Poor Clinical Outcome In Patients Research Articles

PB0002 Transient New-Onset Atrial Fibrillation is Associated with Poor Clinical Outcomes in Patients with Acute Myocardial Infarction

PB0002 Transient New-Onset Atrial Fibrillation is Associated with Poor Clinical Outcomes in Patients with Acute Myocardial Infarction

Associations of comorbid substance use disorders with clinical outcomes in schizophrenia using electronic health record data.

Schizophrenia and comorbid substance use disorders (SUDs) are associated with poor treatment outcomes but differences between the associations of different SUDs with clinical outcomes are poorly characterized. This study examines the associations of comorbid SUDs with clinical outcomes in schizophrenia using a largescale electronic health record (EHR) database. Real-world data (RWD) analysis using the NeuroBlu database; de-identified EHR data were analysed. Multivariable logistic regression, Poisson and CoxPH models were used to compare the associations of specific comorbid SUDs with outcome variables. Comorbid SUD was significantly different on all outcome measures compared to no SUD (U=1.44e7-1.81e7, all ps<.001), except number of unique antipsychotics (U=1.61e7, p=.43). Cannabis (OR=1.58, p<.001) and polysubstance (OR=1.22, p=.007) use disorders were associated with greater CGI-S. Cannabis (IRR=1.13, p=.003) and polysubstance (IRR=1.08, p=.003) use disorders were associated with greater number of unique antipsychotics prescribed, while cocaine (HR=1.87, p<.001), stimulants (HR=1.64, p=.024), and polysubstance (HR=1.46, p<.001) use disorders were associated with a shorter time to antipsychotic discontinuation. Conversely, alcohol use (IRR=0.83, p<.001), cocaine use (IRR=0.61, p<.001), opioid use (IRR=0.61, p<.001), stimulant use (IRR=0.57, p<.001) and polysubstance use (IRR=0.87, p<.001) disorders were associated fewer inpatient days. Comorbid SUDs were generally associated with greater CGI-S and poorer clinical outcomes in patients with schizophrenia. Treatment strategies should target not only schizophrenia symptoms but also comorbid SUD to improve management of both conditions.

SETD1A drives stemness by reprograming epigenetic landscape in hepatocellular carcinoma stem cells.

Cancer stem cells (CSCs) are responsible for tumor progression and recurrence. However, the mechanisms regulating hepatocellular carcinoma (HCC) stemness remain unclear. Applying a genome-scale CRISPR knockout screen, we identify that the H3K4 methyltransferase SETD1A and other members of Trithorax group proteins drive cancer stemness in HCC. SETD1A is positively correlated with poor clinical outcome in HCC patients. Combination of SETD1A and serum AFP significantly improves the accuracy of predicting HCC relapse. Mechanistically, SETD1A mediates transcriptional activation of various histone-modifying enzymes, facilitates deposition of H3K4me3 and H3K27me3 and activates oncogenic enhancers and super-enhancers, leading to activation of oncogenes and inactivation of tumor suppressor genes simultaneously in HCC CSCs. In addition, SETD1A cooperates with PABPC1 to regulate H3K4me3 modification on oncogenes. Our data pinpoint SETD1A as a key epigenetic regulator driving HCC stemness and progression, highlighting the potential of SETD1A as a candidate target for HCC intervention and therapy.

Activation of kappa opioid receptor (KOR) inhibits estrogen receptor (ER)-positive breast cancer through the KOR-ER-XBP1 pathway

