Kaplan-Meier Survival Analysis Research Articles

ALYREF m5C RNA methylation reader predicts bladder cancer prognosis by regulating the tumor immune microenvironment.

5-Methylcytidine (m5C) methylation is a recently emerging epigenetic modification that is closely related to tumor proliferation, occurrence, and metastasis. This study aimed to investigate the clinicopathological characteristics and prognostic value of m5C regulators in bladder cancer (BLCA), and their correlation with the tumor immune microenvironment. Thirteen m5C RNA methylation regulators were analyzed using RNA-sequencing and corresponding clinical information obtained from the TCGA database. The Cluster Profiler package was used to analyze the gene ontology function of potential targets and enriched the Kyoto Encyclopedia of Genes and Genomes pathway. Kaplan-Meier survival analysis was used to compare survival differences using the log-rank test and univariate Cox proportional hazards regression. The correlation between signature prognostic m5C regulators and various immune cells was analyzed. Univariate and multivariate Cox regression analyses identified independence of the ALYREF gene signature. Nine out of the 13 m5C RNA methylation regulators were differentially expressed in BLCA and normal samples and were co-expressed. These 9 regulators were associated with clinicopathological tumor characteristics, particularly high or low tumor risk, pT or pTNM stage, and migration. Consensus clustering analysis divides the BLCA samples into 4 clusters. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment annotation and gene ontology function analysis identified 273 upregulated and 594 downregulated genes in BLCA. Notably, only ALYREF was significantly correlated with OS (P < .05). ALYREF exhibited significant infiltration levels in macrophage cells. Therefore, we constructed a nomogram for ALYREF as an independent prognostic factor. Additionally, we observed that both the mRNA and protein levels of ALYREF were upregulated, and immunofluorescence showed that ALYREF was mainly distributed in nuclear speckles. ALYREF overexpression was significantly associated with poor OS. Our findings demonstrated the potential of ALYREF to predict clinical prognostic risks in BLCA patients and regulate the tumor immune microenvironment. As such, ALYREF may serve as a novel prognostic indicator in BLCA patients.

A novel exosome-related prognostic risk model for thyroid cancer.

The aim was to build an exosome-related gene (ERG) risk model for thyroid cancer (TC) patients. Note that, 510 TC samples from The Cancer Genome Atlas database and 121 ERGs from the ExoBCD database were obtained. Differential gene expression analysis was performed to get ERGs in TC (TERGs). Functional enrichment analyses including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted on the TERGs. Then we constructed a model based on LASSO Cox regression analysis. Kaplan-Meier survival analysis was applied and a Nomogram model was also built. The immune landscape was evaluated by CIBERSORT. Thirty-eight TERGs were identified and their functions were enriched on 591 GO terms and 30 KEGG pathways. We built a Risk Score model based on FGFR3, ADRA1B, and POSTN. Risk Scores were significantly higher in T4 than in other stages, meanwhile, it didn't significantly differ in genders and TNM N or M classifications. The nomogram model could reliably predict the overall survival of TC patients. The mutation rate of BRAF and expression of cytotoxic T-lymphocyte-associated protein 4 were significantly higher in the high-risk group than in the low-risk group. The risk score was significantly correlated to the immune landscape. We built a Risk Score model using FGFR3, ADRA1B, and POSTN which could reliably predict the prognosis of TC patients.

Native T1-mapping as a predictor of progressive renal function decline in chronic kidney disease patients

