Cox Proportional Hazards Model Analysis Research Articles

Association of dietary inflammatory indices with sarcopenia and all-cause mortality in COPD patients

BackgroundSarcopenia frequently occurs as a comorbidity in individuals with COPD. However, research on the impact of Appendicular Skeletal Muscle Mass (ASM) on survival in COPD patients is scarce. Moreover, there is a lack of research on the association between dietary pro-inflammatory capacity and sarcopenia in COPD.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) covering the years 1999 to 2006 and 2011 to 2018. We aimed to investigate the relationship between the Dietary Inflammatory Index (DII) and sarcopenia prevalence among adults diagnosed with COPD in the United States. Furthermore, we sought to explore the relationship between sarcopenia, ASMI, and all-cause mortality. The study included a total of 1,429 eligible adult participants, divided into four groups based on quartiles of DII, with adjustments for sample weights. Methodologically, we used multivariable logistic regression analyses and to examine the association between DII and sarcopenia. Additionally, we used restricted cubic spline (RCS) tests to evaluate potential non-linear relationships. To assess the effect of sarcopenia on overall all-cause mortality, we used Kaplan–Meier models and Cox proportional hazards models. Moreover, we used RCS analyses to investigate potential non-linear relationships between ASMI and all-cause mortality. Subgroup analyses were conducted to confirm the reliability of our study findings.ResultsIn our COPD participant cohort, individuals with higher DII scores were more likely to be female, unmarried, have lower educational attainment, and show lower ASMI. Using multivariable logistic regression models, we found a positive association between the highest quartile of DII levels and sarcopenia incidence [Odds Ratio (OR) 2.37; 95% Confidence Interval (CI) 1.26–4.48; p = 0.01]. However, analysis of RCS curves did not show a non-linear relationship between DII and sarcopenia. Throughout the entire follow-up period, a total of 367 deaths occurred among all COPD patients. Kaplan–Meier survival curves showed a significantly higher all-cause mortality rate among individuals with concurrent sarcopenia (p < 0.0001). Cox proportional hazards model analysis showed a 44% higher risk of all-cause mortality among COPD patients with sarcopenia compared to those without sarcopenia [Hazard Ratio (HR): 1.44; 95% CI 1.05–1.99; p < 0.05]. Additionally, our final RCS analyses revealed a significant non-linear association between ASMI levels and all-cause mortality among COPD patients, with a turning point identified at 8.32 kg/m2. Participants with ASMI levels above this inflection point had a 42% lower risk of all-cause mortality compared to those with ASMI levels below it (HR 0.58; 95% CI 0.48–0.7).ConclusionWe observed a significant association between concurrent sarcopenia and an increased risk of all-cause mortality in COPD patients within the United States. Moreover, ASMI demonstrated a non-linear association with all-cause mortality, with a critical threshold identified at 8.32 kg/m2. Our findings also revealed an association between DII and the presence of sarcopenia. Consequently, further investigations are warranted to explore the feasibility of dietary DII adjustments as a means to mitigate muscle wasting and enhance the prognosis of COPD.

Impact of obesity on the incidence of postoperative pulmonary complications following laparoscopic colorectal surgery

