Kaplan-Meier Survival Analysis Research Articles

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 < 0.001; AI = 13.2° versus 10.0°, p < 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 < 0.001; AI = 14.7° versus 10.2°, p < 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.

The incremental predictive value of arterial stiffness over SCORE2 in the setting of primary cardiovascular prevention: a 6-year follow-up study.

Arterial stiffness hallmarks age-related cardiovascular diseases, precedes their onset and strongly links to accelerated disease progression. However, whether carotid-to-femoral pulse wave velocity (PWV), a proxy of arterial stiffness, predicts cardiovascular risk over and above SCORE2, a newly introduced risk score remains to be investigated. We measured PWV among 747 individuals without established atheromatosis. Study participants were followed up over a 6-year period for the incidence of cardiovascular events [[MACE)-cardiovascular mortality, stroke and myocardial infarction]. PWV emerged as an independent and additive predictor of first cardiovascular events when added in a model encompassing SCORE2 (hazard ratio = 1.10; 95% confidence interval (95% CI) = 1.07-1.14; P < 0.001, Brier score changed from 0.073 (0.060-0.086) to 0.067 (0.055-0.081); P < 0.001, c-statistic increased from 0.71 to 0.75; P = 0.017; likelihood ratio: 20.22; P < 0.001; the overall net reclassification improvement (NRI): 0.577; P < 0.001, AICc changed from 697.81 to 679.60; BIC changed from 702.42 to 688.82]. An increase in PWV predicted a greater risk of future MACEs additively to conventional risk factors (P < 0.05). We performed Kaplan-Meier survival analysis for the tertiles of PWV [first tertile < 8.04 m/s; the second tertile: (8.04-10 m/s); the third tertile: (10-17.10 m/s); (P < 0.05 for all comparisons between the tertiles). PWV tertiles also predicted MACE when added to SCORE2 [for the second tertile: hazard ratio: 5.87 (95% CI: 1.73-19.92); P = 0.004 and for the third tertile: hazard ratio: 9.69 (95% CI: 2.97-31.55); P < 0.001 with the respective change of c-statistic from 0.739 to 0.772; P = 0.012 and continuous NRI = 0.598]. PWV confers additive prognostic value to the newly introduced SCORE2 for adverse outcome in primary prevention.

Three-year clinical performance of direct restorations using low-shrinkage Giomer vs. nano-hybrid resin composite

ObjectivesThe objective of this investigation was to compare the clinical performance of a nano-hybrid resin composite and a low-shrinkage Giomer resin composite.Material and methodsIn total, 35 pairs of restorations were performed using either low-shrinkage Giomer (Beautifil II LS, Shofu Inc.) or nano-hybrid (Clearfil Majesty Posterior) resin composite in 35 patients by two operators using the relevant adhesives, i.e., FL-Bond II (Shofu Inc.) and Clearfil SE Bond (Kuraray), with the self-etching technique according to each manufacturer's instructions. Two clinicians assessed the restorations 2 weeks (baseline); 6 months; and 1, 2, and 3 years after the restorative procedures using FDI (World Dental Federation) criteria (Scores 1–5). Data were analyzed using the marginal homogeneity and McNemar tests. The survival rate was calculated using Kaplan–Meier survival analysis and the survival of the two groups was compared with the log-rank test (p = 0.05).ResultsThe mean observation period was 37.7 ± 6.8 months. All restorations completed their 3-year follow-up. The criteria were mainly rated with high (1 or 2) scores for quality in both groups. Only one restoration in the low-shrinkage Giomer resin composite group was accepted as a failure at the 2-year recall due to retention loss.ConclusionAt the 3-year follow-up, the performance of the restorations using the Giomer and the nano-hybrid resin composite were similar and clinically acceptable.Clinical relevanceThe low-shrinkage Giomer resin composite exhibited a similar clinical performance to the nano-hybrid resin composite after 3 years in service with both materials displaying minor surface deteriorations at the 3-year recall.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier: NCT02823769.

Multi-omics analyses were combined to construct ubiquitination-related features in colon adenocarcinoma and identify ASNS as a novel biomarker.

As one of the malignant tumors with the highest incidence and fatality in the world, colon adenocarcinoma (COAD) has a very complex pathogenic mechanism, which has not yet been fully elucidated. Ubiquitin can regulate cell proliferation, cell cycle, apoptosis, DNA damage repair, and other processes by changing the activity of substrate proteins or causing ubiquitin-proteasome degradation. These are the key links in the pathogenesis of COAD, and ubiquitin plays an important role in the occurrence and development of COAD. We integrated transcriptomics, single-cell and clinical omics, and TCGA and GEO databases of COAD patient data. Cox and Lasso regression was employed to assess ubiquitination genes in COAD for generating ubiquitination-related features. The aim was to evaluate the prognostic value of these features for tumors and their impact on the immune microenvironment. At the same time, the expression level of model genes was further analyzed using single-cell data. Finally, the expression and function of ASNS, a key gene for this trait, were detected in vitro. In our study, based on identifiable changes in the expression of marker genes, this feature can be used to classify patients with COAD. Kaplan-Meier survival analysis indicated that those with elevated risk scores in each cohort experienced inferior outcomes. There is good validation in both the training queue and the validation queue. The results of the immune infiltration analysis showed that the immune infiltration rate was significantly increased in the high-risk group. After the knockdown of ASNS, an important gene in the signature, the activity and migration capacity of SW620 and RKO cell lines and colony formation capacity were dramatically reduced in cell tests. We screened ubiquitination-related genes and constructed ubiquitination-related features, which can be used as reliable prognostic indicators of COAD. ASNS was identified as a possible biomarker for COAD.

Evaluation of Two Different Approaches for Selecting Patients for Postoperative Radiotherapy in Deep-Seated High-Grade Soft Tissue Sarcomas in the Extremities and Trunk Wall.

Two national sarcoma centers have had different approaches for selecting patients with grade 2-3 deep-seated soft tissue sarcomas (STS) for postoperative radiotherapy (RT). We evaluated potential differences in local recurrence in patients treated at the two centers. At Sarcoma Center 1 (SC1), RT was the standard treatment for all tumors except certain small tumors excised with a margin wider than 1 cm. Sarcoma Center 2 (SC2) avoided RT for tumors regardless of tumor size if removed with a margin wider than 1 cm and/or a solid barrier. We included 386 patients (SC1/SC2 = 196/190) over 18 years of age diagnosed with a non-metastatic grade 2-3, deep-seated STS of the extremities or trunk wall, who underwent primary surgical treatment (only tumors excised with a negative margin) from 1 January 2000, to 31 December 2016. Kaplan-Meier survival analysis, competing risk analysis, and cause-specific Cox regression were applied. A total of 284 patients received primary RT, 163 (83%) at SC1 and 121 (64%) at SC2 (p < 0.001). The cumulative incidence of local recurrence at five years was 15% (95% CI: 10-19%) at SC1 and 14% (95% CI: 9-19%) at SC2. Multivariate analysis showed no significant differences in local recurrence between the centers. We concluded that when entering all available patients into the analysis using an intention-to-treat principle, a more selective approach to postoperative RT in patients with grade 2-3 deep-seated STS did not lead to a higher local recurrence rate. However, with this study design, we cannot rule out if the local recurrence rate could have been lower if RT was administered to all tumors removed with a margin wider than 1 cm and/or a solid barrier.

Prognostic modeling of hepatocellular carcinoma based on T-cell proliferation regulators: a bioinformatics approach.

The prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC. This study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis. Among the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways. This bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC.