Independent Factor For Poor Prognosis Research Articles

A nomogram model for predicting postoperative prognosis in patients with aneurysmal subarachnoid hemorrhage using preoperative biochemical indices

ObjectiveThe nutritional status and inflammatory responses of patients with aneurysmal subarachnoid hemorrhage (aSAH) play a vital prognostic role. We investigated the relationship between preoperative prognostic nutritional index (PNI)、neutrophil/albumin ratio (NAR)、platelet/albumin ratio (PAR) and other factors and the clinical prognosis of patients who underwent clipping for aSAH and its predictive model.MethodsThe clinical data of 212 patients with aSAH who underwent neurosurgery at Nanyang Central Hospital between 2018 and 2023 were retrospectively analyzed. Based on the Glasgow Outcome Scale (GOS) score at 6 months postoperatively, the patients were categorized into two groups: poor (GOSI-III) and good (GOSIV-V) prognosis groups. Multivariate logistic regression analysis was performed to determine the predictive value of preoperative PNI、NAR、PAR、hyperlipidemia and Glasgow Coma Scale (GCS) for prognosis. Furthermore, nomograms and prognostic prediction models were constructed. Receiver operating characteristic curves and area under the curve (AUC) were utilized to determine the predictive values.ResultsMultivariate logistic regression analysis revealed that PNI (OR = 1.250, 95%CI 1.060 ~ 1.475, P = 0.008), NAR (OR = 0.000, 95%CI 0.000 ~ 0.004, P = 0.000), PAR(OR = 0.515, 95%CI 0.283 ~ 0.937, P = 0.030), hyperlipidemia (OR = 4.627, 95%CI 1.166 ~ 18.367, P = 0.029), and GCS(OR = 1.446, 95%CI 1.041 ~ 2.008, P = 0.028) are independent risk factors for poor postoperative prognosis. The total score of the nomogram was 200, and the AUC value was 0.972.ConclusionsPNI and NAR can reflect the nutritional status and inflammatory responses of patients.They are significantly associated with the postoperative prognosis of patients with aSAH. Comprehensively analyzing PNI and NAR combined with other clinical indicators can more effectively guide treatment and help predict prognosis.

Eighty-six cases of clinical characteristics and outcomes of systemic lupus erythematosus-associated macrophage activation syndrome: A meta-analysis study.

To improve our understanding of systemic lupus erythematosus (SLE)-macrophage activation syndrome (MAS). A systematic review was performed, to retrieve all those papers on patients with SLE-MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE-MAS. A total of 86 SLE-MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI-2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. SLE-MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.

Correlation analysis of inflammatory markers with the short-term prognosis of acute ischaemic stroke

Stroke is the second leading cause of death worldwide, and China has the highest stroke incidence in the world. The systemic inflammatory response index (SIRI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), neutrophil-to-high-density lipoprotein ratio (NHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) have clinical in predicting the prognosis of acute ischaemic stroke (AIS) patients. No studies have compared the predictive value of these six composite inflammatory markers. This study included 516 AIS patients with AIS symptoms for < 24 h. The short-term prognosis of AIS patients at 30 days was assessed using the modified Rankin scale (mRS), an mRS score > 2 defining poor prognosis. The results of the univariate analysis showed that all six composite inflammatory indices, SIRI, SII, NHR, NLR, PLR and MLR, were associated with a poor prognosis in patients with AIS. All six composite inflammatory indicators correlated with the short-term prognosis of AIS patients. The six composite inflammation indicators were included in the binary logistic regression, and the results showed that SIRI, NLR and PLR were found to be independent risk factors for poor short-term prognosis in AIS patients. Among the six inflammatory markers, SIRI, NLR and PLR were the most clinically valuable for predicting the short-term prognosis of patients with AIS. Peripheral blood indices are easy to obtain clinically and can provide important clinical value for early prognosis and treatment adjustment.

