Elevated pretreatment serum apolipoprotein E level associated with poor prognosis of patients with COVID-19 during the omicron BA.5 and BF.7 wave.

The SARS-CoV-2 virus is responsible for the human disease known as COVID-19. This virus is capable of generating a spectrum of infections ranging from moderate to severe. Serum apolipoprotein E (ApoE) inhibits inflammation by preserving immune regulatory function. Nonetheless, the relationship between serum ApoE and clinical prognosis in omicron remains elusive. A cohort of 231 patients was observed for 65 days, with death as the primary outcome. Based on their ApoE levels, the patients were categorized into patients with elevated ApoE levels and those with lower ApoE levels. To do statistical comparisons, the log-rank test was utilized, and the Kaplan-Meier method was utilized to estimate survival rates. Cox hazard models, both univariate and multivariate, were employed to examine the prognostic relevance. According to our research, omicron had significantly greater ApoE levels. In mild-to-moderate and severe cases, the study identified a statistically significant variation in ApoE levels. Additionally, there was a drop in overall survival that is statistically significant (OS, p < 0.0001) for patients with greater ApoE levels. Multiple Cox proportional hazards regression analysis indicates that an elevated ApoE level was determined to be an adverse and independent prognostic factor of OS in patients with omicron. Taken together, our study found that the level of serum ApoE at the time of initial diagnosis was substantially connected to the severity and prognosis of omicron. Consequently, we propose that ApoE might be a poor prognostic factor in individuals afflicted with the omicron variant.

Elevated serum beta-2 microglobulin level predicts short-term poor prognosis of patients with de novo acute omicron variant COVID-19 infection.

Background: The devastating coronavirus disease of 2019 (COVID-2019) epidemic has been declared a public health emergency, resulting in a worldwide pandemic. The omicron variety is the most common epidemic mutant strain in the globe. Serum beta-2 microglobulin (ß2-MG) is associated with endothelial cell injury and has value in monitoring the progression of inflammation in infected individuals. Nonetheless, the potential functions of ß2-MG in omicron remain elusive. Methods: To investigate the prognostic value of serum ß2-MG levels at diagnosis, we retrospectively analyzed a cohort of 240 people with omicron. Over the course of 65 days, all patients were monitored, and death was the primary outcome. Patients were allocated to two groups: those with high and low ß2-MG levels. The Kaplan-Meier method was used to examine OS, and the log-rank test was used to compare them. Univariate and multivariate Cox hazard models were used to determine the prognostic significance. Results: Our results revealed that ß2-MG was significantly elevated in omicron. ß2-MG levels in severe patients were higher than in mild-to-moderate patients, and the difference was statistically significant. Timely, interleukin-6 (IL-6) and interleukin-10 (IL-10) were observed to be significantly increased in individuals exhibiting elevated levels of ß2-MG. In addition, patients exhibiting elevated levels of ß2-MG demonstrated a statistically significant decrease in overall survival (OS, P < 0.0001). An elevated ß2-MG level (≥4.72 mg/l) was found to be an independent, adverse prognostic factor for OS in omicron patients, according to multivariate Cox proportional hazards regression analysis (P = 0.001). Conclusion: Serum ß2-MG level at initial diagnosis was significantly correlated with omicron severity and prognosis. Thus, we propose that ß2-MG may be an independent poor additional prognostic factor in patients with omicron.

Derivation and External Validation of a Risk Prediction Model for Pulmonary Embolism in Patients With Lung Cancer: A Large Retrospective Cohort Study.

OBJECTIVE: To investigate the risk factors of pulmonary embolism in patients with lung cancer and develop and validate a novel nomogram scoring system-based prediction model. METHOD: We retrospectively analyzed the clinical data and laboratory characteristics of 900 patients with lung cancer who were treated, including patients with lung cancer without pulmonary embolism (LC) and patients with lung cancer with pulmonary embolism (LC + PE). The patients were randomly divided into derivation and internal validation groups in a 7:3 ratio. Using logistic regression analysis, a diagnostic model of the nomogram scoring system was developed by incorporating selected variables in the derivation group and validated in the internal and external validation groups (n = 108). RESULT: Seven variables (adenocarcinoma, stage III-IV LC, indwelling central venous catheter, chemotherapy, and the levels of serum albumin, hemoglobin, and D-dimer) were identified as valuable parameters for developing the novel nomogram diagnostic model for differentiating patients with LC and LC + PE. The scoring system demonstrated good diagnostic performance in the derivation (area under the curve [AUC]; 95% confidence interval [CI], 0.918; 0.893, 0.943; sensitivity, 88.5%; specificity, 80.5%), internal validation (AUC; 95% CI, 0.921; 0.884, 0.958; sensitivity, 90.5%; specificity, 80.4%), and external validation (AUC; 95% CI, 0.929; 0.875, 0.983; sensitivity; 85.0%; specificity; 87.5%) groups. CONCLUSION: In this study, we constructed and validated a nomogram scoring system based on 7 clinical parameters. The scoring system exhibits good accuracy and discrimination between patients with LC and LC + PE and can effectively predict the risk of PE in patients with LC.

