Unfavorable Outcome In Patients Research Articles

Comparing prognostic scoring systems in acute pancreatitis: Bedside Index of Severity in Acute Pancreatitis, WL, and Chinese Simple Scoring System Scores.

Several scoring systems are used to predict prognosis in acute pancreatitis (AP), but their predictive success varies. This study compares the validity of the commonly used Bedside Index of Severity in AP (BISAP) score with the newly developed WL score and the Chinese Simple Scoring System (CSSS) score in predicting mortality and unfavorable prognostic outcomes in AP patients. This retrospective descriptive study included all AP patients presenting to the emergency department from June 2, 2019, to June 2, 2022. Patient demographics, vital signs, laboratory values, and imaging findings were recorded, and WL, CSSS, and BISAP scores were calculated. The effectiveness of these scores in predicting adverse outcomes and mortality was compared. Among 357 patients, 53.2% were male, with a median age of 62 years (interquartile range: 48-75). Area under the curve (AUC) values for 7-day outcomes were 0.956 for WL, 0.759 for CSSS, and 0.871 for BISAP; for 30-day outcomes, AUC values were 0.941 for WL, 0.823 for CSSS, and 0.901 for BISAP; and for poor prognostic outcomes, AUC values were 0.792 for WL, 0.769 for CSSS, and 0.731 for BISAP. In AP patients, WL, CSSS, and BISAP scores are effective predictors of unfavorable prognosis and mortality. WL score outperforms the CSSS and BISAP scores in predicting 7-day and 30-day mortality and poor prognosis. After WL, BISAP is the second-best system for predicting mortality. For predicting unfavorable prognoses, CSSS is the second-best system after WL. The simplicity of calculating the WL score based on four laboratory parameters makes it a preferable choice.

The Inhibition of RXRα and RXRβ Receptors Provides Valuable Insights for Potential Prostate Cancer Treatment, in silico Molecular Docking and Molecular Dynamics Studies.

Prostate cancer has emerged as a widespread health concern, with systemic inflammation believed to substantially contribute to its development and progression. The presence of systemic inflammatory responses has been established as an independent predictor of unfavorable long-term outcomes in prostate cancer patients. The goal of this study is to inhibit RXRα and RXRβ receptors, which are involved in prostate cancer, with Luteolin, Formononetin, and Kaempferol, with varying success. Retinoid X receptors (RXRs) hold crucial roles within the nuclear receptor (NR) superfamily, and compelling evidence from preclinical studies underscores the therapeutic potential of targeting RXRs for treating neurodegenerative and inflammatory conditions. Consequently, the ability to regulate and modulate RXRs using phytoestrogen ligands, Formononetin, Kaempferol, and Luteolin, assume paramount importance in treatment strategies. The comprehensive in silico findings of this study vividly demonstrate the remarkable efficacy of Luteolin in inhibiting and modulating RXRα and RXRβ, while Formononetin emerges as a notably potent suppressor of RXRβ. Kaempferol, as the third compound, also exhibits commendable inhibitory attributes, although its impact is slightly less pronounced compared to the other two. These findings highlight the notable binding and inhibition capabilities to RXRα and RXRβ, offering valuable insights for potential prostate cancer treatment avenues warranting further exploration through in vitro and in vivo analyses.

Exploration of the role of EMC3‑AS1 as a potential diagnostic and prognostic indicator in liver cancer.

