Circ_0000370 Plays an Oncogenic Role in Colorectal Cancer by Regulating the miR-502-5p/SIRT1 Axis.

The importance of circular RNA has been reported in cancer development. However, the role and mechanism of circ_0000370 in CRC progression are still unclear. Quantitative real-time PCR and Western blot assay were performed to measure RNA and protein expression. Cell proliferation was assessed by cell colony formation assay and 5-Ethynyl-2'-deoxyuridine assay. Flow cytometry was used to measure cell apoptosis. Cell migration and invasion were detected by transwell assay. The intermolecular target relations between miR-502-5p and circ_0000370 or SIRT1 were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. A xenograft tumor model was established to examine the role of circ_0000370 in tumor growth in vivo. As compared with controls, the expression of circ_0000370 was upregulated in CRC tissues and cells. Circ_0000370 depletion inhibited CRC cell proliferation, migration and invasion but induced cell apoptosis. Meanwhile, circ_0000370 depletion restrained tumor growth in vivo. In addition, miR-502-5p inhibitor partly reverted the impacts of circ_0000370 knockdown on CRC cells. Moreover, miR-502-5p mimic-caused effects on cell phenotypes were attenuated by SIRT1 overexpression. Circ_0000370 induced the proliferation and metastasis of CRC cells by sponging miR-502-5p and enhancing SIRT1 expression, which provided a possible target for CRC treatment.

The SLC22A2 gene is a determinant of hematological toxicity of oxaliplatin in patients with colorectal cancer.

OBJECTIVE: To investigate the association between polymorphisms in the SLC22A2 gene and the hematological toxicity of oxaliplatin in colorectal cancer (CRC) patients receiving chemotherapy. MATERIALS AND METHODS: A total of 81 patients with colon or rectal cancer were included in the study. The single nucleotide polymorphisms (SNPs) rs3127573, rs316019, and rs1869641 of the SLC22A2 gene were selected for genotyping using the polymerase chain reaction (PCR) and sequence analysis. Oxaliplatin-associated hematological toxicities were evaluated using the Common Toxicity Criteria for Adverse Events (CTCAE, Version 5.0). RESULTS: The rs1869641 genotype was significantly associated with the occurrence of thrombocytopenia (p = 0.047), whereas the rs316019 genotype was significantly associated with severity of leucopenia and neutropenia (p = 0.004 and 0.001, respectively). The rs3127573 genotype was not associated with hematological toxicities arising during chemotherapy with oxaliplatin. CONCLUSION: It is shown here, for the first time, that the rs316019 gene variant of the SLC22A2 gene may be associated with the hematological toxicity of oxaliplatin. Patients with genotype CA/AA of rs316019 are more likely to develop serious hematological adverse effects.

Circ_0005785 Silencing Constrains the Functional Properties of Colorectal Cancer Cells Depending on miR-7-5p/DNMT3A Axis.

Circular RNAs (circRNAs) closely related to the progression of colorectal cancer (CRC). Nevertheless, the study of circ_0005785 in CRC has not been reported. In this test, we aimed to investigate the mechanisms of circ_0005785 in CRC development. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were employed to reveal the expression of genes and proteins. Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry analysis, transwell assay and tube formation experiment were implemented to examine cell growth, apoptosis, invasion and angiogenesis. The relationships among circ_0005785, miR-7-5p and DNA methyltransferase 3 A (DNMT3A) were verified by dual-luciferase reporter assay. Xenograft mouse model was built to evaluate the impacts of circ_0005785 deficiency on CRC growth in vivo. We found that circ_0005785 was increased in CRC patients and cell lines. Circ_0005785 downregulation retarded cell proliferation, invasion, angiogenesis whereas expedited apoptosis in CRC cells. Mechanistically, circ_0005785 could sponge miR-7-5p and the suppressive treads of circ_0005785 in CRC development was attenuated by miR-7-5p down-regulation. DNMT3A was targeted by miR-7-5p and miR-7-5p overexpression constrained cell malignant behaviors, but the addition of DNMT3A counteracted the effects. Additionally, circ_0005785 inhibition hindered the tumor growth in vivo. In conclusion, circ_0005785 aggravated the CRC progression by increasing the level of DNMT3A via adsorbing miR-7-5p.

circHIPK2 Has a Potentially Important Clinical Significance in Colorectal Cancer Progression via HSP90 Ubiquitination by miR485-5p.