BackgroundTo investigate the potential of Native T1-mapping in predicting the prognosis of patients with chronic kidney disease (CKD).MethodsWe enrolled 119 CKD patients as the study subjects and included 20 healthy volunteers as the control group, with follow-up extending until October 2022. Out of these patients, 63 underwent kidney biopsy measurements, and these patients were categorized into high (25–50%), low (< 25%), and no renal interstitial fibrosis (IF) (0%) groups. The study's endpoint event was the initiation of renal replacement therapy, kidney transplantation, or an increase of over 30% in serum creatinine levels. Cox regression analysis determined factors influencing unfavorable kidney outcomes. We employed Kaplan–Meier analysis to contrast kidney survival rates between the high and low T1 groups. Additionally, receiver-operating characteristic (ROC) curve analysis assessed the predictive accuracy of Native T1-mapping for kidney endpoint events.ResultsT1 values across varying fibrosis degree groups showed statistical significance (F = 4.772, P < 0.05). Multivariate Cox regression pinpointed 24-h urine protein, cystatin C(CysC), hemoglobin(Hb), and T1 as factors tied to the emergence of kidney endpoint events. Kaplan–Meier survival analysis revealed a markedly higher likelihood of kidney endpoint events in the high T1 group compared to the low T1 value group (P < 0.001). The ROC curves for variables (CysC, T1, Hb) tied to kidney endpoint events demonstrated area under the curves(AUCs) of 0.83 (95%CI: 0.75–0.91) for CysC, 0.77 (95%CI: 0.68–0.86) for T1, and 0.73 (95%CI: 0.63–0.83) for Hb. Combining these variables elevated the AUC to 0.88 (95%CI: 0.81–0.94).ConclusionNative T1-mapping holds promise in facilitating more precise and earlier detection of CKD patients most at risk for end-stage renal disease.

Identification of activating transcription factor 6 (ATF6) as a novel prognostic biomarker and potential target in oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma (OSCC) is originating from oral mucosal epithelial cells. Autophagy plays a crucial role in cancer treatment by promoting cellular self-degradation and eliminating damaged components, thereby enhancing therapeutic efficacy. In this study, we aim to identify a novel autophagy-related biomarker to improve OSCC therapy. MethodsWe firstly utilized Cox and Lasso analyses to identify that ATF6 is associated with OSCC prognosis, and validated the results by Kaplan-Meier survival analysis. We further identified the downstream pathways and related genes by enrichment analysis and WGCNA analysis. Subsequently, we used short interfering RNA to investigate the effects of ATF6 knockdown on proliferation, migration, apoptosis, and autophagy in SCC-9 and SCC-15 cells through cell viability assay, transwell assay, EdU incorporation assay, flow cytometry analysis, western blot analysis and immunofluorescence analysis, etc. ResultsBioinformatics analyses showed that ATF6 overexpression was associated with prognosis and detrimental to survival. In vitro studies verified that ATF6 knockdown reduced OSCC cell proliferation and migration. Mechanistically, ATF6 knockdown could promote cellular autophagy and apoptosis. ConclusionWe propose that ATF6 holds potential as a prognostic biomarker linked to autophagy in OSCC. This study provides valuable clues for further exploration of targeted therapy against OSCC.

Real-world persistence of multiple sclerosis disease-modifying therapies.

Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Initial [18F]DCFPyL PET/CT in treatment-naïve prostate cancer: correlation with post-ADT PSA outcomes and recurrence.

Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) targeting tracers has emerged as a valuable diagnostic tool for prostate cancer (PCa), androgen deprivation therapy (ADT) stands as the cornerstone treatment for advanced PCa, yet forecasting the response to hormonal therapy poses a significant clinical hurdle. In a prospective cohort of 86 PCa patients undergoing short-term ADT, this study evaluated the prognostic potential of [18F]DCFPyL PET/CT scans. Comprehensive data encompassing clinical profiles, baseline prostate-specific antigen (PSA) levels, and imaging metrics were assessed. We developed predictive models for assessing decreases in PSA levels (PSA50 and PSA70) based on a combination of PET-related parameters and clinical factors. Kaplan-Meier survival analysis was utilized to ascertain the prognostic value of PET-based metrics. In this study, elevated [18F]DCFPyL uptake within the primary tumor, as indicated by a SUV ≥ 6.78 (p = 0.0024), and a reduction in the tumor volume (TV) of primary PSMA-avid tumor with PSMA-TV < 41.96 cm3 (p = 0.038), as well as an increased burden of metastatic PSMA-avid tumor, with PSMA-TV (PSMA-TV ≥ 71.39 cm3) (p = 0.012) were identified in association with diminished progression-free survival (PFS). PET and clinical parameters demonstrated constrained predictive capacity for PSA50 response as indicated by an area under the curve (AUC) of 0.442. Our study revealed that pretreatment [18F]DCFPyL uptake in primary or metastatic tumor sites is prognostically relevant in high-risk PCa patients undergoing ADT. Further research is needed to develop robust predictive models in this multifaceted landscape of PCa management.

