Multivariate Cox Regression Analysis Research Articles

Disulfidptosis-related long non-coding RNA signature predicts the prognosis, tumor microenvironment, immunotherapy, and antitumor drug options in colon adenocarcinoma.

This study aims to investigate the role and prognostic significance of long non-coding RNAs (lncRNAs) associated with disulfidptosis in colon adenocarcinoma (COAD). The TCGA database's clinical data and transcriptome profiles were employed. Analysis of previous studies identified 10 disulfidptosis-related genes (DRGs). We used these genes to construct a signature that could independently and accurately predict the prognosis of patients with COAD. The Kaplan-Meier (K-M) curve analysis showed that the lower-risk group had a better prognosis. With the help of multivariate Cox regression analysis, the risk score produced from the patient's signature might independently predict the outcomes. Utilizing a nomogram, the receiver operating characteristic (ROC) curve, and principal component analysis (PCA), the signature's predictive ability was also confirmed. It's interesting to note that immunotherapy, especially PD-1 immune checkpoint suppression, was more likely to benefit low-risk patients. The IC50 levels for certain anticancer agents were lower in the high-risk group. Finally, qRT-PCR analyses in colon cancer cell lines revealed elevated levels of lncRNAs CASC9, ZEB1-AS1, ATP2A1-AS1, SNHG7, AL683813.1, and AP003555.1, and reduced levels of FAM160A1-DT and AC112220.2, compared to normal cell lines. This signature offers insights into prognosis, tumor microenvironment, and options for immunotherapy and antitumor drugs in patients with COAD.

Current status of etiology and outcomes of acute liver failure in India-A multicentre study from tertiary centres.

Acute liver failure (ALF) is a medical emergency and liver transplantation (LT) may be required as definitive therapy. The etiology varies across geographical locations and is mostly viral dominant in India. We aimed at evaluating the spectrum, impact of interventions (plasma exchange [PLEx], continuous renal replacement therapy [CRRT]) and outcomes of ALF in India in recent times. A multicentre retrospective study across four major tertiary care centres. As many as 183ALF patients (median age, 23years; females, 43.1%; model for end-stage liver disease [MELD], 32.7) from January 2021 to December 2023 were included. Nineteen percent had infection and 40.4% of patients satisfied King's College criteria (KCC) at admission. Most common cause for ALF was hepatitis A virus (HAV) (44.2%) followed by rodenticide poisoning (10.3%). Approximately 35% of patients each received either PLEx or CRRT. The 7, 14 and 21-day transplant-free survival probability was 65.5%, 60.1%, and 57.3%, respectively. Only 3.8% of patients underwent liver transplantation. On multivariable Cox regression analysis, hemoglobin (HR, 0.74 [0.63-0.87]), lactate (HR, 1.14 [1.03-1.26]), advanced hepatic encephalopathy (HE) (HR, 4.87 [1.89-12.5]) and fulfilling KCC [HR, 10.04 [4.57-22.06]) at admission were the independent predictors of mortality. A model including KCC + lactate + HE ≥ 3 with or without hemoglobin had an AUROC of 0.81-0.84 to predict mortality. In those who underwent PLEx, advanced HE (HR, 4.13 [1.75-9.7]), procalcitonin (HR, 1.18 [1.07-1.30]) and KCC (HR, 4.6 [1.6-13.1), while for those who received CRRT, lactate (HR, 1.37 [1.22-1.54]) and KCC (HR, 6.4 [2.5-15.8]) independently predicted mortality. Hepatitis A virus is currently the most common cause for ALF in India, emphasizing the need for universal vaccination programmes. Spontaneous survival in tertiary care centres is 57%. LT rates were low.

A Comprehensive Analysis Exploring the Impact of an Immunogenic Cell Death-Related Panel for Ovarian Cancer.