Opioids are commonly used in patients with breast cancer (BC), both for perioperative analgesia and for the relief of chronic cancer pain. Studies have suggested a potential association of opioid receptors (ORs) with the prognosis of BC patients. However, the exact roles of different ORs remain poorly understood. In this study, we found that κ opioid receptor (KOR) was the only OR (among the four types of ORs) that was significantly decreased in BC tumor tissues compared with peritumoral normal tissues. In addition, decreased expression of KOR correlated with poor clinical outcomes in patients with estrogen receptor (ER)-positive BC. In vitro studies confirmed the anti-tumor effects of KOR agonists in ER-positive MCF-7 and T47D cells by showing that activation of KOR significantly inhibited cellular proliferation and promoted apoptosis. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network (PPI) analysis, we found that KOR-ER-XBP1 was the potential downstream signaling pathway mediating the anti-tumor effects of KOR agonist. Finally, the role of XBP1 was confirmed as KOR activation-induced increase in the proliferative and monoclonal formation abilities of ER-positive BC cells were both significantly abolished after silencing of XBP1. These findings provide us a better understanding of the roles of different ORs in BC, identifying KOR agonists as better opioids than traditional μ opioid receptor (MOR) agonists for providing analgesia in ER-positive BC patients owing to their association with better prognosis.

The benefits of early continuous renal replacement therapy in critically ill patients with acute kidney injury at high-altitude areas: a retrospective multi-center cohort study

Severe hypoxia would aggravate the acute kidney injury (AKI) in high-altitude areas and continuous renal replacement therapy (CRRT) has been used to treat critically ill patients with AKI. However, the characteristics and outcomes of CRRT in critically ill patients at AKI in high altitudes and the optimal timing of CRRT initiation remain unclear. 1124 patients were diagnosed with AKI and treated with CRRT in the ICU, comprising a high-altitude group (n = 648) and low-altitude group (n = 476). Compared with the low-altitude group, patients with AKI at high altitude showed longer CRRT (4.8 vs. 3.7, P = 0.036) and more rapid progression of AKI stages (P < 0.01), but without any significant minor or major bleeding episodes (P > 0.05). Referring to the analysis of survival and kidney recovery curves, a higher mortality but a lower possibility of renal recovery was observed in the high-altitude group (P < 0.001). However, in the high-altitude group, the survival rate of early CRRT initiation was significantly higher than that of delayed CRRT initiation (P < 0.001). The findings showed poorer clinical outcomes in patients undergoing CRRT for AKI at high altitudes. CRRT at high altitudes was unlikely to increase the adverse events. Moreover, early CRRT initiation might reduce the mortality and promote renal recovery in high-altitude patients.

B4GALNT1 promotes hepatocellular carcinoma stemness and progression via integrin α2β1-mediated FAK and AKT activation

β-1,4-N-Acetyl-galactosaminyltransferase 1 (B4GALNT1) has been reported to contribute to the development of human malignancies. However, its role in hepatocellular carcinoma (HCC) remains uncharacterised. In this study, we aimed to elucidate the role of B4GALNT1 in HCC stemness and progression. Immunohistochemical staining was used to evaluate B4GALNT1 expression in HCC tissues and adjacent normal liver tissues. Flow cytometry analysis and sphere formation analysis were performed to investigate the role of B4GALNT1 in HCC stemness. Colony formation, Incucyte, wound-healing, Transwell migration, and invasion assays, and an animal model were used to study the role of B4GALNT1 in HCC progression. RNA-sequencing and co-immunoprecipitation were used to investigate the downstream targets of B4GALNT1. B4GALNT1 was upregulated in HCC and associated with poor clinical outcome of patients with the disease. Moreover, B4GALNT1 promoted HCC stemness, migration, invasion, and growth. Mechanistically, B4GALNT1 not only promoted the expression of the integrin α2β1 ligand THBS4, but also directly interacted with the β subunit of integrin α2β1 ITGB1 to inhibit its ubiquitin-independent proteasomal degradation, resulting in activation of FAK and AKT. Ophiopogonin D inhibited HCC stemness and progression by reducing ITGB1 and THBS4 expression and inhibiting FAK and AKT activation. Our study suggests the B4GALNT1/integrin α2β1/FAK/PI3K/AKT axis as a therapeutic target for the inhibition of HCC stemness and tumour progression. The role and regulatory mechanism of B4GALNT1 in HCC have not been studied previously. Here, we reveal that B4GALNT1 has a crucial role in HCC stemness and progression by activating the integrin α2β1/FAK/PI3K/AKT axis, providing a potential target for HCC therapy. In addition, we find Ophiopogonin D as a potential therapeutic drug for patients with HCC.

