Multivariate Cox Proportional Hazards Regression Research Articles

Analysis of prognostic risk factors for patients with locally advanced gastric cancer in the stage ypT0~2N0M0 after neoadjuvant chemotherapy

Objectives: To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy. Methods: The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival. Results: Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis (P＜0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions: The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.

Efficacy, safety, and biomarker analysis of first-line immune checkpoint inhibitors with chemotherapy versus chemotherapy for advanced gastric cancer: a multicenter, retrospective cohort study

BackgroundRecent phase III randomized controlled trials have demonstrated that first-line immune checkpoint inhibitors (ICIs) improve prognosis in advanced HER-2-negative gastric cancer patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) higher than 5. However, these findings are not confirmed in real-world settings, and the benefits in PD-L1 CPS < 5 patients remain controversial.MethodsIn this multicenter, retrospective cohort study, data from across thirteen medical centers were analyzed by inverse probability of treatment weighting for matching, alongside univariate and multivariate COX proportional hazard regression models. Genomic and transcriptomic analyses were conducted to identify efficacy prognostic models and resistance mechanisms.ResultsThis study included 573 patients with advanced gastric cancer, 265 treated with chemotherapy and 308 with ICIs plus chemotherapy. In the overall cohort and HER-2-negative patients, the combination therapy significantly improved progression-free survival and overall survival, without marked increases in severe adverse events. Notably, patients with PD-L1 CPS 1–4 showed significant overall survival prolongation and a trend towards improved progression-free survival with combination therapy. Patients with unknown PD-L1 status also benefitted from ICIs. SMARCA4 and BRCA2 mutations were more frequent in patients with responses, while CCNE1 and ZFHX3 alternation, alongside high “ABC transporters” signatures, were more common in non-responsive patients. A novel risk model, PGFIC, outperformed traditional biomarkers in predicting treatment outcomes.ConclusionsAdding ICIs to first-line treatment significantly prolongs survival in overall patients and in those with PD-L1 CPS 1–4 or unknown. This study also provides valuable insights into prognostic markers and resistance mechanisms, potentially guiding immunotherapy strategies.

Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes

BackgroundNonarteritic anterior ischemic optic neuropathy (NAION) is an untreatable condition often causing severe and irreversible visual loss in the affected eye. As it has recently been implied that the use of semaglutide associates with NAION, the aim of the present study was to evaluate this risk prospectively in all persons with type 2 diabetes (T2D) in Denmark.MethodsIn a five-year longitudinal cohort study, we identified all persons with T2D in Denmark (n = 424,152) between 2018 and 2024. Patients were stratified according to exposure (n = 106,454) or non-exposure (n = 317,698) to once-weekly semaglutide, and incidence rates and hazard ratios (HR) of NAION were estimated in a multivariable Cox proportional hazard regression model.ResultsAt baseline, median age and hemoglobin A1c were 65 years and 50 mmol/mol, and 54·5% were male. During 1,915,120 person-years of observation, 218 persons developed NAION. Semaglutide exposure was associated with a higher incidence rate (0·228 vs. 0·093 per 1000 person-years, p < 0·001) and independently predicted a higher risk of upcoming NAION (HR 2·19, 95% confidence interval 1·54 − 3·12), even when multiple other factors were taken into account. Overall, 67 persons exposed to semaglutide developed NAION with a median time from first prescription to event of 22·2 months (interquartile range 10·2–37·8 months).ConclusionsDuring five years of observation of all persons with T2D in Denmark, use of once-weekly semaglutide independently more than doubled the risk of NAION. Given the irreversible nature of NAION, it is important to acknowledge this risk, and upcoming studies should aim to identify high-risk subgroups.

L-shaped association between triglyceride-glucose body mass index and short-term mortality in ICU patients with sepsis-associated acute kidney injury

