Cox Regression Research Articles

Epidemiological and microbial trends of infective endocarditis in western Norway: a 7-year prospective observational study

BackgroundIn this prospective, observational study, we aimed to investigate epidemiologic and microbial trends of infective endocarditis in western Norway.MethodsClinical and microbiological characteristics of 497 cases of infective endocarditis from 2016 through 2022 were investigated. Categorical data were analysed using Chi-squared tests. Survival data were analysed using multiple Cox regression and reported using hazard ratios.ResultsThe mean age was 67 years, and 74% were men. The annual incidence rates varied from 10.4 to 14.1 per 100,000 inhabitants per year. Infective endocarditis on native valves was observed in 257 (52%) of the cases, whereas infective endocarditis on prosthetic valves and/or cardiac implantable electronic devices was observed in 240 (48%) of the cases: infection on surgically implanted bioprostheses was observed in 124 (25%) of the patients, infection on transcatheter aortic valve implantation was observed in 47 (10%) patients, and infection on mechanical valves was observed in 34 (7%) cases. Infection related to cardiac implantable electronic devices was observed in a total of 50 (10%) cases.Staphylococcus aureus and viridans streptococci were the most common microbial causes, and isolated in 145 (29%) and 130 (26%) of the cases, respectively.Enterococcal endocarditis showed a rising trend during the study period and constituted 90 (18%) of our total cases of infective endocarditis, and 67%, 47%, and 26% of the cases associated with prosthetic material, transcatheter aortic valve implantation and cardiac implantable electronic devices, respectively.There was no significant difference in 90-day mortality rates between the native valve endocarditis group (12%) and the group with infective endocarditis on prosthetic valves or cardiac implants (14%), p = 0.522. In a model with gender, age, people who inject drugs, microbiology and type of valve affected, only advanced age was significantly associated with fatal outcome within 90 days.ConclusionsThe incidence of infective endocarditis, and particularly enterococcal endocarditis, increased during the study period. Enterococci appeared to have a particular affinity for prosthetic cardiac material. Advanced age was the only independent risk factor for death within 90 days.

The effect of preeclampsia on long-term kidney function among pregnant women with chronic kidney disease.

The association between superimposed preeclampsia and an elevated risk of long-term kidney function decline or end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) has not been determined. This study aimed to analyze the association between preeclampsia and kidney function deterioration in CKD patients. This was a retrospective cohort study that included the clinical information of 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia who were followed-up for a minimum of 1 year after their first pregnancy from January 1, 2009, to May 31, 2022. Robust Cox regression analysis was also conducted to evaluate the effects of preeclampsia on long-term kidney function decline or ESKD in CKD patients. K-M curves were used to compare renal survival within different subgroups via the log-rank test. During the follow-up period, 44 (42.72%) CKD patients with preeclampsia and 20 (19.42%) without preeclampsia had an estimated glomerular filtration rate (eGFR) decrease >30% or developed ESKD. Compared with CKD patients without preeclampsia, the eGFR decreased more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs. 99.43 (79.00, 118.50) to 89.44 (63.69, 105.30) mL/min/1.73 m2; P=0.034]. The rate of eGFR decrease was more pronounced in patients with preeclampsia (17.38% vs. 10.05%, p<0.05). Multivariate analysis revealed that early-onset preeclampsia (preeclampsia that developed before 34 weeks of gestation) (HR=2.61, 95% CI=1.32-5.16, P=0.006) and late-onset preeclampsia (HR=2.54, 95% CI=1.34-4.83, P=0.004) were both risk factors for an eGFR decrease >30% or ESKD. Preeclampsia was associated with a greater risk of long-term kidney function decline or ESKD among CKD patients, especially in patients with early-onset preeclampsia.

