A Retrospective Analysis of Azvudine in Patients with COVID-19 and Pre-existing Cancer.

Objectives: Azvudine has been recommended as a potential treatment for the recently discovered Coronavirus disease (COVID-19) in 2019. However, the effectiveness of Azvudine in individuals who have both COVID-19 and pre-existing cancer remains uncertain. Consequently, we undertook a retrospective analysis to evaluate the clinical efficacy of Azvudine therapy in hospitalized patients with COVID-19 and pre-existing cancer. Methods: This is a single-center retrospective analysis of patients diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, selected from patients admitted to a specialist oncology hospital between June 1, 2022 to June 31, 2023 with positive RT-PCR and pre-existing cancer. After exclusion and propensity score matching, patients in the test group treated with Azvudine and control patients treated with standard antiviral therapy were included. The primary outcome is the interval time from the first dose of Azvudine to the attainment of the first negative result for nucleic acid. Secondary outcomes included the rate of nucleic acid conversion, the duration of hospitalization, and the admission to the intensive care unit (ICU). Cox proportional hazards models were used to analyze the hazard ratio (HR) of event outcomes and to assess whether cancer types and Azvudine treatment will affect the course of COVID-19, specifically the time it takes for primary symptoms to alleviate. Results: In this study, a total of 84 patients were included for analysis. Among them, 42 patients received Azvudine treatment after hospitalization, and the rest were treated with standard antiviral therapy. The results expressed that the time taken for the first negative nucleic acid test was significantly shorter in the Azvudine group compared to the control group [5 (IQR3-7) d vs 12 (IQR9-15) d], p<0.0001. This difference was statistically significant. Furthermore, a multivariate COX analysis indicated that Azvudine treatment could effectively reduce the time required for nucleic acid conversion in cancer patients (HR 1.994, 95% CI 1.064-3.736, p=0.031). And the type of cancer also had an impact on the course of COVID-19 in patients. (HR 3.442, 95%CI 1.214-9.756, p=0.020; HR 3.246, 95% CI 1.925-7.209, p=0.036). Conclusion: Azvudine was correlated with a reduced duration for achieving nucleic acid conversion in individuals diagnosed with cancer. And different types of cancer have a certain impact on the course of COVID-19 for patients.

In-depth analysis of immune cell landscapes reveals differences between lung adenocarcinoma and lung squamous cell carcinoma.

Background: Lung cancer is the leading cause of cancer deaths globally, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being major subtypes. Immunotherapy has emerged as a promising approach for the treatment of lung cancer, but understanding the underlying mechanisms of immune dysregulation is crucial for the development of effective therapies. This study aimed to investigate the distinctive cellular features of LUAD and LUSC and identify potential biomarkers associated with the pathogenesis and clinical outcomes of each subtype. Methods: We used digital cytometry techniques to analyze the RNA-Seq data of 1128 lung cancer patients from The Cancer Genome Atlas (TCGA) database. The abundance of cell subtypes and ecotypes in LUAD and LUSC patients was quantified. Univariate survival analysis was used to investigate their associations with patient overall survival (OS). Differential gene expression analysis and gene co-expression network construction were carried out to explore the gene expression patterns of LUSC patients with distinct survival outcomes. Scratch wound-healing assay, colony formation assay, and transwell assay were used to validate the candidate drugs for LUSC treatment. Results: We found differential expression of cell subtypes between LUAD and LUSC, with certain cell subtypes being prognostic for survival in both subtypes. We also identified differential gene expression and gene co-expression modules associated with macrophages.3/PCs.2 ratio in LUSC patients with distinct survival outcomes. Furthermore, ecotype ratios were found to be prognostic in both subtypes and machine learning models showed that certain cell subtypes, such as epithelial.cells.1, epithelial.cells.5, and endothelial.cells.2 are important for predicting LUSC. Ginkgolide B and triamterene can inhibit the proliferation, invasion, and migration of LUSC cell lines. Conclusion: We provide insight into the distinctive cellular features of LUAD and LUSC, and identify potential biomarkers associated with the pathogenesis and clinical outcomes of each subtype. Ginkgolide B and triamterene could be promising drugs for LUSC treatment.

