Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study.

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.

[Lipid Droplets and Perilipins in Cardiovascular Diseases].

Lipid droplet (LD) are multifunctional organelles which take part into intracellular lipid metabolism,mainly consisting of a neutral lipid core,a single-layer phospholipid shell,and LD-related protein (LRP).LRP on the shell can regulate the storage,transport,and metabolism of lipid.The imbalance of LD regulation could cause the abnormality of lipid metabolism,leading to the blood lipid changes and immune disorders.The available studies have demonstrated that LRP are capable of influencing the lipid metabolism in heart and atherosclerosis (AS) by regulating the physical processes in myocardial and vascular cells.This article reviewed the recent studies about LD in heart and vessels,and illustrated the effects of LD on myocardial cells,the formation of foam cells,and the development of atherosclerosis.Furthermore,we summarized the relationship between LD and cardiovascular diseases,providing new insights for the treatment of such diseases based on LD.

Clinical characteristics and risk factors for ZF2001 fully vaccinated inpatients with COVID-19: A retrospective cohort study.

The ZF2001 vaccine has demonstrated high efficacy in preventing coronavirus disease 2019 (COVID-19). However, the clinical characteristics of breakthrough infections in vaccinated individuals and the risk factors for adverse outcomes in COVID-19 patients remain unclear. We conducted a retrospective single-center cohort study at Xiangya Hospital of Central South University, including 210 fully vaccinated COVID-19 inpatients from December 5, 2022, to January 31, 2023. Data on clinical characteristics, laboratory findings, disease severity, treatment, and prognosis were collected and analyzed. Our findings revealed that COVID-19 inpatients still experienced common symptoms at the onset of illness, but most laboratory findings were within the normal range, except for white blood cell count (WBC), lymphocyte count, and lactate dehydrogenase (LDH) levels. Following standard treatment, 95.7% of patients were discharged from the hospital. We identified seven variables significantly associated with a higher risk of adverse outcomes, including age over 65, elevated WBC count, reduced lymphocyte count, higher levels of blood urea nitrogen (BUN), LDH, troponin, D-dimer, and procalcitonin. This study supports the substantial clinical benefits of the ZF2001 vaccine for COVID-19 patients. Additionally, age over 65, elevated WBC count, reduced lymphocyte count, and higher blood levels of BUN, LDH, D-dimer, and procalcitonin may be used as predictive factors for disease progression in fully vaccinated COVID-19 inpatients.

Association of glucagon-like peptide-1 receptor agonists with risk of cancers-evidence from a drug target Mendelian randomization and clinical trials.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists have been approved by Food and Drug Administration for management of obesity. However, the causal relationship of GLP1R agonists (GLP1RA) with cancers still unclear. METHODS: The available cis-eQTLs for drugs target genes (GLP1R) were used as proxies for exposure to GLP1RA. Mendelian randomizations (MR) were performed to reveal the association of genetically-proxied GLP1RA with 14 common types cancer from large-scale consortia. Type 2 diabetes was used as positive control, and the GWASs data including 80 154 cases and 853 816 controls. Replicating the findings in the FinnGen study and then pooled with meta-analysis. Finally, all the related randomized controlled trails (RCTs) on GLP1RA were systematically searched from PubMed, Embase, and the Cochrane Library to comprehensively synthesize the evidence to validate any possible association with cancers. RESULT: A total of 22 significant cis-eQTL single-nucleotide polymorphisms were included as genetic instrument. The association of genetically-proxied GLP1RA with significantly decreased type 2 diabetes risk [OR (95%)=0.82 (0.79-0.86), P <0.001], which ensuring the effectiveness of identified genetic instruments. The authors found favorable evidence to support the association of GLP1RA with reduced breast cancer and basal cell carcinoma risk [0.92 (0.88-0.96), P <0.001, 0.92 (0.85-0.99), P =0.029, respectively], and with increased colorectal cancer risk [1.12 (1.07-1.18), P <0.001]. In addition, there was no suggestive evidence to support the association of GLP1RA with ovarian cancer [0.99 (0.90-1.09), P =0.827], lung cancer [1.01 (0.93-1.10), P =0760], and thyroid cancer [0.83 (0.63-1.10), P =0.187]. Our findings were consistent with the meta-analysis. Finally, 80 RCTs were included in the systematic review, with a low incidence of different kinds of cancer. CONCLUSIONS: Our study suggests that GLP1RA may decrease the risk of breast cancer and basal cell carcinoma, but increase the risk of colorectal cancer. However, according to the systematic review of RCTs, the incidence of cancer in patients treated with GLP1RA is low. Larger sample sizes of RCTs with long-term follow-up are necessary to establish the incidence of cancers and evaluate the risk-benefit ratios.