Socioeconomic factors and long-term mortality risk after transcatheter aortic valve implantation

Abstract Background There is scarce knowledge about the association between socioeconomic factors and outcome in patients undergoing transaortic valve implantation (TAVI). Therefore, the aim was to explore the association between marital status, educational level and long-term mortality risk in patients who underwent TAVI. Methods The SWEDEHEART registry was used to identify all patients who underwent TAVI due to aortic stenosis in Sweden from 2014 to 2020. Socioeconomic factors and comorbidities were collected from mandatory national registries. Cox regression models adjusted for baseline comorbidities, age, sex, smoking, education and marital status were used to estimate the mortality risk. Median follow-up were 1.9 years (interquartile range 0.8-3.2 years). Results In total, 6280 patients were included (47.1% women) with a mean age of 81.5 years (SD 7.1). Common baseline characteristics were hypertension (84.4%), heart failure (45.9%) and history of smoking (51.0%). During follow-up, 1584 (25.6%) of the patients died, of these, 860 (54.3%) deaths were related to cardiovascular causes. Lowest educational level (&amp;lt;10 years) was associated with a higher risk of mortality compared to patients with the highest education level (&amp;gt;12 years) (adjusted hazard ratio (aHR) 1.17 (95% Confidence interval (CI 1.01–1.35). Never being married/cohabiting, compared to married/cohabiting was not associated with an increased risk of mortality, (aHR 1.21 (95% CI 0.98-1.50)). The risk was increased for men (aHR of 1.45 (95% CI 1.12–1.88)), but not for women (aHR 0.81 (95% CI 0.55–1.19)). Conclusions Disadvantage in socioeconomic status was associated with an increased risk of mortality after TAVI. These findings emphasize the importance to develop strategies to increase health literacy and social support after TAVI, to patients with unfavorable socioeconomic factors.

Amount of ascites impacts survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolization advocating for volumetric assessment

Preliminary work has shown that portal hypertension plays a key role for the prognosis in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Specifically, the presence of ascites appears to be a strong negative predictor for these patients. However, it remains unclear whether different ascites volumes influence prognosis. Therefore, the aim of this work was to investigate the influence of different ascites volumes on survival for patients with HCC undergoing TACE. A total of 327 treatment-naïve patients with HCC undergoing initial TACE at our tertiary care center between 2010 and 2020 were included. In patients with ascites, the fluid was segmented, and the volume quantified by slice-wise addition using contrast-enhanced CT imaging. Median overall survival (OS) was calculated and univariate and multivariate Cox regression analysis has been performed. Ascites was present in 102 (31.9%) patients. Ascites volume as continuous variable was significantly associated with an increased hazard ratio in univariate analysis (p < 0.001) and remained an independent predictor of impaired median OS in multivariate analysis (p < 0.001). Median OS without ascites was 17.1 months, and therefore significantly longer than in patients with ascites (6.4 months, p < 0.001). When subdivided into groups of low and high ascites volume in relation to the median ascites volume, patients with low ascites volume had a significantly longer median OS (8.6 vs 3.6 months, p < 0.001). Ascites in patients with HCC undergoing TACE is strongly associated with a poor prognosis. Our results show that not only the presence but also the amount of ascites is highly relevant. Therefore, true ascites volume as opportunistic quantitative biomarker is likely to impact clinical decision-making once automated solutions become available.

Bleeding risk prediction after acute myocardial infarction-integrating cancer data: the updated PRECISE-DAPT cancer score.

This study assessed the impact of incorporating cancer as a predictor on performance of the PRECISE-DAPT score. A nationally linked cohort of ST-elevation myocardial infarction patients between 1 January 2005 and 31 March 2019 was derived from the UK Myocardial Ischaemia National Audit Project and the UK Hospital Episode Statistics Admitted Patient Care registries. The primary outcome was major bleeding at 1 year. A new modified score was generated by adding cancer as a binary variable to the PRECISE-DAPT score using a Cox regression model and compared its performance to the original PRECISE-DAPT score. A total of 216 709 ST-elevation myocardial infarction patients were included, of which 4569 had cancer. The original score showed moderate accuracy (C-statistic .60), and the modified score showed modestly higher discrimination (C-statistics .64; hazard ratio 1.03, 95% confidence interval 1.03-1.04) even in patients without cancer (C-statistics .63; hazard ratio 1.03, 95% confidence interval 1.03-1.04). The net reclassification index was .07. The bleeding rates of the modified score risk categories (high, moderate, low, and very low bleeding risk) were 6.3%, 3.8%, 2.9%, and 2.2%, respectively. According to the original score, 65.5% of cancer patients were classified as high bleeding risk (HBR) and 21.6% were low or very low bleeding risk. According to the modified score, 94.0% of cancer patients were HBR, 6.0% were moderate bleeding risk, and no cancer patient was classified as low or very low bleeding risk. Adding cancer to the PRECISE-DAPT score identifies the majority of patients with cancer as HBR and can improve its discrimination ability without undermining its performance in patients without cancer.

