Joint Association of Change in Physical Activity and Sitting Time with Metabolic Syndrome Risk: A Prospective Cohort Study.

Background and Aims: The purpose of this study was to investigate the combined impact of variations in physical activity (PA) and sitting time (ST) on the risk of developing metabolic syndrome (MetS). Methods: This study was conducted on a cohort of adults from the general population, aged 40-69 years, who participated in the KOGES community-based cohort study over a span of 10 years. Changes in PA and ST were assessed using the results from PA questionnaires completed during baseline and follow-up surveys. The diagnosis of MetS was determined according to the criteria established by the International Diabetes Federation. To evaluate the combined effect of PA and ST changes on the incidence of MetS, we calculated hazard ratios and 95% confidence intervals using a Cox proportional hazards regression model. Result: The incidence of MetS was reduced by 39% (HR = 0.61, 95% CI = 0.46-0.82) for increased ST/increased PA and 26% (HR = 0.74, 95% CI = 0.58-0.94) for decreased ST/increased PA, compared with increased ST/decreased PA, respectively. In addition, this study confirmed that the combined impact of changes in PA and ST, based on the domain of PA, on the incidence of MetS varied. Conclusion: Changes in ST and PA are associated with the risk of developing MetS. These findings lay the groundwork for further research on the relationship between changes in PA, ST, and the occurrence of diseases.

Relationship between Change in Physical Activity and Risk of Metabolic Syndrome: A Prospective Cohort Study.

Background: This study investigates the relationship between changes in physical activity levels and risk of metabolic syndrome. Methods: This study examined 1,686 adults aged 40 to 69 years from a community-based cohort study with complete 1st to 4th follow-up data between 2011 and 2020. Changes in physical activity were evaluated through baseline and follow-up surveys using physical activity questionnaires. Metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. A survival analysis was conducted using a multivariate extended Cox regression model with a significance level set at P<0.05. Results: Participants were divided into groups according to physical activity levels. The newly inactive group (vigorous physical activity ≤150 minutes at first follow-up) had a 36% increase in the hazard ratio (HR) for metabolic syndrome compared with the consistently inactive group (≤150 minutes at both baseline and first follow-up) (HR, 1.36; 95% confidence interval [CI], 1.04 to 1.79). The newly active group (walking ≤420 minutes per week at baseline and >420 minutes per week at first follow-up) had a 25% decrease in the HR for metabolic syndrome compared with the consistently inactive group (walking ≤420 minutes per week at both baseline and first follow-up) (HR, 0.75; 95% CI, 0.57 to 0.98). Conclusion: Changes in physical activity levels are associated with risk of metabolic syndrome. These results provide important insights for future investigations into the link between physical activity changes and disease occurrence.

Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the EXAcerbations of COPD and their OutcomeS in CardioVascular diseases study in Italy.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) can increase the risk of severe cardiovascular events. OBJECTIVE: Assess the crude incidence rates (IR) of cardiovascular events and the impact of exacerbations on the risk of cardiovascular events within different time periods following an exacerbation. METHODS: COPD patients aged ≥45 years between 01/01/2015 and 12/31/2018 were identified from the Fondazione Ricerca e Salute administrative database. IRs of severe non-fatal and fatal cardiovascular events were obtained for post-exacerbation time periods (1-7, 8-14, 15-30, 31-180, 181-365 days). Time-dependent Cox proportional hazard models compared cardiovascular risks between periods with and without exacerbations. RESULTS: Of 216,864 COPD patients, >55 % were male, mean age was 74 years, frequent comorbidities were cardiovascular, metabolic and psychiatric. During an average 34-month follow-up, 69,620 (32 %) patients had ≥1 exacerbation and 46,214 (21 %) experienced ≥1 cardiovascular event. During follow-up, 55,470 patients died; 4,661 were in-hospital cardiovascular-related deaths. Among 10,269 patients experiencing cardiovascular events within 365 days post-exacerbation, the IR was 15.8 per 100 person-years (95 %CI 15.5-16.1). Estimated hazard ratios (HR) for the cardiovascular event risk associated with periods post-exacerbation were highest within 7 days (HR: 34.3, 95 %CI: 33.1-35.6), especially for heart failure (HR 50.6; 95 %CI 48.6-52.7) and remained elevated throughout 365 days (HR 1.1, 95 %CI 1.02-1.13). CONCLUSIONS: COPD patients in Italy are at high risk of severe cardiovascular events following exacerbations, suggesting the need to prevent exacerbations and possible subsequent cardiovascular events through early interventions and treatment optimization.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

BACKGROUND: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. METHODS: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. RESULTS: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). CONCLUSIONS: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

Life, death, and statins: association of statin prescriptions and survival in older general practice patients.