Colon cancer, as one of the common malignant tumors, has the highest morbidity and mortality. We investigated the clinical significance and possible mechanism of the circular RNA circHIPK2 in the progression of colorectal cancer (CRC). Quantitative analysis of mRNAs, gene microarray hybridization, immunofluorescence, luciferase reporter assay, proliferation assay, EDU staining, subcellular location analysis and Western blotting. circHIPK2 expression was upregulated in patients with CRC compared with paracancerous tissues. In contrast, patients with high circHIPK2 expression had lower overall survival rate and disease-free survival rate than those with low circHIPK2 expression. circHIPK2 expression in normal intestinal epithelial cells was lower than that in CRC cell lines. circHIPK2 promoted CRC progression. miR-485-5p reduced CRC progression. miR-485-5p, as the target of circHIPK2 in CRC model, played a role in promoting CRC progression and expediting HSP90 ubiquitination. HSP90 ubiquitination by miR-485-5p can promote cell proliferation. circHIPK2 has potential clinical significance in CRC progression, which may serve as an exceptional candidate for further therapeutic exploration.

Advanced Devices for Tumor Diagnosis and Therapy.

At present, tumor diagnosis is performed using common procedures, which are slow, costly, and still presenting difficulties in diagnosing tumors at their early stage. Tumor therapeutic methods also mainly rely on large-scale equipment or non-intelligent treatment approaches. Thus, an early and accurate tumor diagnosis and personalized treatment may represent the best treatment option for a successful result, and the efforts in finding them are still in progress and mainly focusing on non-destructive, integrated, and multiple technologies. These objectives can be achieved with the development of advanced devices and smart technology that represent the topic of the current investigations. Therefore, this review summarizes the progress in tumor diagnosis and therapy and briefly explains the advantages and disadvantages of the described microdevices, finally proposing advanced micro smart devices as the future development trend for tumor diagnosis and therapy.

HOXC10 promotes cell migration, invasion, and tumor growth in gastric carcinoma cells through upregulating proinflammatory cytokines.

HOXC10 plays a critical role in many cellular processes, such as proliferation, migration, and invasion, but the function of HOXC10 in gastric carcinoma is not clear. In this study, we aimed to investigate the expression profile of HOXC10 and its role in gastric carcinoma cells and in vivo experiments. HOXC10 expression patterns were detected in clinical samples and gastric cancer cells lines by reverse transcriptase polymerase chain reaction assays, and then, we focused on its role in regulating cell proliferation, cell cycle, migration, and invasion after transfection of silencing and overexpression plasmids in vitro and in vivo. Finally, we confirmed the correlation between HOXC10 and nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), and epidermal growth factor receptor expression. We found that HOXC10 expression increased in clinical samples, especially in poorly differentiated (PD) gastric cancer cells. Silencing HOXC10 suppressed proliferation, migration, and invasion in vitro, and inhibited tumor growth and induced apoptosis in vivo. Overexpression of HOXC10 showed the opposite effect on PD gastric cancer cells. In addition, silencing HOXC10 inhibited the expression of interleukin-6, TNF-α, TGF-ß, and epidermal growth factor, and overexpressing HOXC10 induced their expression both in vitro and in vivo. Luciferase reporter assays and chromatin immunoprecipitation indicated that HOXC10 may activate the NF-κB signaling pathway through regulation of P65 transcriptional activity by binding to the P65 promoter. HOXC10 may play an important role in PD gastric carcinoma cell proliferation, cell cycle, migration, invasion, and metastasis through upregulating proinflammatory cytokines via NF-κB pathway, suggesting HOXC10 may serve as a novel therapeutic target for PD gastric cancer.

Corrigendum to "SOX8 promotes tumor growth and metastasis through FZD6-dependent Wnt/ß-catenin signaling in colorectal carcinoma" [Heliyon 9(12) (December 2023) e22586].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e22586.].

Risk Factors of Gastrointestinal Perforation with a Poor Prognosis.