Statin prescriptions and progression of advanced fibrosis risk in primary care patients with MASLD

ObjectiveWe aimed to determine the association of statins with progression to a high risk for advanced fibrosis in primary care patients with metabolic dysfunction-associated steatotic liver disease (MASLD).DesignThis retrospective cohort...

Smoking and risk for morbidity and mortality in patients who undergoes coronary artery bypass grafting

Abstract Background The association between smoking and prognosis after coronary artery bypass grafting (CABG) is sparsley studied. The few previous studies investigating this association show conflicting results. Purpose The purpose was to explore the association between smoking and long-term risk for morbidity and mortality in patients undergoing CABG. Methods Data from the SWEDEHEART registry were used to identify all patients who underwent isolated CABG in Sweden from 1992 to 2020 and smoking status at time for surgery. Three other mandatory national registries were used to collect data for comorbidities, social factors, and death (Swedish National Inpatient Register, Longitudinal Integration Database for Health Insurance and Labor Market Studies and, Swedish Cause of Death Register). Cox regression models adjusted for age and sex, comorbidities and social factors were used to assess the risk for all cause death, stroke, myocardial infarction. Mean follow-up time was 5.2 years (range 0-10). Results In total, 27,434 patients aged &amp;gt;18 years were identified (18.2% women). The study population was divided into; never smoker (n=8593), former smoker (n=14666) and current smoker (n=4175). The proportion of previous ST Elevation Myocardial Infarction (STEMI), heart failure, previous stroke, peripheral vascular disease, chronic respiratory disease, depression, low education was higher in current smokers than in non-smokers. Compared to never smokers, current smokers had a higher risk for all-cause death (adjusted Hazard ratio (aHR) 1.36 (95% Confidence interval (CI) (1.22-1.52)) and stroke (aHR 1.39 (1.18-1.64)) but not for myocardial infarction (aHR 1.03 (0.87-1.21). Former smoker had higher risk for all cause death (aHR1.17 (1.08-1.28)) compared to never smokers but no increased risk for myocardial infarction 0.91 (0.81-1.03) and stroke (aHR 1.11 (0.98-1.25). Conclusion There is a strong association between smoking at the time for surgery and long-term risk for worse prognosis after CABG. The results emphasize the importance of encouraging and motivate CABG patients to smoking cessation.

Food insecurity and the risk of mortality among Hispanic adults with hypertension

Background and aimsHypertension continues to be a major public health problem affecting almost half of the adults in the US. The intersection of hypertension with food insecurity has not been well-examined specifically among minority populations. We aimed to examine the influence of food insecurity on mortality among adult Hispanics. Methods and resultsData on adult Hispanic (age≥ 20 years) respondents of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 were analyzed. Mortality was assessed by linking these data with the National Death Index through December 31, 2019. Using complex samples Cox regression analysis, the relationship between hypertension, food insecurity, and mortality was assessed. Sociodemographic (age, gender, poverty-income-ratio, marital status, and citizenship status) and health-related characteristics (COPD, diabetes, cardiovascular disease, chronic kidney disease) of the population were included as covariates in the regression analysis to assess mortality risk. The crude hazard ratio (HR) for overall mortality related to hypertension was 4.95 (95% confidence interval [CI] = 4.22–5.82, p < .001). The adjusted HR was elevated, 2.01 (95%CI = 1.50–2.70, p < .001), among individuals with both hypertension and food insecurity. However, among individuals with hypertension and no food insecurity, there was no statistically significant increase in the risk of mortality (HR = 1.09, 95%CI = 0.89–1.34, p > 0.05). ConclusionsIn adult Hispanics, food insecurity significantly increases the risk of mortality among those with hypertension compared to food-secure individuals. Clinicians should be sensitized to the need for food security among Hispanics with hypertension to effectively manage hypertension and reduce premature mortality.

