Cox Proportional Hazards Model Analysis Research Articles

Chronic kidney disease is a major risk factor for mortality in triglyceride deposit cardiomyovasculopathy patients.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare cardiovascular disorder caused by defective intracellular lipolysis of triglyceride, resulting in heart failure and diffuse narrowing atherosclerosis. Recently, the registry of TGCV patients in Japan revealed that the 3-year overall survival rate was 80.1% and the 5-year overall survival rate was 71.8%. In this study, the effect on mortality of chronic kidney disease (CKD), diabetes malleus (DM), hypertension (HT), and dyslipidemia (DL) was analyzed using this retrospective registry of TGCV patients. The 3-year survival rate was 71.3% in the CKD group and 91.7% in the non-CKD group, and the 5-year survival rate was 61.8% in CKD group and 84.4% in the non-CKD group. The Kaplan-Meier analysis revealed that CKD is a risk factor for mortality in TGCV patients (p = 0.006). Although TGCV patients with CKD were older than those without CKD, Cox proportional hazard model analyses including age indicated that CKD has a significant association of the prognosis of TGCV patients (hazard ratio 2.33 [1.12-4.86], p = 0.024). DM, HT, and DL did not increase mortality in TGCV patients, although these risk factors were established in the general population. TGCV might cause cardiac disorders and kidney disease at the same time, because podocyte foot process disorder in the glomeruli might be caused by TGCV itself, while CKD should be a risk factor for mortality in TGCV patients as is true in the general population. In conclusion, CKD is a major risk factor for mortality in TGCV patients and thus should be paid attention to in these patients.

Association of geriatric nutritional risk index with renal prognosis and all-cause mortality among older patients with chronic kidney disease: a secondary analysis of CKD-ROUTE study

Objectives The aim of the study was to assess the association between the geriatric nutritional risk index (GNRI) and incidence of CKD progression, all-cause mortality, and cardiovascular events in the elderly patients with chronic kidney disease (CKD) before dialysis initiation. Methods We performed a post hoc analysis of the CKD-ROUTE database, which included 538 pre-dialysis CKD patients aged ≥65 years in this prospective cohort study. Associations between GNRI and clinical outcomes were estimated using Cox proportional hazards model analysis. Multivariable linear mixed regression models with random intercepts were used to assess the association between GNRI and estimated glomerular filtration rate (eGFR) decline per year. Results During the median follow-up period of 2.92 years, there were 123 (22.86%) CKD progression events, 44 (8.18%) deaths, and 76 (14.13%) cardiovascular events. After adjusting for multiple confounding factors, the hazard ratios (HRs) for CKD progression in patients with GNRI <92 were 1.99 (95% CI, 1.34–2.97; p < 0.001), when compared with a GNRI of ≥92. Patients with a lower GNRI also had a significantly greater rate of eGFR decline over time than well-nourished patients (mean annual difference, −1.69; 95% CI, −2.62 to −0.77; p < 0.001). In the secondary outcomes, this association was consistent for all-cause mortality. Moreover, the associations were generally consistent across several subgroup and sensitivity analyses. Conclusions The lower GNRI is significantly associated with higher risks of renal prognosis and all-cause mortality in elderly patients with CKD.

A national estimate of mental disorders and mortality outcomes in cancer survivors.

This study evaluated the prevalence of various mental disorders and their influence on mortality outcomes in individuals with cancer. The authors' institutional database included patients with cancer diagnosed between 2011 and 2015 who had mental disorders and death information up to 2021. Mental disorders included nonaffective psychotic disorders, affective psychotic disorders, anxiety-related and stress-related disorders, alcohol or drug misuse, and mood disorders without psychotic symptoms. The causes of death were classified as all-cause, cancer-related, or suicide. Individual matching was performed to randomly match cancer survivors with and without mental disorders according to age at cancer diagnosis, year of cancer diagnosis, sex, and cancer site. The association between mental disorders and mortality risk was assessed using a Cox proportional hazards model and competing-risk analyses. Among 637,491 cancer survivors (mean age, 58.9 years), there were 238,654 deaths from any cause and 2255 deaths from suicide. Incidence rates varied across disorders, with the highest rates observed for anxiety-related and stress-related disorders and mood disorders without psychotic symptoms. Mental disorders were associated with an increased risk of all-cause and cancer-related mortality. Adjusted hazard ratios (HRs) for nonaffective psychotic disorders, affective psychotic disorders, anxiety-related and stress-related disorders, alcohol and drug misuse, and mood disorders without psychotic symptoms were as follows: HR, 2.49 (95% confidence interval [CI], 2.22-2.80); HR, 2.38 (95% CI, 2.21-2.57); HR, 1.02 (95% CI, 1.01-1.04); HR, 2.13 (95% CI, 1.87-2.43); and HR, 1.27 (95% CI, 1.24-1.30), respectively, for all-cause mortality. Suicide risk was higher in patients who had mental disorders, especially within the first 6 months after diagnosis. The current findings underscore the impact of mental illness on mortality among cancer survivors in Korea, specifically highlighting the elevated rates of anxiety, stress, and mood disorders.