BackgroundSepsis is a systemic inflammatory response syndrome, with sepsis-associated acute kidney injury (SA-AKI) being a common complication. Insulin resistance (IR) is closely related to the stress response, inflammatory response, and severity of critical illness. The triglyceride-glucose body mass index (TyG-BMI) is a valuable tool for assessing IR. However, the relationships between TyG-BMI and clinical outcomes in patients with SA-AKI remain unclear.MethodsWe conducted a retrospective analysis of ICU patients with SA-AKI using data from the MIMIC-IV database. The Boruta algorithm was employed to select significant features for predicting short-term mortality in SA-AKI patients. Multivariate Cox proportional hazards regression, sensitivity analysis, restricted cubic spline (RCS) models, and Kaplan–Meier (K–M) survival analysis were used to assess the relationship between TyG-BMI and short-term mortality in SA-AKI patients. Subgroup analyses considered the effects of age, sex, ethnicity, comorbidities and septic shock.ResultsThis study included 3,349 patients, with males accounting for 60.5% of the patients. The Boruta analysis identified the TyG-BMI as an important clinical feature. Higher TyG-BMI values were significantly associated with reduced short-term mortality rates (28, 90, and 180 days) in patients with SA-AKI; for each standard deviation increase in TyG-BMI, the risk of all-cause death decreased by 0.2% (p &amp;lt; 0.0001). Kaplan–Meier analysis demonstrated that patients with high TyG-BMIs had significantly lower mortality rates than did those with low TyG-BMIs. The RCS model revealed an L-shaped nonlinear relationship between the TyG-BMI and mortality. Sensitivity analyses indicated that the association remained significant even after excluding patients with myocardial infarction, congestive heart failure, or those who were hospitalized in the ICU for less than 2 days. Subgroup analyses revealed a significant interaction effect on short-term mortality in CRRT patients (p &amp;lt; 0.05).ConclusionThe relationship between the TyG-BMI and short-term mortality in ICU patients with SA-AKI is significant, indicating its potential value for early risk assessment and clinical intervention.

Association of leukocyte telomere length with the risk of digestive diseases: A large-scale cohort study.

Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. After a mean follow-up time of 11.8years, over 20 the International Classification of Diseases 10th Revision (ICD-10) codes were observed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR]= 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR= 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR= 1.58 95% CI: 1.14-2.17), gastritis (K29: HR= 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR= 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR= 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR= 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR= 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR= 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR= 1.50, 95% CI: 1.17-1.94; K44: HR= 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR= 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.

Cardiac Events and Survival in Patients With EGFR-Mutant Non–Small Cell Lung Cancer Treated With Osimertinib

Although it has been reported that osimertinib mesylate provides better survival benefits compared with first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), it remains unclear whether osimertinib is associated with more cancer therapy-related cardiac events (CTRCEs) compared with other EGFR TKIs, as does the extent of the association these adverse effects may have with overall survival. This issue is particularly critical due to the high prevalence of EGFR variants within Asian populations, including that of Taiwan. To compare CTRCEs and their association with survival in patients treated with osimertinib vs other EGFR TKIs. This cohort study was conducted at the National Cheng Kung University Hospital, a college hospital and tertiary academic referral center in Taiwan. The median follow-up duration was 23.2 (IQR, 15.2-31.5) months. A total of 401 patients with EGFR-mutant non-small cell lung cancer (NSCLC) beginning treatment with EGFR TKIs from September 1, 2019, to July 31, 2022, were retrospectively analyzed. CTRCEs included newly emerging arrhythmias, valvular heart diseases (moderate and more), myocardial infarction, and heart failure and were analyzed after adjusting for age, sex, smoking, alcohol consumption, body mass index, cardiovascular comorbidities, thoracic radiotherapy, and cardiovascular medications. Follow-up was completed January 31, 2024. Osimertinib. The Cox proportional hazards model was used to estimate CTRCEs in patients treated with osimertinib or other EGFR TKIs. Considering that death can lower the incidence of CTRCEs, the competing risk method was used to calculate CTRCEs after adjusting for potential confounders. Multivariable Cox proportional hazard regression analysis for overall survival was used to explore whether CTRCEs were independently associated with overall survival. Among the 401 patients (253 [63.1%] female; mean [SD] age, 69.2 [11.3] years), 195 (48.6%) treated with osimertinib were matched with 206 (51.4%) treated with other EGFR TKIs. Occurrence of CTRCEs in patients receiving osimertinib was significantly higher compared with patients treated with other EGFR TKIs (29 [14.9%] vs 9 [4.4%]; hazard ratio [HR], 3.37; 95% CI, 1.56-7.26; P = .002). After adjustment for relevant cardiovascular risk factors, the HR of CTRCEs was significantly higher in the group treated with osimertinib (adjusted subdistribution HR, 4.00; 95% CI, 1.81-8.85; P < .001). In addition, CTRCEs were independently associated with overall survival (HR, 4.02; 95% CI, 2.44-6.63; P < .001). In this cohort study of patients with EGFR-mutant NSCLC, osimertinib was associated with a higher incidence of CTRCEs compared with other EGFR TKIs; CTRCEs were independently associated with overall survival. These findings highlight the need for ongoing cardiac monitoring in these patients, regardless of preexisting cardiac risk factors.

Non-linear dose-response relationship between the visceral adiposity index and diabetes in adults with normoglycemia: a cohort study.

Previous studies have identified a positive link between the visceral adiposity index (VAI) and diabetes in specific populations. Our investigation focused on examining this association in normoglycemic adults in Japan. A cohort study of NAGALA (NAfld in the Gifu Area Longitudinal Analysis) was undertaken from 2004 to 2015 in Japan. The link between VAI and diabetes was evaluated using multivariate Cox proportional hazards regression and restricted cubic spline (RCS) regression models. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the VAI for incident diabetes. Our study included 15,452 participants, with 8,418 men (54.48%) and 7,034 women (45.52%). The average age was 43.71 ± 8.90, and 373 participants (2.41%) developed diabetes. VAI was positively related to diabetes (HR=1.13, 95% CI 1.08-1.18). The inflection point of the non-linear relationship was observed at a VAI value of 4.67. For the VAI values up to 4.67, one unit increase in the VAI related to a 24% increase in new-onset diabetes (HR=1.24, 95% CI 1.12-1.37, p<0.0001). Subgroup analysis detected a more robust relationship in women (HR=1.40, 95% CI 1.14-1.70, p=0.0010). ROC analysis indicated that VAI, with an AUC of 0.7479 (95% CI: 0.7237-0.7720), had good predictive power. Our cohort study validated the positive and non-linear relationship between the VAI and diabetes in normoglycemic adults in Japan. The relevance was more marked in women than in men. For those with a VAI below 4.67, a further reduction in the VAI could potentially lead to a significant decrease in diabetes risk.

Development and Validation of a Survival Prediction Model for Patients with Pancreatic Cancer.

Patients with pancreatic ductal adenocarcinoma (PDAC) face challenging treatment decisions following their diagnosis. We developed and validated a survival prognostication model using routinely available clinical information, patient-reported symptoms, performance status, and initial cancer-directed treatment. This retrospective cohort study included PDAC patients from 2007 to 2020 using linked administrative databases in Ontario, Canada. Patients were randomly selected for model development (75%) and validation (25%). Using the development cohort, a multivariable Cox proportional hazards regression with backward stepwise variable selection was used to predict the probability of survival. Model performance was assessed on the validation cohort using the concordance index and calibration plots. There were 17,450 patients (49% female) with a median age of 72 (IQR 63-81) and a mean survival time of nine months. In the derivation cohort, 1,469 (11%) patients had early stage, 4,202 (32%) had advanced stage disease, and 7,417 (57%) had unknown stage. The following factors were associated with an increased risk of death by more than 10%: tumour in the tail of the pancreas, advanced stage, hospitalization three months prior to diagnosis, congestive heart failure or dementia, low, moderate, or high pain score, moderate or high appetite score, high dyspnea and tiredness score, and a performance status score of 60-70 or lower. The calibration plot indicated good agreement with a C index of 0.76. This model accurately predicted one-year survival for PDAC using clinical factors, symptoms, and performance status. This model may foster shared decision making for patients and their providers.

Red cell distribution width-to-platelet ratio (RPR) as a predictor of prolonged stay at hospital for COVID-19 inpatients.