Comparison of Measurement and Prognostic Power of SUV Between High-Definition and Standard PET Imaging in Non-Small Cell Lung Cancer Patients.

This study aimed to evaluate the measurement and prognostic ability of the SUVmax of whole-body tumors (SUVmaxwb) in non-small cell lung cancer (NSCLC) patients, comparing high-definition (HD) PET imaging with standard-definition (SD) PET imaging. Methods: The study included 242 consecutive NSCLC patients who underwent baseline 18F-FDG PET/CT from April 2018 to January 2021. Two imaging techniques were used: HD PET (using ordered-subsets expectation maximization with point-spread function modeling and time-of-flight techniques and smaller voxels) and SD PET (with ordered-subsets expectation maximization and time-of-flight techniques). SUVmaxwb was determined by measuring all the tumor lesions in the whole body, and tumor-to-background ratio (TBR) was calculated using the background SUVmean of various body parts. Results: The patient cohort had an average age of 68.3 y, with 59.1% being female. During a median follow-up of 29.6 mo, 83 deaths occurred. SUVmaxwb was significantly higher in HD PET than SD PET, with respective medians of 17.4 and 11.8. The TBR of 1,125 tumoral lesions was also higher in HD PET. Univariate Cox regression analysis showed that SUVmaxwb from both HD and SD PET were significantly associated with overall survival. However, after adjusting for TNM (tumor, node, metastasis) stage, only SUVmaxwb from SD PET remained significantly associated with survival. Conclusion: HD PET imaging in NSCLC patients yields higher SUVmaxwb and TBR, enhancing tumor visibility. Despite this, its prognostic value is less significant than SD PET after adjusting clinical TNM stage. Thus, consideration should be given to using HD PET reconstruction to increase tumor visibility, and SD PET is recommended for NSCLC patient prognostication and therapeutic evaluation, as well as for the classification of lung nodules.

Incidence and predictors of acute kidney injury among asphyxiated neonates in comprehensive specialized hospitals, northwest Ethiopia, 2023

Acute kidney injury (AKI) is characterized by a sudden decline in the kidneys' abilities to remove waste products and maintain water and electrolyte homeostasis. This study aims to determine the incidence and predictors of acute kidney injury among neonates with perinatal asphyxia admitted at the neonatal intensive care unit of West Amhara Comprehensive Specialized Hospital, Northwest Ethiopia, 2023. Multicentred institution-based retrospective follow-up study was conducted from October 1, 2021, to September 30, 2023, among 421 perinatal asphyxia neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.0. and analyzed using STATA V.14. The Kaplan–Meier failure curve and log-rank test were employed. Bivariable and multivariable Cox regression was carried out to identify predictors of Acute kidney injury. Statistical significance was declared at a p ≤ 0.05. The overall incidence of AKI was 54 (95% CI 47.07–62.51) per 100 neonate days. C/S delivery (AHR = 0.64; (95% CI 0.43–0.94), prolonged labor (AHR = 1.43; 95% CI 1.03–1.99) low-birth weight times (AHR = 1.49; (95% CI 1.01–2.20), stage three HIE(AHR: 1.68; (95% CI (1.02–2.77), No ANC follow up (AHR = 1.43; 95% CI 1.9 (1.07–3.43) and Hyperkalemia (AHR = 1.56; 95% CI 1.56 (1.05–2.29); 95% CI) were significant predictors. The incidence rate of acute kidney injury was higher than in other studies conducted on other groups of neonates. Cesarean section delivery, prolonged low birthweight, no Anc follow-up, stage 3 HIE, and neonatal hyperkalemia were predictors of acute kidney injury. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention to these predictors.