The efficacy and safety of low-dose temozolomide maintenance therapy in elderly patients with glioblastoma: a retrospective cohort study.

BACKGROUND: Radiotherapy combined with temozolomide chemotherapy (STUPP regimen) is the standard treatment regimen for newly diagnosed glioblastoma (GBM). It is considered feasible to prolong the treatment cycle of temozolomide (TMZ), however, the efficacy and safety of prolonging the treatment cycle of TMZ are still lacking in elderly patients with glioblastoma. This study observed the efficacy and safety of low dose TMZ maintenance therapy in elderly patients with glioblastoma after receiving standard STUPP regimen. METHODS: The clinical data were retrospectively analyzed in 34 patients with glioblastoma aged ≥65 years from April 2017 to April 2021 in Ningbo First Hospital. The patients received conventional radiotherapy (59.4 Gy/28 F/5.5 weeks) and TMZ (75 mg/m2·d) concurrent chemotherapy, followed by sequential TMZ (150-200 mg/m2·d, d1-5, q28d) adjuvant treatment for 6 cycles, and patients with no disease progress or intolerable side effects received low dose TMZ (100 mg/m2·d, d1-5, q28d) maintenance treatment. The patient's progression free survival time (PFS), total survival time (OS) and adverse reactions were observed by telephone, outpatient reexamination and other follow-up methods. Kaplan-Meier method was used to calculate and draw the survival curve for survival analysis. RESULTS: Twenty-four of 34 patients were finally included in the analysis, including 13 males and 11 females (65-74 years old), with a median of 14 cycles (8-38 cycles) of adjuvant TMZ chemotherapy. The median PFS was 11.0 months [95% confidence interval (CI): 8.67-13.33 months] and the median OS was 17.4 months (95% CI: 12.49-22.31 months). The main adverse reactions were digestive tract reactions and hematological toxicity. Three cases of grade III granulocytopenia occurred during the adjuvant treatment, while no grade III or above related adverse reactions occurred during the follow-up TMZ reduction maintenance treatment: leukopenia (5/24), anemia (2/24), decreased blood platelets (2/24), asthenia (5/24), nausea (4/24), and abnormal liver function (3/24). CONCLUSIONS: In general, for elderly patients with good Karnofsky Performance Scale (KPS) scores, further reducing TMZ to maintain chemotherapy after the standard STUPP regimen may improve the PFS and OS to a certain extent, with tolerable adverse reactions and reduced cost. However, prospective randomized grouping study is still needed to determine whether clinical benefits will be achieved.

Dual Roles of Lactate in EGFR-TKI-Resistant Lung Cancer by Targeting GPR81 and MCT1.

Lactate is critical in modeling tumor microenvironment causing chemotherapy resistance; however, the role of lactate in tyrosine kinase inhibitor (TKI) resistance has not been fully known. The aim of this study was to evaluate whether lactate could mediate TKI resistance through GPR81 and MCT1 in non-small-cell lung cancer (NSCLC). Here, we showed that lactate enhanced the cell viability and restrained erlotinib-induced apoptosis in PC9 and HCC827 cells. GPR81 and AKT expression were significantly increased with the addition of lactate, and siGPR81 reduced AKT expression resulting in a raised apoptosis rate with erlotinib treatment. Furthermore, we found that lactate also promoted MCT1 exposure, and inhibiting MCT1 with AZD3965 markedly impaired the glycolytic capacity. A significant increase of GPR81 and MCT1 expression was observed in insensitive tissues compared with sensitive ones by immunostaining in NSCLC patients. Our results indicate that lactate adopts dual strategies to promote TKI resistance in NSCLC, not only activating AKT signaling by GPR81, but also giving energy supply through MCT1-mediated input. Targeting GPR81 and MCT1 may provide new therapeutic modalities for TKI resistance in NSCLC.