Efficacy and safety of tebentafusp in patients with metastatic uveal melanoma: A systematic review and meta-analysis.

Patients with metastatic uveal melanoma (mUM) have a poor prognosis, and few appropriate medications are available. Tebentafusp is approved by the Food and Drug Administration for mUM recently. However, the real efficacy and safety of tebentafusp are still unclear. We searched PubMed, Embase, and Cochrane Library from inception to March 20, 2024. The research was reported based on the preferred reporting items for systematic reviews and meta-analysis guidelines. We used random effects models to aggregate data on the response rates and adverse events of tebentafusp therapy. Six studies met the inclusion criteria with a total sample of 589 participants. The pooled objective response rate was 0.08 (95% CI: 0.05-0.12), and pooled disease control rate was 0.51 (95% CI: 0.44-0.57). The overall incidence was 0.99 (95% CI: 0.95-1.00) for any grade adverse events, 0.50 (95% CI: 0.41-0.59) for grade 3-4 adverse events, and 0.01 (95% CI: 0-0.03) for discontinuation due to adverse events. Tebentafusp exhibits promising treatment outcomes for mUM patients. Although accompanied with a common occurrence of adverse events, which can typically be managed and controlled. Future research is necessary for substantiating these findings and refining guidelines for management of mUM.

Predictors of survival in immunotherapy-based treatments in advanced melanoma: a meta-analysis.

The introduction of immunotherapy-based strategies has significantly improved the prognosis for melanoma patients. Nevertheless, some patients still have dismal outcomes, emphasizing the significance of survival predictive indicators in immunotherapy-based approaches. We systematically searched randomized controlled clinical trials investigating dual immunotherapy or chemoimmunotherapy versus placebo or mono-immunotherapy or chemotherapy alone in advanced melanoma patients. R version 4.3.0. was employed to perform all analyses. A comprehensive analysis was conducted on a total of 13,809 patients with advanced melanoma from 19 randomized clinical trials. Immunotherapy-based strategies (alone or in combination) could significantly lengthen the overall survival(OS) and recurrence-free survival (RFS) compared with corresponding controls. Mono-immunotherapy improved RFS and OS in PD-L1 positive patients, in stage AJCC IIIC, and with 4 or more positive lymph nodes, compared with chemotherapy. Combined immunotherapy statistically improved RFS and OS in those aged < 65, with an Eastern Cooperative Oncology Group (ECOG) status of 0, and LDH ≤ ULN at baseline compared with single treatment alone. Our findings indicated that certain clinicopathological and molecular features could assist in choosing appropriate melanoma patients for immune-based treatments.

Ubiquitin-specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling.

Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin-specific protease 22 (USP22) as a pro-oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin-specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial-mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration-approved drug library screening and identified topotecan as a clinically applicable USP22-targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3-induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22-targeting drug to limit melanoma metastasis.

Immunophenotyping characteristics and outcome of COVID-19 patients: peripheral blood CD8+T cell as a prognostic biomarker for patients with Nirmatrelvir.

Background: Nirmatrelvir has been authorized for the treatment of both hospitalized and non-hospitalized COVID-19 patients. However, the association between T lymphocyte subsets and the outcome of hospitalized COVID-19 patients treated with oral Nirmatrelvir has not been investigated. The objective of this study was to examine whether lymphocyte subsets could serve as biomarkers to assess the risk of mortality in COVID-19 patients undergoing Nirmatrelvir treatment, with the aim of enhancing medication management for COVID-19 patients. Methods: We conducted a retrospective cohort study at the Xiangya Hospital of Central South University in China between December 5, 2022 and January 31, 2023. The study reported demographic, clinical, T lymphocyte subsets, and inflammatory cytokine data of COVID-19 patients. We evaluated the associations of T lymphocyte subsets on admission with the composite outcome or death of patients using univariate and multivariable Cox regression analyses with hazards ratios (HRs) and 95% confidence intervals (CIs). Results: We identified 2118 hospitalized COVID-19 patients during the study period, and conducted a follow-up of up to 38 days. Of these, 131 patients received Nirmatrelvir, with 56 (42.7%) in the composite outcome group, and 75 (57.3%) in the non-composite outcome group. Additionally, 101 (77.1%) patients were discharged, while 30 (22.9%) died. Our results showed a significant decrease in the CD3+, CD4+, and CD8+ T cell counts of patients in the composite outcome group and mortality group compared to the non-composite outcome group and discharged group, respectively. Multivariate Cox regression analysis showed that the significant decrease in CD8+ T cell count in peripheral blood was independently associated with the composite outcome in COVID-19 patients treated with Nirmatrelvir, with an HR of 1.96 (95%CI: 1.01-3.80). The significant decrease in CD4+ and CD8+ T cell counts in peripheral blood increased the hazard of developing mortality, with HRs of 6.48 (95%CI: 1.47-28.63) and 3.75 (95%CI: 1.27-11.11), respectively. Conclusion: Our study revealed a significant positive correlation between a decrease in CD8+ T cell counts and progression and mortality of hospitalized COVID-19 patients treated with Nirmatrelvir. Lower counts (/µL) of CD8+ T cell (<201) were associated with a higher risk of in-hospital severity and death. Our findings may provide valuable references for physicians in optimizing the use of Nirmatrelvir.