Comparison of continuous subcutaneous hydromorphone hydrochloride and morphine hydrochloride injection on skin disorders incidence: a retrospective study

BackgroundContinuous subcutaneous administration of injectable opioids is simple and effective; however, skin disorders may occur when high opioid dosages are used. Therefore, we investigated opioid injection drugs with a low risk of skin disorders.MethodsA retrospective study was conducted using the electronic medical records of patients prescribed 1% hydromorphone hydrochloride or 4% morphine hydrochloride with instructions for continuous subcutaneous administration at Shizuoka Cancer Center from January 2017 to December 2021. The primary endpoint was skin disorders incidence, and the two groups were compared using Cox proportional hazards model analyses and Fisher’s exact test at 5% significance level. Patient background factors expected to influence skin disorders were also investigated, and multivariate logistic analysis of skin disorders incidence was performed.ResultsThe incidence of skin disorders in the hydromorphone hydrochloride and morphine hydrochloride groups were 3.7% (1/27 patients) and 28.1% (9/32 patients), respectively, showing a significant difference in two statistical analyses between the two groups (Cox proportional hazards model analyses HR: 0.09, 95% CI: 0.01–0.70, P = 0.022. Fisher’s exact test OR: 0.10, 95% CI: 0.01–0.84, P = 0.016). In the multivariate analysis, the administration of hydromorphone hydrochloride (OR: 0.04, 95% CI: 0.003–0.48, P = 0.012) was also found to have a significant negative correlation with the occurrence of skin disorders. On the contrary, administration period ≥ 28 days (OR: 18.16, 95% CI: 2.22–148.60, P = 0.007) was a factor with a significant positive correlation.ConclusionsSubcutaneous 1% hydromorphone hydrochloride administration had a lower risk of skin disorders than 4% morphine hydrochloride injection. Moreover, prolonging the administration period increased the risk of developing skin disorders. This suggests that a 1% hydromorphone hydrochloride Injection is a good clinical decision for patients who are likely to have a longer administration period and require a higher dosage of injectable opioids.Trial registrationRetrospectively registered.

N-terminal pro-brain natriuretic peptide and cardiorenal outcome in patients with anaemia in chronic kidney disease.

Blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) may be modified by low renal clearance and anaemia. The aim of this study was to investigate the impact of the blood NT-proBNP level on cardiovascular and renal outcomes in patients with these two manifestations. This post hoc analysis stemmed from the oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN) trial, a large prospective study involving patients with non-dialysis kidney disease experiencing anaemia. The Pearson correlation coefficient was employed to examine the association of baseline NT-proBNP level with renal function or anaemia. Longitudinal assessment of the association of baseline blood NT-proBNP levels with cardiovascular outcomes (cardiac death, acute coronary syndrome, hospitalization due to heart failure or fatal arrhythmia) and renal outcomes [the initiation of maintenance dialysis, kidney transplantation, a 50% decrease in the estimated glomerular filtration rate (eGFR) or an eGFR of ≤6mL/min/1.73m2] was conducted by using restricted cubic spline analysis and Cox proportional hazard model analysis. In total, this study included 1484 patients [mean age, 70.2±11.8years; women, 40.6%; eGFR, 20.3±9.6mL/min/1.73m2; haemoglobin (Hb) level, 9.8±0.9g/dL]. Baseline NT-proBNP levels were a median of 496.0pg/mL [inter-quartile range: 235.0-1090.0pg/mL]. A weak association existed between NT-proBNP levels, on a logarithmic scale, and eGFR (r=-0.131, P<0.001) or Hb levels (r=-0.182, P<0.001) at baseline. During 2.29±0.89years, 92 cardiovascular and 573 renal events were recorded. After adjusting for potential confounders such as eGFR and blood Hb level, a nonlinear relationship existed between blood NT-proBNP levels and cardiorenal outcomes. Patients with a baseline NT-proBNP level ≥1000 and 500-1000pg/mL exhibited a greater risk for cardiovascular outcomes than did patients with an NT-proBNP level <250pg/mL {hazard ratio [HR]=8.10 [95% confidence interval (CI), 2.80-23.40] and 3.35 [95% CI, 1.10-10.18], respectively}. These patients also exhibited a moderate risk for renal outcomes [HR=1.77 (95% CI, 1.36-2.31) and 1.54 (95% CI, 1.19-2.00), respectively]. NT-proBNP provides prognostic insights into cardiovascular and renal outcomes among patients with advanced chronic kidney disease experiencing anaemia.