The triglyceride glucose index as a sensitive predictor for the risk of MACCEs in patients with diabetic foot ulcers: An ambispective longitudinal cohort study.

The triglyceride glucose (TyG) index has been confirmed a predictive value for type 2 diabetes mellitus (T2DM). However, no research has yet confirmed whether there is a linear correlation between the TyG index and MACCEs in DFUs. The present study aimed to delve into the association between the TyG index and the risk of MACCEs in patients with DFUs. A total of 960 inpatients with DFUs were recruited. All participants were followed up every 6 months for 11 years with a median of 83 months. According to the cut-off value of the TyG index acquired from receiver operating characteristic (ROC) analysis, the subjects were divided into two groups: low-level (<9.12, n = 480) and high-level (≥9.12, n = 480). The relationship between the TyG index and MACCEs was evaluated by the multivariable Cox regression model, restricted cubic spline (RCS) model, stratified analysis and the Kaplan-Meier survival analysis. Out of 960 participants, 271 experienced MACCEs (28.22%), of whom 79 (29.15%) died. ROC analysis got the optimal TyG index cut-off value of 9.12. Multivariable Cox regression analysis combined with the RCS model showed that the TyG index was positively associated with MACCEs in an S-shaped non-linear dose-dependent manner within the range of TyG index 7.5-9.5 (p < 0.001). The Kaplan-Meier survival analysis indicated the higher the TyG index, the greater the cumulative incidence of MACCEs (log-rank, p < 0.001). The study first confirmed an S-shaped non-linear dose-dependent positive relationship between the TyG index and the risk of MACCEs in DFUs. Consequently, lowering the TyG index level aids in improving the prognosis of patients with DFUs.

Identification and validation of tryptophan metabolism-related lncRNAs in lung adenocarcinoma prognosis and immune response

BackgroundTryptophan (Trp) is an essential amino acid. Increasing evidence suggests that tryptophan metabolism plays a complex role in immune escape from Lung adenocarcinoma (LUAD). However, the role of long non-coding RNAs (lncRNAs) in tryptophan metabolism remains to be investigated.MethodsThis study uses The Cancer Genome Atlas (TCGA)-LUAD dataset as the training cohort, and several datasets from the Gene Expression Omnibus (GEO) database are merged into the validation cohort. Genes related to tryptophan metabolism were identified from the Molecular Signatures Database (MSigDB) database and further screened for lncRNAs with Trp-related expression. Subsequently, a prognostic signature of lncRNAs related to tryptophan metabolism was constructed using Cox regression analysis, (Least absolute shrinkage and selection operator regression) and LASSO analysis. The predictive performance of this risk score was validated by Kaplan–Meier (KM) survival analysis, (receiver operating characteristic) ROC curves, and nomograms. We also explored the differences in immune cell infiltration, immune cell function, tumor mutational load (TMB), tumor immune dysfunction and exclusion (TIDE), and anticancer drug sensitivity between high- and low-risk groups. Finally, we used real-time fluorescence quantitative PCR, CCK-8, colony formation, wound healing, transwell, flow cytometry, and nude mouse xenotransplantation models to elucidate the role of ZNF8-ERVK3-1 in LUAD.ResultsWe constructed 16 tryptophan metabolism-associated lncRNA prognostic models in LUAD patients. The risk score could be used as an independent prognostic indicator for the prognosis of LUAD patients. Kaplan–Meier survival analysis, ROC curves, and risk maps validated the prognostic value of the risk score. The high-risk and low-risk groups showed significant differences in phenotypes, such as the percentage of immune cell infiltration, immune cell function, gene mutation frequency, and anticancer drug sensitivity. In addition, patients with high-risk scores had higher TMB and TIDE scores compared to patients with low-risk scores. Finally, we found that ZNF8-ERVK3-1 was highly expressed in LUAD tissues and cell lines. A series of in vitro experiments showed that knockdown of ZNF8-ERVK3-1 inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest in the G0/G1 phase and increased apoptosis. In vivo experiments with xenografts have shown that knocking down ZNF8-ERVK3-1 can significantly inhibit tumor size and tumor proliferation.ConclusionWe constructed a new prognostic model for tryptophan metabolism-related lncRNA. The risk score was closely associated with common clinical features such as immune cell infiltration, immune-related function, TMB, and anticancer drug sensitivity. Knockdown of ZNF8-ERVK3-1 inhibited LUAD cell proliferation, migration, invasion, and G0/G1 phase blockade and promoted apoptosis.