Investigation of the relationship between modified Glasgow prognostic score and no-reflow phenomenon in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction

Objectives: No-reflow phenomenon (NRP) is a complication associated with poor clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). The modified Glasgow prognostic score (mGPS) is a novel immune-inflammatory index, derived from C-reactive protein (CRP) and serum albumin levels and has been shown to be associated with prognosis in heart disease. In this study we aimed to investigated the relationship between mGPS and NRP in patients undergoing pPCI for STEMI. Methods: A total of 379 patients (aged 59 ± 9.9 years; 54.9% male) were enrollled. The patients were divided into 2 groups:no-reflow (n = 72) and reflow (n = 307). No-reflow was defined as thrombolysis in myocardial infarction (TIMI) ≤ 2 flow. The mGPS of all patients was calculated from blood samples at admission. Logistic regression analysis was performed to determine the independent predictive factors for NRP. Results: Mean age, pain to balloon duration, troponin T, white blood cell (WBC), Syntax score, neutrophil to lymphocyte ratio (NLR), glucose level, C-reactive protein level (CRP), diabetic and female patient ratio were higher, while left ventricular ejection fraction, ST segment resolution ratio at 60 min, and serum albumin level were lower in the NRP group.Logistic regression analysis showed that WBC count [Hazard ratio (HR): 0.816, 95% confidence interval (CI): 0.728-0.914, p &amp;lt; 0.001], NLR (HR: 0.482, CI: 0.355-0.654, p &amp;lt; 0.001), pain-to-balloon time (HR: 0.976, CI:0.960-0.991, p = 0.002) and mGPS (HR: 3.213, CI: 1.643- 6.283, p = 0.001) were independent predictive factors for NRP. Conclusions: Modified GPS is an independent predictive factor for NRP in patients undergoing pPCI for STEMI.

Scoping Review of Measures of Comorbidities in Heart Failure.

Comorbidities are risk factors for poor clinical outcomes in patients with heart failure. However, no consensus has been reached on how to assess comorbidities related to clinical outcomes in patients with heart failure. The aims of this study were to review (1) how comorbidities have been assessed, (2) what chronic conditions have been identified as comorbidities and (3) the rationale for choosing the comorbidity instruments and/or specific comorbidities when exploring clinical outcomes in patients with heart failure. The clinical outcomes of interest were mortality, hospitalization, quality of life, and self-care. Three electronic databases and reference list searches were used in the search. In this review, we included 39 articles using 3 different ways to assess comorbidities in the relationship with clinical outcomes: using an instrument (ie, Charlson Comorbidity Index), disease count, and including individual comorbidities. A total of 90 comorbidities were investigated in the 39 articles; however, definitions and labels for the diseases were inconsistent across the studies. More than half of the studies (n = 22) did not provide a rationale for selecting the comorbidity instruments and/or all of the specific comorbidities. Some of the rationale for choosing the instruments and/or specific comorbidities was inappropriate. We found several issues related to measuring comorbidities when examining clinical outcomes in patients with heart failure. Researchers need to consider these methodological issues when measuring comorbidities in patients with heart failure. Further efforts are needed to develop guidelines on how to choose proper measures for comorbidities.

DNA hypermethylation driven by DNMT1 and DNMT3A favors tumor immune escape contributing to the aggressiveness of adrenocortical carcinoma

BackgroundAdrenocortical carcinoma is rare and aggressive endocrine cancer of the adrenal gland. Within adrenocortical carcinoma, a recently described subtype characterized by a CpG island methylator phenotype (CIMP) has been associated with an especially poor prognosis. However, the drivers of CIMP remain unknown. Furthermore, the functional relation between CIMP and poor clinical outcomes of patients with adrenocortical carcinoma stays elusive.ResultsHere, we show that CIMP in adrenocortical carcinoma is linked to the increased expression of DNA methyltransferases DNMT1 and DNMT3A driven by a gain of gene copy number and cell hyperproliferation. Importantly, we demonstrate that CIMP contributes to tumor aggressiveness by favoring tumor immune escape. This effect could be at least partially reversed by treatment with the demethylating agent 5-azacytidine.ConclusionsIn sum, our findings suggest that co-treatment with demethylating agents might enhance the efficacy of immunotherapy and could represent a novel therapeutic approach for patients with high CIMP adrenocortical carcinoma.

