Kaplan-Meier Survival Analysis Research Articles

Evaluating the Prognostic Significance of Cystatin C Level Variations Pre- and Post-Radiofrequency Catheter Ablation in the Recurrence of Persistent Atrial Fibrillation.

To investigate the correlation between persistent atrial fibrillation (AF) recurrence and alterations in cystatin C levels pre- and post-radiofrequency catheter ablation (RFCA). This study encompassed 114 patients diagnosed with persistent AF. Their serum cystatin C levels were assessed both prior to and 3 months after undergoing an RFCA procedure. The variance in cystatin C levels before and after RFCA is represented as ΔCystatin C. Subsequently, we compared these values between two groups: patients who did not experience a recurrence of AF (n = 79) and those who did experience a recurrence (n = 35). A significant reduction in cystatin C levels post-RFCA in both groups, with a more pronounced decrease observed in the non-recurrence group. Moreover, the recurrence group exhibited larger left atrial diameter and volume before RFCA compared to the non-recurrence group. Cox regression analysis indicated that smaller reductions in serum cystatin C levels and greater left atrial volumes before RFCA were associated with an increased risk of recurrence, after adjusting for covariates. The receiver operating characteristic curve indicated an elevated probability of clinical recurrence of AF post-RFCA in patients with a cystatin C decline < 0.08 mg/L (AUC 0.64). The Kaplan-Meier survival analysis revealed that patients with a cystatin C decline > 0.08 mg/L exhibited significantly higher rates of remaining free from recurrence following RFCA across a 24-month follow-up period (Log-rank test p = 0.003). Alterations in ΔCystatin C levels pre and post-RFCA in the initial phase could independently predict the recurrence of AF.

One novel transfer learning-based CLIP model combined with self-attention mechanism for differentiating the tumor-stroma ratio in pancreatic ductal adenocarcinoma.

To develop a contrastive language-image pretraining (CLIP) model based on transfer learning and combined with self-attention mechanism to predict the tumor-stroma ratio (TSR) in pancreatic ductal adenocarcinoma on preoperative enhanced CT images, in order to understand the biological characteristics of tumors for risk stratification and guiding feature fusion during artificial intelligence-based model representation. This retrospective study collected a total of 207 PDAC patients from three hospitals. TSR assessments were performed on surgical specimens by pathologists and divided into high TSR and low TSR groups. This study developed one novel CLIP-adapter model that integrates the CLIP paradigm with a self-attention mechanism for better utilizing features from multi-phase imaging, thereby enhancing the accuracy and reliability of tumor-stroma ratio predictions. Additionally, clinical variables, traditional radiomics model and deep learning models (ResNet50, ResNet101, ViT_Base_32, ViT_Base_16) were constructed for comparison. The models showed significant efficacy in predicting TSR in PDAC. The performance of the CLIP-adapter model based on multi-phase feature fusion was superior to that based on any single phase (arterial or venous phase). The CLIP-adapter model outperformed traditional radiomics models and deep learning models, with CLIP-adapter_ViT_Base_32 performing the best, achieving the highest AUC (0.978) and accuracy (0.921) in the test set. Kaplan-Meier survival analysis showed longer overall survival in patients with low TSR compared to those with high TSR. The CLIP-adapter model designed in this study provides a safe and accurate method for predicting the TSR in PDAC. The feature fusion module based on multi-modal (image and text) and multi-phase (arterial and venous phase) significantly improves model performance.

Needle Revision and Digital Ocular Massage for Treatment of Ocular Hypertension Phase after Ahmed Valve Implantation