Evaluation of preoperative visceral fat area / psoas muscle area ratio and prognosis in patients with colorectal cancer

AbstractBackgroundRecent research has focused on the prognostic relevance of preoperative sarcopenia and sarcopenic obesity in various cancers. In this study we investigated the relationship between visceral fat area (VFA), psoas muscle area (PMA), and the prognosis of patients undergoing colorectal cancer surgery.MethodsPatients with stage III colorectal cancer who underwent surgery between July 2013 and April 2020 were included. The analysis was performed on 151 patients who met the criteria. The VFA and PMA were measured at the level of the third lumbar vertebra on computed tomography (CT) scans, and the ratio of VFA to PMA (V/P ratio) was determined.ResultsPatients with high V/P ratios were significantly older (p = 0.0213), had a higher body mass index (BMI) (p &lt; 0.0001), a higher percentage of sarcopenic obesity (p &lt; 0.0001), and more diabetes complications (p &lt; 0.0001). Prognostic analysis showed that the overall survival (OS) (p = 0.0154) and relapse‐free survival (RFS) (p = 0.0378) were significantly worse in patients with a high V/P ratio. Multivariate analysis revealed that a high V/P ratio was an independent poor prognostic factor for OS. Subgroup analysis was then performed in patients with BMI &lt; 25 kg/m2. OS (p = 0.0259) and RFS (p = 0.0275) were significantly worse in the high V/P ratio group. A high V/P ratio was an independent poor prognostic factor in the multivariate analysis.ConclusionIn colorectal cancer, the preoperative V/P ratio is an independent factor for poor prognosis. Preoperative evaluation of the V/P ratio may identify a wide range of high‐risk patients because it is an independent poor prognostic factor in patients without obesity.

Association between oral microbial nitrate metabolism and poor prognosis in acute ischemic stroke patients with a history of hypertension

ABSTRACT Background Oral microbes mediate the production of nitric oxide (NO) through the denitrification pathway. This study aimed to investigate the association between oral microbial nitrate metabolism and prognosis in acute ischemic stroke (AIS) patients. Methods This prospective, observational, single-center cohort study included 124 AIS patients admitted within 24 hours of symptom onset, with 24-hour ambulatory blood pressure data. Oral swabs were collected within 24 hours. Hypertensive AIS patients were stratified by the coefficient of variation (CV) of 24-hour systolic blood pressure. Microbial composition was analyzed using LEfSe and PICRUSt2 for bacterial and functional pathway identification. Results Significant differences in oral microbiota composition were observed between hypertensive AIS patients with varying CVs. Lower CV groups showed enrichment of nitrate-reducing bacteria and “Denitrification, nitrate => nitrogen” pathways. The TAX score of oral nitrate-reducing bacteria, derived from LASSO modeling, independently correlated with 90-day modified Rankin Scale scores, serving as an independent risk factor for poor prognosis. Mediation analyses suggested indirect that the TAX score not only directly influences outcomes but also indirectly affects them by modulating 24-hour systolic blood pressure CV. Conclusions AIS patients with comorbid hypertension and higher systolic blood pressure CV exhibited reduced oral nitrate-reducing bacteria, potentially worsening outcomes.

Systemic immune-inflammation index and serum glucose-potassium ratio predict poor prognosis in patients with spontaneous cerebral hemorrhage: An observational study.

