Low Skeletal Muscle Mass and the Incidence of Delirium in Hospitalized Older Patients: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Both low skeletal muscle mass and delirium are prevalent in older hospitalized patients, while their associations are unclear. This systematic review and meta-analysis aim to investigate the associations between low skeletal muscle mass and the incidence of delirium in hospitalized patients. Methods: The PubMed, Web of Science, and Embase were searched for relevant studies published before May 2022, and we conducted this systematic review and meta-analysis according to the PRISMA and MOOSE guidelines. The summary odds ratios (OR) and 95% confidence intervals (CI) were estimated, and subgroup analyses were also conducted according to the age and major surgeries. Results: Finally, nine studies with 3 828 patients were included. The pooled result showed no significant association between low skeletal muscle mass and the incidence of delirium (OR 1.69, 95% CI 0.85 to 2.52). However, sensitivity analysis suggested that one study caused a significant alteration of the summary result, and the meta-analysis of the remaining 8 studies showed that low skeletal muscle mass was significantly associated with an 88% increased incidence of delirium (OR 1.88, 95% CI 1.43 to 2.33). Furthermore, subgroup analyses indicated that low skeletal muscle mass was associated with a higher incidence of delirium in patients ≥75 years old or undergoing major surgeries instead of those <75 years old or without surgeries, respectively. Conclusions: Hospitalized patients with low skeletal muscle mass might have higher incidence of delirium, particularly in those of older age and undergoing major surgeries. Therefore, great attention should be paid to these patients.

CT-determined low skeletal muscle mass predicts worse overall survival of gastric cancer in patients with cachexia.

BACKGROUND: There were controversies for the association between computed tomography (CT)-determined low skeletal muscle mass (SMM) and overall survival (OS) in gastric cancer (GC). In this study, we investigated whether cachexia could be a potential confounding variable for this issue. METHODS: We retrospectively collected the patients of GC in our institution between July 2016 and January 2021. Preoperative SMM was determined by analyzing the skeletal muscle index of L3 with abdominal CT, and the cut-offs for low SMM were defined as <52.4 (men) and < 38.5 cm2 /m2 (women), respectively. Overall survival (OS) was the primary endpoint. RESULTS: Of the 255 included GC patients, 117 (46%) were classified as having low SMM. Those with low SMM were associated with a higher level of circulating interleukin 6 and C reactive protein but a lower level of albumin than those of normal SMM. The univariate analysis showed that low SMM, tumor-node-metastasis (TNM) stage, body mass index (BMI), postoperative chemotherapy, and cachexia were significantly associated with OS, while in the multivariate analysis, only low SMM and TNM stage were significantly associated with OS. Kaplan-Meier survival curves with log-rank tests indicated that low SMM significantly predicted worse OS of GC. After grouping by cachexia, the low SMM significantly predicted worse OS in patients with cachexia instead of those without cachexia. CONCLUSIONS: CT-determined low SMM predicts worse OS of GC in patients with cachexia instead of those without cachexia, and greater attention should be paid to such patients with synchronous low SMM and cachexia.

Development and external validation of a nomogram for individualized adjuvant imatinib duration for high-risk gastrointestinal stromal tumors: A multicenter retrospective cohort study.

INTRODUCTION: The main emphasis of the research about adjuvant imatinib for high-risk gastrointestinal stromal tumors (GISTs) is prolonging the treatment duration and ignores the heterogeneous that 10-year recurrence rates ranged from about 20%-100%. Thus, this study evaluated the effect of different durations of adjuvant imatinib on outcomes in high-risk GISTs to explore the feasibility of individual treatment. METHODS: We analyzed 855 high-risk GIST patients from three centers who underwent macroscopically complete resection between December 2007 and September 2020. The patients were divided into training (n =564) and two validation cohorts (n = 238 and53) based on their source. Recurrence-free survival (RFS) was the primary point. Cox multivariate analysis was used to develop the nomogram. C-index, time-dependent area under the curves, and calibration plots were used to assess the performance of the nomogram. RESULTS: Univariate analysis showed that longer adjuvant imatinib was significantly associated with better 5-year RFS (p < 0.0001). Further investigation identified that the same high-risk patients with lower tumor-associated recurrence risk benefitted little from prolonged treatment and that the recommended adjuvant imatinib duration was insufficient for those with higher recurrence risk. A nomogram for predicting 2-, 3-, and 5-year RFS based on different treatment durations and four major risk factors, namely, tumor site, size, mitotic count, and rupture status, was built and validated, with a C-index of 0.82, 0.74, and 0.70 in training and two external validation cohorts, respectively. An online dynamic nomogram was further developed for clinical applications (https://ruolinliu666.shinyapps.io/GIST/), offering predictive recurrence rates based on different treatment durations and tumor features. CONCLUSIONS: We developed a nomogram to predict the recurrence risk for high-risk patients according to tumor features and treatment durations of imatinib to help physicians on decision-making for individualized treatment duration.