Purpose: To evaluate the effects and safety of needle revision with 5-fluorouracil (5-FU) subconjunctival injection and digital ocular massage for the treatment of ocular hypertension phase following Ahmed valve implantation (AVI).Methods: We retrospectively analyzed the medical records of patients who underwent needle revision with 5-FU subconjunctival injection and digital ocular massage for treatment of ocular hypertension phase. Changes in visual acuity, intraocular pressure (IOP), and the number of anti-glaucoma medications before and after the procedure were compared. The cumulative success rate of the procedure was analyzed using Kaplan–Meier survival analysis. Success was categorized as complete when the IOP was 6-21 mmHg without medication and qualified when it was 6-21 mmHg with medication.Results: In total, 53 eyes of 53 patients were included in this study. The average time interval between AVI and the first procedure was 25 days, and 2.1 ± 0.8 procedures were performed per patient. The mean IOP before and at 48 weeks after the procedure was 24.4 ± 2.9 and 16.9 ± 3.5 mmHg, respectively. At each follow-up visit, the IOP was significantly lower than that before the procedure. At 48 weeks after the procedure, the complete and qualified success rates were 22.6%, and 81.1%, respectively.Conclusions: Needle revision with 5-FU subconjunctival injection and digital ocular massage are effective and safe for the treatment of ocular hypertension phase following AVI.

Prognostic factors in children with acute T-lymphoblastic leukemia: a single-center clinical study of the CCCG-ALL-2015 protocol

To explore the clinical characteristics of children with acute T-lymphoblastic leukemia (T-ALL) and analyze their relationship with prognosis. A retrospective analysis was conducted on the clinical data and follow-up results of 50 children with T-ALL who were treated using the CCCG-ALL-2015 protocol at the Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University from November 2015 to December 2019. Kaplan-Meier survival analysis and Cox regression analysis were employed to identify factors affecting prognosis. Among the 50 T-ALL patients, there were 7 cases of relapse. There was no statistically significant difference in the baseline clinical data between the relapse group and the non-relapse group (P>0.05). However, the positive rate of minimal residual disease (MRD) (≥0.01%) on day 46 after induction remission therapy in the relapse group was significantly higher than that in the non-relapse group (P=0.037). The 5-year overall survival rate for the 50 patients was (87±5)%, and the 5-year event-free survival rate was (86±5)%. Multivariate Cox regression analysis indicated that the MRD level on day 46 after induction remission therapy was an independent prognostic factor (HR=0.104, 95%CI: 0.015-0.740, P=0.024). MRD is of significant importance for the prognosis of T-ALL children. Personalized treatment should be provided based on MRD levels to prevent relapse and improve prognosis in these patients.

The role of the Ki-67 labelling index as an independent prognostic factor in indonesian glioma patients.

Gliomas are the most common type of brain tumor. However, interpreting glioma morphology is subjective, and identifying mitosis can be challenging. This can impact the determination of the patient's tumor grade, therapy, and prognosis. In addition, the Ki-67 expression level, which reflects the tumor cells' ability to proliferate, is closely related to the patient's survival. This study aims to find a correlation between Ki-67 expression and the overall survival (OS) of glioma patients in the Indonesian population. Ninety-one glioma patients from Sardjito General Hospital were collected for formalin-fixed embedded paraffin (FFPE) samples, and the Ki-67 labeling index (LI) was calculated by determining the percentage of labeled nuclei per 1000 cells using a 40x objective lens in a randomized area (average method). The OS was calculated from the day of pathology diagnosis until death or the last follow-up (for censored cases). Kaplan-Meier survival analysis was used to analyze the OS. Individuals aged ≥60 with high-grade tumors, infratentorial gliomas, and a Ki-67 LI ≥10% had a shorter OS. The p-values associated with these factors were 0.001, 0.018, and 0.006, respectively. In multivariate analysis, age and tumor grade did not significantly correlate with OS. Glioma patients with a Ki-67 LI ≥10% have a significantly shorter OS than those with a lower Ki-67 LI, indicating that Ki-67 LI is an independent prognostic factor in Indonesian glioma patients.