Space Closure with Different Appointment Intervals: A Split-mouth Randomized Controlled Trial

Background: Canine retraction has been successful with various force systems and retraction techniques. The appointment interval for force reactivation in canine retraction along the archwire is 4–8 weeks. Aims: The aim was to evaluate the effect of different reactivation intervals on the rate of space closure. Settings and Design: This split-mouth randomized clinical trial recruited 38 patients indicated for the first premolar extraction. Methods: Monthly digital models were acquired for 6 months. The first premolars were extracted, and temporary anchorage devices were placed for maximum anchorage control. The canines were retracted using elastomeric chains which were replaced every 2, 4, 6, or 8 weeks. The monthly rate of canine retraction was measured. The time to space closure was calculated. The secondary outcome was the mesial drift of the first molars. Statistical Analysis: The Kaplan–Meier survival analysis and the Friedman test evaluated and compared the groups. Results: There was no significant difference between the monthly canine retraction rate or the first molar mesial drift between the groups. The mean time to space closure was 5.74 months in the 2-week reactivation group, which was statistically less than the other groups. Conclusions: The 2-week reactivation interval may reduce time to space closure. Direct anchorage control with miniscrews limited anchorage loss significantly.

Management of aortoesophageal fistula primarily using esophageal preservation

ObjectiveAortoesophageal fistula is a rare, life-threatening condition. There is no consensus regarding the surgical management of the esophagus in this condition. MethodsWe retrospectively evaluated 13 patients diagnosed with aortoesophageal fistulas at a single institution from 2003 to 2021. Descriptive statistics were used to analyze patient characteristics, operative characteristics, and patient outcomes. Kaplan–Meier survival analysis was performed. ResultsPatients’ mean age was 63.5 years, and 6 (46.2%) were female. The most common presenting symptoms were hemoptysis/hematemesis (69.2%), chest/back pain (46.2%), and fever (38.5%). Twelve patients (92.3%) had a history of aortic procedures. The median time between the index operation and repair of the secondary aortoesophageal fistula in the 12 patients was 5 months. The index operation was a thoracic endovascular aortic repair in 10 of 12 patients (83.3%). Eleven patients (84.6%) underwent primary esophageal repair with flap coverage (omentum or muscle). One of these patients needed an esophagectomy within 1 year. The primary surgical management of the aorta was graft excision and replacement, aside from 1 patient who underwent primary repair. The 30-day survival was 69.2%, and 1-year and 5-year survivals were 31.7%. There were no recurrent infections at the esophageal fistula site. ConclusionsAortoesophageal fistula remains a rare condition, but its case numbers have increased with thoracic endovascular aortic repair. It continues to be a difficult condition to manage and has a high fatality rate. Esophageal-preserving surgery may be a safe and less-invasive option for patients with a small defect.

Rationality of the FIGO2023 staging for early-stage endometrial cancer, compared with the FIGO2009 staging

ObjectiveThe International Federation of Gynecology and Obstetrics (FIGO) released a new staging for endometrial cancer (EC), which revised the FIGO2009 staging to include histopathological and molecular features. The purpose of...