AIMS: This study serves as an exemplar to demonstrate the scalability of a research approach using survival analysis applied to general practice electronic health record data from multiple sites. Collection of these data, the subsequent analysis, and the preparation of practice-specific reports were performed using a bespoke distributed data collection and analysis software tool. BACKGROUND: Statins are a very commonly prescribed medication, yet there is a paucity of evidence for their benefits in older patients. We examine the relationship between statin prescriptions for general practice patients over 75 and all-cause mortality. METHODS: We carried out a retrospective cohort study using survival analysis applied to data extracted from the electronic health records of five Australian general practices. FINDINGS: The data from 8025 patients were analysed. The median duration of follow-up was 6.48 years. Overall, 52 015 patient-years of data were examined, and the outcome of death from any cause was measured in 1657 patients (21%), with the remainder being censored. Adjusted all-cause mortality was similar for participants not prescribed statins versus those who were (HR 1.05, 95% CI 0.92-1.20, P = 0.46), except for patients with diabetes for whom all-cause mortality was increased (HR = 1.29, 95% CI: 1.00-1.68, P = 0.05). In contrast, adjusted all-cause mortality was significantly lower for patients deprescribed statins compared to those who were prescribed statins (HR 0.81, 95% CI 0.70-0.93, P < 0.001), including among females (HR = 0.75, 95% CI: 0.61-0.91, P < 0.001) and participants treated for secondary prevention (HR = 0.72, 95% CI: 0.60-0.86, P < 0.001). This study demonstrated the scalability of a research approach using survival analysis applied to general practice electronic health record data from multiple sites. We found no evidence of increased mortality due to statin-deprescribing decisions in primary care.

Association Between Life's Essential 8 Cardiovascular Health Metrics With Cardiovascular Events in the Cardiovascular Disease Lifetime Risk Pooling Project.

BACKGROUND: The American Heart Association recently launched updated cardiovascular health metrics, termed Life's Essential 8 (LE8). Compared with Life's Simple 7 (LS7), the new approach added sleep health as an eighth metric and updated the remaining 7 health factors and behaviors. The association of the updated LE8 score with long-term cardiovascular disease (CVD) outcomes and death is unknown. METHODS: We pooled individual-level data from 6 contemporary US-based cohorts from the Cardiovascular Lifetime Risk Pooling Project. Total LE8 score (0-100 points), LE8 score without sleep (0-100 points), and prior LS7 scores (0-14 points) were calculated separately. We used multivariable-adjusted Cox models to evaluate the association of LE8 with CVD, CVD subtypes, and all-cause mortality among younger, middle, and older adult participants. Net reclassification improvement analysis was used to measure the improvement in CVD risk classification with the addition of LS7 and LE8 recategorization based on score quartile rankings. RESULTS: Our sample consisted of 32 896 US adults (7836 [23.8%] Black; 14 941 [45.4%] men) followed for 642 000 person-years, of whom 9391 developed CVD events. Each 10-point higher overall LE8 score was associated with lower risk by 22% to 40% for CVD, 24% to 43% for congenital heart disease, 17% to 34% for stroke, 23% to 38% for heart failure, and 17% to 21% for all causes of mortality events across age strata. LE8 score provided more granular differentiation of the related CVD risk than LS7. Overall, 19.5% and 15.5% of the study participants were recategorized upward and downward based on LE8 versus LS7 categories, respectively, and the recategorization was significantly associated with CVD risk in addition to LS7 score. The addition of recategorization between LE8 and LS7 categories improved CVD risk reclassification across age groups (clinical net reclassification improvement, 0.06-0.12; P<0.01). CONCLUSIONS: These findings support the improved utility of the LE8 algorithm for assessing overall cardiovascular health and future CVD risk.

Mortality risk factors in the dependent population of Castilla-La Mancha (Spain) before and during the first COVID-19 wave.

