KMT2A Mutations and High Prevalence of dMMR-associated Mutational Signatures as Prognostic Indicators in Metastatic Colorectal Cancer.

The conventional treatment strategies for patients with metastatic colorectal cancer (mCRC) are predominantly guided by the status of RAS and BRAF mutations. Although patients may exhibit analogous pathological characteristics and undergo similar treatment regimens, notable disparities in their prognostic outcomes can be observed. Therefore, tissue and plasma samples from 40 mCRC patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Genomic variations and canonical oncogenic pathways were investigated for their prognostic effects in association with progression-free survival (PFS) of these patients. We found that patients with BRCA2 and KMT2A mutations exhibited worse prognostic outcomes after chemotherapy-based treatment (univariate, P < 0.01). Further pathway analysis indicated that alterations in the homologous recombination pathway and in the KMT2A signaling network were also significantly associated with shortened PFS (univariate, P < 0.01). Additionally, mutation signature analysis showed that patients with higher proportions of defective mismatch repair (dMMR)-related mutational signatures. Had a worse prognosis (univariate, P = 0.02). KMT2A mutations (hazard ratio [HR], 4.47; 95% confidence interval [CI], 1-19.93; P =0.050) and dMMR signature proportions (HR, 3.57; 95% CI, 1.42-8.96; P = 0.007) remained independently associated with PFS after multivariate analysis and the results were further externally validated. These findings may enhance our understanding of this disease and may potentially facilitate the optimization of its treatment approaches.

Prognostic value of neutrophil-to-lymphocyte ratio on proteinuria remission in patients with idiopathic membranous nephropathy.

BACKGROUND: As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. However, NLR in idiopathic membranous nephropathy (IMN) has been rarely studied. We sought to assess the role of NLR in predicting proteinuria remission in IMN. METHODS: This retrospective study involved 561 patients with IMN from January 2018 to December 2022 in Department of Nephrology of Wuhan Central Hospital. All baseline data were collected before the immunosuppressive regiment was administered. The Cox proportional hazards model and Kaplan-Meier curve were applied to assess the prognostic value of NLR for proteinuria remission. RESULTS: The area under the receiver operating characteristic curve revealed that the optimal cut-off NLR value for predicting proteinuria non-remission was 2.63, with a sensitivity and specificity of 58.2% and 72.7%, respectively. Kaplan-Meier curves showed a lower rate of proteinuria remission in patients with high NLR compared with low NLR (Log-rank = 5.04, p = 0.025). Multivariate Cox regression analysis showed that high NLR was an independent risk factor for proteinuria non-remission after adjustment (HR = 1.579, 95% CI 1.052-2.683, p = 0.023). Subgroup analysis indicated that high NLR was a risk factor for proteinuria non-remission especially in IMN patients with 24 h proteinuria ≥ 1 g (HR = 1.818, 95% CI 1.031-2.573, p = 0.012) and chronic kidney disease (CKD) stage 3-4 (HR = 1.935, 95% CI 1.084-2.495, p = 0.015). CONCLUSION: The current study shows that NLR is an independent risk factor for proteinuria non-remission in IMN. More attention should be paid to IMN patients with high NLR, especially for those patients with 24 h proteinuria ≥ 1 g and CKD stage 3-4.

Effect of preoperative arterial diameter on hospitalization and mortality in patients undergoing hemodialysis with forearm arteriovenous fistula access.