The aim of the present study was to evaluate the diagnostic and prognostic significance of the long non-coding RNA (lncRNA) endoplasmic reticulum membrane protein complex subunit 3 antisense RNA 1 (EMC3-AS1) in liver cancer, and its impact on the proliferative and invasive capabilities of liver cancer cells. EMC3-AS1 expression in liver cancer was assessed using data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets, and validated in clinical liver cancer samples using reverse transcription-quantitative PCR. The prognostic and diagnostic potentials of this lncRNA were evaluated using Kaplan-Meier and receiver operating characteristic analyses, respectively. The infiltration of immune cells and differential expression of immune checkpoints (ICs) between high- and low-EMC3-AS1 expression groups were investigated. Therapeutic correlation analyses were also undertaken to assess the impact of EMC3-AS1 in the treatment of liver cancer. In addition, in vitro experiments were conducted using small interfering RNA to knock down the expression of EMC3-AS1 in HepG2, Sk-Hep-1 and Huh-7 cells, and evaluate the effect on cell proliferation, colony formation and migration. The results revealed a significant upregulation of EMC3-AS1 expression in liver cancer tissues compared with that in adjacent normal tissues, which was associated with an unfavorable prognosis and demonstrated diagnostic effectiveness for patients with liver cancer. Furthermore, patients with high EMC3-AS1 expression exhibited increased levels of IC markers in comparison with those with low EMC3-AS1 expression. In addition, EMC3-AS1 was indicated to have clinical significance in the prediction of the response to immunotherapy and chemotherapy. Notably, the in vitro experiments demonstrated that the knockdown of EMC3-AS1 significantly hindered cell proliferation, colony formation and migration. Consequently, it was concluded that EMC3-AS1 is upregulated in liver cancer and serves as a prognostic indicator for unfavorable outcomes in patients with liver cancer. Additionally, targeting EMC3-AS1 through knockdown interventions showed potential in mitigating the ability of liver cancer cells to proliferate and migrate, which highlights its dual role as a biomarker and therapeutic target for liver cancer.

Aortic Arch Calcification in Predicting Unfavorable Angiographic Outcomes for Patients with ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Despite advances in treatment, no-reflow, large thrombus burden (LTB), and myocardial blush grade (MBG) are associated with adverse cardiovascular outcomes in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). Aortic arch calcification (AAC) is associated with subclinical atherosclerosis and adverse cardiovascular events. We aimed to examine the relationship between AAC and unfavorable angiographic outcomes such as no-reflow, MBG, and LTB in STEMI patients undergoing PCI. A total of 269 consecutive patients who presented with STEMI and underwent primary PCI were included in the study prospectively. Patients were divided into 3 groups according to AAC degree: grade 0, grade 1, and grade 2/3. The relationship between AAC and the predictors of unfavorable angiographic outcomes, including LTB, no-reflow, and MBG, was specifically examined. LTB, no-reflow, and MBG 0/1 were significantly higher in the grade 2/3 AAC group compared to the grade 0 and grade 1 groups (all p < 0.05). Moreover, grade 2/3 AAC was found to be an independent predictor for LTB, MBG 0/1, and no-reflow (p = 0.002, p = 0.005, p = 0.004, respectively). Patients were then classified according to thrombus burden, MBG, and no-reflow status. Grade 2/3 AAC was significantly higher than grade 0/1 AAC in the LTB, MBG 0/1, and no-reflow groups (all p < 0.05). AAC can be used as a reliable indicator in predicting no-reflow, MBG 0/1, and LTB in STEMI patients undergoing primary PCI.

Impaired acute-phase humoral immunity is the major factor predicting unfavorable outcomes in multiple myeloma patients with SARS-CoV-2 Omicron variants outbreak infection.

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population.

Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD.

PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.

Evaluation of two-stage hepatectomy using portal vein embolization for colorectal liver metastasis: a retrospective nationwide cohort survey in Japan.

Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM) which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM. We conducted a retrospective cohort study using the nationwide database that included clinical information of 12,519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, chi-squared test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test. Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rate at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95%CI 1.224-14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004). In the Japanese cohort, TSH was confirmed to be a safety procedure with acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcome of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.