Objective: To evaluate the effects of obesity on the incidence of postoperative pulmonary complications (PPCs) following laparoscopic colorectal surgery. Methods: A total of 150 patients with pathological diagnosis of colorectal cancer who accepted laparoscopic colorectal excision from January to May 2023 were retrospectively recruited. All the patients scored 26 points or more in the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) model, making them all in intermediate to high risks of PPCs. Patients were divided into obesity group and non-obesity group depending on whether they were obese or not. Propensity score matching (1∶1) was performed to achieve the balance of clinicopathological characteristics with the matching factors of age, sex, respiratory complications and ARISCAT score. A total of 96 patients were eventually enrolled, with 48 patients in obesity group and 48 patients in non-obesity group. Besides, the patients were divided into 25°-30° Trendelenburg subgroup and ±10°-15° Trendelenburg subgroup according to surgical sites for further analysis. The incidence of PPCs, the intraoperative airway pressure and blood biomarker expression of lung injury, including soluble receptor for advanced glycation end products (sRAGE) and angiopoietin-2 (ANG2) at postoperative day (POD) 1 and POD3 between the two groups were compared. The relationship between obesity and incidence of PPCs within 30 postoperative days were analyzed with unifactorial Cox proportional hazard model. Results: The obesity group was comprised of 35 males and 13 females with a median age of 60 (49, 69) years, and the non-obesity group was comprised of 35 males and 13 females with a median age of 60 (52, 67) years. The incidence of PPCs was 50.0% (24/48) in the obesity group, which was higher than 20.8% (10/48) in the non-obesity group and the incidence of grade Ⅰ PPCs and microatelectasis were 31.3% (15/48) and 33.3% (16/48), higher than the 12.5% (6/48) and 12.5% (6/48) of the non-obesity group (all P<0.05). The peak airway pressure (Ppeak) and plateau airway pressure (Pplat) of patients in obesity group were 34.0(31.5, 36.5) and 30.0(27.0, 32.0) cmH2O(1 cmH2O=0.098 kPa), which were significantly higher than the 26.0 (24.0, 29.5) and 22.0 (21.0, 26.5) cmH2O of the non-obesity group (all P<0.001). The ANG2 level of the obesity group at POD3 was 11.9 (8.4, 16.5) μg/L, which was higher than 9.2 (6.0, 12.3) μg/L of the non-obesity group (P=0.045). In 25°-30°Trendelenburg subgroup, the incidence of PPCs in obese patients were significantly higher than that of non-obese patients [41.4% (12/29) vs 11.4% (4/35), P=0.005]. In ±10°-15°Trendelenburg subgroup, no significant difference was found in PPCs incidence between obese and non-obese patients [63.2% (12/19) vs 46.2% (6/13), P=0.215]. The unifactorial Cox proportional hazard model analysis showed that obesity was a risk factor of PPCs in 30 postoperative days (HR=3.015, 95%CI: 1.438-6.321, P=0.001). Conclusion: In patients undergoing laparoscopic colorectal surgery with intermediate to high risk of PPCs, obesity raises intraoperative airway pressure and aggravates intraoperative lung endothelial injury. Obesity is a risk factor of PPCs in 30 postoperative days.

Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors.

Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs. We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model. A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence. Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.

Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women

BackgroundAlthough it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear.MethodsA total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compressive strength index (CSI) at the narrowest point of the femoral neck.ResultsCompared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased.ConclusionThese results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

Outside in and all inside approach for repair of meniscal tears: post-operative subjective evaluation: a retrospective study

Background: Assess clinical outcomes after using outside-in, all-inside or combination of both approaches for meniscal repair. Methods: 86 patients with diagnosed meniscal tears, operated between January 2017 and January 2019 by one surgeon in Northway Clinic, Vilnius and Vilnius Clinical Hospital were surveyed. The meniscal repair techniques used included all-inside, outside-in, or a combination. Clinical outcomes were evaluated using the International Knee Documentation Committee Subjective Knee Evaluation Form, with meniscal retear indicating failure. Ethical approval was deemed unnecessary for this project. Descriptive statistical analyses were performed using IBM SPSS Statistics 29.01. Results: Patients undergoing the outside-in approach scored 89.4±12.5 on the IKDC questionnaire, compared to 88.5±16.6 for all-inside and 82.8±20.3 for both techniques combined (p=0.194). Kaplan–Meier analysis showed a 5.6-year survival rate of 80.9% with the all-inside approach. Subjective knee function assessment indicated scores of 8.50±1.9 for outside-in, 8.49±1.4 for all-inside, and 8.16±1.95 for both techniques. Cox proportional hazards model analysis suggested that older age and higher BMI trended towards reduced reoperation risk (hazard ratio, 0.93 and 0.98; p=0.246 and p=0.832, respectively). Conclusions: Self-reported outcomes in this study evaluated by IKDC questionnaire and subjective function assessment emphasize that both all-inside, outside-in or combination of the techniques provide similar results. All adverse outcomes defined as meniscal retears were observed using all-inside technique.