Plasma tissue-type plasminogen activator is associated with lipoprotein(a) and clinical outcomes in hospitalized patients with COVID-19

BackgroundPatients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown. ObjectivesTo assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection. MethodsEndogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed. ResultsIn hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non–COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged. ConclusionHigh Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.

Relationship Between Prognostic Nutritional Index and New-Onset Atrial Fibrillation in Patients with Acute ST-Elevation Myocardial Infarction Following Percutaneous Coronary Intervention.

Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.

Monocyte to high-density lipoprotein cholesterol ratio decreased in patients with psoriasis treated with ixekizumab.

Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammatory biomarker which has been associated with cardiovascular diseases. To study MHR in patients with psoriasis treated with biological agents. Between April 2019 and August 2022, MHR was retrospectively evaluated in patients with psoriasis before and 3 months after treatment with infliximab, adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab in a university hospital in Ankara, Turkey. This study included 128 patients, 53 females and 75 males. 39 (30.5%) patients were treated with infliximab, 26 (20.3%) with adalimumab, 8 (6.3%) with etanercept, 18 (14.1%) with ixekizumab, 12 (9.4%) with secukinumab, and 25 (19.5%) with ustekinumab. The median MHR was 0.0127 (0.0086-0.0165) in females and 0.0146 (0.0119-0.0200) in males (p = 0.011). The median MHR decreased after treatment with adalimumab, ixekizumab, secukinumab, and ustekinumab, whereas it increased after treatment with infliximab and etanercept (p = 0.790, p = 0.015, p = 0.754, p = 0.221, p = 0.276, p = 0.889, respectively). MHR significantly decreased in patients with psoriasis after treatment with ixekizumab. Since high MHR levels have been associated with poor clinical outcomes in patients with cardiovascular diseases, ixekizumab might have a positive impact in the treatment of psoriasis patients who had cardiovascular diseases. We suggest that MHR may be useful both in establishing appropriate biological agent treatment and in the follow-up of patients with psoriasis treated with biological agents.

Cholesterol Efflux Drives the Generation of Immunosuppressive Macrophages to Promote the Progression of Human Hepatocellular Carcinoma.

Cholesterol is often enriched in tumor microenvironment (TME); however, its impact on disease progression varies in different tissues and cells. Monocytes/macrophages (Mφ) are major components and regulators of the TME and play pivotal roles in tumor progression and therapeutic responses. We aimed to investigate the profile, effects, and regulatory mechanisms of Mφ cholesterol metabolism in the context of human hepatocellular carcinoma (HCC). Here, we found that patients with high serum levels of cholesterol had shorter survival times and lower response rates to anti-PD-1 treatment. However, the cholesterol content in tumor-infiltrating monocytes/Mφ was significantly lower than that in their counterparts in paired nontumor tissues. The expression of the cholesterol efflux transporter, ABCA1, was upregulated in tumor monocytes/Mφ, and ABCA1 upregulation positively associated with decreased cellular cholesterol content and increased serum cholesterol levels. Mechanistically, autocrine cytokines from tumor-treated monocytes increased LXRα and ABCA1 expression, which led to the generation of immature and immunosuppressive Mφ. Although exogenous cholesterol alone had little direct effect on Mφ, it did act synergistically with tumor-derived factors to promote ABCA1 expression in Mφ with more immunosuppressive features. Moreover, high numbers of ABCA1+ Mφ in HCC tumors associated with reduced CD8+ T-cell infiltration and predicted poor clinical outcome for patients. Our results revealed that dysregulated cholesterol homeostasis, due to the collaborative effects of tumors and exogenous cholesterol, drives the generation of immunosuppressive Mφ. The selective modulation of cholesterol metabolism in Mφ may represent a novel strategy for cancer treatment.