Identifying Risk Factors for Disease Progression in Developmental Dysplasia of the Hip Using a Contralateral Hip Model

Background: Developmental dysplasia of the hip (DDH) can cause pain and premature osteoarthritis. The risk factors and timing for disease progression in adolescents and young adults have not been fully defined. This study aimed to determine the prevalence of and risk factors for contralateral hip pain and surgery after periacetabular osteotomy (PAO) on a dysplastic hip. Methods: Patients undergoing unilateral PAO for DDH were followed for at least 2 years and categorized into contralateral pain and no-pain groups and contralateral surgery and no-surgery groups. Pain was defined with the modified Harris hip score. Univariate analysis tested group differences in demographics, radiographic measures, and range of motion. Kaplan-Meier survival analysis was used to assess pain development and surgery in the contralateral hip over time. Multivariable regression identified risk factors for contralateral pain and surgery. Contralateral pain and surgery predictors were secondarily assessed after categorization of the contralateral hips as dysplastic, borderline, and non-dysplastic and in subgroups based on the lateral center-edge angle (LCEA) and acetabular inclination (AI) in 5° increments. Results: One hundred and eighty-four patients were followed for a mean of 4.6 ± 1.6 years (range, 2.0 to 8.8 years), during which 51% (93) reported contralateral hip pain and 33% (60) underwent contralateral surgery. Kaplan-Meier analysis predicted 5-year survivorship of 49% with contralateral pain development as the end point and 66% with contralateral surgery as the end point. Painful hips exhibited more severe dysplasia compared with no-pain hips (LCEA = 16.5° versus 20.3°, p &lt; 0.001; AI = 13.2° versus 10.0°, p &lt; 0.001). AI was the sole predictor of pain, with every 1° increase in the AI raising the risk by 11%. Surgically treated hips also had more severe dysplasia (LCEA = 14.9° versus 20.0°, p &lt; 0.001; AI = 14.7° versus 10.2°, p &lt; 0.001) and were in younger patients (21.6 versus 24.1 years, p = 0.022). AI and a maximum alpha angle of ≥55° were predictors of contralateral surgery. Conclusions: At 5 years after hip PAO, approximately 50% of contralateral hips will have pain and approximately 35% can be expected to need surgery. More severe dysplasia, based on the LCEA and AI, increases the risk of contralateral hip pain and surgery, with AI being a predictor of both outcomes. Knowing these risks can inform patient counseling and treatment planning. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Antiphospholipid antibody positivity is associated with maturation failure and thrombosis of native arteriovenous fistula: a retrospective study in HD patients

Abstract Background and hypothesis The prevalence of antiphospholipid antibody (aPL) is high among hemodialysis (HD) patients compared to the general population and is inconsistently associated with arteriovenous fistula (AVF) thrombosis or stenosis. The association with maturation failure has never been investigated. This study aims to evaluate native AVF complications (thrombosis, stenosis and maturation failure) and primary patency in aPL positive HD patients. Methods We retrospectively identified 116 HD patients with native AVF. We collected the aPL profiles, the clinical and biological data potentially involved in AVF maturation failure, thrombosis and stenosis and investigated the association of these complications and aPL positivity. Kaplan-Meier survival analysis was performed. Results In our cohort, the prevalence of aPL persistent positivity was 32.7% and the latter was strongly associated with AVF maturation failure defined by ultrasound. aPL persistent positivity was a strong predictor in multivariate analysis and this association was independent of AVF stenosis or thrombosis during maturation process. There was no association with primary and functional primary patency, and stenosis. However, aPL persistent positivity according to ACR/EULAR classification criteria was associated with thrombosis when compared to strictly negative aPL patients. Conclusions In our cohort, aPL persistent positivity was significantly associated with AVF maturation failure and thrombosis but not with AVF stenosis. To our knowledge, we report for the first time, a statistically significant association between aPL positivity and delay or absence of native AVF maturation.

How Does Social Inequality Alter Relationships Between Porous Cranial Lesions and Mortality? Examining the Relationship Between Skeletal Indicators of Stress, Socioeconomic Status, and Survivorship in a Pediatric Autopsy Sample.