We looked at novel hematological composites like the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, red cell distribution width-to-lymphocyte ratio, red cell distribution width-to-platelet ratio, leukocyte-to-C reactive protein ratio, and lymphocyte-to-C reactive protein ratio as explanatory variables for COVID-19 patients´ hospital length of stay (LoS). The association of hematological indices with LoS was analyzed on 2930 COVID-19 patients using the univariate and multivariable Cox proportional hazards regression models with enter method. The Kaplan-Meier survival estimates were applied to LoS. The survivors´ mean LoS was 7.8 ± 24.0 days, but the deaths´ mean LoS was 38.6 ± 41.9 days (W = 31338, p < 0.01). Every hematological scores representative of the inflammatory status was significantly correlated in the univariate analysis with a prolonged LoS (p < 0.001). In the multivariate analysis, it was discovered that just the monocyte-to-lymphocyte and lymphocyte-to-C reactive protein ratios had not achieved statistical significance. However, most systemic inflammation measures showed hazards ratios close to one. One exemption was the red cell distribution width-to-platelet ratio (RPR) index, which can increase the probability of a longer hospital stay by up to ten times (HR(IC95%) = 0.092(0.03-0.29); p < 0.001). The most effective biomarker to identify COVID-19 patients at high risk for extended hospital stay was RPR. IntroductionDetermining hospital Length of Stay (LoS) is vital for resource management, especially for future COVID-19 outbreaks.Previous studies have primarily focused on sociodemographic and clinical attributes, along with resource availability, but have not accounted for other factors like routine laboratory tests, which can significantly impact LoS predictions.This study examines novel hematology scores as predictors of LoS, emphasizing their importance in resource-limited settings like Ecuador.MethodsThis retrospective cohort study analyzed 2,930 COVID-19 patients admitted to Hospital IESS Quito Sur in Ecuador focusing on confirmed cases with complete blood count (CBC) values to assess LoS.The study explored various hematological ratios, such as the neutrophil-to-lymphocyte ratio (NLR) and red cell distribution width-to-lymphocyte ratio (RLR), as potential predictors of LoS and in-hospital outcomes for COVID-19 patients, using a combination of univariate and multivariable Cox proportional hazards regression models.Kaplan-Meier survival estimates and log-rank tests were used to analyze survival and discharge probabilities over time, highlighting sex-dependent effects and the significant association between selected hematological indices and patient outcomes.ResultsThe mean LoS for survivors was significantly shorter compared to those who died (p < 0.001), indicating that longer hospitalization was associated with higher mortality risk.Women had a shorter average LoS (with lower mortality risk (p < 0.001), suggesting an asymmetrical hospitalization pattern based on sex.While most hematological markers had minimal clinical relevance for LoS, the red cell distribution width-to-platelet ratio (RPR) stood out, increasing the likelihood of a longer hospital stay by up to tenfold, making it a critical factor in predicting prolonged hospitalization.DiscussionMen had longer hospital stays and higher mortality rates than women, likely due to differing inflammatory responses, though hyperinflammation markers like NLR, PLR, and Leu-CPR had minimal clinical impact.RPR had the strongest link to longer hospital stays, indicating a higher risk of extended hospitalization in severe COVID-19 cases.Elevated RPR is tied to oxidative stress and coagulation issues, suggesting early identification could help reduce prolonged stays and complications.ConclusionResearch generally points to clinical complications from COVID-19 as the main factor behind prolonged hospitalizations, underlining the importance of early identification and management of these issues.

Survival Analysis of Conversion Surgery in Borderline Resectable and Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma Addressing Selection and Immortal Time Bias: A Retrospective Single-Center Study.

The purpose of this study was to provide a detailed evaluation of the oncological advantages of surgery following neoadjuvant chemotherapy (NAC) for patients with borderline resectable (BR) or unresectable (UR) pancreatic ductal adenocarcinoma (PDAC), with a focus on minimizing biases. Recently, NAC has become the standard care for BR or UR locally advanced (UR-LA) PDAC, however, many studies have assessed survival benefits and favorable variables without consideration for biases, particularly immortal time bias. This study included patients diagnosed with BR or UR-LA PDAC at Juntendo University Hospital from 2019 to 2022. To mitigate bias, we applied methods such as propensity score matching (PSM), time-dependent covariate Cox proportional hazard regression analysis (TDC), landmark analysis, and multivariable Cox proportional hazards regression model. The study analyzed 124 patients, dividing them into a surgery group (n = 57) and a chemotherapy-only group (n = 67). After PSM, there were 21 matched pairs. Survival analysis using TDC analysis showed that the surgery group had significantly better overall survival compared with the chemotherapy-only group in both the entire cohort and the matched pairs. Cox regression analysis of the entire cohort also revealed a similar superiority of surgery, while the landmark analysis showed varying results depending on the landmark setting. After careful adjustment for selection and immortal time biases, surgery following NAC appears to significantly extend survival in patients with BR or UR PDAC.

Coexisting Tubulointerstitial Inflammation and Damage Is a Risk Factor for Chronic Kidney Disease in Patients With Lupus Nephritis.

This study aims to determine whether the concurrent presence of tubulointerstitial inflammation (TII) and tubulointerstitial damage (TID) predicts the progression of chronic kidney disease (CKD) in patients with lupus nephritis (LN). Data from 175 LN patients, collected at the time of renal biopsy, were analyzed. Patients were stratified into two groups based on the presence or absence of coexisting TII/TID. Uni- and multivariable Cox proportional hazard regression models were utilized to identify independent risk factors for CKD in LN patients. Of 175 patients, 110 (62.9%) exhibited coexisting TII/TID, whereas 65 (37.1%) did not. Patients with coexisting TII/TID tended to be older and presented with higher levels of ESR and 24-h proteinuria, as well as lower levels of eGFR and hemoglobin compared to those without coexisting TII/TID. Over a mean follow-up period of 89.9 months, CKD and end-stage renal disease occurred more frequently in patients with coexisting TII/TID. Notably, the presence of coexisting TII/TID was associated with a higher risk of CKD progression, with adjusted hazard ratios of 2.667 (95% CI: 1.333, 5.335, p = 0.006) for all LN patients, 3.265 (95% CI: 1.451, 7.345, p = 0.004) for those with class III, IV, and V LN, and 3.045 (95% CI: 1.289, 7.195, p = 0.011) for those with class III, IV, V LN, and eGFR ≥ 30 mL/min/1.73 m2. LN patients with coexisting TII/TID are at a heightened risk of kidney function deterioration at LN onset and subsequent development of CKD over the long term.