Sideroflexin-1 promotes progression and sensitivity to lapatinib in triple-negative breast cancer by inhibiting TOLLIP-mediated autophagic degradation of CIP2A

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and it lacks specific therapeutic targets and effective treatment protocols. By analyzing a proteomic TNBC dataset, we found significant upregulation of sideroflexin 1 (SFXN1) in tumor tissues. However, the precise function of SFXN1 in TNBC remains unclear. Immunoblotting was performed to determine SFXN1 expression levels. Label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry were used to identify the downstream targets of SFXN1. Mechanistic studies of SFXN1 and cellular inhibitor of PP2A (CIP2A) were performed using immunoblotting, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional experiments were used to investigate the role of SFXN1 in TNBC cells. SFXN1 was significantly overexpressed in TNBC tumor tissues and was associated with unfavorable outcomes in patients with TNBC. Functional experiments demonstrated that SFXN1 promoted TNBC growth and metastasis in vitro and in vivo. Mechanistic studies revealed that SFXN1 promoted TNBC progression by inhibiting the autophagy receptor TOLLIP (toll interacting protein)-mediated autophagic degradation of CIP2A. The pro-tumorigenic effect of SFXN1 overexpression was partially prevented by lapatinib-mediated inhibition of the CIP2A/PP2A/p-AKT pathway. These findings may provide a new targeted therapy for patients with TNBC.

NFKBIA deletions reshape the epigenome antithetical to the IDH mutation and indication of prognosis in diffuse gliomas.

2083 Background: Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. The NFKBIA gene at 14q13.2 encodes IkBa, a protein that regulates the activity of NF-kB in the cytoplasm. Evidence that, in chromatin, nuclear NFKBIA dynamically interacts with histones H2A and H4 to regulate polycomb-dependent transcriptional repression and, thus, stem cell maturation and lineage specification and our characterization of NFKBIA as a tumor suppressor in glioblastoma prompted our investigation of the relationship of NFKBIA deletions to other genetic markers, alterations in the methylome, and the clinical course of gliomas. Methods: We analyzed the genetic profiles of 2,343 WHO grade 2 to 4 diffuse gliomas in multiple clinically well-characterized patient populations, including national randomized phase III consortium trial RTOG 9802, to determine whether incorporation of NFKBIA deletions could enhance the prognostic value of current molecular descriptions. Results: We demonstrate that haploinsufficient deletions of NFKBIA display distinct patterns of occurrence in relation to other genetic markers, including driver mutations IDH, TERT, ATRX, and PTEN, 1p19q codeletion, and CDKN2A/B deletion, and are disproportionally present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation. The methylome changes facilitated through NFKBIA deletions engender a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas and are highly enriched for neural stem cell and neurogenesis genes bearing repressive H3K27 marks. Our findings imply that the NFKBIA deletion in adult gliomas and the H3K27M mutation in pediatric diffuse midline gliomas define aggressive disease subtypes that may share an epigenetic state reflecting a common PRC2 loss-of-function phenotype antipodal to the quasi PRC2 gain-of-function phenotype of IDH mutant gliomas and their favorable clinical course. Lower-grade gliomas harboring NFKBIA deletions behave much like high-grade gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wildtype tumors. A sparse, easily interpretable, and externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas, incorporating NFKBIA deletion and current best-established genetic and clinicopathologic factors, confirms that NFKBIA deletions predict comparatively brief survival. Conclusions: NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into clinical models predicting the disease fate of diffuse gliomas.

Hospital challenges faced by frail patients with ovarian cancer and the adverse outcomes: A nationwide study.

