Evaluation of Biopsy-Based Molecular Risk Prediction in Crescentic Glomerulonephritis

BackgroundThe ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) (NHHR) served as a novel comprehensive lipid indicator. This study aimed to explore the association between NHHR and the incidence of cardiometabolic multimorbidity (CMM).MethodsThis study included 8191 individuals from the China Health and Retirement Longitudinal Study (CHARLS) database. We used multivariable cox proportional hazards regression, logistic regression, and restricted cubic splines (RCS) analysis to evaluate the association between NHHR and CMM. Subgroup analyses and interaction tests were also performed.ResultsThe incidences of CMM among participants in quartiles (Q) 1–4 of NHHR were 7.03%, 8.3%, 10.06%, and 16.55%, respectively. The NHHR was significantly higher in individuals with CMM compared to those without CMM (P < 0.001). When assessed as a continuous variable, NHHR was independently associated with the risk of CMM, as demonstrated by both multivariable cox proportional hazards regression analysis (HR = 1.05, 95% CI = 1.02–1.07, P < 0.001) and logistic regression analysis (OR = 1.09, 95% CI = 1.04–1.15, P < 0.001). Compared to individuals in the lowest quartiles of the NHHR (Q1), the risk of CMM in the highest quartiles (Q4) was increased by 1.25-fold according to multivariable cox proportional hazards regression analysis (HR = 2.25, 95% CI = 1.73–2.93, P < 0.001) and by 1.48-fold according to logistic regression analysis (OR = 2.48, 95% CI = 1.86–3.31, P < 0.001). This association was consistent across nearly all subgroups. RCS analysis revealed a significant nonlinear association between NHHR and CMM. Additionally, the predictive ability of NHHR for CMM was 0.613, which was superior to that of both HDL-C and non-HDL-C (P < 0.05). Furthermore, the composite variable comprising NHHR and other traditional risk factors exhibited the highest predictive value (C statistic = 0.679).ConclusionA higher NHHR was closely associated with an increased risk of CMM. Further studies on NHHR could be beneficial for preventing and treating CMM.

Evaluation of the prognostic value of lymphadenectomy in low-grade serous ovarian cancer: A case-control multicenter retrospective study (177)

Purpose: This study aimed to identify predictive factors for the response to abiraterone in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC).Materials and Methods: This study analyzed the clinical characteristics of 167 patients with high-risk mHSPC who received abiraterone. Univariate and multivariable Cox proportional hazard regression analyses were conducted to identify predictive factors for castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival.Results: The mean age at presentation was 71.62±8.12 years. The prostate-specific antigen level was 218 ng/mL (interquartile range, 70–654 ng/mL). Of the 167 patients, 118 (72%) had a biopsy Gleason grade of 5, 43 patients (28.7%) had CRPC, and 30 patients (18.0%) died after a mean follow-up period of 13.5 months. In the multivariable Cox proportional hazard regression analyses for CRPC-free survival, a Gleason grade of 5 (hazard ratio [HR], 2.888; 95% confidence interval [CI], 1.133–7.361; p=0.026) and bone lesions ≥10 (HR, 4.194; 95% CI, 1.760–9.997; p=0.001) were significantly associated with CRPC-free survival. In the multivariable Cox proportional hazard regression analyses for cancer-specific survival, bone lesions ≥10 (HR, 3.185; 95% CI, 1.215–8.348; p=0.001) was significantly associated with cancer-specific survival.Conclusions: Patients with bone lesions ≥10 and Gleason grade of 5 are at higher risk of developing CRPC, and bone lesions ≥10 is at higher risk of cancer-specific survival in high-risk mHSPC treated with abiraterone.