Left ventricular hypertrophy and ventricular ectopy in mitral valve prolapse.

Sudden deaths ascribed to mitral valve prolapse (MVP) have increased ventricular mass on autopsy. It is unknown if left ventricular hypertrophy (LVH) is a risk factor for ventricular arrhythmia in MVP. We studied all 629 patients aged 18-90 years with MVP on echocardiography between 2016 and 19 at our institution. Echocardiograms were reviewed for LVH, ventricular size and function, and valvular pathology. Complex or frequent ventricular ectopy (cfVE) was defined as ≥2 premature ventricular complexes (PVC) on a 10-s ECG or > 1 % PVC burden or non-sustained ventricular tachycardia on ambulatory ECG. Multivariable logistic regression and cox proportional hazards regression were used to assess the relationships between LVH, mitral valve structural features, and cfVE in MVP. LVH was present in 141 (22.4 %) patients. Of those with LVH, 44 (31.2 %) had cfVE compared to 87 (17.8 %) without LVH (p = 0.001). Independent predictors of cfVE were mitral annular disjunction (OR [95 % CI] 2.34 [1.54-3.56]), bileaflet prolapse (1.78 [1.19-2.66]), heart failure (1.79 [1.15-2.79]), lower ejection fraction (0.18 [0.04-0.83]), coronary artery disease (1.58 [1.04-2.39]), and T-wave inversion (1.51 [1.03-2.22]). However, LVH was not independently associated with cfVE (1.22 [0.82-1.83], p = 0.32). Left ventricular hypertrophy is not an independent risk factor for ventricular arrhythmia in MVP. Ventricular arrhythmogenesis in MVP is predominantly determined by mitral morphological factors and heart failure. Further work is required to better understand the predisposition to sudden death of patients with MVP and increased ventricular mass.

Association of abnormal P-wave parameters with all-cause mortality in diffuse large B-cell lymphoma

Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are at increased risk of developing atrial fibrillation (AF). Abnormal P-wave parameters (PWPs) have been identified as independent predictors of AF, however, their prognostic significance in DLBCL patients remains unknown. Newly diagnosed DLBCL patients from January 2015 to August 2022 were retrospectively included in this study. Patients were devided as with abnormal PWPs or without it. Primary outcome was the all-cause mortality. The median duration of follow-up was 16.3 months. The Kaplan‒Meier method and multivariable COX proportional hazards regression models were used to analyze the relationship between PWPs and all-cause mortality. Logistic regression analyses were performed to identify risk factors associated with PWPs. A total of 374 newly diagnosed DLBCL patients were included, of whom 137 patients exhibited abnormalities in PWPs. Compared to the group with normal PWPs, patients with PWPs abnormalities had a higher proportion of males (p = 0.001), elevated levels of blood urea nitrogen (p = 0.038) and blood creatinine (p = 0.005), and a higher rate of all-cause mortality (p = 0.001). PWPs, particularly P-wave duration (p = 0.017) and P-wave terminal force in lead V1 (PTFV1) (p = 0.001), were independently correlated with all-cause mortality in DLBCL patients. Furthermore, male patients exhibited a higher susceptibility to abnormal PWPs (p = 0.001). PWPs, particularly P-wave duration and PTFV1, serve as simple yet effective prognostic indicators for all-cause mortality in DLBCL patients. Consequently, vigilant monitoring of PWPs, particularly in male patients, is warranted to accurately evaluate the prognosis of DLBCL.

Construction of an immunogenic cell death-related LncRNA signature to predict the prognosis of patients with lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is one of the most common malignant diseases worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD.MethodsThe RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct lncRNA signature. Then, the reliability of the signature was evaluated in the training, validation and whole cohorts. The differences in the immune landscape and drug sensitivity between the low- and high-risk groups were analyzed. Finally, the expression level of the selected ICD-related lncRNAs in LUAD cell lines via reverse transcription quantitative PCR (RT-qPCR). CCK-8 and transwell assays were performed to study biological function of AC245014.3.ResultsA signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan Meier (K-M) survival analysis showed shorter overall survival (OS) in high-risk group. The receiver operating characteristic (ROC) curves and Multivariate Cox regression analysis showed the signature was good predictive and independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of selected ICD-related lncRNAs was validated in LUAD cell lines by RT-qPCR. Knockdown of AC245014.3 significantly suppressed LUAD proliferation, migration and invasion.ConclusionsIn this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.