Recent studies have shown systemic inflammatory response, serum glucose, and serum potassium are associated with poor prognosis in spontaneous intracerebral hemorrhage (SICH). This retrospective study aimed to investigate the association of systemic immune-inflammatory index (SII) and serum glucose-potassium ratio (GPR) with the severity of disease and the poor prognosis of patients with SICH at 3 months after hospital discharge. We reviewed the clinical data of 105 patients with SICH, assessed the extent of their disease using Glasgow Coma Scale score, National Institutes of Health Stroke Scale (NIHSS) score, and hematoma volume, and categorized them into a good prognosis group (0-3 scores) and a poor prognosis group (4-6 scores) based on their mRS scores at 3 months after hospital discharge. Demographic characteristics, clinical, laboratory, and imaging data at admission were compared between the 2 groups, bivariate correlations were analyzed using Spearman's correlation coefficients, multivariate logistic regression analysis was used to determine the independent risk factors for poor prognosis of patients with SICH, and finally, SII, GPR, and platelet/lymphocyte ratio (PLR) were examined using the subject's work characteristics (ROC) curve, lymphocyte/monocyte ratio (LMR), and neutrophil/lymphocyte ratio (NLR) for their predictive efficacy for poor prognosis. Patients in the poor prognosis group had significantly higher SII and serum GPR than those in the good prognosis group, and Spearman analysis showed that SII and serum GPR were significantly correlated with the admission Glasgow Coma Scale score as well as the NIHSS score and that SII and GPR increased with the increase in mRS score. Multivariate logistic regression analysis showed that admission NIHSS score, hematoma volume SII, GPR, NLR, and PLR were independently associated with poor patient prognosis. Analysis of the subjects' work characteristic curves showed that the areas under the SII, GPR, NLR, PLR, LMR, and coSII-GPR curves were 0.838, 0.837, 0.825, 0.718, 0.616, and 0.883. SII and GRP were significantly associated with disease severity and short-term prognosis in SICH patients 3 months after discharge, and SII and GPR had better predictive value compared with NLR, PLR, and LMR. In addition, coSII-GPR, a joint indicator based on SII and GPR, can improve the predictive accuracy of poor prognosis 3 months after discharge in patients with SICH.

GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase.

Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent risk factor for poor prognosis in PDAC. Furthermore, we demonstrated that MUC21 promoted the metastasis and PNI of PDAC cells by activating JNK and inducing epithelial-mesenchymal transition (EMT). Mechanistically, glial cell-derived neurotrophic factor, secreted by Schwann cells, phosphorylates the intracellular domain S543 of MUC21 via CDK1 in PDAC cells, facilitating the interaction between MUC21 and RAC2. This interaction leads to membrane anchoring and activation of RAC2, which in turn activates the JNK/ZEB1/EMT axis, ultimately enhancing the metastasis and PNI of PDAC cells. Our results present a novel mechanism of PNI, suggesting that MUC21 is a potential prognostic marker and therapeutic target for PDAC.

High blood glucose variability may predict poor outcomes in patients with spontaneous cerebellar hemorrhage undergoing surgical operation: a retrospective study

BackgroundElevated blood glucose (BG) variability has been reported as an independent risk factor for poor prognosis in a variety of diseases. This study aimed to investigate the association between BG variability and clinical outcomes in patients with spontaneous cerebellar hemorrhage (SCH) undergoing surgical operation.MethodsThis retrospective cohort study of the consecutive patients admitted to the department of Neurosurgery, the Affiliated Hospital of Qingdao University between January 2014 and June 2022 with the diagnosis of SCH underwent surgical intervention. BG analysis was continuously and routinely performed. BG variability was represented by the standard deviation (SD) of the serial measurements within the first 7 days. The general characteristics, imageological information, blood glucose level, and surgical information were reviewed and compared through medical records.ResultsA total of 115 patients (65 male and 50 female) were enrolled. Out of all 115 patients, the overall clinical outcomes according to the modified Rankin Scale (mRS) were poor (mRS 3–6) in 31 patients (26.96%) and good (mRS 0–2) in 84 patients (73.04%). Twelve of the 115 patients died during hospitalization, and the mortality rate was 10.43%. Multivariate logistic regression analysis showed that SD of BG (odds ratio (OR), 4.717; 95% confidence interval (CI), 1.054–21.115; P = 0.043), GCS (OR, 0.563; 95% CI, 0.330–0.958; P = 0.034), and hematoma volume (OR, 1.395; 95% CI, 1.118–1.748; P = 0.003) were significant predictors. The area under the ROC curve of SD of BG was 0.911 (95% CI, 0.850–0.973; P < 0.001) with a sensitivity and specificity of 90.3% and 83.3%, respectively, and the cut-off value was 1.736.ConclusionsHigh BG Variability is independently correlated with the 6-month poor outcomes in patients with SCH undergoing surgical operation.