Severe immediate hypersensitivity to gadolinium contrast agent after targeted treatment in a patient with alveolar soft part sarcoma: A case report and review of literature.

RATIONALE: Gadolinium-based contrast agents (GBCAs), benefiting from good tolerance and safety, become the priority contrast agents in magnetic resonance imaging. Serious hypersensitivity reactions caused by GBCAs are rare, but occur occasionally. The "immune surveillance" theory proposes that lowered immune function exists in patients with malignance, which decrease the occurrence of atopy. Natural immunosurveillance that enhanced by effective treatment of malignance may increase the risk of hypersensitivity. PATIENT CONCERNS: A 29-year-old female patient suffering from intensive pain with left leg mass was admitted in our hospital. DIAGNOSES: The patient was diagnosed with alveolar soft part sarcoma by histopathology and revealed destruction of the left fibula and lung metastasis by computed tomography scan, and treated with anlotinib hydrochloride, a multi-targeted tyrosine kinase inhibitor. After 4 cycles of effective targeted therapy, the patient developed severe immediate hypersensitivity due to gadopentetate dimeglumine-enhanced magnetic resonance imaging. INTERVENTIONS AND OUTCOMES: The vital signs of the patient returned to normal after rescue. Since then, the patient has not used gadolinium contrast agent again, and currently the condition is stable and still alive. LESSONS: Severe immediate hypersensitivity might be occurred by gadolinium contrast agent in patients with malignance after effective treatment. We explored the potential mechanism of GBCA-inducing hypersensitivity in detail, by especially focusing on the changes of immune environment. Furthermore, we propose new ideas for the safe use of GBCAs in patients with malignancies.

Intra-abdominal infection after tumor surgery: tigecycline combined with ß-lactam antibiotics versus tigecycline alone.

BACKGROUNDS: Tigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus ß-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery. METHODS: This was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student's t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication. RESULTS: In total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time. CONCLUSIONS: Tigecycline plus ß-lactam wasn't superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.

Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials.

Purpose: Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy. Methods: We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method. Results: Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR)tis+chemo/chemo 0.55, 95% CI 0.45-0.67; HRpem+chemo/chemo 0.53, 95% CI 0.47-0.60; ORR: relative risk (RR)tis+chemo/chemo 1.50, 95% CI 1.32-1.71; RRpem+chemo/chemo 1.89, 95% CI 1.44-2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RRtis+chemo/chemo 1.12, 95% CI 1.03-1.21; RRpem+chemo/chemo 1.13, 95% CI 1.03-1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82-1.31), ORR (RR: 0.79, 95% CI 0.59-1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87-1.12), and AEs leading to death (RR 0.70, 95% CI 0.23-2.09). In progression-free survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy. Conclusion: The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy.

Meta-Analysis of Risk Factors and Incidence of Interstitial Pneumonia With CHOP-Like Regimens for Non-Hodgkin Lymphoma.