Hyperfibrinogenemia as a Poor Prognostic Indicator in Myelodysplastic Syndrome.

Background: Myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS. Methods: A cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models. Results: In our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS (P = 0.045) but not for LFS (P = 0.188). Conclusion: Elevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients.

The Prognostic Value of Pretherapy Peripheral Blood Inflammatory Indices in Myelodysplastic Syndromes.

Background: Inflammation appears to have a critical role in carcinogenesis tumor growth according to emerging research. The platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and plasma C-reactive protein (CRP) are considered to reflect the systemic inflammatory response and clinical prognosis. The prognostic value of inflammatory indices in myelodysplastic syndrome (MDS) patients remains unclear. Methods: A total of 213 MDS patients were enrolled for the study. Univariate and multivariate analyses were performed to determine the prognostic significance of various indicators, including PLR, NLR, and CRP. Results: MDS patients with higher PLR, NLR, and CRP levels had significantly shorter overall survival (OS). Based on univariate analysis, age (≥60 years), gender (men), lower hemoglobin level (<10 g/dl), higher bone marrow blast percentage (>5%), poorer karyotype, and higher Revised International Prognostic Scoring System (IPSS-R) score were significantly associated with shorter OS. Patients with higher CRP levels had shorter leukemia-free survival (LFS, P = 0.041). However, higher PLR and NLR had no significant influence on LFS (P > 0.05). Multivariate Cox proportional hazards regression analysis indicated that high PLR and CRP were also independent adverse prognostic factors for OS in MDS. Conclusions: Elevated PLR and CRP predict poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.

Lactate Transporter SLC16A3 (MCT4) as an Onco-Immunological Biomarker Associating Tumor Microenvironment and Immune Responses in Lung Cancer.

Purpose: Lactate, a marker of tumor metabolic reprogramming, maintains the acidic microenvironment and also affects the metabolism and function of immune cells. SLC16A3 is responsible for the extracellular transport of lactate, which is a key component of glycolysis. However, the role of SLC16A3 in immune infiltration and immunosuppression of lung cancer is largely unknown. Our study explored the therapeutic and prognostic value of SLC16A3 in predicting immune infiltration and immune checkpoint efficacy of lung cancer. Methods: SLC16A3 expression was evaluated with TCGA database. Kaplan-Meier analysis was performed for survival rates. GO and KEEG enrichment was conducted to determine predictive signaling pathways. We utilized TIMER and CIBERSORT to analyze the correlation between SLC16A3 and immunocyte infiltration as well as immune checkpoint. Interleukin and HIF-1a expression was measured with ELISA kit and flow cytometry separately. Results: In comparison with normal tissues, SLC16A3 expression was significantly upregulated in both lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC), which was closely related to poor prognosis. GO analysis indicated that SLC16A3 involved in different signal pathways in LUAD and LUSC and linked to HIF-1 signaling in LUAD. High SLC16A3 was correlated with immunosuppressive cells (Treg, Th2 and iDC), immune checkpoint (PD1, PD-L1, PVR, Tim-3, ITGAM) and immunosuppressive factors (foxp3, TGF-ß) in LUAD not LUSC. Furthermore, SLC16A3 was identified to tightly interact with IL-8 which may induce microenvironment immune tolerance. Based on the clinical prediction, we performed experiments with LUAD A549 cells and showed reduced IL-8 and HIF-1a when treated with SLC16A3 knockdown. HIF-1a stimulation by dimethyloxalylglycine (DMOG) could restore IL-8 secretion in SLC16A3 downregulated cells. Conclusion: Taken together, our results suggest that SLC16A3 contributes to a worse prognosis in lung cancer and may play an important role in immune microenvironment and evasion through HIF-1a-IL8 axis, which could be a novel therapeutic target for immunotherapy in lung cancer.