5572 Background: Ovarian cancer is a leading cause of gynecological cancer-related deaths and one of the most common causes of cancer-related fatalities among women. Frailty has been identified as a predictor of unfavorable outcomes for cancer patients, but there is limited research on its impact on individuals with ovarian cancer. We examined the effects of Frailty in hospitalized ovarian cancer patients and the associated outcomes. Methods: National Inpatient Sample (NIS) 2020 was used to identify the patients with a primary diagnosis of ovarian cancer (local/regional and advanced metastatic) and was stratified into patients with and without Frailty. The primary outcome was mortality, and secondary outcomes included length of stay, the total cost of hospitalization, and other in-hospital adverse outcomes. Multivariate logistic regression analysis was used to calculate the outcomes after adjusting for confounding variables. Results: A total of 19790 patients were hospitalized with a primary diagnosis of Ovarian cancer, among which 3215 (16.24%) patients had the concurrent diagnosis of Frailty. The mean age of patients with and without Frailty was 65.76 (+/-13.10) and 60 (+/-14.45),p<0.001, respectively. After adjusting for confounding variables, Frailty was associated with an increased risk of mortality in patients with ovarian cancer (OR=3.01(1.83-4.95); p<0.001). Patients with Frailty were also at risk of increased length of stay (+3.80 Days (3.09-4.50; p<0.001) and total cost of hospitalization (+ $ 34662 (22973-46351); p<0.001). Frail patients also had an increased likelihood of Acute respiratory failure (OR=1.72 (1.22-2.42); p=0.002), Acute kidney injury (OR=2.40 (1.88-3.05); p<0.001), Sepsis (OR=4.97 (3.19-7.75); p<0.001), ICU admission (OR=2.23 (1.44-3.45); p<0.001), Pneumonia (OR=2.63 (1.69-4.10); p<0.001), total parenteral nutrition (OR=14.20 (7.80-25.83); p<0.001) and Intubation (OR=2.11 (1.21-3.69); p=0.008). However, there was no difference in the risk of noninvasive mechanical ventilation (OR=2.07 (0.95-4.52); p=0.48) or enteral feeding (OR=32.73 (0.63-1696); p=0.08). Conclusions: Frailty in ovarian cancer patients is considered an independent predictor of mortality. It is also associated with increased healthcare resource utilization and adverse in-hospital outcomes.[Table: see text]

The efficacy of therapeutic hypothermia in patients with poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

This study evaluates the effectiveness of Therapeutic Hypothermia (TH) in treating poor-grade aneurysmal subarachnoid hemorrhage (SAH), focusing on functional outcomes, mortality, and complications such as vasospasm, delayed cerebral ischemia (DCI), and hydrocephalus. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive literature search was conducted across multiple databases, including Medline, Embase, and Cochrane Central, up to November 2023. Nine studies involving 368 patients were selected based on eligibility criteria focusing on TH in poor-grade SAH patients. Data extraction, bias assessment, and evidence certainty were systematically performed. The primary analysis of unfavorable outcomes in 271 participants showed no significant difference between the TH and standard care groups (risk ratio [RR], 0.87). However, a significant reduction in vasospasm was observed in the TH group (RR, 0.63) among 174 participants. No significant differences were found in DCI, hydrocephalus, and mortality rates in the respective participant groups. TH did not significantly improve primary unfavorable outcomes in poor-grade SAH patients. However, the reduction in vasospasm rates indicates potential specific benefits. The absence of significant findings in other secondary outcomes and mortality highlights the need for further research to better understand TH's role in treating this patient population.

The Effectiveness of Target Temperature Management on Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk(RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, p = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, p = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.

Angiogenesis in nasopharyngeal carcinoma: insights, imaging, and therapeutic strategies.

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in southern China frequently diagnosed at advanced stages owing to subtle early symptoms and associated metastasis. Angiogenesis emerges as a pivotal factor in NPC progression, with numerous angiogenesis-related factors showing aberrant expression and contributing to increased neovascularization within NPC tumors. These abnormal vessels not only nourish tumor growth but also facilitate metastasis, culminating in unfavorable patient outcomes. Multiple studies have demonstrated the applicability of various imaging techniques for assessing angiogenesis in NPC tumors, thus serving as a foundation for personalized treatment strategies and prognostic assessments. Anti-angiogenic therapies have exhibited significant potential for inhibiting NPC angiogenesis and exerting anti-tumor effects. To enhance efficacy, anti-angiogenic drugs are frequently combined with other treatment modalities to synergistically enhance anti-tumor effects while mitigating the side effects associated with single-agent therapies, consequently improving patient prognosis. Identifying the potential mechanisms and key targets underlying NPC angiogenesis and exploring more effective detection and treatment approaches holds promise for shaping the future of NPC diagnosis, treatment, and prognosis, thereby offering new avenues and perspectives for research and clinical practice.