Prediction of prognosis of patients with radical resection of intrahepatic cholangiocarcinoma based on single cell omics

Objectives: To analyze the survival benefit of intrahepatic cholangiocarcinoma (ICC) radical resection based on single cell omics. Methods: This is a retrospective case-series study. ICC single-cell sequencing was integrated from four data sets in the Gene Expression Omnibus Database, with a total of 46 patients undergoing radical resection, to explore the characteristics of the microenvironment. Microarray data of 100 ICC cases was analyzed in the EMBI database with survival data. The infiltration abundance of each epithelial cell cluster was calculated in each microarray data sample using the ssGSEA algorithm. The key epithelial cell cluster associated with poor patient outcomes was explored. The clinical value of key marker genes in this subgroup was studied. Prognostic marker genes were selected using the univariate and multivariate Cox proportional hazards(CoxPH) model. The The CoxPH model was constructed by the target genes and a nomogram was drawn. Kaplan-Meier survival analysis was used to verify the relationship between score and prognosis of patients. The predictive power of the model was evaluated by receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis (DCA). Results: Epithelial cell clusters infiltrated almost exclusively in tumor tissue. The MT2A+ epithelial cell subset was associated with a poorer prognosis for patients with a high invasion abundance and patients characterized by infiltration of this group were defined as antioxidant. After screening marker genes in this cluster using a univariate and multivariate CoxPH model, the following genes were found to be independent prognostic factors: FILPIL, NFKBIA, PEG10, SERPINB5. The CoxPH model was constructed using the four gene expression levels, and the survival rate of patients in the high-risk group was significantly lower than those in the low-risk group (all P<0.05). The constructed nomogram had good discrimination and validity. The ROC curve showed that the predicted area under the curve was 0.779, 0.844 and 0.845 at 1, 3 and 5 years, respectively. Compared to clinical indicators, the model had better predictive power using the calibration curve and the DCA test. Conclusions: The MT2A+ epithelial cell group may be associated with the prognosis of patients with ICC, and the concept of ICC tissue typing of antioxidant and non-antioxidant types is proposed. The type of antioxidant may predict the poor prognosis of the patients, and postoperative adjuvant therapy and other means could be considered to improve the survival of the patients.

135 Guillain-Barré Syndrome After COVID-19 Vaccination: A Systematic Review and Analysis of Case Reports

INTRODUCTION: Cases of Guillain-BarrÉ Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection. METHODS: An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports after COVID-19 vaccine administration. Differences between groups were assessed by Pearson chi-square test. Modified Erasmus GBS Outcome Score for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS. RESULTS: 175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ± 18.83 years, with AMSAN occurring in a rather older group (63.88 ± 20.87 years, p = 0.049). The AstraZeneca vaccine was associated with AIDP (n = 38, 21.71%) more than other vaccines, p = 0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Most GBS patients survived (96%, p = 0.036), however, most patients had low mEGOS scores (4 ± 3.57, p &lt; 0.01). On average, patients developed GBS at 13.43 ± 11.45 days from vaccination (p = 0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p &lt; 0.01). CONCLUSIONS: Guillain-BarrÉ Syndrome can manifest after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca vaccine, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines.

Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes

Background & AimsHepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70 percent of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), FDA-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. MethodsThis retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio (HR) and 95% confidence interval (CI) calculated. ResultsGLP-1RAs were associated with a lower risk of incident HCC with HR of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with six other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. ConclusionsGLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared to other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.

Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients

ObjectiveIndividuals with hyperthyroidism are at an increased risk of atrial fibrillation (AF), but the association between autoantibodies and AF or cardiovascular mortality in individuals who have returned to normal thyroid function remains unclear. MethodsThe study utilized electronic medical records from National Taiwan University Hospital between 2000 and 2022. Each hyperthyroidism patient had at least 1 thyrotropin-binding inhibiting immunoglobulin (TBII) measurement. The relationship between TBII levels and the risk of AF and cardiovascular mortality was assessed using multivariable Cox regression models and Kaplan-Meier survival analysis. ResultsAmong the 14 618 enrolled patients over a 20-year timeframe, 173 individuals developed AF, while 46 experienced cardiovascular mortality. TBII values exceeding 35% were significantly associated with an elevated risk of AF for both the first TBII (hazard ratio {HR} 1.48 [1.05-2.08], P = .027) and mean TBII (HR 1.91 [1.37-2.65], P < .001). Furthermore, after free T4 levels had normalized, a borderline association between first TBII and AF (HR 1.59 [0.99-2.56], P = .056) was observed, while higher mean TBII increased AF (HR 1.78 [1.11-2.85], P = .017). Higher first and mean TBII burden continued to significantly impact the incidence of cardiovascular mortality (HR 6.73 [1.42-31.82], P = .016; 7.87 [1.66-37.20], P = .009). Kaplan-Meier analysis demonstrated that elevated TBII levels increased the risk of AF and cardiac mortality (log-rank P = .035 and .027, respectively). ConclusionIn euthyroid individuals following antithyroid treatment, elevated circulating TBII levels and burden are associated with an elevated risk of long-term incident AF and cardiovascular mortality. Further reduction of TBII level below 35% will benefit to clinical outcomes.