Ovarian cancer (OV) is a malignant tumor that ranks first among gynecological cancers, thus posing a significant threat to women's health. Immunogenic cell death (ICD) can regulate cell death by activating the adaptive immune system. Here, we aimed to comprehensively characterize the features of ICD-associated genes in ovarian cancer, and to investigate their prognostic value and role in the response to immunotherapy. After analyzing datasets from The Cancer Genome Atlas, we utilized weighted gene coexpressionnetwork analysis to screen for hub genes strongly correlated with ICD genes in OV, which was subsequently validated with OV samples from the Gene Expression Omnibus (GEO) database. A prognostic risk model was then constructed after combining univariate, multivariate Cox regression and LASSO regression analysis to recognize nine ICD-associated molecules. Next, we stratified all OV patients into two subgroups according to the median value. The multivariate Cox regression analysis showed that the risk model could predict OV patient survival with good accuracy. The same results were also found in the validation set from GEO. We then compared the degree of immune cell infiltration in the tumor microenvironment between the two subgroups of OV patients, and revealed that the high-risk subtype had a higher degree of immune infiltration than the low-risk subtype. Additionally, in contrast to patients in the high-risk subgroup, those in the low-risk subgroup were more susceptible to chemotherapy. In conclusion, our research offers an independent and validated model concerning ICD-related molecules to estimate the prognosis, degree of immune infiltration, and chemotherapy susceptibility inpatients with OV.

The mitochondrial-derived peptide MOTS-c may refine mortality and cardiovascular risk prediction in chronic hemodialysis patients: a multicenter cohort study.

Introduction Uremic patients exhibit remarkably increased rates of mortality and cardiovascular events, but risk prediction in this setting remains difficult. Systemic mitochondrial dysfunction is pervasive in ESKD and may contribute to CV complications. We tested the clinical significance of circulating MOTS-c, a small mitochondrial-derived peptide, as a biomarker for improving mortality and CV risk prediction in hemodialysis (HD) patients. Methods We conducted a prospective, observational, multicenter study on 94 prevalent HD patients. The study endpoint was a composite of all-cause mortality and non-fatal CV events. The diagnostic and prognostic capacity of predictive models based on cohort-related risk factors were tested before and after the inclusion of MOTS-c. Results MOTS-c levels were higher in HD patients than in controls (p<0.001) and even more elevated (p=0.01) in the 53 individuals experiencing the combined endpoint during follow-up (median duration: 26.5 mo.). MOTS-c was independently associated with the endpoint at either multivariate logistic (OR 1.020; 95%CI 1.011-1.109; p=0.03) or Cox-regression analyses (HR 1.004; 95%CI 1.000-1.025; p=0.05) and the addition of this biomarker to prognostic models including the other cohort-related risk predictors (age, LVMi, E/e', diabetes, pulse pressure) significantly improved the calibration, risk variability explanation, discrimination (ROC-AUC from 0.727 to 0.743; C-index from 0.658 to 0.700) and, particularly, the overall reclassification capacity (NRI 15.87%; p=0.01). Conclusions In HD patients, the mitochondrial-derived peptide MOTS-c may impart significant information to refine CV risk prediction, beyond cohort-related risk factors. Future investigations are needed to generalize these findings in larger and more heterogeneous cohorts.

Immune-related gene signature improves prognosis prediction in patients with breast cancer and associates it with tumor immunity and inflammatory response

BackgroundThe prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients.MethodsWe analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes.ResultsPatients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration.ConclusionsThe immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Prognostic Value of High-Density Lipoprotein Cholesterol in Patients with Overt Hepatic Encephalopathy

Overt hepatic encephalopathy (OHE), a serious complication of liver cirrhosis, is associated with alterations in lipid and lipoprotein metabolism. We evaluated the correlation between high-density lipoprotein cholesterol (HDL-C) levels and transplant-free (TF) mortality in patients with OHE. Patients with OHE admitted to Beijing Ditan Hospital between January 2010 and August 2016 (n = 821) and between September 2016 and December 2020 (n = 480) were included in the training and validation sets, respectively. Independent predictors were explored by a multivariate Cox regression analysis, and the area under the receiver operating characteristic curve (AUC) was used to assess the prognostic value of these factors. The prognostic value of HDL-C was good (AUC at 1 year: 0.745) and was equivalent to that of the Model for End-Stage Liver Disease (MELD) score (AUC at 1 year: 0.788). The optimal threshold values for HDL-C and MELD were 0.5 mmol/L and 17, respectively. The 1-year TF mortality rates in the low-risk (HDL-C ≥ 0.5 mmol/L and MELD < 17) and high-risk (HDL-C < 0.5 mmol/L and MELD ≥ 17) groups were 7.5% and 51.5% in the training set and 10.1% and 48.2% in the validation set, respectively. HDL-C level < 0.5 mmol/L and MELD score > 17 can facilitate the identification of high-risk patients and provide a basis for timely treatment.