Rapidly progressive glomerulonephritis (RPGN) is one of the nephrology emergencies which needs special attention. RPGN is a clinical description which determines by symptoms and signs of glomerulonephritis (GN); edema, hypertension and gross hematuria, and evidence of acute renal failure(severe decrease in glomerular filtration rate presents as oliguria or anuria, and increased serum levels of BUN and creatinine). Definite diagnosis of the disorder is based on kidney biopsy's findings. Early diagnosis and appropriate treatment plays a critical role in renal saving and preventing permanent glomerular damage. This chapter will focus on clinical manifestations, therapeutic protocols and prognostic factors in patients with different subtypes of RPGN. Rapidly progressive glomerulonephritis (RPGN) is defined as a syndrome with abrupt or insidious onset of hematuria, proteinuria, anemia, and rapidly progressing acute renal failure(ARF), and special findings on light microscopy examination of kidney biopsy's specimen; crescentic lesions which usually involved most glomerular architectures (Hirayama, et al., 2008; Rutgersetal., 2004). It also characterized by rapid loss of renal function (GFR 50 % of glomeruli (Couser, 1988). RPGN can be primary or secondary. Secondary forms occur in any form of severe glomerulonephritis including membranoproliferative GN, IgA nephropathy, post infectious GN, and systemic lupus erythematous (SLE). Primary RPGN is an autoimmune disease which is divided into three immunopathologic categories:(Rutgerset al., 2004; Haas .& Eustace, 2004): Type 1 RPGN: glomerulonephritis with antibodies directed against the glomerular basement membrane (GBM) (anti -GBM mediated GN) Type II RPGN: immune-complex induced glomerulonephritis Type III RPGN: Antineutrophil cytoplasmic antibody associated glomerulonephritis (ANCA-associated glomerulonephritis or pauci-immune GN) RPGN type 1 and 2 are responsible for 10 -20 % and 40 % of all cases respectively. RPGN type 2 can be found in different forms of systemic disease such as post infectious GN(PSGN), Ig-A nephropathy, Henoch–Schonlein purpura (HSP), SLE, membranous GN(MGN) or membranoproliferative GN(MPGN). A few cases of idiopathic immune complex-mediated RPGN have been reported (Jindal, 1999).

IgA nephropathy is the most common type of glomerulonephritis in the world. Its clinical and pathological manifestations vary. A few of the patients with IgA nephropathy present with rapidly progressive glomerulonephritis (RPGN) and/or crescent formation. Their conditions are serious and acute, but there are few reports on their characteristics, treatment and outcome. This study aimed to analyze the clinicalopathological features, treatment and prognosis of primary IgA nephropathy in children, to provide a reference for clinical diagnosis and treatment. A retrospective study was conducted in children with primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis admitted to our department from 2000 to 2014. The patients meeting the inclusion and exclusion criteria were included. Patients were divided into RPGN group and non-RPGN group according to the clinical manifestations, crescent formation group and non-crescent group, crescentic IgA nephropathy group and non-crescentic IgA nephropathy group according to renal biopsy. Their clinical manifestations and pathological features, treatment and prognosis were compared. A total of 265 patients were recruited, 10 patients (3.8%) had RPGN, 151 patients (57.0%) had crescent formation, 19 cases (7.2%) showed crescentic IgA nephropathy.Compared with non-RPGN group, RPGN group showed more gross hematuria, higher serum creatinine, lower creatinine clearance correction at biopsy and follow-up, and more crescentic IgA nephropathy (P<0.05). The percent of patients who received methylprednisolone pulse and blood purification therapy in RPGN group is higher than that of non-RPGN group (P<0.05). Compared with non-crescent group, crescent formation group showed more gross hematuria at biopsy and follow-up, higher serum creatinine at biopsy, lower creatinine clearance correction, more 24-hour urinary protein at biopsy and higher serum creatinine at follow-up (P<0.05). The percentage of patients received more methylprednisolone pulse, oral steroids, cyclophosphamide pulse in crescent formation group was higher than that of non-crescent group (P<0.05). Compared with non-crescentic IgA nephropathy group, crescentic IgA nephropathy group showed more RPGN percent, higher serum creatinine, more 24-hour urinary protein at biopsy (P<0.05). The percentage of patients who received more methylprednisolone pulse and blood purification therapy in crescentic IgA nephropathy group was more than non-crescentic IgA nephropathy group (P<0.05). At follow-up, 20.0% of the patients with RPGN and crescent nephritis returned to normal renal function and the percent of crescent glomerulonephritis but not RPGN was 71.4%, RPGN but not crescent glomerulonephritis was 80.0%, crescent formation but not crescent nephritis was 87.5%. In primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis, the patients with both RPGN and crescentic IgA nephropathy showed the worst clinical manifestations, its prognosis was worst while the patients with crescent formation showed the mildest clinical manifestations and best prognosis.