Lactate dehydrogenase predicts disease progression outcome in COVID-19 patients treated with Azvudine.

Background: Azvudine has been approved in China for the treatment of COVID-19 patients. Previous studies have suggested a correlation between high levels of lactate dehydrogenase (LDH) and the severity of COVID-19. However, the impact of LDH levels in COVID-19 patients receiving Azvudine treatment remains unclear. Methods: In this retrospective cohort study, we analyzed the data of 351 hospitalized COVID-19 patients who were consecutively treated with Azvudine, with or without high LDH levels. The clinical features, treatment strategies and prognosis data were collected and analyzed. Results: Among the 351 hospitalized patients with COVID-19 treated with Azvudine (119 with high-LDH levels), the median age was 69 years (range 58-78), and 213 (60.7%) were male. Common symptoms included cough (86.0%), expectoration (73.5%), fever (69.8%), polypnea (47.6%) and poor appetite (46.4%). Patients with high LDH levels exhibited significantly elevated leucocyte and neutrophil counts, elevated level of myocardial enzymes, as well as higher levels of inflammatory markers such as interleukin-6, interleukin-10, procalcitonin, C reactive protein, ferritin, and prolonged erythrocyte sedimentation rate upon admission. COVID-19 patients with high-LDH levels had higher rates of corticosteroid therapy, non-invasive and invasive mechanical ventilation, worsened and death (2.5% vs. 0%). The Cox proportional hazard model demonstrated that high LDH levels (adjusted hazard ratio = 5.27; 95% confidence interval: 1.19, 14.50) were associated with a more unfavorable composite disease progression outcome among COVID-19 patients treated with Azvudine, after accounting for potential confounding variables. Conclusion: High-LDH levels predict a worse composite disease progression outcome in COVID-19 patients treated with Azvudine.

Association of eosinopenia with worsening prognosis in hospitalized Azvudine-treated COVID-19 patients: a retrospective cohort study.

Background: Current guidelines prioritize the use of Azvudine in Coronavirus Disease 2019 (COVID-19) patients, while biomarkers for prognosis in Azvudine-treated COVID-19 patients are still lacking. Here, we aim to assess the prognostic value of eosinopenia in Azvudine-treated COVID-19 patients. Methods: We retrospectively reviewed 290 consecutive Azvudine-treated hospitalized COVID-19 patients. Clinical characteristics and prognosis data were analyzed between patients with eosinopenia and with normal eosinophil levels. Results: A total of 290 patients were enrolled in this study, with a median age of 69 years. Among them, 40.69% presented with eosinopenia and 59.31% had normal eosinophil levels. Common symptoms included cough (87.6%), expectoration (76.2%), fever (67.9%), poor appetite (47.2%), and polypnea (46.6%). Compared to patients with normal eosinophil levels, those with eosinopenia were older and less likely to experience fatigue (25.4% vs. 39.0%, P=0.016). Significant differences in laboratory parameters, particularly in blood routine and blood biochemical indicators, were observed between the two groups. Patients with eosinopenia were also less likely to develop severe illness subtypes, requiring more medication and oxygen support. The Cox proportional hazard model showed that eosinopenia was associated with worsening progression in Azvudine-treated COVID-19 patients (adjusted hazard ratio=2.79, 95% confidence interval: 1.04, 7.50), adjusting for potential confounders. Conclusion: Eosinopenia is associated with worsening prognosis in Azvudine-treated COVID-19 patients.