The coronavirus disease pandemic has had an important impact worldwide. The population aged over 65 years and aged dependent persons are the population groups which have suffered in a highest level the consequences of the pandemic in terms of cases and death. In Spain, the situation is similar to other countries, but regional studies are needed because competencies on long-term care depend on regional public administration. Thus, the aim of this work is to analyse social and individual factors associated with the risk of mortality of legally recognised dependent people during the pandemic compared to a non-pandemic period. The data were extracted from the administrative database on individuals included in Castilla-La Mancha's long-term care system and it was merged with the information from the Spanish National Death Index administered by the Ministry of Health, Consumption and Social Welfare. The results show that the risk of mortality between March and June 2020 was positively associated with being male; being older than 65, with an especially high impact in the group aged over 90; having a higher level of dependency; living in a nursing home; and living in a place with more population density. Intraregional differences related to health areas also exists in both pandemic and non-pandemic periods. These findings are critical with a view to enhancing protocols for the care of the most vulnerable population groups.

Double lung transplantation is better than single lung transplantation for end-stage chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Lung transplantation is one of the most common treatment options for patients with end-stage chronic obstructive pulmonary disease. However, the choice between single and double lung transplantation for these patients remains a matter of debate. Therefore, we performed a systematic search of medical databases for studies on single lung transplantation, double lung transplantation, and chronic obstructive pulmonary disease. METHODS: The rate ratio and hazard ratio of survival were analyzed. The meta-analysis included 15 case-control and retrospective registry studies. RESULTS: The rate ratios of the 3-year survival (0.937 and P = 0.041) and 5-year survival (0.775 and P = 0.000) were lower for single lung transplantation than for double lung transplantation. However, the hazard ratio did not differ significantly between the two. CONCLUSIONS: Double lung transplantation was found to provide better benefits than single lung transplantation in terms of the long-term survival in patients with chronic obstructive pulmonary disease.

Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram.

BACKGROUND: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. METHODS: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. RESULTS: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. CONCLUSIONS: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.

Meta-research: How many diagnostic or prognostic models published in radiological journals are evaluated externally?

OBJECTIVES: Prognostic and diagnostic models must work in their intended clinical setting, proven via "external evaluation", preferably by authors uninvolved with model development. By systematic review, we determined the proportion of models published in high-impact radiological journals that are evaluated subsequently. METHODS: We hand-searched three radiological journals for multivariable diagnostic/prognostic models 2013-2015 inclusive, developed using regression. We assessed completeness of data presentation to allow subsequent external evaluation. We then searched literature to August 2022 to identify external evaluations of these index models. RESULTS: We identified 98 index studies (73 prognostic; 25 diagnostic) describing 145 models. Only 15 (15%) index studies presented an evaluation (two external). No model was updated. Only 20 (20%) studies presented a model equation. Just 7 (15%) studies developing Cox models presented a risk table, and just 4 (9%) presented the baseline hazard. Two (4%) studies developing non-Cox models presented the intercept. Just 20 (20%) articles presented a Kaplan-Meier curve of the final model. The 98 index studies attracted 4224 citations (including 559 self-citations), median 28 per study. We identified just six (6%) subsequent external evaluations of an index model, five of which were external evaluations by researchers uninvolved with model development, and from a different institution. CONCLUSIONS: Very few prognostic or diagnostic models published in radiological literature are evaluated externally, suggesting wasted research effort and resources. Authors' published models should present data sufficient to allow external evaluation by others. To achieve clinical utility, researchers should concentrate on model evaluation and updating rather than continual redevelopment. CLINICAL RELEVANCE STATEMENT: The large majority of prognostic and diagnostic models published in high-impact radiological journals are never evaluated. It would be more efficient for researchers to evaluate existing models rather than practice continual redevelopment. KEY POINTS: • Systematic review of highly cited radiological literature identified few diagnostic or prognostic models that were evaluated subsequently by researchers uninvolved with the original model. • Published radiological models frequently omit important information necessary for others to perform an external evaluation: Only 20% of studies presented a model equation or nomogram. • A large proportion of research citing published models focuses on redevelopment and ignores evaluation and updating, which would be a more efficient use of research resources.

External Validation of a Prognostic Model for Survival of Patients With Abdominal Aortic Aneurysms Treated by Endovascular Aneurysm Repair.

OBJECTIVE: Current guidelines recommend diameter monitoring of small and asymptomatic abdominal aortic aneurysms (AAAs) due to the low risk of rupture. Elective AAA repair is recommended for diameters ≥ 5.5 cm in men and ≥ 5.0 cm in women. However, data supporting the efficacy of elective treatment for all patients above these thresholds are diverging. For a subgroup of patients, life expectancy might be very short, and elective AAA repair at the current threshold may not be justified. This study aimed to externally validate a predictive model for survival of patients with an asymptomatic AAA treated by endovascular aneurysm repair (EVAR). METHODS: This was a multicentre international retrospective observational cohort study. Data were collected from four European aortic centres treating patients between 2001 and 2021. The initial model included age, estimated glomerular filtration rate (eGFR), and chronic obstructive pulmonary disease (COPD) as independent predictors for survival. Model performance was measured by discrimination and calibration. RESULTS: The validation cohort included 1 500 patients with a median follow up of 65 months, during which 54.6% of the patients died. The external validation showed slightly decreased discrimination ability and signs of overfitting in model calibration. However, a high risk subgroup of patients with impaired survival rates was identified: octogenarians with eGFR < 60 OR COPD, septuagenarians with eGFR < 30, and septuagenarians with eGFR < 60 and COPD having survival rates of only 55.2% and 15.5% at five and 10 years, respectively. CONCLUSION: EVAR is a valuable treatment option for AAA, especially for patients unsuitable for open repair. Nonetheless, not all these patients will benefit from EVAR, and an individualised treatment recommendation should include considerations on life expectancy. This study provides a risk stratification to identify patients who may not benefit from EVAR using the present diameter thresholds.

Association of systolic blood pressure with incident chronic kidney disease estimated by marginal structural model: a nationwide population-based study.

Background: We aimed to investigate the association between systolic blood pressure (SBP) and risk of incident chronic kidney disease (CKD) using marginal structural model (MSM) to reflect mutual effects of exposure and confounders on the outcome. Methods: A total of 195,970 adults with an estimated glomerular filtration rate (eGFR) of >60 mL/min/1.73 m2 and no proteinuria were included from a nationally representative sample cohort of Korean population. SBPs were measured through national health examinations. Primary outcome was incident CKD, defined as a composite of events of a decrease in eGFR to <60 mL/min/1.73 m2 or a newly developed proteinuria for at least two consecutive measurements. The association between SBP and risk of CKD was examined using Cox model, time-dependent Cox model, and MSM. Results: During a follow-up of 5 years, CKD occurred in 3,355 participants (1.7%). With SBP treated as a continuous variable, each 10-mmHg increment was associated with higher risk for incident CKD, regardless of analytical models used. Compared to SBP group of 120-129 mmHg, hazard ratios (95% confidence intervals) for incident CKD for SBP groups of <110, 110-119, 130-139, and ≥140 mmHg in MSM were 0.70 (0.62-0.80), 0.85 (0.77-0.95), 1.16 (1.05-1.27), and 1.63 (1.47-1.80), respectively. Conclusion: In this nationwide study, we found a significant relationship between higher SBP and higher risk of incident CKD. Further studies are warranted to verify the potential significance of high SBP as a preventable risk factor for the development of CKD in those with preserved renal function.

[Evaluation of Efficacy and Prognosis Analysis of Stage III-IV SMARCA4-deficient 
Non-small Cell Lung Cancer Treated by PD-1 Immune Checkpoint Inhibitors plus 
Chemotherapy and Chemotherapy].