Circ_0011232 contributes to hepatocellular carcinoma progression through miR-503-5p/AKT3 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a type of primary liver cancer with high mortality. Circular RNAs (circRNAs) have been confirmed to be involved in the development of HCC, but the functions of circ_0011232 in HCC remain ill-defined. METHODS: Quantitative real-time polymerase chain reaction, western blot assay, or immunohistochemistry assay was performed to determine the levels of circ_0011232, miR-503-5p, and AKT3. RNase R assay and actinomycin D assay were conducted to analyze the feature of circ_0011232. Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, flow cytometry analysis, wound-healing assay, and transwell assay were conducted to evaluate HCC cell proliferation, colony formation, apoptosis, migration, and invasion. Dual-luciferase reporter assay was carried out to confirm the relationships among circ_0011232, miR-503-5p, and AKT3. The murine xenograft assay was conducted to verify the function of circ_0011232 in tumor growth in vivo. RESULTS: Circ_0011232 and AKT3 were upregulated, while miR-503-5p was decreased in HCC tissues and cells. Circ_0011232 knockdown repressed HCC cell proliferation, colony formation, migration, and invasion, and promoted apoptosis in vitro and blocked tumor growth in vivo. MiR-503-5p was a target of circ_0011232. MiR-503-5p inhibition reversed the effects of circ_0011232 knockdown on HCC cell development. Moreover, AKT3 was confirmed to be a target of miR-503-5p, and AKT3 overexpression abolished the inhibitory effects on HCC cell progression caused by miR-503-5p. CONCLUSION: Circ_0011232 facilitated HCC progression via miR-503-5p/AKT3 axis, which might provide a novel treatment strategy for HCC.

Associations of ABCB1 and XPC genetic polymorphisms with susceptibility to colorectal cancer and therapeutic prognosis in a Chinese population.

Associations between ABCB1 and XPC genetic polymorphisms and risk of developing colorectal cancer (CRC) as well as clinical outcomes in CRCs with chemotherapy were investigated. A case-control study was performed on the ABCB1 C3435T, G2677T/A and XPC Lys939Gln polymorphisms in 428 CRC cases and 450 hospital- based, age and sex frequency-matched controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. We observed that the ABCB1 3435CT or CC+CT variants were significantly linked with increasing risk of developing CRC (adjusted OR (95% CI): 1.814 (1.237-2.660), P=0.0022; adjusted OR (95% CI): 1.605 (1.117-2.306), P=0.0102, respectively). Moreover, the distribution frequency of XPC AC genotype or AC+CC genotypes also showed a tendency towards increasing the suscepbility for CRC (P=0.0759 and P=0.0903, respectively). Kaplan-Meier curves showed that the ABCB1 C3435T variant was associated with a tendency toward longer progression-free survival (PFS) (n=343, Log-rank test: P=0.063), and the G2677T/A variant genotypes (GT+TT+GA+AA) with a tendency for longer OS in postoperative oxaliplatin-based patients (n=343, Log-rank test: P=0.082). However, no correlation of the XPC Lys939Gln polymorphism was found with PFS and OS in patients with postoperative oxaliplatin-based chemotherapy (n=343). Our study indicated that ABCB1 polymorphisms might be candidate pharmacogenomic factors for the prediction of CRC susceptibility, but not for prognosis with oxaliplatin chemosensitivity in CRC patients.