Background: Tamoxifen is a standard endocrine therapy for both pre- and postmenopausal ER-positive breast cancer patients. Patients with ER-positive disease have a long-term risk of distant recurrence, thus, long-term follow-up studies are essential to understand true treatment benefit. Clinically used tumor characteristics are prognostic 5-10 years after primary diagnosis, however, whether these characteristics are predictive of long-term tamoxifen benefit is largely unexplored. Therefore, we aimed to determine the long-term tamoxifen therapy benefit by the clinically used tumor characteristics in pre- vs postmenopausal patients in the Stockholm tamoxifen (STO)-trials with 20-years complete follow-up. Methods: Secondary analysis of 1242 ER-positive/HER2-negative patients from the STO-trials, randomized to at least 2 years of 40 mg tamoxifen vs no endocrine therapy (control). Premenopausal lymph node-positive patients were allocated to chemotherapy as standard of care and postmenopausal high-risk patients were further randomized to chemotherapy vs radiotherapy. Tumor immunohistochemical analysis was recently conducted. Complete 20-year follow-up was obtained from Swedish high-quality registries. Long-term distant recurrence-free interval (DRFI) was assessed by multivariable Cox proportional hazard regression and time-varying analysis using flexible parametric modelling. Results: Premenopausal patients showed significantly improved long-term DRFI from tamoxifen vs control if they were lymph node-negative (Hazard Ratio [HR]=0.46; 95% CI, 0.24-0.87), PR-positive (HR=0.61; 95% CI, 0.41-0.91), or of genomic low risk (HR=0.47; 95% CI, 0.26-0.85), see Table. In postmenopausal patients, significantly improved long-term DRFI from tamoxifen vs control was seen for all good prognosis tumor characteristics, i.e. small tumor size (pT≤20mm: HR=0.55; 95% CI, 0.39-0.77), tumor grade 1-2 (HR=0.55; 95% CI, 0.41-0.73), lymph node-negative (HR=0.44; 95% CI, 0.30-0.64), PR-positive (HR=0.60; 95% CI, 0.44-0.80), Ki-67-low (&amp;lt; 15%: HR=0.51; 95% CI, 0.38-0.68), and genomic low risk (HR=0.53; 95% CI, 0.37-0.74), see Table. Also, postmenopausal patients with large tumor size (pT&amp;gt;20mm: HR=0.64; 95% CI, 0.44-0.94) and PR-negative tumors (HR=0.51; 95% CI, 0.32-0.81) showed significant long-term tamoxifen benefit. Time-varying analysis in premenopausal patients indicated that tamoxifen therapy benefit diminished over time. Significant tamoxifen benefit until year 5, 10, and 15 after primary diagnosis was observed for PR-positive, lymph node-negative, and genomic low-risk patients, respectively. Postmenopausal patients had a significant long-term tamoxifen benefit if they had tumors of small or large tumor size, tumor grade 1-2, lymph node-negative status, PR-positive status, low Ki-67 levels, or genomic low risk. Conclusions: This study suggests a differential long-term tamoxifen therapy benefit in pre- vs postmenopausal patients. Clinically defined low-risk postmenopausal patients have long-term tamoxifen benefit, whereas the benefit is absent or diminish over time for premenopausal patients. Improved long-term prognostic and endocrine therapy predictive markers in premenopausal breast cancer patients with poor prognosis and long life-expectancy is needed, which could involve molecular tools. Long-term tamoxifen benefit in premenopausal and postmenopausal breast cancer patients by the clinically used tumor characteristics. Table Multivariable Cox proportional hazard regression analysis of 20-year distant recurrence-free interval (DRFI) for patients with ER-positive/HER2-negative tumors, comparing patients randomized to tamoxifen vs patients randomized to no endocrine therapy (control). Adjusted for age, randomization year, tumor size, tumor grade, lymph node status, PR status, Ki-67 status, chemotherapy, radiotherapy, and type of surgery. Citation Format: Annelie Johansson, Huma Dar, Anna Nordenskjöld, Gizeh Perez-Tenorio, Christina Yau, Christopher C. Benz, Laura J. Esserman, Laura Van’t Veer, Bo Nordenskjöld, Olle Stål, Tommy Fornander, Linda S. Lindström. Differential Long-Term Benefit from Adjuvant Tamoxifen Therapy in Estrogen Receptor (ER)-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Premenopausal and Postmenopausal Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-11.