Impact of Mechanical Ventilation and Renal Replacement Therapy on Clinical Outcomes among Critically Ill COVID-19 Patients

Background: Poor clinical outcomes in patients with severe COVID-19 occur due to many factors that require elucidation. The objective of this study was to describe the outcomes of critically ill patients with COVID-19 and identify the risk factors for mortality. Materials and Methods: The study was a single-centered cross-sectional, observational study involving COVID-19 patients admitted to the intensive care units (ICUs) of a tertiary care hospital in the Middle East and North Africa (MENA) region. The patients were admitted between 1 March and 31 December 2020. Logistic regression analysis was used to identify risk factors for mortality. Results: Of 107 patients admitted, 98 (91.6%) were ≥40 years old and 84 (78.5%) were males. The mean oxygen saturation at admission was 79.6 ± 12.6%, the duration of ICU stay was 13.0 ± 11.6 days, and 65 (60.7%) of the patients received mechanical ventilation. Major comorbidities included hypertension (57%), diabetes (56%), and chronic kidney disease (CKD) (15.5%). The overall mortality rate was 51.4%; this was higher in patients who received mechanical ventilation (60 vs. 38.1%; p = 0.03) and those with co-morbid hypertension (60.7 vs. 39.1%; p = 0.03). Risk factors for mortality were: need for mechanical ventilation agent of record adjusted Odds ratio (aOR) 4.4 (1.6–12.6), co-morbid hypertension aOR 5.8 (1.6–21.1), having CKD aOR 5.4 (1.2–25.6) and receiving renal replacement therapy aOR 4.3 (1.4–13.0). Conclusions: The use of mechanical ventilation or renal replacement therapy among critically ill COVID-19 patients could potentially predict worse outcomes. Patients with existing hypertension or CKD may carry a higher mortality risk.

Role of protein tyrosine phosphatase receptor type M in epithelial ovarian cancer progression

BackgroundEpithelial ovarian cancer (EOC) is often diagnosed at advanced stages with low survival rates. Protein tyrosine phosphatase receptor type M (PTPRM) is involved in cancer development and progression; however, its role in EOC remains unclear. In this study,we aimed to detect PTPRM expression in ovarian epithelial tumors, analyze its relationship with the clinicopathological features and survival prognosis of patients with EOC, and provide a theoretical basis for new targets for EOC treatment. Fifty-seven patients with EOC treated at our hospital between January 2012–January 2014 were included; along with 18 borderline and 30 benign epithelial ovarian tumors and 15 normal ovarian and uterine tube tissue samples from patients surgically treated at our hospital during the same period. PTPRM expression was immunohistochemically detected, and we analyzed its relationship with clinicopathological features and prognosis. Associations between PTPRM expression and survival prognosis of patients with EOC were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter databases.ResultsPTPRM had the highest expression rates in normal ovarian and uterine tube tissues, followed by benign and borderline epithelial ovarian tumors; the lowest positive expression rate was observed in EOC tumors. PTPRM expression differed significantly among groups (P < 0.05). The positive PTPRM expression rate significantly decreased with age, progressing clinical stage, and tumor recurrence, and the larger the mass diameter, the higher the positive PTPRM expression rate. PTPRM expression was significantly lower in ovarian cancer compared with that in normal tissues in the GEPIA database (P < 0.05). The overall survival (OS) and disease-free survival(DFS) rates were higher in the PTPRM high-expression group, with statistically significant (P < 0.05) and insignificant (P > 0.05) differences, respectively. The OS rate of the high-expression group compared with the low-expression group in the Kaplan–Meier Plotter database was higher, although without statistical significance (P > 0.05), and progression-free survival(PFS) was higher with statistical significance (P < 0.05).ConclusionPTPRM expression was low in patients with EOC, and the PTPRM positive-expression rate significantly decreased with progressing stages of EOC and tumor recurrence, suggesting that PTPRM acts as a tumor suppressor in EOC progression. Negative PTPRM expression may predict poor clinical outcomes in patients with EOC.