"GLI1 Subcellular Localization and Overexpression as Prognostic Factors for Disease-Free Survival in Colorectal Carcinoma".

Glioma-associated oncogene homolog-1 (GLI1) is amplified in human glioblastoma, and there is growing evidence suggesting its significant role in tumor development and metastasis. Our aim was to investigate the role of the GLI-1 gene in the progression of colorectal cancer (CRC) and its correlation with various clinicopathological features. Additionally, we examined the impact of the GLI-1 gene and other factors on the prognosis of CRC. We analyzed a total of 98 confirmed CRC cases and adjacent normal tissue controls. Patients suspected of having colon cancer underwent a colonoscopy and targeted biopsy, while those with rectal cancer underwent CT scans and MRI. GLI1 expression was detected using real-time PCR assay, Western blotting, and immunohistochemistry. The GLI1 gene was observed to be overexpressed in tumor tissues at both the protein and mRNA levels (p < 0.05). In addition, GLI1 overexpression was significantly associated with various factors such as tumor invasion (T3/T4), presence of lymph nodes, lymph node metastasis (LNM), stage (III/IV), tumor site (colon), tumor size (≥ 3cm), localization (nucleocytoplasmic), strong staining intensity and recurrence (p < 0.05). The results of survival analysis showed that the patients with overexpression of GLI1 had a significantly lower DFS rate which was 21months compared to those with normal expression who had 31months (p < 0.05). Moreover, individuals with early onset disease (15months) were more likely to have cytoplasmic localization of the GLI1 gene as opposed to nucleo-cytoplasmic localization of GLI1 which presented late-onset disease( 23months) (p < 0.05). Finally, Stage and PNI (p < 0.05) were found to independently affect outcomes of CRC according to Cox regression analysis. High expression of GLI-1 in CRC is associated with adverse pathology and poor prognosis for patients. The correlation between cytoplasmic localization of GLI-1 and reduced disease-free survival holds potential for guiding prognosis and treatment. Further research is needed to develop strategies targeting GLI-1 for improved outcomes.

PIK3/Akt/mTOR pathway alterations in metastatic castration-sensitive prostate cancer.

Alterations in the PIK3/Akt/mTOR pathway are commonly seen in metastatic castration-sensitive prostate cancer (mCSPC), however their role in outcomes is unknown. We aim to evaluate the prognostic significance as well as the genetic landscape of PIK3/Akt/mTOR pathway alteration in mCSPC. Fourhundred and seventy-two patients with mCSPC were included who underwent next generation sequencing. PIK3/Akt/mTor pathway alterations were defined as mutations in Akt1, mTOR, PIK3CA, PIK3CB, PIK3R1, PTEN, TSC1, and TSC2. Endpoints of interests were radiographic progression-free survival (rPFS), time to development of castration resistant prostate cancer (tdCRPC), and overall survival (OS). Kaplan-Meier analysis was performed and Cox regression hazard ratios (HR) were calculated. One hundred and fifty-two (31.9%) patients harbored a PIK3/Akt/mTOR pathway alteration. Median rPFS and tdCRPC were 23.7 and 21.0 months in PIK3/Akt/mTOR altered compared to 32.8 (p = 0.08) and 32.1 months (p = 0.002) in wildtype tumors. On multivariable analysis PIK3/Akt/mTOR pathway alterations were associated with tdCRPC (HR 1.43, 95% CI, 1.05-1.94, p = 0.02), but not rPFS [Hazard ratio (HR) 1.20, 95% confidence interval (CI), 0.90-1.60, p = 0.21]. PIK3/Akt/mTOR pathway alterations were more likely to be associated with concurrent mutations in TP53 (40% vs. 28%, p = 0.01) and TMPRSS2-ERG (37% vs. 26%, p = 0.02) than tumors without PIK3/Akt/mTOR pathway alterations. Concurrent mutations were typically associated with shorter median times to rPFS and tdCRPC. DAVID analysis showed p53 signaling and angiogenesis pathways were enriched in PIK3/Akt/mTOR pathway altered tumors while beta-catenin binding and altered BRCA pathway were enriched in PIK3/Akt/mTOR pathway wildtype tumors. PIK3/Akt/mTOR pathway alterations were common in mCSPC and associated with poorer prognosis. The genetic landscape of PIK3/Akt/mTOR pathway altered tumors differed from wildtype tumors. Additional studies are needed to better understand and target the PIK3/Akt/mTOR pathway in mCSPC.

