Effectiveness of immune checkpoint inhibitors in combination with tyrosine kinase inhibitors in patients with advanced or metastatic colorectal carcinoma with either mismatch repair proficient or metastatic microsatellite stable disease: A systematic review and meta­analysis.

Immune checkpoint inhibitors (ICIs) have limited efficacy in mismatch repair proficient (pMMR) or metastatic microsatellite stable (MSS) advanced or metastatic colorectal cancer (mCRC). ICIs, in conjunction with tyrosine kinase inhibitors (TKIs) possessing anti-angiogenic properties, serve as a potential strategy for circumventing the resistance exhibited by MSS or pMMR mCRC to immunotherapeutic interventions. The present study aimed to evaluate efficacy and safety of ICIs + TKIs and provide a reference for the treatment of CRC. The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to July 28, 2023. A total of 14 studies were included in qualitative and quantitative analyses, with a total of 819 patients enrolled. The Newcastle-Ottawa scale scores of the 14 cohort studies included were ≥7, indicating they were of a high quality. The objective response rate (ORR) of ICIs + TKIs was 14% [95% confidence interval (CI), 0.08-0.24; P=0.132] in patients with advanced or metastatic MSS/pMMR CRC. The disease control rate (DCR) was 65% (95% CI, 0.58-0.74; P<0.0001). The overall incidence of adverse events of varying severity linked to combination of ICIs and TKIs in patients with advanced or metastatic MSS/pMMR CRC was 64% (95% CI, 0.52-0.78; P<0.0001). The incidence of grade ≥3 adverse reactions was 24% (95% CI, 0.14-0.4; P<0.0001). The sensitivity analysis indicated that the exclusion of individual studies did not yield statistically significant variations in combined analysis results. Based on the examination of publication bias, ORR and DCR, Begg's and Egger's tests had P-values of 0.114 and 0.395, respectively. Overall publication bias overall was absent in the Begg's funnel plot, as there was no apparent asymmetry. Nonetheless, the P-values of the Egger's and Begg's tests for adverse reactions and adverse reactions grade ≥3 were P=0.008 and P=0.048, respectively. The asymmetry of the Begg's funnel plots was evident, suggesting the presence of potential publication bias regarding adverse event results. In conclusion, the combination of ICIs and TKIs demonstrates a favorable effectiveness and notable safety profile in the management of patients with advanced or metastatic MSS/pMMR CRC.

Comparison of enteral immunonutrition and enteral nutrition in patients undergoing gastric cancer surgery: a systematic review and meta-analysis of randomized, controlled trials.

OBJECTIVE: Enteral immunonutrition is a nutritional intervention that has been studied in postoperative patients with gastric cancer, but its effectiveness is controversial. This study aimed to investigate the effects of enteral immunonutrition and enteral nutrition on immune function in patients who undergo gastric cancer surgery. METHODS: We performed a systematic review and meta-analysis. A comprehensive search was conducted in PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov from the inception of the review until 10 March 2023. Twelve studies were included for qualitative and quantitative analyses. RESULTS: We studied 1124 patients, including 565 patients in the enteral immunonutrition group and 559 in the enteral nutrition (controls) group. All included randomized, controlled trials were high quality. CD4+ levels, lymphocytes, transferrin concentrations, and systemic inflammatory response syndrome were not significantly different between the enteral immunonutrition and enteral nutrition groups. However, CD8+, immunoglobulins G and M, and proalbumin concentrations, CD4+/CD8+, and infectious complications were significantly higher in the enteral immunonutrition group than in the enteral nutrition group. A sensitivity analysis showed consistent results after excluding each study. Begg's test showed no publication bias. CONCLUSIONS: Enteral immunonutrition is an effective nutritional intervention that improves immune function in patients who have undergone gastric cancer surgery.

Landscape of immune checkpoint inhibitor-related adverse events in Chinese population.