BACKGROUND: As pointed out by the recent Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Vascular Access, the current quality of evidence supporting preoperative vascular anatomy and patient outcomes is suboptimal and insufficient to make recommendations. This study assessed arteriovenous fistulas (AVFs) created with different preoperative arterial diameters on hospitalization and mortality rates in patients undergoing hemodialysis at the authors' center. METHODS: Data from 261 patients who underwent HD between 2017 and 2019 were retrospectively examined. Differences in mortality and hospitalization rates between patients with different preoperative arterial diameters were compared, and risk factors for mortality and hospitalization were analyzed. RESULTS: Smaller preoperative artery diameter (<2 mm) was associated with all-cause mortality (risk ratio [RR] 1.61 [95% confidence interval (CI) 1.45-1.90]; p < 0.01), and access-related (RR 1.68 [95% CI 1.24-2.44]; p < 0.01), and congestive heart failure (CHF)-related (RR 0.67 [95% CI 0.38-1.01]; p = 0.04) hospitalization. Longer catheter-dependent duration (⩾60 days) was associated with access-related hospitalization (RR 1.48 [95% CI 1.07-2.11]; p = 0.03), and higher postoperative brachial artery blood flow (⩾1500 mL/min) was associated with CHF-related hospitalization (RR 1.58 [95% CI 1.02-2.29]; p < 0.01). Higher postoperative brachial artery blood flow (⩾1500 mL/min) was associated with all-cause mortality (hazard ratio [HR] 1.20 [95% CI 1.09-2.32]; p = 0.04), whereas preoperative artery diameter (HR 0.98 [95% CI 0.93-1.86]; p = 0.08) and catheter-dependent duration (HR 1.06 [95% CI 0.47-2.13]; p = 0.82) were not associated with all-cause mortality. CONCLUSION: In this cohort, smaller preoperative artery diameter was associated with all-cause and access-related hospitalizations, while a larger preoperative artery and higher postoperative brachial blood flow were associated with CHF-related hospitalization. However, only higher postoperative brachial blood flow was associated with all-cause mortality.

The effect of early conversion from central venous catheter to arteriovenous fistula on hospitalization and mortality in incident haemodialysis patients.

BACKGROUND: Controversy remains as to whether initiating haemodialysis (HD) with a central venous catheter (CVC) and vascular access conversion are associated with the risk of morbidity and mortality in incident HD patients. METHODS: At our dialysis centre, the vascular access strategy is to create an arteriovenous fistula (AVF) early and use the AVF to initiate HD. In emergency situations, HD is initiated with a CVC and subsequent conversion from a CVC to an AVF as soon as possible. The effects of early AVF conversion on hospitalization and mortality were analysed. RESULTS: At HD initiation, 35.42% used AVF, 15.63% used CVC with immature AVF and 48.96% used CVC, and all patients were able to convert from CVC to AVF within approximately 3 months. Compared to starting HD using an AVF, using a CVC was associated with access-related hospitalizations at 2 years, regardless of whether an AVF was created before (incidence rate ratio (IRR) = 3.02, 95% CI 0.89-10.24, p = 0.03) or after (IRR = 4.10, 95% CI 1.55-10.85, p < 0.01) HD initiation. The Kaplan-Meier method showed that the 2-year survival probability was not statistically significant between the three groups (log-rank χ2 = 0.165, p = 0.921). Multivariate Cox proportional hazards regression showed that starting HD with a CVC was not associated with mortality at 2 years (p > 0.05). CONCLUSION: In this cohort, initiating HD with a CVC was associated with more access-related hospitalizations. Under the impact of an early AVF conversion strategy, despite initiating HD with a CVC, subsequent conversion from a CVC to an AVF within approximately 3 months had no impact on all-cause mortality in incident HD patients.

The association between platelet-lymphocyte ratio and the risk of all-cause mortality in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) patients have high levels of inflammatory mediators. These inflammatory mediators contribute to the increased risk of cardiovascular events and all-cause mortality. Platelet-lymphocyte ratio (PLR) has recently been recognized as a novel inflammatory marker and has been shown to be associated with the prognosis in CKD patients. However, the quality of these studies varies and their results are controversial. The purpose of this meta-analysis was to investigate the relationship between PLR and all-cause mortality in CKD patients. METHODS: A systematic literature search of PubMed, EMBASE, CENTRAL and ISI Web of Science was conducted. The databases were searched from their inception dates up to the latest issue (31 October 2021). Two reviewers independently searched the databases and screened studies. Data were extracted using a standardized collection form. Meta-analysis was performed to compare PLR values between CKD and non-CKD patients, and to investigate the association between PLR and all-cause mortality in CKD patients. This meta-analysis is reported in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: A total of 11 studies involving 4244 participants were selected. The pooled data indicated that PLR values were significantly higher in CKD patients than non-CKD controls (weighted mean difference = 21.6, 95% CI 17.39-25.81, p < 0.01), and PLR is associated with an increased risk of all-cause mortality in CKD patients (hazard ratio = 2.49, 95% CI 1.78-3.49, p < 0.01). CONCLUSIONS: Patients with CKD have higher PLR values compared to non-CKD patients. Meanwhile, PLR values were highly associated with all-cause mortality in CKD patients. PLR is a valid predictor as a clinically accessible indicator for patients with CKD.