High SLC20A1 Expression Indicates Poor Prognosis in Prostate Cancer.

High expression of solute carrier family 20 member 1 (SLC20A1) indicates poor clinical outcomes for patients with breast cancer subtypes treated with endocrine therapy and radiotherapy. However, the association between SLC20A1 expression and clinical outcomes in prostate cancer remains to be determined. Open-source datasets (The Cancer Genome Atlas prostate, Stand Up to Cancer-Prostate Cancer Foundation Dream Team, and The Cancer Genome Atlas PanCancer Atlas) were downloaded and analyzed. SLC20A1 expression was analyzed in prostate cancer and normal prostate tissue. Survival analysis using Kaplan-Meier curves and Cox regression analysis were performed to examine patient prognosis, as well as the effects of endocrine therapy and radiotherapy on high SLC20A1 expression in patients with prostate cancer. SLC20A1 was higher in prostate cancer than in normal prostate tissues. High SLC20A1 expression predicted poor disease-free and progression-free survival. Following endocrine therapy, no significant difference in prognosis was observed between patients with high SLC20A1 and those with low SLC20A1 expression. However, following radiotherapy, high SLC20A1 expression tended to be associated with a poor clinical outcome. SLC20A1 may serve as a prognostic biomarker for prostate cancer, and the recommended treatment for patients with high SLC20A1 expression is endocrine therapy.

Body mass index as a predictor of the outcomes of acute clozapine toxicity: a cross-sectional study.

Acute antipsychotic overdose is frequently reported nowadays. Clozapine is one of the atypical agents that are highly lipophilic, highly protein-bound, has a large volume of distribution, and accumulates in the brain and other tissues. Obesity is an essential factor controlling patients' treatment and clinical course. The current study aimed to study the prognostic value of body mass index (BMI) in patients with acute clozapine poisoning. All patients were evaluated on admission using the Poison Severity Score (PSS) and Glasgow Coma Score (GCS). The BMI was calculated. Mortality and the need for ICU admission were defined as primary outcomes, whereas secondary outcomes included cardiovascular complications and the need for mechanical ventilation. Thirty-eight patients presented with acute clozapine poisoning. The mean age of included patients was 25.2±6. Patients were categorized regarding BMI into average weight (26.3%), overweight (31.6%), and obese (42.1%). Pearson's correlation indicated a significant positive correlation between BMI and respiratory rate (r=.364, p=.025). A significant negative correlation existed between BMI and GCS (r=.674, p≤.001). ROC curve reveals that BMI is an excellent predictor for the requirement of mechanical ventilation area under the curve (AUC>.9), a fair predictor of ICU admission AUC (.747). BMI had a sensitivity of 100% and specificity of 51.7 for the prediction of ICU admission. In conclusion, obesity increased the severity of toxicity and the incidence of poor clinical outcomes in patients with acute clozapine poisoning.

Multiparametric magnetic resonance imaging discerns glioblastoma immune microenvironmental heterogeneity.