Elevated Leukocyte Glucose Index Is Associated with Long-Term Arteriovenous Fistula Failure in Dialysis Patients.

(1) Background: Arteriovenous fistula (AVF) is the preferred type of vascular access for dialysis in patients with end-stage kidney disease (ESKD). However, the primary patency of AVF at one year is under 70% due to several risk factors and comorbidities. Leukocyte glucose index (LGI), a new biomarker based on blood leukocytes and glucose values, has been found to be associated with poor outcomes in cardiovascular disease. The aim of this study is to analyze the impact of LGI on the long-term primary patency of AVF following dialysis initiation. (2) Methods: We conducted a retrospective observational study in which we initially enrolled 158 patients with ESKD admitted to the Vascular Surgery Department of the Emergency County Hospital of Targu Mures, Romania, to surgically create an AVF for dialysis between January 2020 and July 2023. The primary endpoint was AVF failure, defined as the impossibility of performing a chronic dialysis session due to severe restenosis or AVF thrombosis. After follow-up, we categorized patients into two groups based on their AVF status: "functional AVF" for those with a permeable AVF and "AVF failure" for those with vascular access dysfunction. (3) Results: Patients with AVF failure had a higher prevalence of atrial fibrillation (p = 0.013) and diabetes (p = 0.028), as well as a higher LGI value (1.12 vs. 0.79, p < 0.001). At ROC analysis, LGI had the strongest association with the outcome, with an AUC of 0.729, and an optimal cut-off value of 0.95 (72.4% sensitivity and 68% specificity). In Kaplan-Meier survival analyses, patients in the highest tertile (T3) of LGI had a significantly higher incidence of AVF failure compared to those in tertile 1 (p = 0.019). Moreover, we found that patients with higher baseline LGI values had a significantly higher risk of AVF failure during follow-up (HR: 1.48, p = 0.003). The association is independent of age and sex (HR: 1.65, p = 0.001), cardiovascular risk factors (HR: 1.63, p = 0.012), and pre-operative vascular mapping determinations (HR: 3.49, p = 0.037). (4) Conclusions: In conclusion, high preoperative values of LGI are positively associated with long-term AVF failure. The prognostic role of the biomarker was independent of age, sex, cardiovascular risk factors, and pre-operative vascular mapping determinations.

Hip Arthroscopy Patients With Lower Back Pain Show Delayed Clinical Improvement and Inferior Time-Dependent Survivorship: A Propensity Matched Study at Mid-Term Follow-Up