BACKGROUND: The SMARCA4 mutation has been shown to account for at least 10% of non-small cell lung cancer (NSCLC). In the present, conventional radiotherapy and targeted therapy are difficult to improve outcomes due to the highly aggressive and refractory nature of SMARCA4-deficient NSCLC (SMARCA4-DNSCLC) and the absence of sensitive site mutations for targeted drug therapy, and chemotherapy combined with or without immunotherapy is the main treatment. Effective SMARCA4-DNSCLC therapeutic options, however, are still debatable. Our study aimed to investigate the efficacy and prognosis of programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy in patients with stage III-IV SMARCA4-DNSCLC. METHODS: 46 patients with stage III-IV SMARCA4-DNSCLC were divided into two groups based on their treatment regimen: the chemotherapy group and the PD-1 ICIs plus chemotherapy group, and their clinical data were retrospectively analyzed. Efficacy assessment and survival analysis were performed in both groups, and the influencing factors for prognosis were explored for patients with SMARCA4-DNSCLC. RESULTS: Male smokers are more likely to develop SMARCA4-DNSCLC. There was no significant difference in the objective response rate (76.5% vs 69.0%, P=0.836) between chemotherapy and the PD-1 ICIs plus chemotherapy or the disease control rate (100.0% vs 89.7%, P=0.286). The one-year overall survival rate in the group with PD-1 ICIs plus chemotherapy was 62.7%, and that of the chemotherapy group was 46.0%. The difference in median progression-free survival (PFS) between the PD-1 ICIs plus chemotherapy group and the chemotherapy group was statistically significant (9.3 mon vs 6.1 mon, P=0.048). The results of Cox regression analysis showed that treatment regimen and smoking history were independent influencing factors of PFS in patients with stage III-IV SMARCA4-DNSCLC, and family history was an individual influencing factor of overall survival in patients with stage III-IV SMARCA4-DNSCLC. CONCLUSIONS: Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.

Direct deep learning-based survival prediction from pre-interventional CT prior to transcatheter aortic valve replacement.

PURPOSE: To investigate survival prediction in patients undergoing transcatheter aortic valve replacement (TAVR) using deep learning (DL) methods applied directly to pre-interventional CT images and to compare performance with survival models based on scalar markers of body composition. METHOD: This retrospective single-center study included 760 patients undergoing TAVR (mean age 81 ± 6 years; 389 female). As a baseline, a Cox proportional hazards model (CPHM) was trained to predict survival on sex, age, and the CT body composition markers fatty muscle fraction (FMF), skeletal muscle radiodensity (SMRD), and skeletal muscle area (SMA) derived from paraspinal muscle segmentation of a single slice at L3/L4 level. The convolutional neural network (CNN) encoder of the DL model for survival prediction was pre-trained in an autoencoder setting with and without a focus on paraspinal muscles. Finally, a combination of DL and CPHM was evaluated. Performance was assessed by C-index and area under the receiver operating curve (AUC) for 1-year and 2-year survival. All methods were trained with five-fold cross-validation and were evaluated on 152 hold-out test cases. RESULTS: The CNN for direct image-based survival prediction, pre-trained in a focussed autoencoder scenario, outperformed the baseline CPHM (CPHM: C-index = 0.608, 1Y-AUC = 0.606, 2Y-AUC = 0.594 vs. DL: C-index = 0.645, 1Y-AUC = 0.687, 2Y-AUC = 0.692). Combining DL and CPHM led to further improvement (C-index = 0.668, 1Y-AUC = 0.713, 2Y-AUC = 0.696). CONCLUSIONS: Direct DL-based survival prediction shows potential to improve image feature extraction compared to segmentation-based scalar markers of body composition for risk assessment in TAVR patients.

Effect of regional medical disparities on complications in patients with hypertension: Cox's proportional hazard models.

Objective: Complications associated with hypertension can be alleviated by providing necessary medical services. However, there may be disparities in their provision depending on regional differences. Thus, this study aimed to examine the effects of regional healthcare disparities on complications in patients with hypertension in South Korea. Methods: Data from the National Health Insurance Service National Sample Cohort (2004-2019) were analyzed. The position value for the relative composite index was used to identify medically vulnerable regions. The diagnosis of hypertension within the region was also considered. The risk of complications associated with hypertension included cardiovascular, cerebrovascular, and kidney diseases. Cox proportional hazards models were used for statistical analysis. Results: A total of 246,490 patients were included in this study. Patients who lived in medically vulnerable regions and were diagnosed outside their residential area had a higher risk of complications than those living in non-vulnerable regions and were diagnosed outside the residential area (hazard ratio: 1.156, 95% confidence interval: 1.119-1.195). Conclusion: Patients living in medically vulnerable regions who were diagnosed outside their residential areas were more likely to have hypertension complications regardless of the type of complication. Necessary policies should be implemented to reduce regional healthcare disparities.