Background: Despite medical progress, mortality from gastrointestinal perforation was relatively high. Our study's objective was to identify risk factors associated with a poor prognosis for gastrointestinal perforation. Methods: Patients diagnosed with gastrointestinal perforation at the Longchuan County People's Hospital between January 2019 and February 2022 were the subject of a retrospective analysis of their laboratory data. Patients were grouped based on length of hospital stay, septic shock, and mortality. Results: A total of 240 patients participated in our study. Using univariate and multivariate analysis, we identified several risk factors for gastrointestinal perforation associated with a dismal prognosis. Lower digestive tract perforation (OR=2.418, 95% CI 1.119-5.227, P=0.025), low total protein (OR=0.934, 95% CI 0.879-0.992, P=0.026) and low hemoglobin (OR=0.985, 95% CI 0.971-0.999, P=0.039) were linked to a longer length of stay, especially hemoglobin (OR=0.978, 95% CI 0.966-0.991, P=0.001) in upper digestive tract. High ratio of neutrophils to lymphocytes (NLR) (OR=1.043, 95% CI 1.012-1.076, P=0.007), high lymphocyte-to-monocyte ratio (LMR) (OR=2.158, 95% CI 1.495-3.115, P<0.001) and low prognostic nutrition index (PNI) (OR=0.814, 95% CI 0.751-0.833, P<0.001) predicted septic shock. In upper digestive tract, PLR (OR=1.001, 95% CI 1.000-1.002, P=0.067), LMR (OR=2.160, 95% CI 1.440-3.240, P<0.001) and PNI (OR=0.843, 95% CI 0.767-0.926, P<0.001) were risk factors for septic shock, and total protein (OR=0.796, 95% CI 0.686-0.923, P=0.003) was a risk factor for septic shock in lower digestive tract. High NLR (OR=1.056, 95% CI 1.019-1.093, P=0.003), high LMR (OR=1.760, 95% CI 1.177-2.632, P=0.006) and low PNI (OR=0.832, 95% CI 0.754-0.918, P<0.001) were the risk factors of mortality. In subgroup analysis of perforation site, albumin (OR=0.820, 95% CI 0.719-0.934, P=0.003) and LMR (OR=1.506, 95% CI 1.069-2.123, P=0.019) were risk factors for mortality in upper digestive tract and PNI (OR=0.636, 95% CI 0.445-0.908, P=0.013) was a risk factor for mortality in lower digestive tract. Conclusion: Our research found that the perforation site, total protein, albumin, hemoglobin, NLR, LMR, PLR and PNI were risk factors for gastrointestinal perforation with a poor prognosis.

SOX8 promotes tumor growth and metastasis through FZD6-dependent Wnt/ß-catenin signaling in colorectal carcinoma.

SOX8 plays an important role in several physiological processes. Its expression is negatively associated with overall survival in patients with colorectal carcinoma (CRC), suggesting SOX8 is a potential prognostic factor for this disease. However, the role of SOX8 in CRC remains largely unknown. In this study, our data showed that SOX8 expression was upregulated in CRC cell lines and tumor tissues. Stable knockdown of SOX8 in CRC cell lines dramatically reduced cell proliferation, migration, and invasion. Furthermore, the knockdown of SOX8 decreased the phospho-GSK3ß level and suppressed Frizzled-6 (FZD6) transcription; restoration of FZD6 expression partially abolished the effect of SOX8 on Wnt/ß-catenin signaling and promote CRC cell proliferation. In conclusion, our findings suggested that SOX8 served as an oncogene in CRC through the activation of FZD6-dependent Wnt/ß-catenin signaling.

IL23R as an indicator of immune infiltration and poor prognosis in intrahepatic cholangiocarcinoma: a bioinformatics analysis.

Background: Although the incidence of intrahepatic cholangiocarcinoma (CHOL) is low, the prognosis is very poor. The expression level of interleukin 23 receptor (IL23R) is linked to the occurrence and development of cancers. This study aimed to identify the role of IL23R in CHOL using bioinformatics tools and experimental validation. Methods: Circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database, and R software was used for data analysis and visualization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional enrichment analysis, which was verified with gene set enrichment analysis software. Clinical data were obtained from The Cancer Genome Atlas (TCGA), and survival analyses were performed using the DriverDBv3 database and the Gene Expression Profiling Interactive Analysis website. The TIMER2.0 database provided us for immune cell infiltration analysis results of IL23R. Real-time quantitative polymerase chain reaction (RT-qPCR) was used for IL23R expression verification. Results: Differentially expressed (DE) mRNAs were enriched in phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, immune-related tumor microenvironment (TME), and amino acid metabolism, etc. In addition, expression of IL23R was associated with immune infiltration-related cells. Furthermore, a circRNA-miRNA-IL23R network and a IL23R protein-protein interaction network were established. Most importantly, IL23R, as a prognostic gene, was found to have a low expression in CHOL. Conclusions: A circRNA-miRNA-IL23R network was identified, and it was found that IL23R may be a prognostic and immune-related biomarker in CHOL, which is worthy of further exploration.

Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation.

Background: Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. Methods: The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. Results: WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. Conclusion: IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC.

Treatment efficacy and prognosis analysis in locally advanced or metastatic colorectal cancer patients with hydronephrosis.

The effect of hydronephrosis, a common complication of metastatic colorectal cancer (CRC), on the treatment outcome and prognosis of locally advanced or metastatic CRC remains to be elucidated. The present study investigated the clinical characteristics, outcomes, and prognoses of patients with locally advanced or metastatic colorectal cancer (CRC) with hydronephrosis. Clinical data of patients with locally advanced or metastatic CRC who were attending Peking University Shenzhen Hospital and Shenzhen Cancer Hospital between January 2016 and December 2020 were retrospectively collected. A total of 52 patients with hydronephrosis based on CT or MRI findings were selected, and their clinical characteristics, treatment outcomes, and survival times were analyzed. Of the 52 patients, 33 were male (63.5%), and the median age was 49 years (range, 31-76 years). A total of 15 (28.8%) patients with CRC had synchronous hydronephrosis and the remaining 37 patients had metachronous hydronephrosis. Ureters were either compressed by peritoneal or abdominal cavity metastatic lymph nodes in 34 cases (65.4%) or by direct tumor invasion in 18 cases (34.6%). However, objective response rate (ORR) was higher in the group in which ureters were compressed by peritoneal or abdominal cavity metastatic lymph nodes; ORR, disease control rate and median progression-free survival (PFS) between the two groups were not statistically different. (P>0.05). The median survival period was only 27.0 months (95% CI, 20.549-33.451) in patients complicated with malignant hydronephrosis. Univariate and multivariate analyses showed that CA19-9 might be a prognostic factor for locally advanced and metastatic CRC patients with hydronephrosis. Metachronous metastatic CRC has a high incidence rate of complicated hydronephrosis. Targeted drugs in combination with chemotherapy improve the treatment efficacy and prognosis of patients. Notably, the present study found that CA19-9 level might be a prognostic factor in CRC patients with hydronephrosis.

Retrospective Analyses of Complete Resection Combined with Systemic Chemotherapy and Targeted Therapy for Patients with Ovarian Metastases from Colorectal Cancer.

Background: The aim of the study is to evaluate clinical outcomes of patients with ovarian metastases from colorectal cancer (OM-CRC) treated with complete resection combined with chemotherapy and targeted therapy. Materials and Methods: Fifty female patients with OM-CRC who were treated in two different hospitals were categorized into three groups: 14 patients with OM-CRC received resection and chemotherapy combined with targeted therapy, 16 patients with OM-CRC only received chemotherapy combined with targeted therapy, and 20 patients with non-OM-CRC (NOM-CRC) received chemotherapy combined with targeted therapy. The primary outcomes, including overall survival (OS), the objective response rate (ORR), disease control rate (DCR), safety, and progression-free survival (PFS), were observed. Results: The ORR of OM-CRC was significantly lower compared with NOM-CRC (36.7% vs. 70.0%, p = 0.021), and the DCR of OM-CRC was also lower compared with NOM-CRC (76.7% vs. 90.0%, p = 0.229). The following chemotherapy and targeted therapy in the additional surgical resection of OM-CRC were positively associated with longer PFS and OS compared to no surgical resection (9.0 vs. 6.0 months and 21.0 vs. 15.0 months, respectively, p < 0.001), but the PFS and OS were best in patients with NOM-CRC (9.0 and 35.0 months). Improved OS was associated with R0 resection (23.0 vs. 17.0 months, p < 0.001). Multivariate analysis indicated that patients with well-differentiated pathology and unilateral ovarian metastasis had a better prognosis. Conclusion: Multidisciplinary treatment strategy, including systemic chemotherapy, targeted therapy, and complete surgery, may contribute to the prolongation of OS and be safe for treatment of OM-CRC.

Intratumoral CD8+ T cells as a potential positive predictor of chemoimmunotherapy response in PD-L1-negative advanced gastric cancer patients: a retrospective cohort study.

