Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis

Background In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). Objective To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. Results Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). Conclusion CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

The Value of Platelet-to-Lymphocyte Ratio as a Prognostic Marker in Cholangiocarcinoma: A Systematic Review and Meta-Analysis

The platelet-to-lymphocyte ratio (PLR), an inflammatory parameter, has shown prognostic value in several malignancies. The aim of this meta-analysis was to determine the impact of pretreatment PLR on the oncological outcome in patients with cholangiocarcinoma (CCA). A systematic literature search has been carried out in the PubMed and Google Scholar databases for pertinent papers published between January 2000 and August 2021. Within a random-effects model, the pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to investigate the relationships among the PLR, overall survival (OS), and disease-free survival (DFS). Subgroup analysis, sensitivity analysis, and publication bias were also conducted to further evaluate the relationship. A total of 20 articles comprising 5429 patients were included in this meta-analysis. Overall, the pooled outcomes revealed that a high PLR before treatment is associated with impaired OS (HR = 1.14; 95% CI = 1.06–1.24; p < 0.01) and DFS (HR = 1.57; 95% CI = 1.19–2.07; p < 0.01). Subgroup analysis revealed that this association is not influenced by the treatment modality (surgical vs. non-surgical), PLR cut-off values, or sample size of the included studies. An elevated pretreatment PLR is prognostic for the OS and DFS of CCA patients. More high-quality studies are required to investigate the pathophysiological basis of the observation and the prognostic value of the PLR in clinical management as well as for patient selection.

The Prognostic value of the Fibrinogen to pre-albumin ratio in malignant tumors of the digestive system: a systematic review and meta-analysis

Background In recent years, the Fibrinogen to pre-albumin ratio (FPR) has been reported in many studies to be significantly associated with the prognosis of various cancers. This systematic review and meta-analysis aimed to investigate the prognostic value of FPR in malignant tumors of the digestive system based on available evidence. Methods The relevant articles published before July 1, 2021, were systematically retrieved from electronic databases to evaluate the effect of Fibrinogen to pre-albumin ratio (FPR) on the prognosis of patients with malignant digestive system tumors and calculate the hazard ratio (HR) and the corresponding 95% confidence interval (CI). Result Thirteen articles, all from China, including 15 cohort studies and a total of 5116 cases, were included in this study. A high FPR was associated with poor overall survival (HR = 1.88, 95%CI 1.53–2.32, P < 0.001), recurrence-free survival (HR = 2.29, 95%CI 1.91–2.76, P < 0.001), progression-free survival (HR = 1.96, 95%CI: 1.33–2.90, P = 0.001), complications (HR = 1.78, 95%CI: 1.06–3.00, P = 0.029), disease-free survival (HR = 1.46, 95%CI: 1.08–1.97, P = 0.013) was significantly associated with cancer-specific survival (HR = 1.44, 95%CI: 1.15–1.79, P = 0.001). Even though intergroup differences were present, FPR was strongly associated with overall and relapse-free survival, and sensitivity analysis suggested that our results were stable. Conclusion FPR can be used as a valuable indicator to predict the prognosis of patients with malignant digestive system tumors.

Prognostic Value of Serum/Plasma Neurofilament Light Chain for COVID-19 Associated Mortality

Given the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), early predictors of coronavirus disease 19 (COVID-19) mortality might improve patients outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuro-axonal injury, have been observed in patients with severe COVID-19. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality. We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID-19 patients. In cohort 1, we found significantly elevated NfL levels only in critically ill COVID-19 patients compared to healthy controls. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following two other prognostic markers of COVID-19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between LDH and ALC abnormalities and subsequent rise of NfL implicate multi-organ failure as a likely cause of neuronal injury at the later stages of COVID-19. Addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. In conclusion, although substantial increase in serum/plasma NfL reproducibly enhances COVID-19 mortality prediction, NfL has clinically meaningful prognostic value only close to death, which may be too late to alter medical management. When combined with other prognostic biomarkers, rising longitudinal NfL measurements triggered by LDH and ALC abnormalities would identify patients at risk of COVID-19 associated mortality who might still benefit from escalated care.

The Prognostic Value of the Prognostic Nutritional Index in Operable High-Grade Glioma Patients and the Establishment of a Nomogram

BackgroundStudies confirmed the predictive value of the prognostic nutrition index (PNI) in many malignant tumors. However, it did not reach a consensus in glioma. Therefore, this study investigated the prognostic value of preoperative PNI in operable high-grade glioma and established a nomogram.MethodsClinical data of high-grade glioma patients were retrospectively analyzed. The primary endpoint was overall survival (OS). Survival analysis was conducted by the Kaplan–Meier method, log-rank test, and Cox regression analysis. A nomogram was established. The prediction effect of the nomogram covering PNI was verified by area under the curve (AUC).ResultsA total of 91 operable high-grade glioma patients were included. Kaplan–Meier analysis showed that among grade IV gliomas (n = 55), patients with higher PNI (&gt;44) showed a trend of OS benefit (p = 0.138). In grade III glioma (n = 36), patients with higher PNI (&gt;47) had longer OS (p = 0.023). However, the intersecting Kaplan–Meier curve suggested that there may be some confounding factors. Cox regression analysis showed that higher PNI was an independent prognostic factor for grade IV glioma (HR = 0.388, p = 0.040). In grade III glioma, there was no statistically relationship between PNI levels and prognosis. When evaluating the prognostic ability of PNI alone by ROC, the AUC in grade III and IV gliomas was low, indicating that PNI alone had poor predictive power for OS. Interestingly, we found that the nomogram including preoperative PNI, age, extent of resection, number of gliomas, and MGMT methylation status could predict the prognosis of patients with grade IV glioma well.ConclusionThe PNI level before surgery was an independent prognostic factor for patients with grade IV glioma. The nomogram covering PNI in patients with grade IV glioma also proved the value of PNI. However, the value of PNI in grade III glioma needs to be further evaluated. More prospective studies are needed to verify this conclusion.