In prior exploration of modern and archeological populations, lower SES has been associated with an increased risk of mortality. However, SES is often difficult to ascertain in archeological populations. Thus, explorations of skeletal lesions and their association with mortality may be subject to confounding factors that alter the strength and/or direction of this association. The present study uses data from a modern, documented coronial pediatric dataset to examine the association between porous cranial lesions (PCLs) (cribra orbitalia [CO] and porotic hyperostosis [PH]) and age at death while controlling for SES, as inferred through housing type, with manufactured or apartment housing identified as reflecting individuals from lower SES backgrounds in this context. We include 887 (535 males, 352 females) individuals aged 0.5-20.9 years from New Mexico who died between 2011 and 2022. Kaplan-Meier survival analysis was used to assess survivorship as related to PCLs and SES. Low SES is associated with lower survivorship. CO does not have a significant association with age at death when not controlling for SES; PH alone is associated with older age at death. Disadvantaged individuals with PCLs have significantly reduced survivorship than those with higher SES. The findings of this study demonstrate that low SES results in reduced survivorship, and those with low SES and PCLs have worse survivorship than less disadvantaged individuals with PCLs. Thus, the strong contribution of SES to mortality necessitates the consideration of the sociocultural context as a confounding factor when examining associations between variables of interest (such as lesions) and mortality in both past and present populations.

Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in individuals with diabetes or prediabetes: a cohort study from NHANES 2005–2018

Weight-adjusted waist index (WWI) is a new marker of central obesity. This study explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in individuals with diabetes or prediabetes. 6551 participants with diabetes or prediabetes from the National Health and Nutrition Examination Survey (NHANES) records between 2005 and 2018 were included. The association of WWI with all-cause and CVD mortality was assessed using Kaplan-Meier survival analysis, Cox proportional hazards model (Cox regression), and restricted cubic spline (RCS). The predictive value of WWI for mortality was analyzed using time-dependent receiver operating characteristic curves (ROC). There were 1083 all-cause deaths and 360 CVD deaths. Multivariable-adjusted Cox regression analyses showed WWI was positively correlated with the risk of all-cause and CVD mortality in subjects with diabetes or prediabetes. Multivariate-adjusted RCS analyses showed a linear and positive correlation of WWI with all-cause mortality risk, and a nonlinear relationship with CVD mortality, with a threshold of 12.35. The area under the curve (AUC) for 3, 5, and 10-years survival for all-cause mortality was 0.795, 0.792, and 0.812, respectively, and for CVD mortality was 0.815, 0.833, and 0.831, respectively. WWI is a valuable predictor of all-cause mortality risk in patients with diabetes and prediabetes, and a valuable predictor of CVD mortality risk when patients with diabetes and prediabetes are considered as a whole.

Is there value in the routine inclusion of chest computed tomography for patients with gastrointestinal stromal tumor?

PurposeNational Comprehensive Cancer Network guidelines suggest chest CT when gastrointestinal stromal tumors are larger than 2 cm. We evaluate the value of screening the chest region during initial and follow-up CT. MethodSingle institution retrospective analysis of GIST cancer registry for patients diagnosed between May 2010 and November 2019 with tumor > 2 cm. We collected the patient demographics and clinical data; reviewed all CT scans of the chest region and recorded the lung nodules. Patients were grouped into lung nodule group and non-nodule group. Categorical variables were compared with the Chi square test and continuous variables with the Mann-Whitney U test. The survival probability was determined from Kaplan-Meier survival analysis and log-rank test for comparing differences. ResultsThe final cohort included 382 patients (median age 61 years-old [interquartile range: 52–71]) and grouped into non-nodule group (n = 284) and lung nodule group (n = 98). The frequency of the CT scan was more in lung nodule group (8 [5–12]) than in non-nodule group (4 [2–9], p < 0.001). The lung nodule group had more CT including the chest region (6 [3–10] vs 3 [1–7], p < 0.001). In progressive lung nodules (8/98 [8 %]), only one patient had confirmed lung metastasis from GIST (1/382 [3 %]). There was no difference in overall survival between nodule groups (p = 0.12). ConclusionsGIST patients with tumors larger than 2 cm have extremely low risk for lung metastasis. Routine inclusion of chest CT scan in staging and follow up is unnecessary.

Associations between nine dietary minerals intake and all-cause mortality in individuals with atherosclerotic cardiovascular disease.