The diagnostic value of contrast-enhanced ultrasound and superb microvascular imaging in differentiating benign from malignant solid breast lesions: A systematic review and meta-analysis.

OBJECTIVE: To investigate the added value of contrast-enhanced ultrasound (CEUS) and superb microvascular imaging (SMI) to the conventional ultrasound (US) in the diagnosis of breast lesions. METHODS: PubMed, EMBASE, Web of Science, Chinese national knowledge infrastructure databases, Chinese biomedical literature databases, and Wanfang were searched for relevant studies from November 2015 to November 2021. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Studies (QUADAS) tool. Meta-Disc version 1.4 was used to calculate sensitivity (SEN), specificity (SPE), positive likelihood ratio (LR+), negative likelihood ratio (LR-), area under curve (AUC), and diagnostic odds ratio (DOR). Meta-regression analysis was performed using STATA 16.0 software to compare the diagnostic accuracy of the two techniques. RESULTS: In the five studies included, 530 patients were eligible for this meta-analysis. For SMI, the pooled SEN and SPE were 0.75 (95% confidence interval [CI]: 0.69-0.91) and 0.88 (95% CI: 0.83-0.91), respectively, LR+ was 5.75 (95% CI: 4.26-7.78), LR- was 0.29 (95% CI: 0.23-0.36), DOR was 21.42 (95% CI, 13.61-33.73), and AUC was 0.8871. For CEUS, the pooled SEN and SPE were 0.87 (95% CI: 0.82-0.91) and 0.86 (95% CI: 0.82-0.89), respectively, LR+ was 5.92 (95% CI: 4.21-8.33), LR- was 0.16 (95% CI: 0.11-0.25), DOR was 38.27 (95% CI: 18.73-78.17), and AUC was 0.9210. CONCLUSIONS: Adding CEUS and (or) SMI to conventional US could improve its diagnostic performance in differentiating benign from malignant solid breast lesions.

The association between the locations of arteriovenous fistulas and patency rates: A systematic review and meta-analysis.

BACKGROUND: The arteriovenous fistulas (AVF) continue to be the most prevalent type of vascular access for hemodialysis (HD). However, the appropriate locations of AVF are controversial. We conducted the meta-analysis to investigate the differences in patency between upper-arm and forearm AVF. METHODS: PubMed, EMBASE, CENTRAL, and ISI Web of Science were searched to identify studies with differences in AVF patency at different locations. Reviewers searched the database, screened studies according to inclusion criteria, and conducted Meta-analysis. RESULTS: A total of 12 studies involving 3437 patients were selected. Pooled data showed that primary patency (PP) of AVF were higher in upper-arm than forearm at 1 and 2 years (odds ratio [OR] = 1.54, p = 0.0005; OR = 2.45, p = 0.001), but the differences in cumulative patency (CP) were not statistically significant at 1 and 2 years (OR = 2.10, p = 0.08; OR = 2.16, p = 0.1). The differences in PP and CP between upper-arm and forearm AVF in patients older than 65 years were not statistically significant at 1 (OR = 1.61, p = 0.05; OR = 2.05, p = 0.17) and 2 years (OR = 3.40, p = 0.13; OR = 1.38, p = 0.16). In Asian patients, the differences in PP and CP between upper-arm and forearm AVF were not statistically significant at 1 (OR = 1.17, p = 0.41; OR = 1.02, p = 0.94) and 2 years (OR = 2.95, p = 0.08; OR = 1.23, p = 0.41). CONCLUSIONS: In this study, the CP of upper-arm and forearm AVF was similar in overall population. There was no difference in PP and CP of AVF between upper-arm and forearm in Asian population or the elderly. The forearm AVF could be consider to be the first choice. for Asian patients or the elderly.