Imaging timing after surgery for glioblastoma: an evaluation of practice in Great Britain and Ireland (INTERVAL-GB)- a multi-centre, cohort study.

Post-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear. Multi-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3-6 months) and EANO (Post-operative scan < 48h, MRI every 3 months). There were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54-70), yielding 10,100 (median, 12.5/person, IQR 5.2-19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0-4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46-0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79-1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45-0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84-1.16, P = 0.874). Regular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes.

Relationship between enteral nutrition timing and 28-day mortality in critically ill stroke patients in the MIMIC-IV database

BackgroundThe ideal timing for commencing enteral nutrition (EN) in critically ill stroke patients in the intensive care unit (ICU) remains a subject of debate, with ongoing controversy regarding the impact of early EN (EEN) initiation. In this study, we investigated the association between the timing of EN initiation and 28-day mortality using data from the MIMIC-IV database.MethodsThis study employed a retrospective cohort design using the MIMIC-IV database to identify stroke patients who received EN during their hospital stay. The main focus of this investigation was to examine 28-day mortality among these patients following hospital admission. Various demographic, clinical, laboratory, and intervention variables were considered as covariates. The Cox regression analysis was employed to assess the correlation between the timing of EN initiation and 28-day mortality, and restricted cubic splines (RCS) analysis was used to test for non-linear correlation. Patients were then stratified into two cohorts depending on the timing of EN initiation: within 2 days (n = 564) and beyond 2 days (n = 433). A multivariate Cox regression analysis was used to investigate the difference in 28-day mortality between the groups.ResultsA total of 997 participants were included in this study, with 318 (31.9%) dying within 28 days. We observed that the timing of EN initiation correlated with 28-day mortality, but this correlation was not significant after adjusting for covariates (crude HR: 0.94, 95% CI: 0.88–1, p = 0.044; adjusted HR: 0.96, 95% CI: 0.9–1.02, p = 0.178). The RCS analysis showed that the correlation was not non-linear. Notably, in the multivariate regression models, early EN initiation was associated with a higher mortality rate compared to late EN initiation [odds ratio (OR) = 1.34, 95% CI: 1.06–1.67, p = 0.012]. After adjusting for various confounding factors in the multivariate Cox regression models, we identified that patients in the early EN group had a 28% higher risk of mortality than those in the reference group (OR = 1.27, 95% CI: 1–1.61, p = 0.048). These associations remained consistent across various patient characteristics, as revealed through stratified analyses.ConclusionsEarly commencement of EN in critically ill stroke patients may be linked to a higher risk of 28-day mortality, highlighting the need for further investigation and a more nuanced consideration of the optimal timing for commencing EN in this patient population.

Characterization of SUSD3 as a novel prognostic biomarker and therapeutic target for breast cancer.

Breast cancer (BC) remains a significant global health challenge, contributing substantially to cancer-related deaths worldwide. Its prevalence and associated death rates remain alarmingly high, highlighting the persistent public health burden. The objective of this study was to systematically examine the involvement of SUSD3 (Sushi Domain-Containing 3) in BC, highlighting its crucial role in the pathogenesis and progression of this disease. BC-related gene microarray data, along with corresponding clinicopathological information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Leveraging TIMER and HPA databases, we conducted comparative analyses to evaluate SUSD3 expression in BC. We then analyzed the association between SUSD3 and clinical traits, as well as the prognostic value of SUSD3. SUSD3-related differential expression genes (DEGs) were sent for analysis utilizing GO, KEGG, and GSEA. We utilized SUSD3 mRNA expression to assess immune cells' scores in BC tissues calculated by single-sample enrichment analyses based on "CIBERSORT" R package. Drug sensitivity analysis was used to screen potential drugs sensitive to SUSD3. R software was used for statistical analyses and graphical representation of the data. Our findings confirmed a significant upregulation of SUSD3 expression in BC, which correlated with a favorable prognosis. Clinical correlation analysis further emphasized the strong association between SUSD3 expression and key clinical parameters like estrogen receptor (ER) status, progesterone receptor (PR) status, stage, and T classification in breast cancer. Univariate and multivariate Cox regression analyses showed that SUSD3 could be used as an independent prognostic factor for BC. Differentially expressed genes (DEGs) co-expressed with SUSD3 were significantly associated with various biological processes, such as the cell cycle, DNA replication, p53 signaling pathway, cancer-related pathways, and Wnt signaling pathway, as indicated by gene set enrichment analysis (GSEA). Furthermore, our analysis demonstrated that SUSD3 generally exhibited negative associations with immune modulators. Drug sensitivity analysis revealed positive correlations between SUSD3 and the efficacy of Fulvestrant, Raloxifene, and Fluphenazine. The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.