Varied intake of dietary minerals critically affects cardiovascular health. This study examines the associations of nine dietary minerals intake with all-cause mortality in atherosclerotic cardiovascular diseases (ASCVDs). This study analyzed 4,125 individuals with ASCVD from the National Health and Nutrition Examination Survey, employing Kaplan-Meier survival analyses, weighted Cox models, and restricted cubic splines to assess linear and nonlinear relationships between dietary minerals intake and all-cause mortality. Associations across different body mass index (BMI) categories were also evaluated separately. Over 6.25 years of median follow-up, 1,582 deaths were documented. Adjusted for potential covariates, results show a negative linear correlation between dietary magnesium intake and all-cause mortality (p for trend <0.001). Compared to the lowest quartile, all-cause mortality risk in the highest quartile was found to be 0.63 (95% CI 0.49-0.81). The associations between intake of the other eight dietary minerals and all-cause mortality were not robust. BMI significantly influenced the links between dietary minerals intake and all-cause mortality (p for interaction <0.05). Across BMI categories, significant negative associations were found between intake of magnesium, phosphorus, potassium, sodium, and copper and all-cause mortality in underweight or normal weight groups. In overweight individuals, intake of calcium, iron, magnesium, and potassium was negatively linked to all-cause mortality. For obese groups, sodium intake negatively affected all-cause mortality (p for trend <0.001). Unlike other dietary minerals, increased magnesium intake significantly reduced all-cause mortality risk in ASCVD. BMI influenced the associations between dietary minerals intake and all-cause mortality.

Exploring the Mechanism of Centipeda minima in Treating Nasopharyngeal Carcinoma Based on Network Pharmacology.

Centipeda minima (CM) is a traditional Chinese herbal medicine used for the treatment of sinusitis and rhinitis, and it possesses anti-cancer properties. However, the mechanism of CM in the treatment of nasopharyngeal carcinoma (NPC) remains unclear. This study aimed to explore the mechanism of CM in the treatment of NPC using a network pharmacology approach. The active components and targets of CM and NPC were screened using TCMSP, SwissTarget, and GeneCards database. The association between CM components and NPC targets or pathways was analyzed using String, Cytoscape 3.9.1, David 6.7, and AutoDock Vina. The Sangerbox platform was used to conduct differential expression and Kaplan-Meier survival analysis of core genes. We identified 17 active compounds of CM and 146 corresponding targeted proteins in NPC. These targets may modulate pathways in cancer, PI3K-Akt, apoptosis, prolactin, relaxin, and TNF signaling. The top 5 core genes of the PPI network were found to be AKT1, STAT3, CASP3, EGFR, and SRC, which may be the main targets of CM in treating NPC. Molecular docking confirmed the binding energies of quercetin with CASP3, 8-Hydroxy-9,10-diisobutyryloxythymol with AKT1, and plenolin with AKT1, which were particularly low, suggesting robust and stable interactions. The expression levels of AKT1, CASP3, EGFR, SRC, MMP9, CCND1, and PTGS2 were significantly higher in head and neck squamous cell carcinoma (HNSC) samples compared to normal samples. In addition, the hub genes could predict the prognosis of HNSC as the Kaplan-Meier survival curve showed that patients with lower expressions of AKT1, STAT3, CASP3, EGFR, MMP9, ESR1, PTGS2, and PPARG had better overall survival. By conducting a network pharmacology approach, we revealed the main ingredients, key targets, and regulatory pathways of Centipeda minima in the treatment of NPC.

Mediation effect analysis of lipoprotein levels on BMI and cardiovascular outcomes in patients with heart failure

BackgroundAmong heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox.MethodsThe study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints.ResultsIn MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p<0.001, obese vs underweight), cardiovascular mortality (HR=0.46, 95%CI 0.30~0.73, p<0.001, obese vs underweight) and the incidence of MACCEs (HR=0.68, 95%CI 0.53~0.88, p=0.003, obese vs underweight). Mediation analysis revealed that TG was the strongest mediator between BMI and endpoints, with proportions of mediated effects of 6.6% (95%CI 2.2%~18.0%, p=0.0258, in all-cause death),7.0% (95%CI 2.3%~18.9%, p=0.0301, in cardiovascular death) and 10.2% (95%CI 3.3%~27.4%, p=0.0185, in MACCEs).ConclusionsThere is an "obesity paradox" in patients with heart failure, and lipoprotein levels especially triglyceride mediate the association between BMI and cardiovascular outcomes.