Prognostic impact of beta-blocker use by N-terminal pro-brain natriuretic peptide level in acute heart failure patients.

Both patients with heart failure (HF) with reduced ejection fraction (HFrEF) and those with HF with preserved ejection fraction (HFpEF) present with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) and have multiple comorbidities; consequently, the prognostic effect of NT-proBNP according to beta-blocker (BB) use is unknown. This retrospective study evaluated patients admitted for acute HF between January 2012 and December 2017 at Ulsan University Hospital. Clinical, echocardiographic, laboratory and drug prescription data, including BB data, were collected from the hospital database. Information on mortality was collected by reviewing medical records or using national death data. Of the 472 patients evaluated, 216 (45.8%) and 256 (54.2%) patients were and were not prescribed BB at discharge, respectively. A total of 224 (47.5%) patients died within a median follow-up duration of 44months. The Kaplan-Meier analysis showed reduced all-cause mortality with BB in HFrEF (ejection fraction≤40%) but not in HFpEF (ejection fraction>40%). In the multivariate Cox regression analysis, transmitral to tissue Doppler imaging, early diastolic velocity ratio (E/E'), NT-proBNP and BB use were independent predictors of all-cause mortality in HFrEF. Meanwhile, haemoglobin and NT-proBNP levels were independent predictors of HFpEF. The NT-proBNP cut-off value for determining all-cause mortality was set to 4800pg/mL. Among HFrEF patients with NT-proBNP<4800pg/mL, the survival rate was higher for patients with BB use than those with no BB use (log-rank P<0.001). However, in the HFpEF group, the survival rate associated with BB use did not differ according to the NT-proBNP levels. Both HFrEF and HFpEF patients with NT-proBNP levels of ≥4800pg/mL presented with multiple comorbidities, including lower body mass index and haemoglobin levels and higher creatinine levels, NT-proBNP levels and E/E'. In patients with acute HF, BB use is associated with reduced all-cause mortality in those with HFrEF but not in those with HFpEF. HFrEF patients with NT-proBNP levels of <4800pg/mL treated with BB have a higher survival rate than those not treated with BB. However, this benefit is not seen in HFrEF patients with NT-proBNP levels of ≥4800pg/mL or in all HFpEF patients, regardless of the NT-proBNP level. NT-proBNP levels are elevated in multiple comorbid conditions, and these comorbidities may contribute to the attenuated effects of BB on all-cause mortality.

Enhancing prognostic prediction in hepatocellular carcinoma post-TACE: a machine learning approach integrating radiomics and clinical features

ObjectiveThis study aimed to investigate the use of radiomics features and clinical information by four machine learning algorithms for predicting the prognosis of patients with hepatocellular carcinoma (HCC) who have been treated with transarterial chemoembolization (TACE).MethodsA total of 105 patients with HCC treated with TACE from 2002 to 2012 were enrolled retrospectively and randomly divided into two cohorts for training (n = 74) and validation (n = 31) according to a ratio of 7:3. The Spearman rank, random forest, and univariate Cox regression were used to select the optimal radiomics features. Univariate Cox regression was used to select clinical features. Four machine learning algorithms were used to develop the models: random survival forest, eXtreme gradient boosting (XGBoost), gradient boosting, and the Cox proportional hazard regression model. The area under the curve (AUC) and C-index were devoted to assessing the performance of the models in predicting HCC prognosis.ResultsA total of 1,834 radiomics features were extracted from the computed tomography images of each patient. The clinical risk factors for HCC prognosis were age at diagnosis, TNM stage, and metastasis, which were analyzed using univariate Cox regression. In various models, the efficacy of the combined models generally surpassed that of the radiomics and clinical models. Among four machine learning algorithms, XGBoost exhibited the best performance in combined models, achieving an AUC of 0.979 in the training set and 0.750 in the testing set, demonstrating its strong prognostic prediction capability.ConclusionThe superior performance of the XGBoost-based combined model underscores its potential as a powerful tool for enhancing the precision of prognostic assessments for patients with HCC.