Combined effects of nutrition, inflammatory status, and sleep quality on mortality in cancer survivors

BackgroundCancer survivors face many challenges in long-term health management, including malnutrition, systemic inflammation, and sleep issues, which significantly affect their survival and quality of life.MethodsA prospective cohort study was derived from the National Health and Nutrition Examination Survey from 2005–2018 harboring 1,908 cancer survivors (weighted population, 11,453,293), of whom 688 deaths (220 from cancer mortality, 468 from non-cancer mortality). The Advanced Lung Cancer Inflammation Index (ALI) was used as a measure of nutritional status and systemic inflammation in cancer patients. Weighted multivariable Cox proportional hazards regression models were utilized to explore the independent and combined effects of ALI and sleep quality on mortality outcomes.ResultsThe participants with a high ALI were more likely to be female, aged 40 to 64 years, non-Hispanic white, and have a higher BMI. We observed that elevated ALI levels were associated with decreased risks of all-cause mortality (Hazard ratio [HR] = 0.601, 95% Confidence interval [CI] = 0.521–0.695, P < 0.001), cancer-specific mortality (HR = 0.659, 95% CI = 0.497–0.870, P = 3.34 × 10–3) and non-cancer-specific mortality (HR = 0.579, 95% CI = 0.478–0.701, P < 0.001). Similarly, better sleep quality (e.g., without sleep troubles) was associated with lower risks of all-cause mortality (HR = 0.761, 95% CI = 0.620–0.933, P = 8.79 × 10–3) and non-cancer-specific mortality (HR = 0.713, 95% CI = 0.572–0.890, P = 2.80 × 10–3). Notably, the joint analysis showed that cancer survivors with higher ALI levels and better sleep quality (e.g., standard sleep duration) had the lowest risks of all-cause (HR = 0.468, 95% CI = 0.352–0.622, P < 0.001), cancer-specific mortality (HR = 0.631, 95% CI = 0.333–0.672, P = 7.59 × 10–3) and non-cancer-specific mortality (HR = 0.440, 95% CI = 0.315–0.615, P < 0.001).ConclusionsThis study suggests that better nutritional and inflammatory status, combined with good sleep quality, may contribute to improved survival among cancer survivors. These results underscore the potential clinical importance of integrating nutritional and sleep quality assessments into the long-term care of cancer survivors to enhance their overall prognosis.

Establishment and Validation of Diagnostic and Prognostic Prediction Models for Liver Metastasis in Patients with Rectal Cancer: A SEER-based Study

Background: Rectal cancer is one of the most common gastrointestinal tumors, among which the liver is the most common site of distant metastasis and liver metastasis that leads to poor prognosis. This study aimed to develop and validate a diagnostic nomogram to predict the occurrence of rectal cancer with liver metastasis (RCLM) and a prognostic nomogram to predict cancer-specific survival (CSS) in RCML patients. Methods: Data on patients with rectal cancer diagnosed between 2010 and 2013 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate logistic regression and multivariate logistic regression were used to determine the independent risk factors of RCLM. Univariate Cox proportional hazards regression and multivariate Cox proportional hazards regression were used to identify independent prognostic factors for RCLM. This study then developed two novel nomograms, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: A total of 29367 patients with rectal cancer were included. Among them, 3403 patients (11.59%) had liver metastases at the time of diagnosis. The independent risk factors of RCLM included sex, race, tumor grade, AJCC N, CEA, marital status, tumor size, total number of primary tumors, and histological type. Age, chemotherapy, total number of primary tumors, surgery sites, and histological type were independent prognostic factors of patients with RCLM. The results of ROC curves, calibration curves, and DCA in the development, validation, and testing sets confirmed that the diagnostic nomogram can precisely predict the occurrence of RCLM. The results of ROC curves, calibration curves, DCA, C-indexes, and Kaplan–Meier (K-M) survival curves in the development, validation, and testing sets confirmed that the prognostic nomogram could precisely predict the prognosis of RCLM. Conclusion: The two nomograms are expected to be effective tools for predicting the risk of liver metastasis for patients with rectal cancer and personalized prognosis prediction for patients with RCLM, which may benefit clinical decision-making.