Objectives: Interstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine and prednisone)-like chemotherapy, negatively affected patients' clinical outcome and quality of life. We aimed to explore patient-related, disease-related and drug-related risk factors associated with IP and gain a better understanding of the incidence in NHL patients. Methods: Databases, including PubMed, Ovid, China National Knowledge Internet (CNKI), and Wanfang Database from inception to January 20, 2022, were searched to identify studies evaluating the risk factors and incidence of IP. The included studies were assessed by Newcastle-Ottawa Quality Scale and above 7 points was considered high quality. The statistical analysis of risk factors was assessed by RevMan software (version 5.3) and incidence of IP was calculated by R software (version 4.1.2). Fixed-or random-effects models were applied to estimated the relative risks (RRs) and 95% confidence interval (Cl). Results: A total of 12 studies comprised of 3423 NHL patients were included in the analysis. Among the 3 available patient-related risk factors, 6 disease-related risk factors and 3 drug-related risk factors, it was found that only drug-related risk factors were significantly associated with IP development: pegylated liposomes doxorubicin (PLD) replacement (RR = 3.25, 95% CI = 1.69-6.27, I2 = 64%), rituximab (RTX) addition (RR = 4.24, 95% CI = 2.58-6.96, I2 = 0) and granulocyte colony stimulating factor (G-CSF) administration (RR = 5.80, 95% CI = 3.05-11.05, I2 = 0). The pooled incidence of CHOP, R-CHOP, and R-CDOP regimen was 1.0% (95% CI 0.00-0.01, I2 = 8%), 7.0% (95% CI 0.05-0.09, I2 = 64%) and 22.0% (95% CI 0.13-0.32, I2 = 87%) respectively. Conclusion: PLD replacement, RTX addition and G-CSF administration were significant risk factors of IP for NHL patients received the CHOP-like chemotherapy. Clinicians should focus on these patients to detect and treat the IP development timely, which might bring benefit in patients' survival. Systematic Review Registration: PROSPERO, identifier CRD42022309884.

Management of adverse effects associated with pegylated Escherichia coli asparaginase on coagulation in the treatment of patients with NK/T-cell lymphoma.

ABSTRACT: Natural killer/T-cell lymphoma (NK/TL) is a chemotherapy-sensitive disease, and asparaginase-based chemotherapy has become the standard primary treatment for patients with this malignancy recently. The objective of this study was to evaluate the adverse reactions on blood coagulation of the administered pegylated Escherichia coli (E coli) asparaginase (PEG-ASP) to the NK/TL patients. Clinical data of 71 NK/TL patients (range 13-73 years), who received 239 cycles of chemotherapy treatment containing PEG-ASP in the Hematology Department of Shanxi Province Cancer Hospital of China from January 2016 to December 2019 were analyzed retrospectively. Data of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), and antithrombinIII (ATIII) were obtained at the time points routinely and statistically analyzed. There were statistical differences between the monitored parameters of baseline day0 (the day before use of PEG-ASP, named day0) and those of day3 (the 3rd day after treatment) to day6, and data showed all of the indicators could recover within 21 days. The events included PT prolonged in 33 patients (46.5%), APPT prolonged in 41 patients (57.7%, 20 patients with APTT >60 seconds), FBG decreased in 49 patients (69.0%, 12 patients with FBG <1 g/L), and ATIII decreased in 52 patients (73.2%). The patients' average number of cycles received was 2.3 for PT (>14 seconds), 2.5 for APTT (>35 seconds), 2.7 for FBG (<2 g/L), and 2.6 for D-dimer (>550 ng/mL). Compared with those at day0, PT and APTT prolonged sharply at day3 (P < .05), reached the peak at day12, maintained the prolonged level from day3 to day15, and gradually recovered at day 21. FBG and ATIII significantly decreased at day6 and day3 respectively (P < .05), both of them fell to the minimum at day12, and then returned the normal. The D-dimer levels were no significantly change during the whole treatment course. The APTT >60 seconds or FBG <1 g/L side effects were improved by symptomatic treatment of supplementation of fresh frozen plasma or cryoprecipitate infusion, no concomitant bleeding or thrombotic events emerging. Our data suggested although chemotherapy including PEG-ASP impacted moderately on the coagulation function of NK/TL patients, clinically monitored regularly were necessary and most NK/TL patients can complete the chemotherapy cycles successfully.

mFOLFOX4 with or without radiation in neoadjuvant treatment of locally advanced middle and low rectal cancer.