Introduction to the special issue based on contributions from ‘A celebration of 50 Years of the Cox model in memory of Sir David Cox’, 10 November 2022, London School of Hygiene &amp; Tropical Medicine

Introduction to the special issue based on contributions from ‘A celebration of 50 Years of the Cox model in memory of Sir David Cox’, 10 November 2022, London School of Hygiene &amp; Tropical Medicine

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics

BackgroundThe prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored.MethodsWe Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model’s performance.ResultsThe enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram’s good predictive performance and clinical utility.ConclusionIntegrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Subsequent biologic and targeted synthetic disease modifying anti rheumatic drugs after fulfilling difficult-to-treat rheumatoid arthritis criteria: a survival analysis.

To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation. Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation. Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation. Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention ratesin patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival.

Risks of KD and MIS-C in pediatric patients with COVID-19 infection: A TriNetX based cohort study.

The associations of COVID-19 with Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) remain unclear. Few large-scale studies have estimated the cumulative incidence of MIS-C and KD after COVID-19 in children. Data were obtained from TriNetX. After propensity score matching was completed, data from 258,645 patients with COVID-19 (COVID-19 group) and 258,645 patients without COVID-19 (non-COVID-19 group) were analyzed using Cox regression. Hazard ratio (HR), 95% confidence interval (CI), and cumulative incidence of MIS-C and KD were calculated for both groups. Stratified analysis was performed to validate the results. After matching for age at baseline and sex, the risks of MIS-C and KD were higher in the COVID-19 group than in the non-COVID-19 group (HR: 3.023 [95% CI: 2.323 to 3.933] and 1.736 [95% CI: 1.273 to 2.369], respectively). After matching for age at baseline, sex, race, ethnicity, and comorbidities, the risks of MIS-C and KD remained significantly higher in the COVID-19 group than in the non-COVID-19group (HR: 2.899 [95% CI: 2.173 to 3.868] and 1.435 [95% CI: 1.030 to 2.000]). When stratified by age, the risk of MIS-C was higher in the COVID-19 group-for patients aged > 5 years and ≤ 5 years (HR: 2.399 [95% CI: 1.683 to 3.418] and 2.673 [95% CI: 1.737 to 4.112], respectively)-than in the non-COVID-19 group. However, the risk of KD was elevated only in patients aged ≤ 5 years (HR: 1.808; 95% CI: 1.203 to 2.716). When stratified by COVID-19 vaccination status, the risks of MIS-C and KD were elevated in unvaccinated patients with COVID-19 (HR: 2.406 and 1.835, respectively). Patients with COVID-19 who are aged < 18 and ≤ 5 years have increased risks of MIS-C and KD, respectively. Further studies are required to confirm the role of COVID-19 in the pathogenesis of MIS-C and KD.

Transitioning from the University to the Workplace: A Duration Model with Grouped Data

Labor market surveys usually measure unemployment duration in time intervals. In these cases, traditional duration models such as Cox regression and parametric survival models are not suitable for studying the duration of unemployment spells. In order to deal with this above issue, we use Han and Hausman’s ordered logit model for grouped durations, which has more flexibility than standard specifications. In particular, its flexibility arises from the fact that we do not need to specify any functional form for the baseline hazard function—it also circumvents problems associated with heterogeneity. The focus of interest is on the first unemployment duration of higher education graduates. The analysis is accomplished by using a large dataset from a graduate survey of Spanish university graduates. The results show that the university-to-work transition of higher education graduates is significantly associated with the graduate’s age, participation in internship programs, field of study, type of university, and gender. Specifically, graduates who participated in internship programs, engineering graduates, and graduates from private universities experience a smooth transition.

The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes

We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36–0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32–0.74), and (HR 0.51, 95% Cl 0.35–0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D.