Radiofrequency Ablation for the Treatment of Benign Thyroid Nodules: 10-Year Experience.

Background: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. Methods: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan-Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. Results: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24-143 months). The mean VRR was 81% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA (n = 33) or surgery (n = 4) or left under observation (n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared with nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183-4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms (n = 4) or newly detected thyroid tumors (n = 22), one benign and 21 malignant. The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. Conclusion: RFA is safe and effective for treating benign thyroid nodules, with a high VRR at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients.

Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Assessment of survival prediction after surgery in spinal metastases patients using the Global Spine Study Tumor Group (GSTSG) risk calculator; an external validation from a tertiary cancer hospital.

We aim to validate the Global Spine Tumor Study Group (GSTSG) score compared to previous prognostic scoring systems in spinal metastasis. We conducted a retrospective study from January 2013 to December 2022. The survival prediction was compared between the GSTSG, Tomita Score, Revised Tokuhashi Score, and Skeletal Oncology Research Group (SORG) Nomogram. Single-variable factors associated with survival rate were analyzed using univariate Cox regression and multivariable Cox proportional hazard model. Receiver operating characteristic was used for external validity analysis at 3, 6, 12, and 24months. The overall survival rate was reported using the Kaplan-Meier survival curve. 248 spinal metastasis patients were included. The mean age was 59.23 ± 12.55years. The mean duration of follow-up time was 470.29 ± 441.98days. The external validity of GSTSG was the highest at all follow-up times (sufficiently accurate AUC > 0.7), which was about the same as SORG at 3months (both AUC of GSTSG and SORG = 0.76) and higher than modified Tokuhashi and Tomita score at 12months (AUC of GSTSG = 0.78, SORG = 0.71, Tomita = 0.64, and modified Tokuhashi = 0.61, respectively). From our study, the Multivariate Cox regression analysis indicates that the significant factors related to survival rate are regular analgesic use of weak opioids, lung metastasis, and previous chemotherapy. Compared to other traditional spinal metastases prognostic scoring systems, GSTSG shows the highest AUC for external validity in all follow-up times up to 24months.

59 Risk Factors of Immune Related Adverse Events in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Abstract Background Immune checkpoint inhibitor (ICI) based combinations have become the standard of care for first-line treatment in patients with metastatic renal cell carcinoma (mRCC). However, ICI can be responsible for immune-related adverse events (irAEs). Herein, we aimed to identify risk factors of immune related adverse events (irAEs) in patients treated with current first line (1L) combination of ICIs (ICI+ICI) or ICI with vascular endothelial growth factor (VEGF) targeted therapy (ICI+VEGF). Methods Data was collected retrospectively from patients treated for mRCC at Dana-Farber Cancer Institute, either receiving dual ICI or ICI+VEGF as 1L treatment regimen. Patients were categorized into two groups: those who developed grade ≥ 2 irAEs and those with grade 1 or no AEs. Time to toxicity (TT) was defined as the primary outcome. Univariate Cox regression analysis was initially conducted to identify potential predictive factors associated with irAEs. Subsequently, significant variables related to treatment adverse events were included in a multivariate Cox regression analysis with adjustments for multiple baseline factors. Results Among the 158 patients included, 122 (77.2%) were male, and 36 (22.8%) were female. Median age of patients at the treatment start date of therapy was 61 years (Q1-Q3: 62-69). A total of 57 (36.1%) patients developed grade ≥ 2 irAEs. The median follow-up of patients was 25.7 months. Univariate analysis showed that diabetes, male sex, and ccRCC may indeed influence the development of irAEs with a trend towards significance. However, thrombocytosis could be a protective factor against developing irAEs (p &amp;lt;0.05, Table). Upon multivariate analysis, only ccRCC remained significant as a risk factor for irAEs compared to other subtypes, with a HR of 2.93 (95% CI:1.05-8.18, p = 0.04) (Table). Table: Cox regression analysis for assessment of risk factors associated with irAEs Conclusions In this real-world study, we investigated potential clinical risk factors at baseline related to irAEs in patients with mRCC undergoing ICI-combination therapy. ccRCC histology was significantly associated with a higher risk of developing irAEs compared to other RCC subtypes. The retrospective design and the number of patients could be potential limitations of our findings.