Background: Previous studies have shown that PD-L1-positive advanced gastric cancer (GC) patients could achieve clinical benefit after receiving immune checkpoint inhibitors (ICI) in initial or subsequent therapy. A number of prospective studies such as Keynote-158 have demonstrated that PD-L1-negative patients who tested as microsatellite instability-high (MSI-H) or tumor mutational burden-high (TMB-H) can benefit from ICIs. In the search for more biomarker for immunotherapy, some studies showed that patients with a specific characteristic to tumor microenvironment (TME) were associated with better prognosis. This study aimed to explore the association between the TME and immunotherapy in PD-L1 negative GC patients. Methods: This study was a retrospective cohort study. Twenty-six CPS PD-L1 negative stage IV advanced GC patients treated with chemoimmunotherapy in Shenzhen Hospital of Peking University were retrospectively enrolled according to the inclusion criteria. Their clinical characteristics were assessed and recorded by independent clinicians. Follow-up data was conducted through the Internet or visit. Respond to treatment was evaluated by RECIST 1.1. The primary outcome was progression-free survival (PFS). The level of tumor-infiltrating lymphocytes (TILs) was measured by multiplex immunofluorescence (mIF) among these patients. Cox proportional hazards analysis was performed to analyzed the correlation between PFS and clinical characteristics including TILs. Results: Among 26 patients, 5 patients (19.2%) were on complete response (CR) and 9 patients (34.6%) were in partial response (PR), while 7 patients (26.9%) experienced stable disease (SD). Intratumoral CD8+ T cells were obviously increased in CPS PD-L1 negative patients who responded to chemoimmunotherapy, compared with patients who did not respond (P=0.011). And higher level of CD8+ TILs was demonstrated to associate with better PFS in CPS PD-L1-negative patients treated with chemoimmunotherapy (HR =23.70, 95% CI: 1.15-488.30, P=0.04). Conclusions: Intratumoral CD8+ TILs may be a potential positive predictive factor of clinical response for chemoimmunotherapy in PD-L1-negative advanced GC. However, the results need to be further confirmed in a cohort with more subjects due to a limited sample sizes in present study.

Association of neutralizing breadth against SARS-CoV-2 with inoculation orders of heterologous prime-boost vaccines.

BACKGROUND: Emerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear. METHODS: We conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA. FINDINGS: We observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders. CONCLUSIONS: Our data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism. FUNDING: National Key R&D Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.

Prognostic Impact of Sarcopenia on Clinical Outcomes in Malignancies Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: The effect of sarcopenia on the clinical outcomes of patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is unclear. The aim of this study was to evaluate the effect and survival of patients with malignancies and sarcopenia receiving ICIs. METHODS: We systematically searched related studies in PubMed, Embase, and Cochrane Library up to March 2021 according to the inclusion and exclusion criteria. Information pertaining to the hazard ratio (HR) corresponding to 95% confidence interval (CI) of overall survival (OS) and progression-free survival (PFS) as determined by univariate and multivariate analyses; the odds ratio (OR) corresponding to the 95% CI of the disease control rate (DCR) and objective response rate (ORR); and immune-related adverse events (irAEs) was collected and analyzed using the RevMan 5.4 software. Study heterogeneity and sensitivity were also assessed. RESULTS: A total of 19 studies were finalized that included 1763patients with lung, gastrointestinal, and head and neck cancers as well as those with melanoma, renal cell carcinoma, urothelial carcinoma, pancreatic cancer, and soft tissue sarcoma. According to univariate and multivariate analyses, patients with sarcopenia at pre-immunotherapy had poorer PFS and OS than those without. HRs and the corresponding 95% CI of PFS were 1.91(1.55-2.34, p <0.00001) and 1.46 (1.20-1.78, p =0.0001), respectively, and HRs and the corresponding 95% CI of OS were 1.78 (1.47-2.14, p <0.00001) and 1.73 (1.36-2.19, p <0.0001), respectively. Patients with sarcopenia showed poor PFS and OS during treatment. In addition, patients with sarcopenia had worse ORR (OR 0.46, 95% CI 0.28-0.74, p = 0.001) and DCR (OR 0.44, 95% CI 0.31-0.64, p<0.0001); however, the incidence of irAEs of any grade and high-grade in patients with sarcopenia did not increase, OR and the corresponding 95% CI were 0.58(0.30-1.12, p = 0.10) and 0.46(0.19-1.09, p = 0.08). Further, we performed subgroup analysis, skeletal muscle mass index (SMI) and psoas muscle mass index (PMI) stratification. In the SMI group, patients with sarcopenia had poor ORR, DCR, PFS, and OS than those without. In the PMI group, sarcopenia had poor ORR,DCR, and was a poor prognostic factor for PFS and OS according to univariate analysis but had no effect on PFS and OS according to multivariate analysis. CONCLUSIONS: Patients with malignancies and sarcopenia at pre-immunotherapy or follow-up visits had poorer clinical outcomes than those without, and sarcopenia was a poor predictive factor of ICI immunotherapy outcomes.