The influence of advanced maternal age on congenital malformations, short- and long-term outcomes in offspring of nulligravida: a Korean National Cohort Study over 15 years.

To assess the influence of advanced maternal age on congenital malformations, and short- and long-term outcomes in offspring of nulligravida. A retrospective study was conducted using the Korean National Health Insurance Service database spanning from January 2005 to December 2019. All live-born offspring of nulligravida (n=3,685,817) were included. The maternal age was subdivided into the following subgroups: <25 years (n=153,818), 25-29 years (n=845,355), 30-34 years (n=1,738,299), 35-39 years (n=787,530), 40-44 years (n=151,519), and >44 years (n=9,296). Outcomes were assessed based on ICD-10 codes. Adjusted odds ratios (aORs) were calculated with the group of 25-29 years as a reference using logistic regression and Cox proportional hazards model analysis. Most congenital malformations showed an age-dependent increase, but cleft lip and abdominal wall defect exhibited a U-shape curve, indicating an increase even in those <25 years old. Similarly, various disorders included in the neonatal composite outcomes from short-term outcomes showed an age-dependent escalation. However, preterm birth from the short-term outcomes and most of the long-term developmental outcomes, except for motor developmental delays and Tics, showed a U-shaped pattern. The aOR of autism and cerebral palsy, showing the most obvious U-shaped curved in the long-term outcomes, was 1.50 (95% CI 1.24-1.82) and 1.54 (95% CI 1.17-2.03), respectively in the >44 years old group and 1.18 (95% confidence interval [CI], 1.11-1.25) and 1.19 (95% CI, 1.09-1.30) in the <25 years old group. Overall, an advanced maternal age shows an age-dependent correlation with most congenital malformations, as well as short- and long-term outcomes of neonates.

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study

To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients.

Distinct presentation of melanoma in Black patients may inform strategies to improve outcomes.

Melanoma guidelines stem largely from data on non-Hispanic White (NHW) patients. We aimed to identify features of melanoma within non-Hispanic Black (NHB) patients to inform strategies for earlier detection and treatment. From 2004 to 2019 Surveillance, Epidemiology, and End Results (SEER)data, we identified nonmetastatic melanoma patients with known TN category and race. Kaplan-Meier cancer-specific survival (CSS) estimates and multivariable Cox proportional hazard modeling analyses were performed. Of 492 597 patients, 1499 (0.3%) were NHB, who were younger (21% vs. 17% age <50) and more commonly female (54% vs. 41%) than NHW, both p < 0.0005. For NHBs, lower extremity was the most common site (52% vs. 15% for NHWs, p < 0.0001), T category was higher (55% Tis-T1 vs. 82%; 27% T3-T4 vs. 8%, p < 0.0001) and stage at presentation was higher (19% Stage III, vs. 6%, p < 0.0001). Within the NHB cohort, males were older, and more often node-positive than females. Five-year Stage III CSS was 42% for NHB males versus 71% for females, adjusting for age and clinical nodal status (hazard ratio 2.48). NHB melanoma patients presented with distinct tumor characteristics. NHB males with Stage III disease had inferior CSS. Focus on this high-risk patient cohort to promote earlier detection and treatment may improve outcomes.

Cumulative blood pressure predicts risk of stroke in individuals with type 2 diabetes

AimsTo determine whether cumulative blood pressure (BP) could predict stroke in individuals with type 2 diabetes (T2D). MethodsBP levels at baseline and the initial three visits were obtained from individuals participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who had not experienced a stroke. Cumulative elevations in BP were assessed by adding the weighted mean BP values at various time intervals. The association of cumulative BP with stroke was evaluated by a multivariate-adjusted Cox proportional hazard model analysis. ResultsOverall, 8282 participants were included (62.10% males and 37.90% females; mean age, 62.73 years). With a median follow-up period of 6.36 years, 324 (3.91%) and 305 (3.68%) patients had any and nonfatal stroke events, respectively. Only baseline systolic BP (SBP) independently predicted any stroke after adjustment for potential confounders, whereas cumulative SBP and pulse pressure independently predicted elevated stroke events. A strong dose–response relationship between cumulative BP and stroke was identified, and conventional risk factors combined with cumulative SBP improved prediction efficiency. ConclusionCumulative SBP independently predicts stroke in individuals with T2D and provides an incremental predictive value for stroke compared with baseline BP assessments. Trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00000620)