Prognostic value of serum high-mobility group box 1 in neonates with neonatal encephalopathy.

This study aimed to investigate the diagnostic potential of serum high-mobility group box 1 (HMGB1) in neonatal encephalopathy (NE). A retrospective study was conducted, analyzing 216 neonates diagnosed with NE. The neonates were divided into two groups based on their outcomes at 28 days. Serum HMGB1 levels were compared between the two groups. ROC analysis was used to determine the predictive value of HMGB1. At 28 days, 174 infants had a good prognosis, while 42 had a poor prognosis. Infants with a poor prognosis had higher serum HMGB1 concentrations within 24 h of birth. Multifactorial analysis revealed that extremely preterm birth, extremely low birth weight, an Apgar score of 0-3 at 5 min, premature rupture of membranes by the mother, moderate to severe NE, and serum HMGB1 > 6.14 ng/mL are independent risk factors for poor prognosis. HMGB1 has predictive value for short-term prognosis with an area under the curve of 0.79. Elevated HMGB1 levels in the acute phase of NE are associated with poor short-term neonatal outcomes. The decrease in HMGB1 concentrations over time correlates with a good prognosis; whereas an increase suggests a poor prognosis. Early measurement of serum HMGB1 could aid in the prognostic assessment of neonates with NE. Although serum HMGB1 has emerged as a potential predictor of neonatal outcomes in neonatal encephalopathy, the relationship of HMGB1 levels to neonatal encephalopathy severity remains unclear. The current results demonstrate that infants with a poor prognosis had higher serum HMGB1 concentrations within 24 h of birth. Importantly, elevated serum HMGB1 levels in the acute phase of neonatal encephalopathy are associated with poor short-term neonatal outcomes. Our findings reveal the clinical values of HMGB1 in the prediction of neonatal outcomes in NE patients.

High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome.

Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC. CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells. In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12-2.81) and 2.20 (95% CI 1.39-3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression. CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target.

E-Cadherin Mutational Landscape and Outcomes in Breast Invasive Lobular Carcinoma

Invasive lobular carcinomas (ILC) are characterized by the loss of E-cadherin expression and CDH1 gene inactivation. Diagnostic reproducibility for this tumor type is currently suboptimal and could be improved by a better understanding of its histomolecular and clinical heterogeneity. We have analyzed the relationship between the presence, type, or position of CDH1 mutations, E-cadherin expression, and clinicopathological features (including outcome) in a retrospective series of 251 primary ILC with a long follow-up (median: 9.5 years). The mutational status of E-cadherin gene (CDH1) was determined by RNA sequencing from frozen tumor samples. E-cadherin immunohistochemistry (IHC) was performed with antibodies directed against the intracellular domain (clone 4A2C7) and the extracellular domain (clone NCH38). IHC expression of p120 and β-catenin was also assessed in E-cadherin diffusely positive cases. Three major patterns of E-cadherin membrane expression were identified by IHC, with good agreement between the 2 clones (overall concordance: 83.8%, Kappa 0.67): null/focal expression (≤10%) (72.8% of cases for 4A2C7 and 83.8% for NCH38), heterogeneous expression (11%-89%) (19.2% of cases for 4A2C7 and 6.9% for NCH38), and diffuse expression (≥90%) (8% of cases for 4A2C7 and 9.3% for NCH38). E-cadherin membranous expression, when present, was abnormal (incomplete labeling and/or reduced intensity). ILC with diffuse E-cadherin expression showed abnormal β-catenin or p120-catenin staining in 21% of cases. Interestingly, these cases with diffusely expressed E-cadherin had a CDH1 mutation rate as high as the E-cadherin null/focal cases (∼70%) but were enriched in nontruncating mutations. Regarding CDH1 mutation location, intracytoplasmic domain mutations correlated with a divergent E-cadherin IHC phenotype between the 2 antibodies (4A2C7 ≤ 10%/NCH38 ≥ 10%). Clinico-pathological correlation analyses found that stromal amount (inversely correlated with tumor cellularity) and TILs were less abundant in ILC with E-cadherin null/focal cases. In addition, CDH1 truncating mutations were associated with radiohistologic size discordance and were identified in multivariate survival analysis as an independent poor prognosis factor in terms of metastasis risk and breast cancer-related mortality. Overall, our study highlights the importance of the precise mutational status of CDH1 in the clinical, radiological, histologic, and phenotypic expression of lobular carcinomas. These findings should be taken into account in future attempts to improve diagnostic criteria or methods for ILC, as well as for clinicobiological studies dedicated to this tumor type.