Poor clinical outcomes for patients with glioblastoma are in part due to dysfunction of the tumor-immune microenvironment. An imaging approach able to characterize immune microenvironmental signatures could provide a framework for biologically based patient stratification and response assessment. We hypothesized spatially distinct gene expression networks can be distinguished by multiparametric Magnetic Resonance Imaging (MRI) phenotypes. Patients with newly diagnosed glioblastoma underwent image-guided tissue sampling allowing for co-registration of MRI metrics with gene expression profiles. MRI phenotypes based on gadolinium contrast enhancing lesion (CEL) and non-enhancing lesion (NCEL) regions were subdivided based on imaging parameters (relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC)). Gene set enrichment analysis and immune cell type abundance was estimated using CIBERSORT methodology. Significance thresholds were set at a p-value cutoff 0.005 and an FDR q-value cutoff of 0.1. Thirteen patients (eight men, five women, mean age 58 ± 11years) provided 30 tissue samples (16 CEL and 14 NCEL). Six non-neoplastic gliosis samples differentiated astrocyte repair from tumor associated gene expression. MRI phenotypes displayed extensive transcriptional variance reflecting biological networks, including multiple immune pathways. CEL regions demonstrated higher immunologic signature expression than NCEL, while NCEL regions demonstrated stronger immune signature expression levels than gliotic non-tumor brain. Incorporation of rCBV and ADC metrics identified sample clusters with differing immune microenvironmental signatures. Taken together, our study demonstrates that MRI phenotypes provide an approach for non-invasively characterizing tumoral and immune microenvironmental glioblastoma gene expression networks.

Polyglycerol-Amine Covered Nanosheets Target Cell-Free DNA to Attenuate Acute Kidney Injury.

Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials is regarded as a promising remedy for cfDNA-associated diseases, but a nanomaterial-based cfDNA scavenging strategy has not yet been reported for AKI treatment. Herein, polyglycerol-amine (PGA)-covered MoS2 nanosheets with suitable size are synthesized to bind negatively charged cfDNA in vitro, in vivo and ex vivo models. The nanosheets exhibit higher cfDNA binding capacity than polymer PGA and PGA-based nanospheres owing to the flexibility and crimpability of their 2D backbone. Moreover, with low cytotoxicity and mild protein adsorption, the nanosheets effectively reduced serum cfDNA levels and predominantly accumulated in the kidneys to inhibit the formation of neutrophil extracellular traps and renal inflammation, thereby alleviating both lipopolysaccharide and ischemia-reperfusion induced AKI in mice. Further, they decreased the serum cfDNA levels in samples from AKI patients. Thus, PGA-covered MoS2 nanosheets can serve as a potent cfDNA scavenger for treating AKI and other cfDNA-associated diseases. In addition, this work demonstrates the pivotal feature of a 2D sheet-like structure in the development of the cfDNA scavenger, which can provide a new insight into the future design of nanoplatforms for modulating inflammation.

Integrated bioinformatics analysis reveals the function and prognostic value of OSBPL3 in hepatocellular carcinoma

BackgroundLiver hepatocellular carcinoma (LIHC), a variety of highly-aggressive malignancy, has been the major cause of cancer-related mortality. Recent studies have shown that oxysterol-binding protein-like 3 (OSBPL3) plays a crucial role in human cancers. Nevertheless, the specific functional roles and potential clinical values of OSBPL3 in LIHC are not completely known. MethodsMultiple web portals and publicly available tools were used in this study. Comprehensive expression files of OSBPL3 in pan-cancers and the relationship between OSBPL3 expression and clinical traits of patients with LIHC were investigated using TCGA database through UALCAN platform. TIMER database was used to investigate the effect of OSBPL3 on the tumor immune infiltration status in LIHC. Moreover, LinkedOmics, STRING databases, and Gene Ontology analysis were utilized to select OSBPL3-related differentially expressed genes (DEGs) and construct a protein–protein interaction (PPI) network. ResultsUpregulated OSBPL3 was observed in LIHC tumor tissues compared with that in normal controls, especially in patients with higher grades and more advanced stages. Furthermore, overexpressed OSBPL3 was closely associated with poor clinical outcomes of patients with LIHC. Six hub genes were selected from the PPI network, which were significantly increased in LIHC and closely associated with poor prognosis. Pathway enrichment showed that OSBPL3-related DEGs were primarily enriched in protein binding, mitotic cytokinesis, inorganic anion transport, and I-kappaB kinase/NF-kappaB signaling processes. ConclusionsOSBPL3 exerts critical functions in hepatocarcinogenesis and it could serve as an available biomarker and effective treatment target for LIHC.