Tumor necrosis drives prognosis in osteosarcoma: No difference in chemotherapy response and survival between chondroblastic and osteoblastic osteosarcoma

IntroductionThe percentage of tumor necrosis is a crucial prognostic factor in osteosarcoma. Many studies adopt a 90 % cutoff based on osteoblastic osteosarcoma, but these findings are generalized to all conventional subtypes, including chondroblastic osteosarcoma. We sought to answer these questions: (1) Is tumor necrosis ≥90 % associated with better overall survival (OS) and disease-free survival (DFS) in osteoblastic and chondroblastic osteosarcoma? (2) Does the osteosarcoma subtype impact tumor necrosis? (3) Does the osteosarcoma subtype in “good” responders (tumor necrosis ≥90 %) affect OS and DFS?. Materials and methodsWe conducted a retrospective study of 156 patients with osteoblastic and chondroblastic osteosarcoma treated at our institution. All patients received a standardized chemotherapy protocol and underwent surgery with the goal of achieving negative margins (R0 resection). Propensity-score matching was performed to adjust for potential confounders. Kaplan-Meier survival analysis and Cox proportional hazards modeling were performed. ResultsPatients with osteoblastic osteosarcoma and tumor necrosis ≥90 % had higher 5- and 10-year OS and DFS compared to those with necrosis <90 %. In chondroblastic osteosarcoma, a trend towards higher OS and DFS was seen in patients with tumor necrosis ≥90 %; this, however, was not significant. Chondroblastic osteosarcoma was not a risk factor for either tumor necrosis <90 % (p = 0.89) or tumor necrosis <70 % (p = 0.57). Patients with osteoblastic or chondroblastic osteosarcoma that were deemed “good” responders (tumor necrosis ≥90 %) had similar OS and DFS at the 5- and 10-year marks. ConclusionConventional osteosarcoma subtype was not a risk factor for “poor” response. Survival outcomes (OS and DFS) were similar for osteoblastic and chondroblastic osteosarcoma with good response to chemotherapy.

What Is the Prognostic Value of the Pathologic Response after Neoadjuvant Radiotherapy in Soft Tissue Sarcoma? An Institutional Study Using the EORTC-STBSG Response Score.

Background/Objectives: The relationship between pathologic findings in soft tissue sarcoma (STS) after neoadjuvant treatment and oncological outcomes remains uncertain due to varying evaluation methods and cut-off values. This study aims to assess pathologic findings after neoadjuvant radiotherapy in STS using the EORTC-STBSG response score and evaluate its prognostic value. Methods: Clinical and outcome data from 44 patients were reviewed. Resected specimens were re-evaluated to measure viable cells, necrosis, fibrosis, and hyalinization. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier survival analysis. Cox proportional hazards regression was used for univariate and multivariate analyses to correlate outcomes with pathologic response. Results: The median percentages of viable cells, necrosis, and fibrosis/hyalinization were 20%, 11%, and 40%, respectively. A pathologic complete response (pCR), defined as ≤5% viable cells, was achieved in 25% of cases. Local recurrence occurred in 33% of cases, with a significantly higher rate of 64% after R1 resection compared to 22% after R0 resection. Distant metastases were observed in 42% of patients, primarily in the lungs. The 3-year rates for LRFS, DMFS, and OS were 65%, 54%, and 67%, respectively. A correlation between outcomes and tumor size, grade and histological subtype was observed. Classifying pathologic response by the EORTC-STBSG score failed to show an association with outcomes. Patients achieving pCR showed lower risk of LR and improved OS. Conclusions: While the EORTC-STBSG score did not show a prognostic value, resection specimens with ≤5% viable cells were linked to improved LRFS and OS.

Prognostic value of PSMA PET in predicting long-term biochemical control following curative intent treatment for prostate cancer.