Oncological Outcomes of Transoral Laser Microsurgery for Early Stage Glottic Cancer with Involvement of the Anterior Commissure.

To assess the value of carbon dioxide transoral laser microsurgery (CO2 TOLMS) for early-stage glottic cancer with special regard to involvement of the anterior commissure (AC). Single-center retrospective cohort study. Grade-A tertiary hospital. A retrospective analysis of patients with early-stage (Tis-T2) glottic cancer who underwent CO2 TOLMS. All patients had at least 2 years of follow-up. The univariate and multivariate survival analyses were used to identify the risk factors for recurrence and the Kaplan-Meier method was used to analyze OS and DSS rates. A total of 102 patients were included in the study. Eleven patients (10.78%) had recurrence. The univariate analysis showed that the recurrence was associated with the AC classification, T staging, tumor size, and tobacco use (P < .05). However, on multivariate analysis, the AC classification was the only independent risk factor for recurrence (P < .001, HR = 3.179). AC classification were distributed as follows: 59 (57.84%) AC0, 29 (28.43%) AC1, 8 (7.84%) AC2, and 6 (5.88%) AC3, 2-year/5-year OS and DSS rates were progressively reduced in the AC0, AC1, AC2, and AC3 groups (P < .001). At the same T staging, the OS rates incrementally decreased as the level of involvement of the AC became higher (P = .004). CO2 TOLMS is an effective treatment for early-stage glottic cancer. AC involvement is an independent risk factors for recurrence and poor prognosis. The AC classification system may be better at grading the prognosis of patients with early-stage glottic cancer and has prognostic value independent of T staging.

Sex Differences in Outcome of Aneurysmal Subarachnoid Hemorrhage and Its Relation to Postoperative Cerebral Ischemia.

Whether there is a sex difference in the outcome of aneurysmal subarachnoid hemorrhage (aSAH) remains controversial, and clarifying the role of women in postoperative cerebral ischemic events can help us to understand its relationship with poor prognosis. Therefore, the purpose of this study was to elucidate the relationship between the three aspects of sex differences, postoperative cerebral ischemia, and poor prognosis after aSAH. A total of 472 patients admitted within 72h after aSAH between January 2018 and December 2022 were included. We systematically analyzed the characteristics of sex differences in aSAH and explored the relationship between delayed cerebral ischemia (DCI), surgery-related cerebral infarction (SRCI), and poor prognosis (modified Rankin Scale > 2). Compared with women, men were in worse condition and had more intracerebral hematoma (p = 0.001) on admission, whereas women were older (p < 0.001) and had more multiple aneurysms (p = 0.002). During hospitalization, men were more likely to experience emergency intubation (p = 0.036) and tracheotomy (p = 0.013). Women achieved functional independence at discharge at a similar rate to men (p = 0.394). Among postoperative complications, the incidence of DCI (22% vs. 12%, p = 0.01) and urinary tract infection (p = 0.022) was significantly higher in women. After adjusting for age, multivariable regression analysis showed that hypertension (odds ratio [OR] 2.139, 95% confidence interval [CI] 1.027-4.457), preoperative rerupture (OR 12.240, 95% CI 1.491-100.458), pulmonary infection (OR 2.297, 95% CI 1.070-4.930), external ventricular drainage placement (OR 4.382, 95% CI 1.550-12.390), bacteremia (OR 14.943, 95% CI 1.412-158.117), SRCI (OR 8.588, 95% CI 4.092-18.023), venous thrombosis (OR 5.283, 95% CI 1.859-15.013), higher modified Fisher grades (p = 0.003), and Hunt-Hess grades (p = 0.035) were associated with poor prognosis, whereas DCI (OR 1.394, 95% CI 0.591-3.292) was not an independent risk factor for poor prognosis. The proportion of patients who fully recovered from cerebral ischemia was higher in the DCI group (p < 0.001) compared with the SRCI group, and more patients were discharged with modified Rankin Scale > 2 in the SRCI group (p = 0.005). Women have a higher incidence of DCI, but there is no sex difference in outcomes after aSAH, and poor prognosis is associated with worse admission condition and perioperative complications. SRCI is a strong independent risk factor for poor prognosis, whereas DCI is not.