Prognostic impact of sarcopenia on immune-related adverse events in malignancies received immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Whether sarcopenia has an impact on immune-related adverse events (irAEs) in patients with malignant neoplasms receiving immune checkpoint inhibitors (ICIs) is not consistent. This study aimed to evaluate the impact of sarcopenia on all grades of irAEs. METHODS: PubMed, Embase, and Cochrane Library databases were systematically searched for related studies up to May 2021. Eligible studies were included according to the PICOS criteria. The risk of bias of the included studies was assessed according to the Newcastle-Ottawa Scale (NOS). The odds ratio (OR), corresponding to the 95% confidence interval (CI) of all grades of irAEs, was collected and analyzed, and a further subgroup analysis of serious adverse events was conducted. All analyses were conducted using the RevMan 5.4 software downloaded from the Cochrane website. The heterogeneity and sensitivity of the study were assessed. RESULTS: Of the 135 references identified, only 8 studies were analyzed, including 519 patients comprising 250 with sarcopenia and 269 without sarcopenia. No obvious bias was observed in the included studies. An increased incidence of irAEs was not observed in patients with sarcopenia at pre-immunotherapy compared to those without sarcopenia. The OR and corresponding 95% CI were 0.97 and 0.62-1.53, respectively (P=0.90), with low heterogeneity (P=0.17, I2 =32%). Further, severe adverse events were analyzed in three studies, and the results showed that sarcopenia was not related to irAEs (P=0.97). CONCLUSIONS: Malignancies with sarcopenia at pre-immunotherapy may not increase the incidence of irAEs, and sarcopenia may not be a predictive factor for irAEs.

Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19.

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.

Efficacy of Olanzapine-Triple Antiemetic Regimen in Patients with Gastrointestinal Tumor and High Risk of Chemotherapy-Induced Nausea and Vomiting Receiving Moderately Emetogenic Chemotherapy: A Retrospective Study.

PURPOSE: Dexamethasone combined with 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RA) dual regimen is the standard prophylaxis regimen for patients receiving moderately emetogenic chemotherapy (MEC). However, it has been found in real-world practice that chemotherapy-induced nausea and vomiting (CINV) remains poorly controlled among patients with gastrointestinal tumor, especially in those with high-risk factors for vomiting, such as female, young, and non-alcoholic individuals. Hence, we aimed to evaluate the efficacy of an olanzapine-containing triple regimen in this clinical setting. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of gastrointestinal tumor patients who received mFOLFOX6, XELOX, or FOLFIRI chemotherapy at two institutions. All patients included were female and less than 55 years old, with no history of drinking. The patients were divided into two groups for olanzapine-containing triple therapy (olanzapine, tropisetron, and dexamethasone) and non-olanzapine dual therapy (tropisetron and dexamethasone). The study outcomes were complete response (CR), complete control (CC), nausea control, and quality of life (QoL) by the functional living index-emesis (FLIE) questionnaire. RESULTS: A total of 93 patients were included in the study (olanzapine: 40; control: 53). The CR rate in the olanzapine group was significantly higher than that in the control group in delayed and overall phase (75.0% vs 54.7%, p=0.044; 70.0% vs 47.2%; p=0.028). The CC rate in the overall phase was also better in the olanzapine group (62.5% vs 39.6%, p=0.029). The control of nausea in the overall phase showed a superior trend in the olanzapine group (p=0.059). The olanzapine group exhibited higher FLIE scores, which demonstrated better QoL. More patients in the olanzapine group exhibited somnolence and dizziness. Conversely, the incidence of insomnia and anorexia in the olanzapine group was lower. CONCLUSION: This retrospective study indicates that in gastrointestinal tumor patients with high-risk factors for CINV who were receiving MEC, olanzapine-containing triple antiemetic regimen exhibit better efficacy and QoL as compared to non-olanzapine dual regimen. Further randomized studies are required to confirm these results.