Association of Severe Maternal Morbidity With Subsequent Birth

Women who experience severe maternal morbidity (SMM) might have lasting health issues, and the association of SMM with the probability of future reproductive intentions is unknown. To examine the association between SMM in a first birth and the probability of a subsequent birth. Retrospective, population-based cohort study conducted among 1 046 974 women in Sweden who had their first birth between 1999 and 2021. Overall SMM and SMM subtypes were identified among all deliveries at 22 weeks of gestation or later (including complications within 42 days of delivery) from the Swedish Medical Birth Register and National Patient Register. All women with a recorded first delivery were followed up from 43 days postpartum until the first day of the last menstrual period of the second pregnancy that resulted in a birth (stillbirth or live birth) or until death, emigration, or end of follow-up on December 31, 2021. Multivariable Cox proportional hazards regression was used to estimate associations between SMM and time to subsequent birth with adjusted hazard ratios (aHRs). Sibling analysis was performed to evaluate potential genetic and familial confounding. A total of 36 790 women (3.5%) experienced an SMM condition in their first birth. Women with any SMM had a lower incidence rate of subsequent birth compared with those without SMM in their first delivery (136.6 vs 182.4 per 1000 person-years), with an aHR of 0.88 (95% CI, 0.87-0.89). The probability of subsequent birth was substantially lower among women with severe uterine rupture (aHR, 0.48; 95% CI, 0.27-0.85), cardiac complications (aHR, 0.49; 95% CI, 0.41-0.58), cerebrovascular accident (aHR, 0.60; 95% CI, 0.50-0.73), and severe mental health conditions (aHR, 0.48; 95% CI, 0.44-0.53) in their first birth. The associations were not influenced by familial confounding as indicated by sibling analyses. Our findings suggest that women who experience SMM in their first birth are less likely to have a subsequent birth. Adequate reproductive counseling and enhancing antenatal care are crucial for women with a history of SMM.

Mediation Analysis of Serum Fibroblast Growth Factor 20 and Poor Prognosis After Ischemic Stroke.

We aimed to examine the relationship between serum FGF20 (fibroblast growth factor 20) levels and stroke prognosis in a multicenter cohort study. Patients with ischemic stroke/transient ischemic attack were prospectively recruited from 5 participating centers and followed up at 3 months and 1 year. FGF20 levels were measured using the ELISA method. The primary outcome was poor stroke functional outcome (modified Rankin Scale score of 3-6), and secondary outcomes included death and composite vascular events. Multivariable logistic regression analysis or Cox proportional hazards regression analysis was employed to estimate the relationship between FGF20 and study outcomes. Mediation analysis was conducted to examine the mediating effects of traditional risk factors on the association between FGF20 and stroke outcomes. A total of 1011 patients with ischemic stroke were included in the study. After adjusting for potential confounding factors, an elevated serum FGF20 level was associated with a reduced risk of the poor outcome and death. Multivariable adjusted spline regression analysis demonstrated a linear correlation between serum FGF20 levels and the stroke outcomes. The incorporation of FGF20 alongside conventional risk factors marginally enhanced the reclassification of adverse outcomes. Renal function and white blood cell count partially mediated the relationship between FGF20 and the prognosis of ischemic stroke. Elevated FGF20 level is associated with decreased risks of adverse outcomes after ischemic stroke, which was partially mediated by renal function and white blood cells with a modest amount, indicating that serum FGF20 might serve as a promising biomarker for predicting stroke prognosis. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100051104.

Time to development of macrovascular complications and its predictors among type 2 diabetes mellitus patients at Jimma University Medical Center