This study aimed to describe the landscape of Immune checkpoint inhibitors (ICIs)-related adverse events (AEs) in a predominantly Chinese cohort. We searched electronic datasets including PubMed, Web of Science and Embase to identify and recruit relevant trials up to September 2, 2019. Clinical trials focusing on ICIs in Chinese patients or a predominantly Chinese population were included. Incidences of treatment-related AEs (TRAEs) and immune-related AEs (irAEs) were pooled and compared. In total, we recruited 13 trials consisting of 1063 patients, with 922 (86.7%) receiving ICI monotherapy and 141 (13.3%) receiving combination of ICI with chemotherapy or anti-angiogenesis. The pooled incidence of any grade TRAEs, grade 1-2, grade 3-5 TRAEs, any grade irAEs, grade 1-2 irAEs and grade 3-5 irAEs in all 1063 patients were 84.1%, 63.3%, 20.9%, 43.3%, 40.0% and 3.0%, respectively. Moreover, 4.3% (44/1018) of patients experienced treatment discontinuation and only 8 (0.8%) patients experienced treatment-related death. Compared to ICI monotherapy, combination significantly increased grade 3-5 TRAEs (46.1% vs. 17.0%, P < 0.001) and grade 3-5 irAEs (7.1% vs. 2.0%, P = 0.015). By comparing the toxicity profiles between different ICIs, we found some drug-specific AEs such as reactive capillary haemangiomas for camrelizumab (58.6%), hyperglycemia for toripalimab (55.6%) and pyrexia for tislelizumab (54.3%). Additionally, nivolumab has the lowest incidence of any grade (64.1%) and grade 3-5 (11.8%) TRAEs. ICI-related AEs were generally mild and tolerable for a predominantly Chinese cohort. However, we should pay attention to the combination of ICI with chemotherapy as it could increase grade 3-5 TRAEs and irAEs.

ABO blood group and risk of newly diagnosed nonalcoholic fatty liver disease: A case-control study in Han Chinese population.

BACKGROUND: ABO blood group has been associated with cardiovascular disease and cancer. However, whether ABO blood group is associated with nonalcoholic fatty liver disease (NAFLD) remains unknown. The present study aimed to clarify this issue. METHODS: A hospital-based case-control study was performed in southwestern China. A total of 583 newly ultrasound-diagnosed NAFLD cases and 2068 controls were included. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of developing NAFLD were calculated by multivariate logistic regression. A propensity score was developed for adjustment and matching. RESULTS: The proportions of blood groups A, B, AB and O were 31%, 26%, 8% and 35%, respectively. Non-O blood groups were found to be significantly associated with an increased risk of NAFLD (the fully adjusted OR = 1.51, 95% CI: 1.19, 1.91); moreover, compared with blood group O, the fully adjusted ORs of developing NAFLD were 1.50 (95% CI: 1.13, 1.99) for blood group A, 1.59 (95% CI: 1.19, 2.14) for blood group B, and 1.37 (95% CI: 0.86, 2.18) for blood group AB. Similar results were obtained in both propensity-score-adjusted and propensity-score-matched analyses. No evidence of significant effect modification for the association of ABO blood group with the risk of NAFLD was found (all Pinteraction>0.05). CONCLUSIONS: Non-O blood groups are significantly associated with an increased risk of NAFLD. Our findings provide some epidemiological evidence for a possible role of ABO glycosyltransferase in the pathogenesis of NAFLD. However, these findings need to be validated by future studies.

Evolutionary role of chemotherapy in advanced nasopharyngeal carcinoma: a literature-based network meta-analysis.

PURPOSE: The role of chemotherapy has evolved greatly in advanced nasopharyngeal carcinoma (NPC). We undertook this network meta-analysis to establish the optimal chemotherapy strategy in advanced NPC. MATERIALS AND METHODS: This network meta-analysis recruited randomized clinical trials involving patients with advanced NPC randomly allocated to induction chemotherapy plus concurrent chemoradiotherapy (CRT; induction + CRT), CRT plus adjuvant chemotherapy (CRT + adjuvant), CRT or radiotherapy (RT) alone. Pairwise meta-analysis was first conducted, then network meta-analysis was performed using the frequentist approach. Effect size was expressed as HR and 95% CI. RESULTS: In total, we analyzed 15 studies involving 4,067 patients with 880 (21.6%) patients receiving induction + CRT, 897 (22.1%) receiving CRT + adjuvant, 1,421 (34.9%) receiving CRT, and 869 (21.4%) receiving RT alone. Induction + CRT achieved significantly better distant failure-free survival (HR, 0.67; 95% CI, 0.53-0.86) and locoregional failure-free survival (HR, 0.69; 95% CI, 0.54-0.89) than CRT, and CRT + adjuvant achieved better overall survival than CRT (HR, 0.82; 95% CI, 0.67-1.00). However, no significant survival difference was found between the induction + CRT and CRT + adjuvant groups. Additionally, RT alone is always worse than the other three treatments. In terms of P-score, induction + CRT ranked best for distant and locoregional failure-free survival, while CRT + adjuvant ranked best for overall survival. CONCLUSION: Both induction + CRT and CRT + adjuvant were equally effective and feasible choices for patients with advanced NPC.