Evaluation of recurrence risk for patients with stage I invasive lung adenocarcinoma manifesting as solid nodules based on 18F-FDG PET/CT, imaging signs, and clinicopathological features.

BACKGROUND: Stage I lung adenocarcinoma is a heterogeneous group. Previous studies have shown the prognostic evaluation value of PET/CT in this cohort; however, few studies focused on stage I invasive adenocarcinoma manifesting as solid nodules. This study aimed to evaluate the recurrence risk for patients with stage I invasive lung adenocarcinoma manifesting as solid nodules based on 18F-FDG PET/CT, CT imaging signs, and clinicopathological parameters. METHODS: We retrospectively enrolled 230 patients who underwent 18F-FDG PET/CT examination between January 2013 and July 2019. Metabolic parameters: maximum standard uptake value (SUVmax), mean standard uptake value, tumor metabolic volume (MTV), and total tumor glucose digestion were collected. Kaplan-Meier method was used to evaluate recurrence-free survival (RFS), and the multivariate Cox proportional hazards model was used to determine the independent risk factors associated with RFS. The time-dependent receiver operating characteristic curve (ROC) method was used to calculate the optimal cutoff value of metabolic parameters. RESULTS: The 5-year RFS rate for all patients was 71.7%. Multivariate Cox analysis revealed that the International Association for the Study of Lung Cancer Pathology Committee (IASLC) pathologic grade 3 [Hazard ratio (HR), 3.96; 95% Confidence interval (CI), 1.11-14.09], the presence of cavity sign (HR 5.38; 95% CI 2.23-12.96), SUVmax (HR 1.23; 95% CI 1.13-1.33), and MTV (HR 1.05; 95% CI 1.01-1.08) were potential independent prognostic factors for RFS. Patients with IASLC grade 3, the presence of cavity sign, SUVmax > 3.9, or MTV > 5.4 cm3 were classified as high risk, while others were classified as low risk. There was a significant difference in RFS between the high-risk and low-risk groups (HR 6.04; 95% CI 2.17-16.82, P < 0.001), and the 5-year RFS rate was 94.1% for the low-risk group and 61.3% for the high-risk group. CONCLUSIONS: We successfully evaluate the recurrence risk of patients with stage I invasive adenocarcinoma manifesting as solid nodules for the first time. The 5-year RFS rate in the high-risk group was significantly lower than in the low-risk group (61.3% vs. 94.1%). Our study may aid in optimizing therapeutic strategies and improving survival benefits for those patients.

Postoperative prognostic nomogram for adult grade II/III astrocytoma in the Chinese Han population.

Background: Prognostic models of glioma have been the focus of many studies. However, most of them are based on Western populations. Additionally, because of the complexity of healthcare data in China, it is important to select a suitable model based on existing clinical data. This study aimed to develop and independently validate a nomogram for predicting the overall survival (OS) with newly diagnosed grade II/III astrocytoma after surgery. Methods: Data of 472 patients with astrocytoma (grades II-III) were collected from Qilu Hospital as training cohort while data of 250 participants from Linyi People's Hospital were collected as validation cohort. Cox proportional hazards model was used to construct the nomogram and individually predicted 1-, 3-, and 5-year survival probabilities. Calibration ability, and discrimination ability were analyzed in both training and validation cohort. Results: Overall survival was negatively associated with histopathology, age, subtotal resection, multiple tumors, lower KPS and midline tumors. Internal validation and external validation showed good discrimination (The C-index for 1-, 3-, and 5-year survival were 0.791, 0.748, 0.733 in internal validation and 0.754, 0.735, 0.730 in external validation, respectively). The calibration curves showed good agreement between the predicted and actual 1-, 3-, and 5-year OS rates. Conclusion: This is the first nomogram study that integrates common clinicopathological factors to provide an individual probabilistic prognosis prediction for Chinese Han patients with astrocytoma (grades II-III). This model can serve as an easy-to-use tool to advise patients and establish optimized surveillance approaches after surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00223-0.

Comparison of Different Modeling Approaches for Prescription Opioid Use and Its Association With Adverse Events.