The aim of this study is to investigate the prognostic value of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) metrics in predicting long-term biochemical failure-free survival (BFFS) following curative intent treatment for prostate cancer. We completed a prospective study that followed men who had PSMA PET for staging of newly diagnosed prostate cancer between 2015 and 2017 who went on to have curative intent treatment with radiotherapy (RT) or radical prostatectomy (RP). PSMA PET CT imaging was reported and the intraprostatic maximum standardised uptake value (SUVmax) was recorded. The primary outcome was BFFS. Statistical analysis included descriptive statistics, Cox proportional hazards (PH) models, Kaplan-Meier survival analysis and a regression tree structured method. A total of 183 men were included in the analysis with a median age of 66 years and the majority of patients (55.2%) had ISUP grade 1-3 disease. All patients had PSMA PET staging prior to curative intent treatment with RP (66.1%) or external beam radiotherapy (33.9%). PSMA-avid pelvic nodes were present in 26 patients but were not associated with worse biochemical control. A PSMA SUVmax of the prostate primary greater than the median (>5.6) was associated with a lower BFFS (HR: 4.4, 95% CI 1.42-3.72, P = 0.01). A multivariate Cox model incorporating initial biopsy grade, age and PSMA SUVmax showed that PSMA SUVmax was an independent predictor of BFFS. The RT-structured method identified an optimal threshold of 6.8 for PSMA SUVmax, above which patients with ISUP 1-3 disease had a significantly worse BFFS. PSMA SUVmax is a strong predictor of BFFS in patients with non-metastatic prostate cancer who underwent curative intent treatment. Patients with low-risk disease on biopsy (ISUP 1-3) but high PSMA SUVmax may have biochemical failure risk analogous to higher-risk disease (ISUP 4-5). These findings allow for further risk stratification and prognosis of patients with newly diagnosed prostate cancer planned for definitive treatment.

MUC17 is a potential new prognostic biomarker and promotes pancreatic cancer progression in obstructive jaundice.

Our working group has previously shown that bile acids (BAs) accelerate carcinogenic processes in pancreatic cancer (PC) in which mucin 4 (MUC4) expression has a central role. However, the role of other mucins in PC are less clear, especially in bile-induced cancer progression. The study aim was to investigate expression of MUC17 in BAs- or human serum-treated pancreatic ductal adenocarcinoma (PDAC) cell lines and use different assays with RNA silencing/overexpression to study the role of MUC17 in cancer progression. Protein expression of MUC17 was evaluated in 55 human pancreatic samples by immunohistochemistry, and Kaplan-Meier survival analysis was used to compare survival curves. Expression of MUC17 increased in PDAC patients, especially in obstructive jaundice (OJ) and the elevated MUC17 expression associated with poorer overall survival (10.66±1.99 vs. 15.05±2.03 months; Log rank: 0.0497). Treatment of Capan-1 and AsPC-1 cells with BAs or with human serum obtained from PDAC + OJ patients enhanced the expression of MUC17, as well as the proliferative potential of the cells, whereas knockdown of MUC17 alone or in combination with MUC4 decreased BAs-induced carcinogenic processes. Our results demonstrated that MUC17 has a central role in bile-induced PC progression, and in addition to MUC4, this isoform also can be used as a novel prognostic biomarker.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung.

Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors. The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Real-World Evidence of Clinical Outcomes of the Use of the Adalimumab Biosimilar SB5 in Rheumatic and Gastrointestinal Immune-Mediated Inflammatory Diseases: 12-Month Data from the PERFUSE Study.