PurposeTo evaluate patient-reported outcomes (PROs) and survivorship at mid-term follow-up after hip arthroscopy (HA) for femoroacetabular impingement syndrome (FAIS) in patients with and without preoperative lower back pain (LBP). MethodsPatients with self-endorsed preoperative LBP who underwent HA for FAIS with mid-term follow-up were identified and propensity matched 1:1 to patients without back pain by age, sex, and body mass index. PROs collected preoperatively and at postoperative years 1, 2, and 5 included: Hip Outcome Score Activities of Daily Living (HOS-ADL) and Sports Subscale (HOS-SS), International Hip Outcome Score 12 (iHOT-12), modified Harris Hip Score (mHHS), Visual Analog Scale (VAS) for Pain. Achievement of minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) were compared. Survivorship was compared with Kaplan-Meier analysis. Results119 patients with LBP were matched to 119 patients without LBP. Group demographic factors were as follows, age (37.4±11.9 years vs 37.6±12.6, p=0.880), sex (64.4% female vs 67.7%, p=0.796), and BMI (25.3±5.1 kg/m2 vs 25.3±5.4, p=0.930). Average follow-up duration was 6.0 ± 1.9 years. LBP patients showed similar preoperative PROs, yet lower 1-year scores for all PROs (p ≤ 0.044). At final follow-up, similar PROs were shown between groups (p ≥ 0.196). LBP and non-LBP patients had similar MCID achievement for HOS-ADL (59.3%vs.63.1%,p=0.640), HOS-SS (73.9%vs.70.8%,p=0.710), mHHS (66.7%vs.73.4%, p=-.544), iHOT-12 (85.1%vs.79.4%,p=0.500), and VAS-Pain (75.6%vs.69.9%,p=0.490). Groups also had similar PASS achievement for HOS-ADL (63.5%vs.61.3%,p=0.777), HOS-SS (57.0%vs.62.5%,p=0.461), mHHS (81.9%vs.79.1%, p=0.692), iHOT-12 (54.6%vs.61.2%,p=0.570), and VAS-Pain (51.0%vs.55.4%,p=0.570).with similar MCID (p ≥ 0.490) and PASS (p ≥ 0.386) achievement. Conversion to total hip arthroplasty occurred in 3.4% of hips with LBP and 0.8% of hips without LBP (p=0.370), Back pain patients demonstrated inferior time-dependent survivorship compared to patients without back pain on Kaplan-Meier survival analysis (p = 0.023). ConclusionsPatients undergoing primary hip arthroscopy for femoroacetabular impingement syndrome with LBP achieve comparable PROs and CSOs to patients without back pain at mid-term, despite lower 1-year PRO scores. LBP patients show inferior reoperation-free time-dependent survivorship compared to those without LBP.

Treatment outcome of coronal pulpotomy and indirect pulp capping in mature permanent molars with symptoms of moderate pulpitis: A randomized clinical trial.

This clinical trial aimed to compare the clinical success of coronal pulpotomy and indirect pulp capping (IPC) in managing symptomatic deep proximal caries in molars with moderate pulpitis over a 12-month period. A total of 108 vital mature permanent molars with moderate pulpitis were randomly allocated to the IPC (n = 54) or coronal pulpotomy group (n = 54). Dycal and Biodentine were used as pulp-capping materials, followed by composite restoration. The absence of periapical infection and asymptomatic teeth that positively responded to the cold pulp sensitivity test (only in IPC) was considered posttreatment success at 12 months. Data from the study were analyzed using the Chi-square test and Kaplan-Meier survival analysis. There was a statistically significant difference between preoperative symptoms and the cold pulp sensibility test response (P = 0.000), indicating an association between symptoms and pulp sensibility. The average remaining dentine thickness (RDT) value was 0.48 ± 0.5 mm, with no statistically significant difference found between the location of caries and RDT (P = 0.084, P > 0.05). Compared to the IPC group, the pulpotomy group had a greater number of patients at 12 months after treatment that required no intervention. The Kaplan-Meier survival analysis revealed that the mean survival duration for pulpotomy was 48 weeks, and for IPC, it was 42.3 ± 2.35 weeks. Coronal pulpotomy with Biodentine proved more effective in reducing symptoms, achieving radiographic success, and ensuring tooth survival compared to IPC with calcium hydroxide.

Linc00958 Promotes Lung Cancer Proliferation and Migration Through Regulating microRNA-490-3p

This study aimed to investigate the role of long intergenic non-protein coding RNA 00958 (Linc00958) in lung cancer (LCa) progression and its underlying mechanism. The study assessed Linc00958 expression in LCa tissues and adjacent tissues using qRT-PCR, and its impact on patient prognosis was analyzed through Kaplan-Meier survival analysis. Additionally, Linc00958 expression in LCa and normal lung cell lines was examined in vitro. Functional assays, including CCK-8, EdU, and transwell assays, were conducted to evaluate the effects of Linc00958 knockdown on LCa cells. To uncover the molecular mechanism, a dual-luciferase reporter assay was used to confirm the binding relationship between Linc00958 and microRNA-490-3p, a downstream gene. Co-transfection experiments were performed to elucidate microRNA-490-3p’s role in Linc00958’s impact on LCa cell functions. The results showed that Linc00958 was overexpressed in LCa tissues and cells, and high Linc00958 expression correlated with reduced patient survival. in vitro experiments revealed that Linc00958 promoted tumor proliferation and migration in LCa cells. Both computational predictions and dual-luciferase reporter assays demonstrated binding sites between microRNA-490-3p and Linc00958. Co-transfection experiments confirmed that Linc00958 facilitated LCa cell proliferation and migration through modulating microRNA-490-3p expression. In summary, Linc00958 promotes LCa cell proliferation and migration by regulating microRNA-490-3p.