Previous research linking opioid prescribing to adverse drug events has failed to properly account for the time-varying nature of opioid exposure. This study aimed to explore how the risk of opioid-related emergency department visits, readmissions, or deaths (composite outcome) varies with opioid dose and duration, comparing different novel modeling techniques. A prospective cohort of 1,511 hospitalized patients discharged from 2 McGill-affiliated hospitals in Montreal, 2014-2016, was followed from the first postdischarge opioid dispensation until 1 year after discharge. Marginal structural Cox proportional hazards models and their flexible extensions were used to explore the association between time-varying opioid use and the composite outcome. Weighted cumulative exposure models assessed cumulative effects of past use and explored how its impact depends on the recency of exposure. The patient mean age was 69.6 (standard deviation = 14.9) years; 57.7% were male. In marginal structural model analyses, current opioid use was associated with a 71% increase in the hazard of opioid-related adverse events (adjusted hazard ratio = 1.71, 95% confidence interval: 1.21, 2.43). The weighted cumulative exposure results suggested that the risk cumulates over the previous 50 days of opioid consumption. Flexible modeling techniques helped assess how the risk of opioid-related adverse events may be associated with time-varying opioid exposures while accounting for nonlinear relationships and the recency of past use.

Selected hematological, biochemical, and echocardiographic variables as predictors of survival in canine patients with myxomatous mitral valve disease and congestive heart failure.

INTRODUCTION/OBJECTIVES: We investigated the association of breed, age, weight, duration of therapy, and selected blood and echocardiographic variables with the survival of dogs with congestive heart failure (CHF) due to myxomatous mitral valve disease. We also sought to identify differences in selected echocardiographic and routine blood variables between dogs with stable and unstable CHF and between hospitalized and non-hospitalized patients. ANIMALS, MATERIALS AND METHODS: This retrospective study included dogs with a complete cardiovascular workup. Blood analysis and the initial and final echocardiographic results were included. Covariates were analyzed using Cox proportional hazards models. RESULTS: One hundred sixty-five dogs with myxomatous mitral valve disease were evaluated in this study: 96 stable patients and 69 unstable CHF patients. In total, 107 dogs (64.8%) died, and 58 (35.2%) were censored. The median survival time of the dogs that died was 11.5 months (range 11 days to 4.3 years). Unstable CHF patients had significantly higher neutrophils and lower potassium concentrations than stable CHF patients, and hospitalized patients had higher white blood cell, neutrophil, and monocyte counts and urea and creatinine concentrations than non-hospitalized patients. Variables negatively associated with survival were older age, unstable CHF, duration of therapy, white blood cell count, urea concentration, and left atrium to aorta ratio. Chihuahuas had a lower risk of death. CONCLUSIONS: Selected blood and echocardiographic variables distinguish dogs with stable and unstable CHF and predict survival.

Comparison of nivolumab and sorafenib for first systemic therapy in patients with hepatocellular carcinoma and Child-Pugh B cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis are excluded or underrepresented in clinical trials of systemic therapies for hepatocellular carcinoma (HCC) and comparisons of available therapies are lacking. We aimed to compare overall survival for patients with HCC and Child-Pugh B cirrhosis treated with nivolumab or sorafenib as first systemic treatment. METHODS: We performed a retrospective cohort study in patients with HCC and Child-Pugh B cirrhosis treated at Veterans Affairs medical centers to compare overall survival, adverse events, and reason for discontinuation of therapy between patients treated with nivolumab or sorafenib as first systemic treatment. All statistical tests were 2-sided. RESULTS: Of those meeting inclusion criteria, 431 patients were treated with sorafenib and 79 with nivolumab. Median OS was 4.0 months (95% CI 3.5-4.8) in the sorafenib cohort and 5.0 months (95% CI 3.3-6.8) in the nivolumab cohort. In the multivariable Cox proportional hazards model, nivolumab was associated with a significantly reduced hazard of death compared to sorafenib (HR 0.69; 95% CI 0.52-0.91; p = 0.008). In a secondary analysis using propensity score methods, results did not reach statistical significance (HR 0.77; 95% CI 0.55-1.06; p = 0.11). Treatment was discontinued due to toxicity in 12% of patients receiving nivolumab compared to 36% receiving sorafenib (p = 0.001). CONCLUSION: In patients with HCC and Child-Pugh B cirrhosis, nivolumab treatment may be associated with improved overall survival and improved tolerability compared to sorafenib and should be considered for the first systemic treatment in this population.