Decreased serum apolipoprotein A1 level predicts poor prognosis of patients with de novo myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that apolipoproteins A1(ApoA1) are associated with disease risk in many cancer types. However, there still lacks evidence regarding the link between ApoA1 and MDS. This study was designed to investigate the prognostic value of pretreatment ApoA1 levels in MDS patients. METHODS: We retrospectively analyzed a cohort of 228 MDS patients to explore the prognostic value of the serum ApoA1 levels at diagnosis. Patients were divided into the high ApoA1 group and the low ApoA1 group. The prognostic significance was determined by univariate and multivariate Cox hazard models. RESULTS: MDS patients with low ApoA1 levels had significantly shorter overall survival (OS, P < 0.0001) along with a higher frequency of TP53 mutation (P = 0.002). Based on univariate analysis, age (≥ 60 years), gender (male), lower levels of hemoglobin (< 10 g/dl), HDL (≤0.91 mmol/L), higher bone marrow blast percentage (> 5%), higher IPSS-R scores and poorer karyotype were significantly associated with decreased OS. However, low ApoA1 level did not influence leukemia-free survival (LFS, P = 0.367). Multivariate Cox proportional hazards regression analysis indicated that low ApoA1 level (≤ 1.02 g/L) was also an independent adverse prognostic factor for OS in MDS (P = 0.034). CONCLUSIONS: Decreased ApoA1 level predicts a poor prognosis of MDS patients and thus provides a novel evaluation factor for them that is independent of the IPSS-R system.

Prognostic value of lactate transporter SLC16A1 and SLC16A3 as oncoimmunological biomarkers associating tumor metabolism and immune evasion in glioma.

Background: Hypoxic microenvironment is immunosuppressive and protumorigenic, and elevated lactate is an intermediary in the modulation of immune responses. However, as critical lactate transporters, the role of SLC16A1 and SLC16A3 in immune infiltration and evasion of glioma is not fully elucidated. Methods: Gene expression in low- and high-grade glioma (LGG and GBM) was evaluated with TCGA database. The TISIDB, TIMER and CIBERSORT databases were utilized for the analysis of the correlation between SLC16A1 or SLC16A3 and immunocyte infiltration as well as immune checkpoints. Results: Compared with normal tissues, a significant increase of both SLC16A1 and SLC16A3 was found in LGG and GBM, and closely related to the poor prognosis only in LGG. Cancer SEA indicated that SLC16A1 was involved in hypoxia while SLC16A3 contributed to metastasis and inflammation in glioma. The SLC16A3 expression was significantly correlated with neutrophil activation by GO analysis. TISCH showed the distribution of SLC16A1 on glioma cells and SLC16A3 on immune cells, which was correlated to tumor-associated macrophages and neutrophils that are immunosuppressive. SLC16A1 and SLC16A3 were identified to tightly interacted with diverse immune checkpoints (especially PD1, PD-L1, PD-L2, Tim-3) and immunosuppressive factors (TGF-ß and IL-10) in glioma. Furthermore, SLC16A3 had a positive correlation to activation markers of tumor-associated neutrophils and chemokines such as CCL2, CCL22, CXCR2, CXCR4 in LGG and CCL7, CCL20 CXCL8 in GBM, which could enhance infiltration of immunosuppressive cells to the tumor microenvironment. Conclusion: In general, our results suggest that SLC16A1 and SLC16A3 act as a bridge between tumor metabolism and immunity by promoting immunosuppressive cell infiltration, which contributes to immune evasion and a worse prognosis in glioma. Targeting SLC16A1 and SLC16A3 may provide novel therapeutic strategy for immunotherapy in glioma.

The Application Value of Spiral CT Lung Densitometry Software in the Diagnosis of Radiation-Induced Lung Injury.

In order to study the application value of spiral CT lung density measurement software in the diagnosis of radioactive lung injury, the average CT values of lung apex, hilum, and diaphragm were measured by Pulmo automatic evaluation software of 16-slice spiral CT in 96 patients with different types of radiation lung injury diagnosed by conventional CT and 80 healthy subjects. The radiation lung injury on CT slices was classified, and the lung density was measured. In 96 patients with different types of radiation lung injury, 56 patients had different degrees of increase in average lung density, which was most obvious in the type of air insufficiency and chronic fibrosis. CT values of lung density in the ground glass stage and patch stage of acute radiation pneumonia had little influence due to the range and time of exposure. The lung density of 35 patients with radiation injury was measured in the normal range. There was a significant difference between normal lung density and abnormal lung density in different types of radiation lung injury (X 2 = 56.718, P < 0.001). The mean lung density of 68 cases was normal and that of 12 cases was abnormal. There was a significant difference in lung density between the lung injury group and the normal group (X 2 = 18.027, P < 0.001). Spiral CT lung density measurement can accurately evaluate the lung density values of different types of radiation lung injury and judge the correlation between lung density and different types of radiation lung injury. It is of great value to diagnose, locate, and master the radiation dose of different types of radiation lung injury.