Arterial stiffness progression in metabolic dysfunction–associated fatty liver disease subtypes: A prospective cohort study

Background and aimsWe aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk. Methods and resultsUsing data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non–MAFLD, overweight/obese (OW–MAFLD), lean/normal weight (lean–MAFLD) and diabetes (DM–MAFLD) groups. Among the participants with a median follow–up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW–, lean– and DM–MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non–MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81–16.94), 25.33 (7.84–42.83) and 38.49 (27.88–49.10) in OW, lean and DM–MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10–1.95), 3.56 (1.72–5.40) and 3.94 (2.82–5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM–, lean–, OW with metabolic abnormalities (MA)–, and OW without MA–MAFLD. ConclusionMAFLD, especially DM–MAFLD and lean–MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.

Significance of the cribriform morphology area ratio for biochemical recurrence in Gleason score 4 + 4 prostate cancer patients following robot-assisted radical prostatectomy.

In prostate cancer, histological cribriform patterns are categorized as Gleason pattern 4, and recent studies have indicated that their size and percentage are associated with the risk of biochemical recurrence (BCR). However, these studies included a mixture of cases with various Gleason scores (GSs). We therefore examined the prognostic value of the area and percentage of cribriform patterns in patients with GS 4 + 4 prostate cancer. We investigated 108 patients with GS 4 + 4 prostate cancer who underwent robot-assisted radical prostatectomy (RARP). After digitally scanning the hematoxylin and eosin-stained slides, we measured the area of the entire cancer and cribriform patterns. Predictive factors for BCR were explored using log-rank test and Cox proportional hazard model analyses. Sixty-seven (62.0%) patients had a cribriform pattern in RARP specimens, and 32 (29.6%) experienced BCR. The median total cancer area, cribriform pattern area, and percentage of cribriform pattern area (% cribriform) were 427.70 mm2 (interquartile range [IQR], 171.65-688.53 mm2 ), 8.85 mm2 (IQR, 0-98.83 mm2 ), and 2.44% (IQR, 0%-33.70%), respectively. Univariate analyses showed that higher preoperative serum prostate-specific antigen (PSA) levels, positive resection margins, advanced pathological T stage, extraprostatic extension, larger total cancer area, larger cribriform morphology area, and higher % cribriform values were significantly associated with BCR. A multivariate analysis demonstrated that the PSA level (hazard ratio [HR], 1.061; 95% confidence interval [CI], 1.011-1.113; p = 0.017) and % cribriform (HR, 1.018; 95% CI, 1.005-1.031; p = 0.005) were independent predictors of BCR. An increased % cribriform value was associated with BCR in patients with GS 4 + 4 prostate cancer following RARP.

Efficacy and Safety of Hepatic Arterial Infusion Therapy with Cinobufacini in Advanced Hepatocellular Carcinoma with Macrovascular Invasion: A Retrospective Cohort Study.

The presence of macrovascular invasion (MVI) is associated with poor prognosis in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of Cinobufacini therapy via hepatic arterial infusion (HAI) in advanced HCC patients with MVI. The clinical records of 130 consecutive patients with unresectable advanced HCC and MVI who had received Cinobufacini or cisplatin plus 5-fluorouracil (CF) treatment via HAI were retrospectively analyzed. The therapeutic efficacy, overall survival (OS), progression-free survival (PFS), and adverse events were compared between the two treatment groups. The Cinobufacini group demonstrated significant curative effects on treatment via HAI compared with the CF group, including the objective response rate (44.9% vs 27.9%, P=0.048), the median OS (14.8 months vs 11.1 months, P=0.010), and the median PFS (10.3 months vs 6.0 months, P=0.006). Result in subgroup analysis of portal vein invasion grade supported the efficacy in Cinobufacini treatment, especially in the median OS of Vp1-2 (18.3 months vs 14.3 months, P=0.043) and Vp3 (15.0 months vs 11.4 months, P=0.046), as well as the median PFS of Vp1-2 (14.8 months vs 10.2 months, P=0.028) and Vp3 (10.8 months vs 6.6 months, P=0.033) compared with CF treatment. Cox proportional hazards model and forest plot analysis of factors confirmed the survival benefit from HAI with Cinobufacini over CF (hazard ratio [HR], 0.61; 95% CI: 0.40-0.91; P=0.010). Multivariable analysis identified portal vein invasion grade (Vp4; HR, 1.78; 95% CI: 1.03-2.16; P=0.032) and AFP (>1000; HR, 1.61; 95% CI: 1.08-1.91; P=0.039) as the independent factors for prognosis. Moreover, the total incidence of adverse events in the Cinobufacini group was significantly lower than in the CF group (60.9% vs 82.0%, P=0.009). Cinobufacini therapy via HAI is a viable strategy for curing advanced HCC with MVI, due to prolonged survival and a superior safety profile.

Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells and activates the integrin αvβ3-PI3K-Akt signaling pathway.

Individual patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Here, we aimed to search for a stable prognostic marker from platelet-treated ovarian cancer cells, and explore its functions and mechanisms. Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells. Relevant studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by differentially expressed genes (DEGs), Venn diagram drawing, protein-protein interaction (PPI) network, Cox proportional hazards model and Kaplan-Meier analysis. The expression of TGFBI in clinical samples was assessed by immunehistochemical staining (IHC), and the association of TGFBI levels with the clinic-pathological characteristics and prognosis in ovarian cancer patients was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study. TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. An analysis of bioinformatics data revealed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) in ovarian cancer patients. Tissue microarray results showed that TGFBI was an independent factor for ovarian cancer, and TGFBI expression predict poor prognosis. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3. We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway.

A Greater Variety of Social Activities Is Associated With Lower Mortality Risk.

More frequent engagement in social activity is often associated with better physical health outcomes. Yet, less is known about whether engagement in a greater variety of social activities such as a mix of volunteering and attending club meetings (social activity variety) is important for health. The current study assessed whether social activity variety relates to mortality risk after adjusting for social activity frequency, nonsocial activity frequency and variety, and sociodemographic covariates, and how this relationship varies depending on age. Using data from the Health and Retirement Study, we included 5,017 adults aged 51 and older who completed questions about social activity participation in 2008 and whose mortality status was recorded up to 2019. We also examined whether age moderated the relationship between social activity variety and mortality risk. Cox proportional hazard model analyses revealed that those with higher activity variety in social activities were more likely to survive over the following 11 years than those with low social activity variety. Moreover, age moderation indicated that the association between social activity variety with mortality risk was stronger among the oldest adults. Findings suggest that a greater variety of social activities is linked to mortality risk even after adjusting for social activity frequency, nonsocial activities, and health status across adulthood.

Prognostic significance of left atrial strain combined with left ventricular strain using cardiac magnetic resonance feature tracking in patients with heart failure with preserved ejection fraction.

We aimed to evaluate the prognostic value of left ventricular global longitudinal strain (LVGLS) and left atrial strain (LAS) obtained from magnetic resonance imaging (MRI) feature tracking in patients with heart failure with preserved ejection fraction (HFpEF). We retrospectively enrolled consecutive patients with HFpEF admitted to our hospital who underwent cardiac MRI. LVGLS and LAS were obtained from cine MRI by feature tracking. The end point was defined as a composite of all-cause death, myocardial infarction, and hospitalization due to decompensated HF. One-hundred patients with HFpEF were enrolled. Mean LVGLS and LAS were -13.7 ± 3.7% and 22.5 ± 11.6%, respectively. During follow-up of 4.4 ± 1.9years, 24 events occurred. Multivariate Cox proportional hazards model analysis demonstrated LAS was independently associated with adverse cardiac events. Kaplan-Meier curve analysis revealed that the patients with both LVGLS and LAS worse than the median (LVGLS ≥ -12.2% and LAS ≤ 13.8%) had a significantly lower event-free rate compared to those with preserved strain (Log-rank P < 0.001). Simultaneous assessment of LVGLS and LAS using MRI was useful for risk stratification in the patients with HFpEF.