Prediction of prognosis in patients with systemic sclerosis based on a machine-learning model.

The clinical manifestations of systemic sclerosis (SSc) are highly variable, resulting in varied outcomes and complications. Diverse fibrosis of the skin and internal organs, vasculopathy, and dysregulated immune system lead to poor and varied prognoses in patients with SSc subtypes. Therefore, this study aimed to develop a personalized tool for predicting the prognosis of patients with SSc. A cohort of 517 patients with SSc were recruited between January 2009 and November 2021 at Xijing Hospital in China, and 266 patients completed the follow-up and performed in the survival analysis. Risk factors for death were identified using Cox survival analysis and random survival forest-based machine-learning methods separately. The consistency index, area under the curve (AUC), and integrated Brier scores were used to compare the predictive performance of the different prognostic models. The results of Cox-based multivariate regression analysis suggested that pulmonary arterial hypertension, digital ulcer, and Modified Rodnan Skin Score (mRSS) were independent risk factors for poor prognosis in patients with SSc and significant risk factors in random survival forest (RSF) surveys. A nomogram was plotted to evaluate the prognostic risk to facilitate clinical assessment; the RSF model had better predictive performance than the Cox model, with 3- and 5-year AUCs of 0.74 and 0.78, respectively. Machine-learning models can help us better understand the prognosis of patients with SSc and comprehensively evaluate the clinical characteristics of each individual. The early identification of the characteristics of high-risk patients can improve the prognosis of those with SSc. Key Points • Regarding predictive performance, the random survival forest model was more effective than the Cox model and had unique advantages in analyzing nonlinear effects and variable importance. • Machine learning using the simple clinical features of patients with systemic sclerosis (SSc) to predict mortality can guide attending physicians, and the early identification of high-risk patients with SSc and referral to experts will assist rheumatologists in monitoring and management planning.

S100A8/A9hi neutrophils induce mitochondrial dysfunction and PANoptosis in endothelial cells via mitochondrial complex I deficiency during sepsis

S100a8/a9, largely released by polymorphonuclear neutrophils (PMNs), belongs to the S100 family of calcium-binding proteins and plays a role in a variety of inflammatory diseases. Although S100a8/a9 has been reported to trigger endothelial cell apoptosis, the mechanisms of S100a8/a9-induced endothelial dysfunction during sepsis require in-depth research. We demonstrate that high expression levels of S100a8/a9 suppress Ndufa3 expression in mitochondrial complex I via downregulation of Nrf1 expression. Mitochondrial complex I deficiency contributes to NAD+-dependent Sirt1 suppression, which induces mitochondrial disorders, including excessive fission and blocked mitophagy, and mtDNA released from damaged mitochondria ultimately activates ZBP1-mediated PANoptosis in endothelial cells. Moreover, based on comprehensive scRNA-seq and bulk RNA-seq analyses, S100A8/A9hi neutrophils are closely associated with the circulating endothelial cell count (a useful marker of endothelial damage), and S100A8 is an independent risk factor for poor prognosis in sepsis patients.

The prognostic impact of severe grade immune checkpoint inhibitor related pneumonitis in non-small cell lung cancer patients.

To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP. A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis. The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070-16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis. In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.

Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study

BackgroundTertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and...

Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare?