Link between remnant cholesterol and the reversion to normoglycemia in Chinese adults with prediabetes: a 5-year cohort study

Despite the clear association between remnant cholesterol (RC)and diabetes risk, no study to date has examined the relationship between RC and reversal of prediabetes to normoglycemia. This retrospective cohort study included a total of 15,023 patients with prediabetes who underwent a physical examination between 2010 and 2016. The link between initial RC levels and the reversion from prediabetes to normoglycemia was analyzed using the Cox proportional-hazards regression model. Additionally, the study explored the possible relationship between RC and the probability of returning normoglycemia by applying Cox proportional hazards regression models with cubic spline functions. To address competing risks, a multivariate Cox regression analysis was undertaken, treating the onset of diabetes as a competing risk event for reversing prediabetes to normoglycemia. Additionally, the study incorporated extensive subgroup analyses alongside multiple sensitivity analyses, enhancing the reliability and robustness of the results. After adjusting for covariates, the findings indicated that RC was inversely associated with the likelihood of reverting to normoglycemia (per 5 mg/dL increase, HR = 0.918, 95% CI 0.909–0.927). The analysis also revealed a nonlinear relationship between RC and normoglycemia reversion, with an inflection point at 51.08 mg/dL. For RC values below this inflection point (RC < 50.08 mg/dL), the HR for the probability of returning to normoglycemia was 0.907 (95% CI 0.897–0.917 per 5 mg/dL). Additionally, the competing risks model demonstrated a negative relationship between RC and the reversal of prediabetes to normoglycemia (SHR = 0.92, 95% CI 0.91–0.93). Sensitivity analyses confirmed the robustness and stability of these results. This study demonstrated a negative and non-linear association between RC and the probability of reversion to normoglycemia in Chinese adults with prediabetes. By actively intervening to reduce RC levels, at least to below 51.08 mg/dL, further reduction of RC may significantly increase the probability of returning to normoglycemia from prediabetes.

Unbalanced circulating Humanin levels and cardiovascular risk in chronic hemodialysis patients: a pilot, prospective study.

Mortality and cardiovascular (CV) risk prediction in individuals with end-stage kidney disease (ESKD) on chronic hemodialysis (HD) remains challenging due to the multitude of implicated factors. In a multicenter ESKD-HD cohort, we tested the prognostic yield of the assessment ofcirculating Humanin, a small mitochondrial-derived peptide involved in CV protection, on CV events and mortality. We conducted a prospective, observational, pilot study on 94 prevalent HD patients. The prognostic capacity of circulating Humanin levelswas tested on a primary composite (all-cause mortality + non-fatal CV events) and a secondary exploratory endpoint (all-cause mortality alone). Baseline Humanin levelwas comparable in patients reaching the primary or secondary endpoint as compared to others (p = 0.69 and 0.76, respectively). Unadjusted followed by multivariable Cox regression analyses adjusted for age, left ventricular mass index (LVMi), E/e', pulse pressure and diabetes mellitus indicated a non-linear relationship between Humanin levels and the composite outcome with the highest Hazard Ratio (HR) associated with very low (< 450.7pg/mL; HR ranging from 4.25 to 2.49) and very high (> 759.5pg/mL; HR ranging from 5.84 to 4.50) Humanin values. Restricted cubic splines fitting univariate and multivariate Cox regression analyses visually confirmed a curvilinear trend with an increasing risk observed for lower and higher Humanin values around the median, respectively. A similar, u-shaped association was also evidenced with the secondary endpoint. Altered Humanin levels may impart prognostic information in ESKD-HD patients at risk of death or CV events. Future investigations are needed to confirm whether Humanin measurement could improve CV and mortality risk prediction beyond traditional risk models.