BackgroundType 2 diabetes mellitus is a serious metabolic disease that is often associated with vascular complications. The increasing prevalence of type 2 diabetes mellitus poses significant public health challenges, particularly in Low and Middle-Income Countries where healthcare resources are often limited. In Africa, the burden of T2DM is rising rapidly, leading to a consequential increase in macrovascular complications such as cardiovascular disease and stroke. These complications not only affect the quality of life but also significantly contribute to morbidity and mortality among affected individuals. The main objective of this study was to assess the time to development of macrovascular complications and identify its predictors among type 2 diabetes mellitus patients in Jimma University medical center from 2018–2022.MethodsInstitutional-based retrospective follow-up study was conducted in Jimma University Medical Center among newly diagnosed type 2 diabetes mellitus patient from 2018, to 2022. A systematic sampling technique was used to recruit 452 records of type 2 diabetes mellitus patients. The Kaplan–Meier curve and the log-rank tests were used to determine the time to macro-vascular complications, and evaluate the significant difference in survival probability among predictors respectively. The overall goodness of the Cox proportional hazard model was checked by Cox-Snell residuals. Bivariable and multivariable cox-proportional hazard regression were used to identify the association between the variables and survival time.ResultsThe median survival time to development of macro vascular complications was 24 months. Urban residence [(Adjusted hazard ratio = 2.02; 95% CI: (1.33, 3.05)], having hypertension at start of diabetic treatment [(AHR = 1.52; 95% CI: (1.06, 2.13)], baseline age ≥ 60 years [(AHR = 4.42; 95% CI: (1.72, 11.29)], having dyslipidemia at baseline [(AHR = 1.82; 95% CI: (1.13, 2.93)], High density lipoprotein cholesterol levels < 40 mg/dl [(AHR = 2.11; (1.16, 3.81)], triglycerides > 150 mg/dl [(AHR = 1.48; 95% CI:( 1.02, 2.13)], Hemoglobin A1C level > 7% [(AHR = 1.49; 95% CI: (1.04, 2.14)], and Oral hypoglycemic agents + insulin [(AHR = 2.73; 95% CI: (1.81, 4.09)] were the significant predictors of the time to development of macro vascular complications.ConclusionFindings in this study indicated that the median time to development of macro vascular complications among type 2 diabetes mellitus patients was 24 months. Baseline age category in years, residence, presence of hypertension, presence of dyslipidemia, High density lipoprotein-cholesterol level < 40 mg/dl, triglyceride > 150 mg/dl, HgbA1C > 7% at baseline, and medication regimens were identified as independent significant predictors of the time to development of macro vascular complications among type 2 diabetes mellitus patients. The findings call attention to the role of treatment regimens, particularly the use of combination therapies involving oral hypoglycemic agents and insulin, which were associated with increased hazards for complications. High incidence of macrovascular complications within a short follow-up period underscores the need for proactive, individualized care strategies in T2DM management. By focusing on early identification of at-risk patients and tailoring treatment plans accordingly, healthcare providers can potentially improve outcomes and reduce the burden of macro vascular complications in this population.

Use of Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drugs and Cancer Risk

The Oral Rheumatoid Arthritis Trial Surveillance demonstrated an increased cancer risk among patients with rheumatoid arthritis (RA) taking tofacitinib compared with those taking tumor necrosis factor inhibitors (TNFis). Although international cohort studies have compared cancer outcomes between TNFis, non-TNFi drugs, and Janus kinase inhibitor (JAKis), their generalizability to US patients with RA is limited. To assess the comparative safety of TNFis, non-TNFi drugs, and JAKis among US patients with RA (ie, the cancer risk associated with the use of these drugs among these patients). This retrospective cohort study used US administrative claims data from Merative Marketscan Research Databases from November 1, 2012, to December 31, 2021. Follow-up occurred up to 2 years after initiation of biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). Participants included individuals aged 18 to 64 years with RA, identified using at least 2 RA International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes on or before the date of TNFi, non-TNFi, or JAKi initiation ("index date"). Statistical analysis took place from June 2022 to September 2024. New initiations of TNFis, abatacept, interleukin 6 inhibitors (IL-6is), rituximab, or JAKis. Individuals could contribute person-time to more than 1 treatment exposure if treatment escalation mimicked typical clinical practice but were censored if they switched to a previously trialed medication class. Incident cancer, excluding nonmelanoma skin cancer, after at least 90 days and within 2 years of initiation of biologic or targeted synthetic DMARDs. Outcomes were associated with the most recent drug exposure. Of the 25 305 individuals who initiated treatment and who met the inclusion criteria, most were female (19 869 [79%]), had a median age of 50 years (IQR, 42-56 years), and were from the South US (12 516 [49%]). Of a total 27 661 drug exposures, drug initiations consisted of 20 586 TNFi exposures (74%), 2570 JAKi exposures (9%), 2255 abatacept exposures (8%), 1182 rituximab exposures (4%), and 1068 IL-6i exposures (4%). Multivariable Cox proportional hazards regression analysis showed that rituximab was associated with a higher risk of incident cancer compared with TNFis (hazard ratio [HR], 1.91; 95% CI, 1.17-3.14), followed by abatacept (HR, 1.47; 95% CI, 1.03-2.11), and JAKis (HR, 1.36; 95% CI, 0.94-1.96). In this cohort study of individuals with RA and new biologic or targeted synthetic DMARD exposures, individuals initiating rituximab, abatacept, and JAKis demonstrated higher incidence rates and statistically significantly increased risks of incident cancers compared with those initiating TNFis in the first 2 years after initiation of biologic or targeted synthetic DMARDs. Given the limitations of administrative claims data and confounding by indication, it is likely that these patients may have a higher disease burden, resulting in channeling bias. To better understand these associations, larger studies with longer follow-up time are needed.