Context: Neoadjuvant therapy can reduce the recurrence rate of locally advanced middle and low rectal cancer. Radiation therapy can not only bring benefits but also produce acute and late toxicity, which will affect the quality of life and organ function of patients; the application of neoadjuvant chemotherapy can avoid the toxicity of radiotherapy. Aims: To investigate the efficiency and side effects of preoperative modified FOLFOX4 (mFOLFOX4) chemotherapy with or without radiotherapy for locally advanced middle and low rectal cancer (LAMLRC). Methods and Material: This study included 431 patients with LAMLRC receiving mFOLFOX4 chemotherapy independently or combined with radiotherapy before operation. The basic information, efficacy indicators, and adverse reactions of the two groups were recorded in detail. Side effects were evaluated using the Common Terminology Criteria for Adverse Events v. 3.0. Statistical Analysis Used: Statistical analyses were conducted using SPSS (Statistical Package for Social Science, IBM SPSS Statistics, Version 22). Mann-Whitney test and Chi-square test were used for comparative analysis. Statistical significance was defined as P < 0.05. Results: Of 128 patients who met the inclusion criteria, 52 received neoadjuvant chemotherapy (NCT), and 76 received neoadjuvant chemoradiotherapy (NCRT). The average operation time in the NCT group was 2.71 h, and that in the NCRT group was 3.35 h (P = 0.005). The pathological complete remission rates in the NCT and NCRT groups were 1.9% and 17.1%, respectively (P = 0.007). There was no significant difference in the T-stage decline rate and lymph node positive rate between the two groups. There were higher rates of leukopenia (32.7% vs. 57.9%; P < 0.05) and diarrhea (0% vs. 9.2%; P < 0.05) in the NCRT group. The 3-year overall survival rates in the NCT and NCRT groups were 80.3% and 82.8% (P = 0.715), respectively, and the respective 3-year disease-free survival rates were 68.8% and 70.5% (P = 0.966). Conclusions: NCT with mFOLFOX4 independently resulted in a lower pathological complete remission rate, with less toxicity and shorter operation time. NCT with mFOLFOX4 has certain clinical usefulness.

Cryotherapy for Prevention of Taxane-Induced Peripheral Neuropathy: A Meta-Analysis.

PURPOSE: Taxanes are widely used in gynecological cancer therapy, however, taxane-induced peripheral neuropathy (TIPN) limits chemotherapy dose and reduces patients' quality of life. As a safe and convenient intervention, cryotherapy has been recommended as a promising intervention in the recent clinical guidelines for the prevention of TIPN. Although there are a considerable number of studies which explored the use of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN), there is insufficient large-scale clinical evidence. We performed a meta-analysis on the current available evidence to examine whether cryotherapy can prevent TIPN in cancer patients receiving taxanes. METHODS: We searched databases including PubMed, Embase, and Cochrane from inception to August 3, 2021 for eligible trials. Clinical trials that examined the efficacy of cryotherapy for prevention of TIPN were included. The primary outcome was the incidence of TIPN, and secondary outcomes were incidence of taxane dose reduction and changes in nerve conduction studies. The meta-analysis software (RevMan 5.3) was used to analyze the data. RESULTS: We analyzed 2250 patients from 9 trials. Assessments using the Common Terminology Criteria for Adverse Events (CTCAE) score showed that cryotherapy could significantly reduce the incidence of motor and sensory neuropathy of grade≥2 (sensory: RR 0.65, 95%CI 0.56 to 0.75, p<0.00001; motor: RR 0.18, 95% CI [0.03, 0.94], p=0.04). When evaluated using the Patient Neuropathy Questionnaire (PNQ), cryotherapy demonstrated significant reduction in the incidence of sensory neuropathy (RR 0.11, 95% CI 0.04 to 0.31], p<0.0001), but did not show significant reduction in the incidence of motor neuropathy (RR 0.46, 95% CI 0.11 to 1.88, p=0.28). Cryotherapy was associated with reduced incidences of taxane dose reduction due to TIPN (RR 0.48, 95% CI [0.24, 0.95], p=0.04) and had potential to preserve motor nerves. CONCLUSIONS: Cryotherapy is likely to prevent TIPN in patients receiving taxanes. High quality and sufficient amount of evidence is warranted.

Dehydrocorydaline Protects Against Sepsis-Induced Myocardial Injury Through Modulating the TRAF6/NF-κB Pathway.