Clinicopathological features and outcomes of PLA2R-related membranous nephropathy with renal glycosuria.

Membranous nephropathy (MN) is an immune complex-mediated disease. Massive proteinuria can lead to Fanconi syndrome, clinically manifesting as renal glycosuria. The prevalence and prognosis of M-type phospholipase A2 receptor (PLA2R)-related MN with renal glycosuria remain unknown. Patients diagnosed with PLA2R-related MN with renal glycosuria were reviewed, and the control group comprised patients with MN without renal glycosuria who were randomly selected at a ratio of 1:3. 50 patients diagnosed with PLA2R-related MN with renal glycosuria from January 2015 to January 2020 were included, with a prevalence of 2.3%. Compared with patients without renal glycosuria, those with renal glycosuria exhibited greater proteinuria, lower estimated glomerular filtration rate (eGFR), and higher use of diuretics, anticoagulants, antibiotics, traditional Chinese medicine, and tacrolimus within 3 months prior to renal biopsy (all p<0.05). Histologically, patients with renal glycosuria exhibited more severe pathological stages, acute/chronic tubulointerstitial lesions, and tubulointerstitial inflammation (all p<0.05). Of the 10 patients treated with rituximab (RTX), proteinuria remission was maintained in 6 (60%) patients, and urine glucose remission was achieved in 5 of these 6 patients (83.3%). Multivariate Cox regression analysis showed that renal glycosuria and age >50 years were independent risk factors for end-stage renal disease (ESRD) or a 30% reduction in the eGFR in patients with PLA2R-related MN. PLA2R-related MN patients with renal glycosuria presented with more severe clinicopathological manifestations and worse prognoses. Nephrotoxic drugs should be administered rationally, and RTX should be considered as a promising treatment option.

Mortality in acute ischemic stroke patients with new cancer diagnosed during the index hospitalization versus after discharge

BackgroundEarly diagnosis of previously unknown cancer (i.e., occult cancer) after an acute ischemic stroke (AIS) could result in faster initiation of cancer therapy and potentially improve clinical outcomes. Our study aimed to compare mortality rates between AIS patients with occult cancer diagnosed during the index stroke hospitalization versus those diagnosed after hospital discharge. MethodsAmong consecutive AIS patients treated at our stroke center from 2015 through 2020, we identified new cancer diagnoses made within the year after the AIS. We used multivariable Cox regression analyses to evaluate the association between the timing of occult cancer diagnosis (during the AIS hospitalization versus after discharge) and long-term survival. ResultsOf 3894 AIS patients with available long-term follow-up data, 59 (1.5 %) were diagnosed with a new cancer within one year after index stroke. Of these, 27 (46 %) were diagnosed during the index hospitalization and 32 (54 %) were diagnosed after discharge. During a median follow-up of 406 days (interquartile range, 89–1073), 70 % (n = 19) of patients whose cancer was diagnosed during hospitalization had died, compared to 63 % (n = 20) of patients whose cancer was diagnosed after discharge (p= 0.58). In our main multivariable model, there was no difference in long-term mortality between patient groups (adjusted hazard ratio, 1.16; 95 % confidence interval, 0.53–2.52; p= 0.71). ConclusionsIn this analysis, timing of a new cancer diagnosis after AIS did not seem to influence patients’ long-term survival. Given the fairly small number of included patients with previously occult cancer, larger multicenter studies are needed to confirm our results.

Personalized approach to malignant struma ovarii: Insights from a web-based machine learning tool.