To explore the correlation between albumin (Alb) combined with diuretic treatment and the mortality risk of septic patients with pre-existing congestive heart failure based on the United States Critical Care Medical Information Database-IV (MIMIC-IV), and to conduct the external validation. A retrospective cohort study was conducted. The clinical data of septic patients with pre-existing congestive heart failure admitted to the intensive care unit (ICU) from 2008 to 2019 in the MIMIC-IV 2.0 were extracted, including demographic characteristics, comorbidities, laboratory indicators on the first day of ICU admission, severity of illness, treatment measures, etc. For external validation, clinical data were collected from septic patients with pre-existing congestive heart failure admitted to the ICU of the Second People's Hospital of Shenzhen from October 2022 to December 2023. The patients were divided into Alb alone group and Alb combined with diuretic group. The ICU mortality was defined as the primary outcome event, and the 30-day and 60-day mortality were defined as the secondary outcomes. Multivariate Cox proportional hazard regression analysis was conducted to investigate the relationship between Alb combined with diuretic treatment and the mortality risk of ICU and 30 days in septic patients with pre-existing congestive heart failure, and subgroup analysis was performed. Kaplan-Meier survival curve was plotted to compared the 60-day cumulative survival rate between the Alb alone group and Alb combined with diuretic group. (1) Analysis results of data from MIMIC-IV: a total 1 754 patients were enrolled, of which 378 in the Alb alone group, and 1 376 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients in the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.11% (263/1 376) vs. 30.42% (115/378), 30-day mortality: 18.90% (260/1 376) vs. 32.54% (123/378), 60-day mortality: 24.49% (337/1 376) vs. 39.15% (148/378), all P < 0.05]. Based on the multivariate Cox proportional hazard regression adjusted models considering demographic characteristics, comorbidities, laboratory indicators, severity of illness, and treatment measures, it was shown that the use of Alb combined with diuretic was significantly associated with a reduced risk death of ICU and 30 days [ICU mortality risk: hazard ratio (HR) = 0.597, 95% confidence interval (95%CI) was 0.460-0.774, P < 0.001; 30-day mortality risk: HR = 0.557, 95%CI was 0.433-0.716, P < 0.001]. Subgroup analysis revealed that after adjusting for variables, regardless of gender, age, and whether or not patients had comorbidities such as hypertension, diabetes, severe liver disease, acute renal insufficiency, and sequential organ failure assessment (SOFA) score, the ICU mortality risk was significantly reduced in patients treated with Alb combined with diuretic (all HR < 1, P < 0.05), with no interaction observed (all P > 0.05). Kaplan-Meier survival curve showed the 60-day cumulative survival rate of patients in the Alb combined with diuretic group was significantly higher than that in the Alb alone group (Log-rank test: χ 2 = 49.62, P < 0.05). (2) External validation: a total of 385 patients were enrolled, of which 144 in the Alb alone group, and 241 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients of the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.92% (48/241) vs. 31.25% (45/144), 30-day mortality: 19.09% (46/241) vs. 28.47% (41/144), 60-day mortality: 24.07% (58/241) vs. 34.03% (49/144), all P < 0.05]. The results of multivariate Cox proportional hazard regression analysis, subgroup analysis, and Kaplan-Meier survival curve analysis were consistent with the data analysis of the MIMIC-IV database. Combination therapy of Alb and diuretic was associated with reduced mortality risk in septic patients with pre-existing congestive heart failure.

BackgroundThe CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is a key regulator of the programed death receptor ligand-1 (PD-L1) protein. However, the usefulness of CMTM6 expression as a prognostic indicator and the relationship between CMTM6 and PD-L1 expression in gastric cancer (GC) remains unclear.ObjectivesWe evaluated the expression and prognostic implications of CMTM6 in GC tissue and its relationship with PD-L1 expression.Patients and methodsThe protein expressions of CMTM6 and PD-L1 were detected in 122 cases of postoperative GC tissue using immunohistochemical (IHC) assays. Kaplan–Meier survival analysis was used to calculate the survival probability and a log-rank test was used to compare the survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the clinically-related factors associated with survival. Pearson’s correlation was used to determine the correlation analysis and estimate the statistical significance. The univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically-related factors and PD-L1 expression.ResultsKaplan–Meier survival analysis showed that patients with high CMTM6 expression had shorter overall survival (OS) than those with low expression (P < 0.001). The expression of CMTM6 was an independent risk factor for prognosis in multivariate Cox proportional hazard regression analyses (HR:2.221, CI% [1.36–3.628], P = 0.001). The OS of patients with positively expressed PD-L1 was significantly shorter than those with negatively expressed PD-L1 (P = 0.003). The expression of CMTM6 was significantly related to the positive expression of PD-L1 in gastric cancer tissues (r = 0.186, P = 0.041). The expression of CMTM6 was the independent risk factor for PD-L1 expression in multivariate logistic regression analysis (OR:2.538, CI% [1.128–5.714], P = 0.024).ConclusionCMTM6 expression is significantly related to PD-L1 and may be a useful prognostic indicator and a specific therapeutic target for cancer immunotherapy for GC patients.