Maturation and survival of arteriovenous fistula: The challenge starts from the preoperative assessment stage.

BACKGROUND: It is necessary to assess the association between the preoperative indicators and the maturation and survival of arteriovenous fistula (AVF). METHODS: We retrospectively identified 236 patients with a new AVF created between 2016 and 2018 in our Dialysis Center. RESULTS: Multivariate Logistic regression showed that preoperative arterial diameter (odds ratio [OR] = 1.452, 95% confidence interval [CI] [1.233, 1.710], p < 0.001), preoperative venous diameter (OR = 1.296, 95% CI [1.166, 1.477], p < 0.001), left ventricular ejection fraction (LVEF) (OR = 1.187, 95% CI [1.103, 1.277], p < 0.001), and diabetes mellitus (OR = 0.245, 95% CI [0.107, 0.560], p = 0.01) were independent influential factors for AVF maturation. Two years after the AVF surgery follow-up, multivariate Cox proportional-hazards model showed that the preoperative arterial diameter (OR = 0.510, 95% CI [0.320, 0.813], p = 0.005), preoperative venous diameter (OR = 0.940, 95% CI [0.897, 0.985], p = 0.010) and diabetes mellitus (OR = 1.785, 95% CI [1.117, 2.855], p = 0.016) was prognostic factors of AVF survival. The Kaplan-Meier method showed that the primary survival of AVF in patients with different preoperative arterial diameter was statistically significant (log-rank χ2 = 15.415, p < 0.001), while the secondary survival was not statistically significant (log-rank χ2 = 0.131, p = 0.717). CONCLUSION: In our cohort, the preoperative arterial and venous diameter and diabetes mellitus were independent influential factors for AVF maturation and prognostic factors of AVF survival. However, the preoperative LVEF only associated with the maturation of AVF. Meanwhile, smaller arterial diameter (≤2.15 mm) was associated with AVF maturation failure, but did not impact secondary survival of AVF.

Circulating irisin level in chronic kidney disease patients: a systematic review and meta-analysis.

BACKGROUND: Irisin is not only a myokine but also an adipokine that is critical in many diseases including in the development of such diseases as obesity, diabetes mellitus, metabolic syndrome, coronary artery disease, and chronic inflammation. However, the association between irisin and chronic kidney disease (CKD) is unclear. This systematic review aimed to assess circulating irisin levels in patients with CKD and compare them with those in non-CKD patients. METHODS: PubMed, EMBASE, CENTRAL, ISI Web of Science, and CNKI were searched to identify observational studies of circulating irisin levels in patients with CKD. Two reviewers independently searched the databases and screened studies according to the inclusion criteria. Data were extracted using a standardized collection form. Meta-analysis was performed to compare the differences in circulating irisin levels between CKD and non-CKD patients. RESULTS: A total of 9 studies (6 cross-sectional and 3 case controls) involving 859 CKD patients and 393 non-CKD individuals were selected. The pooled data indicated that circulating irisin concentrations were significantly lower in CKD nondialysis patients (WMD = - 84.79, 95% CI - 170.23, 0.50; p < 0.05), peritoneal dialysis patients (WMD = - 235.81, 95% CI - 421.99, - 49.62; p = 0.01), and hemodialysis patients (WMD = - 217.46, 95% CI - 381.35, - 53.57; p = 0.009) than in healthy controls. CONCLUSIONS: This study confirmed that irisin levels were decreased in patients with CKD. Moreover, circulating irisin levels were lower in dialysis patients than in nondialysis patients.