Sarcopenia is a possible risk factor for amputation after peripheral arterial interventions.

Sarcopenia has been demonstrated to be related to unfavorable clinical outcomes in patients with vascular diseases. The purpose of this study is to evaluate the relationship between sarcopenia and clinical results in patients with peripheral arterial disease who underwent endovascular therapy (EVT). This single-center retrospective study involved patients with PAD who underwent peripheral EVT at Ankara City Hospital, between January 2018 and December 2021. Two groups of patients were created: sarcopenic and non-sarcopenic patients according to computed tomography angiography muscle measurements. Primary outcome measures were major and minor amputation and survival. Mortality, amputation, and clinical characteristics were compared between the two patient groups. Hazard ratios (HRs) for amputation were calculated for each risk factor via univariate and multivariate analyses. Secondary outcomes included length of hospital stay and post-procedural complications. The mean follow-up period was 29.9 ± 9months for all patients. A total number of 100 patients (mean age 63.5 ± 9.2years) were involved in the study cohort. A significant association was identified between mortality and sarcopenia (p < .001). The mortality rate in the group with sarcopenia was significantly higher than the other group; 65.7% (23 patients) versus (20%, 13 patients) (p < .001). The major amputation rate in the group with sarcopenia was 57.1%, the major amputation rate in the group without sarcopenia was calculated as 15.4%, revealing that the major amputation rate was detected to be significantly higher in the sarcopenia group (p < .001). Multivariate regression analyses showed that only sarcopenia (HR, 0.52; 95% CI, 0.21-1.27; p = 0.15) was independently associated with major amputation in patients with PAD after EVT. Kaplan-Meier analysis revealed a statistically significant difference between the survival curves of sarcopenia and non-sarcopenia patients (p < .001). Sarcopenia seems to be a possible risk factor associated with amputation in patients with PAD who undergo EVT. The results of this study imply that sarcopenia is a possible risk factor for overall survival in patients with PAD.

SLAMF8 can predict prognosis of pan-cancer and the immunotherapy response effectivity of gastric cancer.

SLAMF8, the eighth member of the Signaling Lymphocytic Activation Molecule Family (SLAMF), functions in the regulation of the development and activity of diverse immune cells as a costimulatory receptor within the SLAMF family. Studies had revealed that SLAMF8 is expressed higher in several autoimmune inflammation diseases and tumors. Nevertheless, the connection between SLAMF8 and pan-cancer remains undisclosed. The research investigated the correlation between SLAMF8 and various factors including the immune microenvironment, microsatellite instability, immune novel antigen, gene mutation, immune regulatory factors, immune blockade TMB, and immune or molecular subtypes of SLAMF8 in verse cancer types. Immunohistochemistry was ultimately employed to validate the presence of the SLAMF8 gene in various tumor types including hepatocellular carcinoma, prostate adenocarcinoma, and kidney renal clear cell carcinoma. Furthermore, the relationship between SLAMF8 expression and the therapeutic efficacy of the PD1 blockade agent, Sintilimab, treatment in gastric cancer was validated. The result of differential analysis suggested that SLAMF8 was over-expressed in pan-cancer compared with paracancerous tissues. The analysis of survival indicated a connection between SLAMF8 and the overall prognosis in different types of cancers, where higher levels of SLAMF8 were found to be significantly linked to unfavorable outcomes in patients but favorable outcome of immunotherapy in gastric cancer. Significant correlations were observed between SLAMF8 levels and pan-cancer tumorigenesis, tumor metabolism, and immunity. As a result, SLAMF8 may become an important prognostic biomarker in the majority of tumors and a hopeful gene target for immunotherapy against gastric cancer.