To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post-transplantation clinical outcomes after living donor kidney transplantation. Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 - Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log-rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection-free survival, and the unpaired t-test and multivariate linear regression to assess post-transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor-specific antibody positivity and medically complex living donors as explanatory variables. Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death-censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post-transplantation did not differ within the groups. Post-transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant. The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long-term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.

B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias.

BackgroundThe prognostic benefit of extensive lymphadenectomy remains controversial in esophageal squamous cell carcinoma (ESCC). The purpose of this retrospective study was to investigate the potential effect of solitary mediastinal (SM) lymph node metastasis and solitary celiac (SC) lymph node metastasis on the short- and long-term outcomes for patients who underwent minimally invasive McKeown esophagectomy.MethodsFrom September 2009 to December 2020, a total of 934 cases were diagnosed with ESCC and underwent minimally invasive McKeown esophagectomy in our department; 223 cases met the inclusion and exclusion criteria. Propensity score matching (PSM) was utilized to contrast the postoperative results and long-term survival of Group 1 (SM) and Group 2 (SC). Univariate and multivariate Cox proportional hazards regression analyses were used on possible predictors of survival.ResultsOne hundred forty-seven patients were available for outcome comparison after PSM. The postoperative results were not significantly different between the two groups. In terms of long-term survival, the 5-year disease-free survival (DFS) was 37.6% and 57.3% (p = 0.191) and 5-year disease-specific survival (DSS) was 39.7% and 68.4% (p = 0.028) for Group 1 (SM) and Group 2 (SC), respectively. Univariate and multivariate Cox proportional hazards regression analyses showed that body mass index (BMI), pathologic stage (pStage), and SC/SM grouping had significant hazard ratios (HRs), which suggested that SC is associated with better DSS.ConclusionThis cohort study showed that SC lymph node metastasis has a better long-term survival compared with SM lymph node metastasis in esophagectomy of ESCC. The results challenge the current understanding and need confirmation in further research.

This study was performed to probe the clinical significance of serum lncRNA FOXP4-AS1 in nasopharyngeal carcinoma (NPC) tumorigenesis. LncRNA FOXP4-AS1 from nasopharyngeal carcinoma patients and healthy volunteers were abstracted and converged. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of FOXP4-AS1. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of FOXP4-AS1. Kaplan-Meier survival analysis and log-rank test were used to assess the patients' survival prognosis. Independent risk factors for overall survival (OS) and progression-free survival (PFS) were assessed by univariate and multivariate cox proportional hazards regression analysis. In this study, we observed that the levels of FOXP4-AS1 were significantly upregulated in nasopharyngeal carcinoma patients compared to healthy volunteers. Besides, the expression of FOXP4-AS1 was closely associated with T stage, lymph node metastasis, and clinical stage. Meanwhile, ROC analysis found that FOXP4-AS1 had diagnostic values to distinguish tumor patients from healthy volunteers. Furthermore, patients with high FOXP4-AS1 expression level had poorer OS and PFS than those with low FOXP4-AS1 expression. Finally, univariate and multivariate Cox proportional hazards regression analysis found that the T stage, lymph node metastasis, clinical stage, FOXP4-AS1 expression might be independent risk factors for OS and PFS of nasopharyngeal carcinoma patients. This study firstly clarified that FOXP4-AS1 was overexpressed in nasopharyngeal carcinoma. And FOXP4-AS1 may act as a diagnostic and prognostic biomarker, and hopeful therapeutic target for nasopharyngeal carcinoma patients.