PERSISTENCE WHILE ON LABELED MAINTENANCE DOSE AMONG ADVANCED THERAPY-NAÏVE PATIENTS WITH ULCERATIVE COLITIS INITIATED ON USTEKINUMAB OR ADALIMUMAB

Abstract BACKGROUND In the real-world setting, biologic therapy in patients with ulcerative colitis (UC) may require dose escalation if initial response is limited or due to loss of response. Dose escalation leads to higher treatment costs and may cause difficulties obtaining prior authorization and approvals from health plans. This study compared treatment persistence while on labeled maintenance dose among advanced therapy (ADT)-naïve patients with UC on ustekinumab or adalimumab. METHODS Adults with UC initiated on ustekinumab or adalimumab (index date: 10/21/2019 - 03/02/2022) were selected from the IQVIA PharMetrics® Plus database. Patients were ADT-naïve (i.e., no claim for UC-indicated ADT) and had no other autoimmune diseases in the 12-month baseline period before the index date. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Persistence while on the labeled maintenance dose was defined as (1) no gaps between days of therapy supply (ustekinumab, &amp;gt;120 days; adalimumab, &amp;gt;60 days), and (2) absence of any dose change from the maintenance dose per US label. Composite endpoints of being persistent while corticosteroid-free (&amp;lt;14 consecutive days of corticosteroid supply after day 90 post-index) and persistent while on monotherapy (no immunomodulators or ADT) were also evaluated. Endpoints were assessed from the maintenance phase start until the earliest of discontinuation (event), corticosteroid use (event), immunomodulator or ADT use (event), dose change (censored), 12 months follow-up, or data end (censored) using weighted Kaplan-Meier and Cox proportional hazards model analyses. RESULTS There were 371 and 1,726 patients in the weighted ustekinumab versus adalimumab cohort, respectively (Fig. 1). At 12 months after the maintenance phase start, 88.6% and 61.7% of the ustekinumab versus adalimumab cohort were persistent while on the labeled maintenance dose; persistence was 4.21 times higher in the ustekinumab cohort (p-value: &amp;lt;0.001; Fig 2a). Further, 70.0% and 43.9% of the ustekinumab versus adalimumab cohorts were persistent and corticosteroid-free while on the labeled maintenance dose; persistence was 2.31 times higher in the ustekinumab cohort (p-value: &amp;lt;0.001; Fig 2b). Finally, 84.4% and 55.1% of the ustekinumab versus adalimumab cohorts were persistent while on monotherapy and on the labeled maintenance dose; persistence was 3.38 times higher in the ustekinumab cohort (p-value: &amp;lt;0.001; Fig 2c). CONCLUSIONS ADT-naïve patients with UC initiated on ustekinumab were significantly more persistent while on the labeled maintenance dose, including persistent while corticosteroid-free and while on monotherapy, compared to patients initiated on adalimumab. Results may help with selecting a biologic for ADT-naive patients with UC. Figure 1 Selected baseline characteristics in weighted ustekinumab and adalimumab cohorts Figure 2 Persistence while on US labelled dose among weighted ustekinumab and adalimumab cohorts: a) persistent on index biologic, b) persistent and corticosteroid-free, c) persistent and on monotherapy

Association between sodium-to-potassium ratio in spot urine and hospitalization due to heart failure in high-risk Japanese patients

BackgroundIn Japanese cardiovascular (CV) high-risk patients, the ESPRIT (Evaluation of Sodium Intake for the Prediction of Cardiovascular Events in Japanese High-risk Patients) study showed that high sodium excretion (≥4.0 g/day) was associated with a composite CV events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and CV deaths. In this context, the sodium-to-creatinine (Na/Cr) ratio in spot urine was found to be significantly associated with HF hospitalizations. Since a stable potassium balance plays a particularly relevant role for CV patients, this post-hoc study was designed to investigate the extent to which consideration of the sodium-to-potassium (Na/K) ratio represents a better predictor of HF hospitalizations in the ESPRIT study population. MethodsThis is a post-hoc analysis of a previously reported ESPRIT study (n = 520, 60 HF hospitalizations). ResultsReceiver operating curve analysis yielded optimal Na/K ratio cut-off value of 2.9 for detecting HF hospitalization. Kaplan–Meier curve showed that high Na/K ratio in spot urine was associated with increased HF hospitalization (p < 0.001). Cox proportional hazards model analysis revealed that high Na/K ratio was associated with HF hospitalization with a hazard ratio of 2.97 (confidence interval: 1.67–5.61). An association between high Na/K ratio and HF hospitalization remained after adjustments for Na/Cr ratio in spot urine or the use of diuretics. ConclusionThe Na/K ratio in spot urine is associated with HF hospitalization in high-risk Japanese patients.