BACKGROUND Little is known about outcomes of pediatric patients transplanted using donor liver grafts with abnormal biopsy results. We assessed donor liver biopsy data to report characteristics and outcomes of abnormal livers transplanted in pediatric patients. MATERIAL AND METHODS We identified pediatric patients who received a liver transplant from a biopsied deceased donor between 2015 and 2022 using the national database UNOS Standard Transplant Analysis and Research files. Recipients were excluded if they received multi-organ transplants or were lost to follow-up. Livers with ≤5% macrosteatosis, no fibrosis, and no inflammation were classified as normal livers (NL). Allografts with >5% macrosteatosis, any fibrosis, or any inflammation were considered abnormal livers (AL). Donor and recipient demographic data and outcomes were examined. RESULTS Of the 3808 total pediatric liver transplants in the study period, there were 213 biopsied donor liver allografts transplanted into pediatric recipients. Of those, 114 were NL and 99 were AL. 35.4% (35/99) of the AL had >5% macrosteatosis with a mean of 7.6±11.4%, 64.6% (64/99) had any inflammation, and 18.2% (18/99) had any fibrosis. AL donors were significantly older than NL donors. AL recipients had higher PELD scores. There were no significant differences in length of stay, rejection rates and causes, or allograft survival between AL and NL. Multivariable analysis revealed that inflammation was independently associated with a significantly greater risk for graft failure. CONCLUSIONS Outcomes of abnormal livers are excellent. Inflammation was an independent risk factor for poor graft prognosis. Donor biopsies in pediatric liver transplantation can be a useful adjunct to assess outcomes.

Pathogenic spectrum and drug resistance of bloodstream infection in patients with acute myeloid leukaemia: a single centre retrospective study.

Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital. From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI. A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%. In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes.

Nomograms incorporating hsa_circ_0029325 highly expressed in exosomes of hepatocellular carcinoma predict the postoperative outcomes

BackgroundLiquid biopsies, for example, exosomal circular RNA (circRNA) can be used to assess potential predictive markers for hepatocellular carcinoma (HCC) in patients after curative resection. This study aimed to search for effective prognostic biomarkers for HCC in patients after surgical resection based on exosomal circRNA expression profiles. We developed two nomograms incorporating circRNAs to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients.MethodPlasma exosomes isolated from HCC patients and healthy individuals were used for circRNA microarray analysis to explore differentially expressed circRNAs. Pearson correlation analysis was used to evaluate the correlation between circRNAs and clinicopathological features. Cox regression analysis was used to explore the correlation between circRNA and postoperative survival time as well as recurrence time. A nomogram based on circRNA and clinicopathological characteristics was established and further evaluated to predict prognosis and recurrence.ResultAmong 60 significantly upregulated circRNAs and 25 downregulated circRNAs, hsa_circ_0029325 was selected to verify its power for predicting HCC outcomes. The high expression level of exosomal hsa_circ_0029325 was significantly correlated with OS (P = 0.001, HR = 2.04, 95% CI 1.41–3.32) and RFS (P = 0.009, HR = 1.62, 95% CI 1.14–2.30). Among 273 HCC patients, multivariate regression analysis showed that hsa_circ_0029325 (HR = 1.96, 95% CI 1.21–3.18), tumor size (HR = 2.11, 95% CI 1.33–3.32), clinical staging (HR = 2.31, 95% CI 1.54–3.48), and tumor thrombus (HR = 1.74, 95% CI 1.12–2.7) were independent risk factors for poor prognosis in HCC patients after radical resection. These independent predictors of prognosis were incorporated into the two nomograms. The AUCs under the 1-year, 3-year, and 5-year survival and recurrence curves of the OS and RFS nomograms were 0.755, 0.749, and 0.742 and 0.702, 0.685, and 0.642, respectively. The C-index, calibration curves, and clinical decision curves showed that the two prediction models had good predictive performance. These results were verified in the validation cohort with 90 HCC patients.ConclusionOur study established two reliable nomograms for predicting recurrence and prognosis in HCC patients. We also show that it is feasible to screen potential predictive markers for HCC after curative resection through exosomal circRNA expression profile analysis.