Most colorectal cancer (CRC) patients are at an advanced stage when they are first diagnosed. Risk factors for predicting overall survival (OS) in advanced stage CRC patients are crucial, and constructing a prognostic nomogram model is a scientific method for survival analysis. A total of 2956 advanced stage CRC patients were randomised into training and validation groups at a 7:3 ratio. Univariate and multivariate Cox proportional hazards regression analyses were used to screen risk factors for OS and subsequently construct a prognostic nomogram model for predicting 1-, 3-, 5-, 8- and 10-year OS of advanced stage CRC patients. The performance of the model was demonstrated by the area under the curve (AUC) values, calibration curves and decision curve analysis (DCA). Kaplan-Meier curves were used to plot the survival probabilities for different strata of each risk factor. There was no statistically significant difference (p > 0.05) in the 32 clinical variables between patients in the training and validation groups. Univariate and multivariate Cox proportional hazards regression analyses demonstrated that age, location, TNM, chemotherapy, liver metastasis, lung metastasis, MSH6, CEA, CA199, CA125 and CA724 were risk factors for OS. We estimated the AUC values for the nomogram model to predict 1-, 3-, 5-, 8- and 10-year OS, which in the training group were 0.826 (95% CI: 0.807-0.845), 0.836 (0.819-0.853), 0.839 (0.820-0.859), 0.835 (0.809-0.862) and 0.825 (0.779-0.870) respectively; in the validation group, the corresponding AUC values were 0.819 (0.786-0.852), 0.831 (0.804-0.858), 0.830 (0.799-0.861), 0.815 (0.774-0.857) and 0.802 (0.723-0.882) respectively. Finally, the 1-, 3-, 5-, 8- and 10-year OS rates for advanced stage CRC patients were 73.4 (71.8-75.0), 49.5 (47.8-51.4), 43.3 (41.5-45.2), 40.1 (38.1-41.9) and 38.6 (36.6-40.8) respectively. We constructed and validated an original nomogram for predicting the postoperative OS of advanced stage CRC patients, which can help facilitates physicians to accurately assess the individual survival of postoperative patients and identify high-risk patients.

Oral squamous cell carcinoma (OSCC) is a major malignant cancer of the head and neck. Long non-coding RNAs (lncRNAs) have emerged as critical regulators during the development and progression of cancers. This study aimed to identify a lncRNA-related signature with prognostic value for evaluating survival outcomes and to explore the underlying molecular mechanisms of OSCC. Associations between overall survival (OS), disease-free survival (DFS) and candidate lncRNAs were evaluated by Kaplan–Meier survival analysis and univariate and multivariate Cox proportional hazards regression analyses. The robustness of the prognostic significance was shown via the Gene Expression Omnibus (GEO) database. A total of 2,493 lncRNAs were differentially expressed between OSCC and control samples (fold change >2, p < 0.05). We used Kaplan–Meier survival analysis to identify 21 lncRNAs for which the expression levels were associated with OS and DFS of OSCC patients (p < 0.05) and found that down-expression of lncRNA AC012456.4 especially contributed to poor DFS (p = 0.00828) and OS (p = 0.00987). Furthermore, decreased expression of AC012456.4 was identified as an independent prognostic risk factor through multivariate Cox proportional hazards regression analyses (DFS: p = 0.004, hazard ratio (HR) = 0.600, 95% confidence interval(CI) [0.423–0.851]; OS: p = 0.002, HR = 0.672, 95% CI [0.523–0.863). Gene Set Enrichment Analysis (GSEA) indicated that lncRNA AC012456.4 were significantly enriched in critical biological functions and pathways and was correlated with tumorigenesis, such as regulation of cell activation, and the JAK-STAT and MAPK signal pathway. Overall, these findings were the first to evidence that AC012456.4 may be an important novel molecular target with great clinical value as a diagnostic, therapeutic and prognostic biomarker for OSCC patients.

The objective of this study is to investigate the risk factors of renal flare in patients with membranous lupus nephritis (class V lupus nephritis). Biopsy-proven pure membranous lupus nephritis patients diagnosed between January 1997 and September 2017 were studied. We assessed and compared the clinical and pathological parameters between patients who experienced renal flare and those who did not. To identify risk factors of renal flare, multivariable Cox proportional hazard regression analysis was performed. Out of the 53 patients with pure membranous lupus nephritis, 17 patients (32.1%) experienced renal flare during a median follow-up of 121.5 months (range 44.4–196.9). Patients who experienced renal flare had significantly higher proportion of tubulointerstitial inflammation (76.5% vs. 36.1%, p = 0.006) and tubular atrophy/interstitial fibrosis (70.6% vs. 27.8%, p = 0.003) at baseline. In multivariable Cox proportional hazard regression analysis, the presence of tubulointerstitial inflammation [adjusted hazard ratio (HR) 5.532, 95% confidence interval (CI) 1.722–17.776, p = 0.004] and tubular atrophy/interstitial fibrosis (adjusted HR 4.328, 95% CI 1.450–12.916, p = 0.009) at baseline was significantly associated with increased risk of renal flare. The presence of tubulointerstitial inflammation and tubular atrophy/interstitial fibrosis is associated with increased risk of renal flare in patients with membranous lupus nephritis.