Nonlinear association of fibrinogen levels with functional prognosis in patients with acute ischemic stroke: a prospective cohort study

ObjectiveFibrinogen, essential in primary hemostasis, platelet aggregation, and leukocyte-endothelial interactions, is also associated with a heightened risk of acute ischemic stroke (AIS). However, its influence on AIS patient outcomes is unclear. This study examines the correlation between fibrinogen levels and the risk of unfavorable outcomes three months post-AIS.MethodsThis is a secondary analysis of a prospective cohort study conducted in Korea. The sample consisted of 1851 AIS patients who received treatment at a Korean hospital between January 2010 and December 2016. Statistical models were established to understand the relationship between fibrinogen levels(mg/dL) and unfavorable outcomes(mRs ≥ 3), including logistic regression models, Generalized Additive Models (GAM), and smooth curve fitting (penalized splines). The log-likelihood ratio test has been utilized to evaluate the best fit. To ensure the robustness of the results, sensitivity analyses were conducted by reanalyzing the relationship after excluding participants with TG > 200 mg/dl and BMI > 25 kg/m2. Subgroup analyses were also performed to assess whether influencing factors modify the association between fibrinogen levels and unfavorable outcomes.ResultsAfter adjusting for multiple covariates including age, BMI, sex, LDL-c, TG, HGB, HDL-c, BUN, FPG, ALB, PLT, AF, hypertension, smoking, DM, mRs score at admission, the binary logistic regression model demonstrated revealed a significant positive association between fibrinogen levels and the risk of unfavorable outcomes in AIS patients (OR = 1.215, 95% CI: 1.032–1.429, p = 0.019). Sensitivity analyses supported these findings, with similar ORs observed in subsets of patients with TG < 200 mg/dL (OR = 1.221, 95% CI: 1.036–1.440) and BMI < 25 kg/m2 (OR = 1.259, 95% CI: 1.051–1.509). Additionally, the relationship between fibrinogen levels and outcomes was nonlinear, with a critical threshold of 2.74 g/L. Below the inflection point, the OR for unfavorable outcomes was 0.666 ((95% CI: 0.360, 1.233, p = 0.196), whereas above it, the OR increased to 1.374 (95% CI: 1.138, 1.659).ConclusionsThis study has provided evidence of a positive and nonlinear correlation between fibrinogen levels and 3-month poor functional outcomes in patients with AIS. When fibrinogen levels exceeded 2.74 g/L, a significant and positive association was observed with the risk of poor outcomes. This study provides a further reference for optimizing rehabilitation exercises and facilitating clinical counseling in patients with acute ischemic stroke.

Association of pulse pressure with hematoma expansion in patients with spontaneous supratentorial intracerebral hemorrhage.

Recent reports have demonstrated that a wider pulse pressure upon admission is correlated with heightened in-hospital mortality following spontaneous supratentorial intracerebral hemorrhage (ssICH). However, the underlying mechanism remains ambiguous. We investigated whether a wider pulse pressure was associated with hematoma expansion (HE). Demographic information, clinical features, and functional outcomes of patients diagnosed with ssICH were retrospectively collected and analyzed. Multivariate logistic regression was conducted to identify independent predictors of HE. Weighted logistic regression, restricted cubic spline models, and propensity score matching (PSM) were employed to estimate the association between pulse pressure and HE. We included 234 eligible adult ssICH patients aged 60 (51-71) years, and 55.56% were male. The mean pulse pressure was 80.94 ± 23.32 mmHg. Twenty-seven patients (11.54%) developed early HE events, and 116 (49.57%) experienced a poor outcome (modified Rankin scale 3-6). A wider mean pulse pressure as a continuous variable was a predictor of HE [odds ratios (OR) 1.026, 95% confidence interval (CI) 1.007-1.046, p = 0.008] in multivariate analysis. We transformed pulse pressure into a dichotomous variable based on its cutoff value. After adjusting for confounding of HE variables, the occurrence of HE in patients with ssICH with wider pulse pressure levels (≥98 mmHg) had 3.78 times (OR 95% CI 1.47-9.68, p = 0.006) compared to those with narrower pulse pressure levels (<98 mmHg). A linear association was observed between pulse pressure and increased HE risk (P for overall = 0.036, P for nonlinear = 0.759). After 1:1 PSM (pulse pressure ≥98 mmHg vs. pulse pressure <98 mmHg), the rates of HE events and poor outcome still had statistically significant in wider-pulse pressure group [HE, 12/51 (23.53%) vs. 4/51 [7.84%], p = 0.029; poor outcome, 34/51 (66.67%) vs. 19/51 (37.25%), p = 0.003]. Widened acute pulse pressure (≥98 mmHg) levels at admission are associated with increased risks of early HE and unfavorable outcomes in patients with ssICH.

PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

Squamous metaplasia is an indicator of acute exacerbation in patients with usual interstitial pneumonia / idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a potentially lethal event in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF). However, to date, no pathological predictors of AE have been identified. This retrospective study aimed to elucidate the pathological features that could predict AE in patients with UIP. MethodsWe reviewed the pathological findings of 91 patients with UIP/IPF and correlated these findings with AE events. Thirteen histological variables related to acute lung injury were evaluated by three independent observers and classified as positive or negative. The patients’ clinical data during follow-up were collected and reviewed for AE. A recursive partition using the Gini index for the prediction of AE was performed, with each pathological finding as a candidate for branching. ResultsTwenty patients (22%) developed AE during the median follow-up duration of 40 months. Thirty-eight patients died (15 due to AE and 23 for other reasons). The median time interval from surgical lung biopsy to AE onset was 497 (interquartile range: 901–1657) days. Histologically, squamous metaplasia was positively associated with AE (odds ratio: 4.7, P = 0.015) and worse event-free survival in patients with UIP (P = 0.04). Leaf scoring based on the Gini index for recursive partition, including five positive findings (squamous metaplasia, neutrophilic infiltration, septal widening, Kuhn's hyaline, and fibrin), showed a sensitivity of 90% with a specificity of 74.7% (area under curve: 0.89). ConclusionsWe found that squamous metaplasia is an important histopathological finding that predicts AE events and tends to unfavorable outcome in patients with UIP/IPF.

MiR-99a-3p downregulates TRIM21 to promote gastric cancer development.

Gastric cancer (GC) stands as one of the most formidable malignancies worldwide. It is well-established that miRNAs play a crucial role in the initiation and progression of various human cancers. Among these, miR-99a-3p has been implicated in the pathogenesis of GC. In the context of our study, we embarked on the comprehensive examination of miR-99a-3p expression in GC cells. Additionally, we sought to establish a correlation between miR-99a-3p expression levels and the overall survival (OS) of GC patients, and our findings hinted at its potential role in predicting an unfavorable prognosis. To further investigate the functional implications of miR-99a-3p in GC, we conducted a series of cell-based experiments after successfully knocking down miR-99a-3p. These investigations uncovered a substantial inhibition of cellular events associated with tumor progression. Moreover, employing TargetScan, we identified Tripartite motif-containing protein 21 (TRIM21) as a putative target with a binding site for miR-99a-3p. Subsequent dual-luciferase reporter gene assay confirmed the direct interaction between miR-99a-3p and TRIM21. Western blot analysis validated the alteration in TRIM21 expression levels, revealing an upregulation upon miR-99a-3p knockdown. Building on these molecular findings, we extended our investigations to human GC tissues, where we observed a downregulation of TRIM21, which, notably, correlated with shorter overall survival. Lastly, to further solidify our conclusions, we conducted a series of in vitro and in vivo rescue experiments, collectively suggesting that miR-99a-3p promoted the progression of GC cells through the downregulation of TRIM21. In summary, our study comprehensively explored the role of miR-99a-3p in GC, revealing its association with unfavorable patient outcomes, functional implications in tumor progression, and a direct regulatory relationship with TRIM21. These findings collectively underscore the significance of miR-99a-3p in the pathogenesis of GC and present a potential therapeutic avenue for further investigation.