There is a need for published data on real-world use of SB5, an adalimumab (ADL) biosimilar approved in Europe in 2017, on the basis of evidence from pre-clinical and analytic data as well as phase I and III clinical studies demonstrating equivalent efficacy and comparable pharmacokinetics, safety and immunogenicity profiles as the reference ADL. The purpose of this study was to estimate patient persistence on SB5 at 12 months post-initiation using clinical and healthcare claims data from the French Système National des Données de Santé (national healthcare claims database, SNDS) in addressing data gaps. PERFUSE is a 12-month, observational, multi-centre cohort study of patients with rheumatic or gastrointestinal immune-mediated inflammatory diseases (IMIDs) who initiated routine SB5 treatment between October 2018 and October 2020, either as their first ADL (naïve) or transitioning from another ADL (switched). Clinical data, including disease activity scores, C-reactive protein levels, and dosing information, were collected as available from patient records captured during routine visits to specialist physicians. Persistence data were supplemented with data from the French national healthcare claims database (SNDS). Analyses of clinical data were descriptive, while persistence was assessed using a Kaplan-Meier survival analysis. Overall, 911 patients were included: 507 from rheumatology centres [116 with rheumatoid arthritis (RA), 78 psoriatic arthritis (PsA), and 313 ankylosing spondylitis (AS)] and 404 from gastroenterology centres [316 with Crohn's disease (CD) and 88 ulcerative colitis (UC)]. Among naïve patients, 12-month remission/low activity rates were 58% for RA, 66% for PsA, 59% for AS, 94% for CD, and 85% for UC, increasing significantly from baseline for all indications (p < 0.05). Switched patients' remission rates remained stable between baseline and month 12 (M12) for all indications (p > 0.05). Persistence (95% CI) at M12 among naïve patients was 59% (46.5, 68.8) for RA, 65% (49.7, 77.1) for PsA, 56% (48.3, 62.6) for AS, 70% (63.0, 75.7) for CD, and 42% (30.7, 53.1) for UC, compared to 60% (42.7, 73.7) for RA, 57% (37.3, 72.1) for PsA, 55% (45.8, 64.0) for AS, 63% (53.4, 71.7) for CD, and 56% (27.2, 77.6) for UC among switched patients. No significant differences were observed between naïve and switched patients (p > 0.05). SNDS pairing provided information on 68 of the 132 patients (52%) who were lost to follow-up in the clinical database, of whom 57 (84%) were confirmed persistent at M12 and 11 (16%) non-persistent. Primary treatment failure (naïve patients) and patient decision (switched patients) were the most common reasons stated for treatment discontinuation. SB5 provides clinically effective treatment of both gastrointestinal and rheumatic IMIDs for naïve and switched patients, with no loss of control observed when switching. Persistence was comparable between naïve and switched populations, though the reasons for non-persistence differed. Trial registration number: Clinical Trials identifier NCT03662919. Trial registration date: 10 September 2018.

Association between lactate/albumin ratio and 28-day all-cause mortality in critically ill patients with acute myocardial infarction

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Early identification of high-risk patients is crucial for timely interventions and improved outcomes. The lactate/albumin ratio (LAR) has been suggest as a significant correlate for assessing the risk of mortality in critically ill patients. This study aimed to utilize the American eICU Collaborative Research Database to explore the association between baseline LAR and all-cause mortality within 28 days in ICU of critically ill patients diagnosed with AMI. We conducted a retrospective cohort study of 989 AMI patients from the eICU Collaborative Research Database. Patients were included based on ICD-9 code 410 and the universal definition of AMI. LAR was calculated as the ratio of baseline lactate to albumin levels within the first 24 h of ICU admission. The outcome was all-cause mortality within 28 days after ICU admission. Multivariable logistic regression models were used to evaluate the independent association between LAR and the risk of death, adjusting for potential confounders including demographics, comorbidities, vital signs, and laboratory parameters. Subgroup analyses and nonlinear modeling were performed to further explore the relationship. Of the 989 AMI patients, 171 (17.3%) died within 28 days after ICU admission. Patients who died had significantly higher LAR compared to survivors (1.66 vs. 0.96, p < 0.001). Multivariable analysis showed that each unit increase in LAR was associated with a 2.15-fold higher risk of all-cause mortality within 28 days after ICU admission (95% CI: 1.64–2.83, p < 0.001). Subgroup analyses confirmed the consistent association across different patient characteristics. Nonlinear modeling revealed a threshold effect, where LAR above 2.15 was no longer significantly associated with mortality. Kaplan-Meier survival analysis demonstrated lower survival probabilities for patients with higher LAR(1.0526–5.8235). The findings suggest that a higher LAR was associated with an increased risk of 28-day all-cause mortality for critically ill patients with AMI after ICU admission.