Geriatric nutritional risk index as a predictor for fragility fracture risk in elderly with type 2 diabetes mellitus: A 9-year ambispective longitudinal cohort study

The elderly are prone to fragility fractures, especially those suffering from type 2 diabetes mellitus (T2DM) combined with osteoporosis. Although studies have confirmed the association between GNRI and the prevalence of osteoporosis, the relationship between GNRI and fragility fracture risk and the individualized 10-year probability of osteoporotic fragility fractures estimated by FRAX remains unclear. This study aims to delve into the association between the GNRI and a fragility fracture and the 10-year probability of hip fracture (HF) and major osteoporotic fracture (MOF) evaluated by FRAX in elderly with T2DM. A total of 580 patients with T2DM aged ≥60 were recruited in the study from 2014 to 2023. This research is an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 3.8 years through outpatient services, medical records, and home fixed-line telephone interviews. According to the tertiles of GNRI, all subjects were divided into three groups: low-level (59.72-94.56, n=194), moderate-level (94.56-100.22, n=193), and high-level (100.22-116.45, n=193). The relationship between GNRI and a fragility fracture and the 10-year probability of HF and MOF calculated by FRAX was assessed by receiver operating characteristic (ROC) analysis, Spearman correlation analyses, restricted cubic spline (RCS) analyses, multivariable Cox regression analyses, stratified analyses, and Kaplan-Meier survival analysis. Of 580 participants, 102 experienced fragile fracture events (17.59%). ROC analysis demonstrated that the optimal GNRI cut-off value was 98.58 with a sensitivity of 75.49% and a specificity of 47.49%, respectively. Spearman partial correlation analyses revealed that GNRI was positively related to 25-hydroxy vitamin D [25-(OH) D] (r=0.165, P<0.001) and bone mineral density (BMD) [lumbar spine (LS), r=0.088, P=0.034; femoral neck (FN), r=0.167, P<0.001; total hip (TH), r=0.171, P<0.001]; negatively correlated with MOF (r=-0.105, P=0.012) and HF (r=-0.154, P<0.001). RCS analyses showed that GNRI was inversely S-shaped dose-dependent with a fragility fracture event (P<0.001) and was Z-shaped with the 10-year MOF (P=0.03) and HF (P=0.01) risk assessed by FRAX, respectively. Multivariate Cox regression analysis demonstrated that compared with high-level GNRI, moderate-level [hazard ratio (HR)=1.950; 95% confidence interval (CI)=1.076-3.535; P=0.028] and low-level (HR=2.538; 95% CI=1.378-4.672; P=0.003) had an increased risk of fragility fracture. Stratified analysis exhibited that GNRI was negatively correlated with the risk of fragility fracture, which the stratification factors presented in the forest plot were not confounding factors and did not affect the prediction effect of GNRI on the fragility fracture events in this overall cohort population (P for interaction>0.05), despite elderly females aged ≥70, with body mass index (BMI) ≥24, hypertension, and with or without anemia (all P<0.05). Kaplan-Meier survival analysis identified that the lower-level GNRI group had a higher cumulative incidence of fragility fractures (log-rank, all P<0.001). This study confirms for the first time that GNRI is negatively related to a fragility fracture and the 10-year probability of osteoporotic fragility fractures assessed by FRAX in an inverse S-shaped and Z-shaped dose-dependent pattern in elderly with T2DM, respectively. GNRI may serve as a valuable predictor for fragility fracture risk in elderly with T2DM. Therefore, in routine clinical practice, paying attention to the nutritional status of the elderly with T2DM and giving appropriate dietary guidance may help prevent a fragility fracture event.