Malignant struma ovarii (MSO) is a rare ovarian tumor characterized by mature thyroid tissue. The diverse symptoms and uncommon nature of MSO can create difficulties in its diagnosis and treatment. This study aimed to analyze data and use machine learning methods to understand the prognostic factors and potential management strategies for MSO. In this retrospective cohort, the Surveillance, Epidemiology, and End Results (SEER) database provided the data used for this study's analysis. To identify the prognostic variables, we conducted Cox regression analysis and constructed prognostic models using five machine learning algorithms to predict the 5-year survival. A validation method incorporating the area under the curve of the receiver operating characteristic curve was used to validate the accuracy and reliability of the machine learning models. We also investigated the role of multiple therapeutic options using the Kaplan-Meier survival analysis. The study population comprised 329 patients. Multivariate Cox regression analysis revealed that older age, unmarried status, chemotherapy, and the total number of tumors in patients were poor prognostic factors. Machine learning models revealed that the multilayer perceptron accurately predicted outcomes, followed by the random forest classifier, gradient boosting classifier, K-nearest neighbors, and logistic regression models. The factors that contributed the most were age, marital status, and the total number of tumors in the patients. The present study offers a comprehensive approach for the treatment and prognosis assessment of patients with MSO. The machine learning models we have developed serve as a practical, personalized tool to aid in clinical decision-making processes.

Comprehensive assessment of postoperative recurrence and survival in patients with cervical cancer

BackgroundThe prediction of postoperative recurrence and survival in cervical cancer patients has been a major clinical challenge. The combination of clinical parameters, inflammatory markers, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and MRI-derived radiomics is expected to support the prediction of recurrence-free survival (RFS), disease-free survival (DFS), tumor-specific survival (CSS), and overall survival (OS) of cervical cancer patients after surgery. MethodsA retrospective analysis of 181 cervical cancer patients with continuous follow-up was completed. The parameters of IVIM-DWI and radiomics were measured, analyzed, and screened. The LASSO regularization was used to calculate the radiomics score (Rad-score). Multivariate Cox regression analysis was used to construct nomogram models for predicting postoperative RFS, DFS, CSS, and OS in cervical cancer patients, with internal and external validation. ResultsClinical stage, parametrial infiltration, internal irradiation, D-value, and Rad-score were independent prognostic factors for RFS; Squamous cell carcinoma antigen, internal irradiation, D-value, f-value and Rad-score were independent prognostic factors for DFS; Maximum tumor diameter, lymph node metastasis, platelets, D-value and Rad-score were independent prognostic factors for CSS; Lymph node metastasis, systemic inflammation response index, D-value and Rad-score were independent prognostic factors for OS. The AUCs of each model predicting RFS, DFS, CSS, and OS at 1, 3, and 5 years were 0.985, 0.929, 0.910 and 0.833, 0.818, 0.816 and 0.832, 0.863, 0.891 and 0.804, 0.812, 0.870, respectively. ConclusionsNomograms based on clinical and imaging parameters showed high clinical value in predicting postoperative RFS, DFS, CSS, and OS of cervical cancer patients and can be used as prognostic markers.

The prognostic value of changes in pulmonary vein flow patterns after surgical repair for primary mitral regurgitation

Background: The pulmonary vein (PV) flow pattern is influenced by the presence of mitral regurgitation (MR). After a successful reduction in MR severity, the pattern is expected to be changed. We aimed to evaluate the prognostic value of a change in the PV flow pattern in patients with primary MR undergoing mitral valve repair (MVR). Methods: The PV flow pattern was assessed with transthoracic echocardiography in 216 patients (age 65 [IQR 56–72] years, 70% male) with primary MR before and after surgical MVR. The population was divided according to a change in the PV flow pattern following MVR into ‘improvers’ and ‘non-improvers’. Results: Non-improvers (15%) had a higher prevalence of paroxysmal AF at baseline (46% vs. 22%, p = 0.004), left ventricular dysfunction (LVEF ≤60%) (39% vs. 21%, p = 0.020), and had lower systolic pulmonary artery pressure (28[IQR 25–38] vs. 35[IQR 26–48] mmHg, p = 0.018) compared to improvers (85%). After a median follow-up of 83[IQR 43–140] months, 26(12%) patients died. Non-improvers had higher mortality rates than improvers (p = 0.009). On multivariable Cox regression analysis, a lack of improvement in the PV flow pattern remained independently associated with all-cause mortality (HR 2.322, 95% CI 1.140 to 4.729, P = 0.020). Conclusion: A lack of improvement in the PV flow pattern is independently associated with worse long-term survival in patients with primary MR undergoing MVR.