgical outcomes. This comparison included examining the range of activated brain regions and the spreading rate of ictal activities. We then evaluated whether regional iEEG power values were a function of fractional anisotropy (FA) from diffusion tensor imaging across regions over time. Seizures from patients with unfavorable outcomes exhibited significantly higher maximum activation sizes in various frequency bands. Notably, we provided quantifiable evidence that in seizures associated with unfavorable surgical outcomes, the spread of beta-band power across brain regions is significantly faster, detectable as early as the first second after seizure onset. There was a significant correlation between beta power during seizures and FA in the corresponding areas, particularly in the unfavorable outcome group. Our findings further suggest that integrating structural and functional features could improve the prediction of epilepsy surgical outcomes. Our findings suggest that ictal iEEG power dynamics and the structural-functional relationship are mechanistic factors associated with surgical outcomes in TLE.

Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer.

Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy. Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy. Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001). Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.

Blood Lactate Levels during Therapeutic Hypothermia and Neurodevelopmental Outcome or Death at 18–24 Months of Age in Neonates with Moderate and Severe Hypoxic-Ischemic Encephalopathy

Introduction: Blood lactate levels in neonates with hypoxic-ischemic encephalopathy (HIE) vary, and their impact on neurodevelopmental outcome is unclear. We assessed blood lactate course over time in neonates with HIE during therapeutic hypothermia (TH) and investigated if blood lactate values were associated with neurodevelopmental outcome at 2 years of age. Methods: This is a retrospective cohort study of neonates with HIE born between 2013 and 2019, treated at the University Children’s Hospital Zurich. We recorded blood lactate values over time and calculated time until lactate was ≤2 mmol/L. Neurodevelopmental outcome was assessed at 18–24 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and categorized as favorable or unfavorable. We investigated associations between blood lactate values and outcome using logistic regression and adjusted for Sarnat stage. Results: 33/45 neonates (69%) had a favorable and 14 (31%) an unfavorable neurodevelopmental outcome. Mean initial lactate values were lower in the favorable (13.9 mmol/L, standard deviation [SD]: 2.9) versus unfavorable group (17.1 mmol/L, SD 3.2; p = 0.002). Higher initial and maximal blood lactate levels were associated with unfavorable outcome, also when adjusted for Sarnat stage (adjusted odds ratio [aOR]: 1.37, 95% CI: 1.01–1.88, p = 0.046, and aOR: 1.35, 95% CI: 1.01–1.81, p = 0.041, respectively). Conclusion: In neonates with HIE receiving TH, initial and maximal blood lactate levels were associated with neurodevelopmental outcome at 18–24 months of age, also when adjusted for Sarnat stage. Further investigations to analyze blood lactate as a biomarker for prognostic value are needed.

Assessing the predictive capability of machine learning models in determining clinical outcomes for patients with cervical spondylotic myelopathy treated with laminectomy and posterior spinal fusion

BackgroundCervical spondylotic myelopathy (CSM) is a prevalent degenerative condition resulting from spinal cord compression and injury. Laminectomy with posterior spinal fusion (LPSF) is a commonly employed treatment approach for CSM patients. This study aimed to assess the effectiveness of machine learning models (MLMs) in predicting clinical outcomes in CSM patients undergoing LPSF.MethodsA retrospective analysis was conducted on 329 CSM patients who underwent LPSF at our institution from Jul 2017 to Jul 2023. Neurological outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) scale preoperatively and at the final follow-up. Patients were categorized into two groups based on clinical outcomes: the favorable group (recovery rates ≥ 52.8%) and the unfavorable group (recovery rates < 52.8%). Potential predictors for poor clinical outcomes were compared between the groups. Four MLMs—random forest (RF), logistic regression (LR), support vector machine (SVM), and k-nearest neighborhood (k-NN)—were utilized to predict clinical outcome. RF model was also employed to identify factors associated with poor clinical outcome.ResultsOut of the 329 patients, 185 were male (56.2%) and 144 were female (43.4%), with an average follow-up period of 17.86 ± 1.74 months. Among them, 267 patients (81.2%) had favorable clinical outcomes, while 62 patients (18.8%) did not achieve favorable results. Analysis using binary logistic regression indicated that age, preoperative mJOA scale, and symptom duration (p < 0.05) were independent predictors of unfavorable clinical outcomes. All models performed satisfactorily, with RF achieving the highest accuracy of 0.922. RF also displayed superior sensitivity and specificity (sensitivity = 0.851, specificity = 0.944). The Area under the Curve (AUC) values for RF, Logistic LR, SVM, and k-NN were 0.905, 0.827, 0.851, and 0.883, respectively. The RF model identified preoperative mJOA scale, age, symptom duration, and MRI signal changes as the most significant variables associated with poor clinical outcomes in descending order.ConclusionsThis study highlighted the effectiveness of machine learning models in predicting the clinical outcomes of CSM patients undergoing LPSF. These models have the potential to forecast clinical outcomes in this patient population, providing valuable prognostic insights for preoperative counseling and postoperative management.

Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Adjuvant mFOLFIRINOX (mFFX) for resected pancreatic cancer (PC): Long term clinical and genomic outcomes.

4170 Background: Adjuvant chemotherapy with mFFX is the standard for pts with ECOG 0-1 (1) after pancreatectomy for resectable PC. Herein, we report long-term survival data on an expanded cohort and present comprehensive genomic analyses. Methods: Pts with resected PC who received &gt;1 dose of adjuvant mFFX identified from institutional databases. Primary endpoints: Recurrence Free Survival (mRFS) and Overall Survival (mOS) calculated from start of treatment until recurrence or death. Key secondary endpoints: clinical factors, genomic descriptors ( KRAS status, whole genome doubling (WGD), and homologous recombination deficiency (HRD)) associated with outcome. Kaplan-Meier method used to estimate RFS and OS. Univariate Cox proportional hazards model correlated clinico-genomic characteristics with RFS and OS. Results: N=147 identified between 01/2015-01/2022. Median age: 67 years; N= 22 (15%) &gt; 75 years. Several prognostically unfavorable groups; N=52 (36%) stage III disease/ N2 nodal status; N=115 (78%) lymphovascular invasion (LVI); N=133 (90%) perineural invasion (PNI). Median time from surgery to start mFFX: 1.78m (IQR; 1.45, 2.12). Median CA 19-9 at start mFFX: 21 (range 0-1,124). N=124 (84%) pts completed 12 doses mFFX (+/- 12 doses oxaliplatin). N=98 pts (67%) stopped oxaliplatin early for neuropathy. With the median follow up 35.1m (range 5.1, 73.0), mRFS 27m (95% CI 20, 39) and OS not reached (NR). For &gt;75 cohort, mRFS 12m (95% CI 9.6, NR) and mOS 30m (95% CI 19, NR). mFFX started &lt;8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p= 0.033) and OS (HR 0.53; 95% CI 0.3, 0.94; p= 0.030). T3 tumors associated with worse RFS (HR 2.82, 95% CI 1.28, 6.20; p=0.010) and OS (HR 5.10, 95% CI 1.45, 18; p=0.011). Genomic variables summarized (Table). KRASmutation (+), WGD (+), and higher KRAS CNV trended to shorter RFS and OS; statistical significance limited by small subgroups. HRD status did not confer differences in OS. Conclusions: Adjuvant mFFX is an effective therapy and results in long-term OS outcome in resected PC in a non-trial setting, including for pts &gt;75 years. Early initiation of adjuvant mFFX may optimize outcome. Trends observed for improved outcome in select genomic subsets, which require large-scale validation. 1. Conroy, JAMA Onc, 2022. [Table: see text]