The relationship of KRAS expression with KRAS status, prognosis, and tumor-infiltrated T lymphocytes in colorectal cancer.

The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and prognosis warrants further investigation. While high KRAS expression is commonly linked with poorer prognosis in other cancers, its role in CRC remains relatively understudied. To explore the correlation between KRAS expression, KRAS status, prognosis, and tumor-infiltrating T lymphocyte density in CRC. Single-center retrospective study. Conducted between 2010 and 2020, this study utilized tumor samples to assess KRAS expression and quantify CD3+/CD8+ T lymphocytes. The Cox proportional hazards model and linear regression analysis were employed to examine the relationship between KRAS expression, prognosis, and tumor-infiltrating T lymphocytes. This study included 265 CRC patients who underwent radical surgery. No significant association was observed between KRAS expression and KRAS status (p > 0.05). High KRAS expression was associated with poorer overall survival and disease-free survival (p < 0.05). Subgroup analysis revealed that high KRAS expression remained indicative of a worse prognosis in the group with mismatch repair-deficient (dMMR) and KRAS mutant type (p < 0.05). Multivariate analysis confirmed KRAS expression as an unfavorable prognostic factor (p < 0.05). However, the significance of KRAS expression was lost in the dMMR and KRAS mutant-type group regarding overall survival (p > 0.05). Notably, KRAS expression showed a negative correlation with the density of CD8+ T lymphocytes in tumor tissue (p < 0.05), a finding also observed in the dMMR group (p < 0.05). No association was found between KRAS expression and KRAS mutation status in CRC. Higher KRAS expression was indicative of poorer prognosis for CRC patients, except for those with proficient mismatch repair and KRAS wild type. In addition, in patients with dMMR, KRAS expression was associated with a lower density of CD8+ T lymphocytes in tumor tissue.

Standardized multi-institutional data analysis of fixed and removable prosthesis: estimation of life expectancy with regards to variable risk factors.

This study aims to assess and predict lifespan of dental prostheses using newly developed Korean Association of Prosthodontics (KAP) criteria through a large-scale, multi-institutional survey. Survey was conducted including 16 institutions. Cox proportional hazards model and principal component analysis (PCA) were used to find out relevant factors and predict life expectancy. 1,703 fixed and 815 removable prostheses data were collected and evaluated. Statistically significant factors in fixed prosthesis failure were plaque index and material type, with a median survival of 10 to 18 years and 14 to 20 years each. In removable prosthesis, factors were national health insurance coverage, antagonist type, and prosthesis type (complete or partial denture), with median survival of 10 to 13 years, 11 to 14 years, and 10 to 15 years each. For still-usable prostheses, PCA analysis predicted an additional 3 years in fixed and 4.8 years in removable prosthesis. Life expectancy of a prosthesis differed significantly by factors mostly controllable either by dentist or a patient. Overall life expectancy was shown to be longer than previous research.

Impact of Platelet-to-HDL-Cholesterol Ratio on Long-Term Mortality in Coronary Artery Disease Patients with or Without Type 2 Diabetes: Insights from a Chinese Multicenter Cohort.

Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status. A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality. Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.18; HR 1.21, 95% CI 1.14-1.29; HR 1.43, 95% CI 1.34-1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08-1.30; HR 1.58, 95% CI 1.44-1.74; HR 1.89, 95% CI 1.72-2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P <0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity >0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets. In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group. The Cardiorenal ImprovemeNt II registry NCT05050877.