We aim to investigate the effect and mechanism of dehydrocorydaline (Deh), an alkaloidal component isolated from Rhizoma corydalis, in the treatment of sepsis-mediated myocardial injury. Lipopolysaccharide (LPS) was taken to construct an in-vitro sepsis-myocardial injury models H9C2 cardiomyocytes. The in-vivo model of sepsis in C57BL/6 mice was induced by intraperitoneal injection of Escherichia coli (E. coli). The in-vitro and in-vivo models were treated with Deh in different concentrations, respectively. Hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemistry (IHC) staining were taken to evaluate the histopathological changes of the heart. ELISA was applied to evaluate the levels of inflammatory factors, including IL-6, IL-1ß, TNFα, IFNγ, and oxidized factors SOD, GSH-PX in the plasma or culture medium. Western blot was used to measure the expressions of Bax, Bcl2, Caspase3, iNOS, Nrf2, HO-1, TRAF6, NF-κB in heart tissues and cells. The viability of H9C2 cardiomyocytes was detected by the CCK8 method and BrdU assay. The ROS level in the H9C2 cardiomyocytes were determined using immunofluorescence. As a result, Deh treatment improved the survival of sepsis mice, reduced TUNEL-labeled apoptosis of cardiomyocytes. In vitro, Deh enhanced the viability of LPS-induced H9C2 cardiomyocytes and inhibited cell apoptosis. Additionally, Deh showed significant anti-inflammatory and anti-oxidative stress functions via decreasing IL-1ß, IL-6, TNFα, and IFNγ levels, mitigating ROS level, up-regulating Nrf2/HO-1, SOD, and GSH-PX expressions dose-dependently. Mechanistically, Deh inhibited TRAF6 expression and the phosphorylation of NF-κB p65. The intervention with a specific inhibitor of TRAF6 (C25-140) or NF-κB inhibitor (BAY 11-7082) markedly repressed the protective effects mediated by Deh. In conclusion, Deh restrains sepsis-induced cardiomyocyte injury by inhibiting the TRAF6/NF-κB pathway.

miR-141-5p suppresses vascular smooth muscle cell inflammation, proliferation, and migration via inhibiting the HMGB1/NF-κB pathway.

MicroRNAs (miRNAs) have been identified as significant modulators in the pathogenesis of atherosclerosis (AS). Additionally, the dysregulation of vascular smooth muscle cells (VSMCs) is a crucial biological event during AS. Our study aimed to explore the functional roles and molecular mechanisms of miR-141-5p in VSMCs dysfunction. C57BL/6 mice were used to establish AS animal model. Human VSMCs were treated by oxidized low-density lipoprotein (ox-LDL) to establish AS cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to probe miR-141-5p and high-mobility group box 1 (HMGB1) mRNA expressions in VSMCs or plasma samples of the mice. Inflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. Cell counting kit-8 and bromodeoxyuridine assays were performed to evaluate cell proliferation. Cell migration and apoptosis were detected with Transwell assay and flow cytometry analysis, respectively. The target gene of miR-141-5p was predicted with the TargetScan database, and the interaction between miR-141-5p and HMGB1/nuclear factor-κB (NF-κB) was further validated by dual-luciferase reporter assay, qRT-PCR, and Western blot analysis. miR-141-5p was found to be decreased in the plasma of patients and mice model with AS. Its expression was also downregulated in VSMCs treated by ox-LDL. miR-141-5p overexpression inhibited the inflammation, proliferation, migration of VSMCs, and promoted the apoptosis of VSMCs. HMGB1 was identified as a direct target of miR-141-5p, and miR-141-5p could repress the activity of HMGB1/NF-κB signaling. HMGB1 restoration reversed the effects of miR-141-5p, and NF-κB inhibitor JSH-23 showed similar effects with miR-141-5p mimics. miR-141-5p inhibits VSMCs' dysfunction by targeting the HMGB1/NF-κB pathway, which probably functions as a protective factor during the development of AS.