Genetic overlap between breast cancer and sarcopenia: exploring the prognostic implications of SLC38A1 gene expression

BackgroundSarcopenia, an age-related syndrome characterized by a decline in muscle mass, not only affects patients’ quality of life but may also increase the risk of breast cancer recurrence and reduce survival rates. Therefore, investigating the genetic mechanisms shared between breast cancer and sarcopenia is significant for the prevention, diagnosis, and treatment of breast cancer.MethodsThis study downloaded gene expression datasets and clinical data related to breast cancer and skeletal muscle aging from the GEO database. Data preprocessing, integration, differential gene identification, functional enrichment analysis, and construction of protein-protein interaction networks were performed using R language. Subsequently, COX proportional hazards model analysis and survival analysis were conducted, and survival curves and nomograms were generated. The expression levels of genes in tissues were detected using qRT-PCR, and the Radiant DICOM viewer software was used to delineate the pectoralis major muscle area in CT images.ResultsWe identified 152 differentially expressed genes (P < .05) and 226 sarcopenia-related genes (r > .4) associated with skeletal muscle aging. The TCGA-BRCA dataset revealed 106 genes associated with breast cancer (P < .05, logFC = 1). Functional enrichment analysis indicated significant enrichment in cell proliferation and growth pathways. The PPI network identified critical molecules involved in muscle aging and tumor progression. After dimensionality reduction, a strong correlation was observed between the expression of the muscle aging-related gene set and the prognosis of breast cancer patients (P < .01). The expression of SLC38A1 identified through multivariate COX analysis was significantly associated with poor prognosis in breast cancer patients (P = .03). Incorporating SLC38A1 expression, the prognostic model precisely forecasted breast cancer survival (P < .01). External validation confirmed the higher expression of the SLC38A1 gene in breast cancer tissues compared to adjacent non-cancerous tissues (P < .01). The SLC38A1 index, calculated in combination with the patient’s age and BMI, can optimize the prognostic prediction model, providing a powerful tool for personalized treatment of breast cancer.ConclusionHigh SLC38A1 gene expression was significantly associated with poor prognosis in breast cancer patients. The combination of SLC38A1 expression and the pectoralis major muscle area provided an optimized prognostic prediction model, offering a potential tool for personalized breast cancer treatment.

Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy

BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio (GPR) levels in patients with solitary hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) following radical resection has not been established. AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBV-related HCC patients. METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed. GPR levels were compared with 908 non-HCC individuals. Overall survival (OS) and recurrence-free survival (RFS) were evaluated, and cox proportional hazard model analyses were performed to identify independent risk factors. Differences in characteristics were adjusted by propensity score matching (PSM). Subgroup and stratified survival analyses for HCC risks were performed, and a linear trend of the hazard ratio (HR) according to GPR levels was constructed. RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas, chronic hepatitis B and healthy control (adjusted P &lt; 0.05). Variable bias was diminished after the PSM balance test. The low GPR group had improved OS (P &lt; 0.001) and RFS (P &lt; 0.001) in the PSM analysis and when combined with other variables. Multivariate cox analyses suggested that low GPR levels were associated with a better OS (HR = 0.5, 95%CI: 0.36-0.7, P &lt; 0.001) and RFS (HR = 0.57, 95%CI: 0.44-0.73, P &lt; 0.001). This same trend was confirmed in subgroup analyses. Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction. Moreover, stratified survival analyses found that GPR &gt; 0.6 was associated with a worse OS and higher recurrence rate (P for trend &lt; 0.001). CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBV-related HCC.

Association between Home-Base Primary Care and Post-Discharge Outcomes among Older Adults in Korea

This study aimed to evaluate the association between home-based primary care (HBPC) and postdischarge outcomes in Korean older adults. HBPC was a service that provided medical care by visiting the homes of older adults with limited mobility. In this study, data from the National Health Insurance Service (NHIS) were used, and groups with and without HBPC services were matched 1:1 through propensity score matching. Cox proportional hazards model and linear regression analysis were performed to compare the HBPC group with the control group. Overall, 1580 older adults in Korea who used HBPC services after discharge from hospital and 1580 propensity score-matched older adults who did not use HBPC services were included. For 30-day readmission, hospitalizations, and admission to long-term care hospitals or facilities after discharge, this study used a Cox proportional hazards regression model. And linear regression analysis was performed considering that the dependent variable was a continuous variable to examine the average total medical costs after discharge from acute hospital. Older adults who used HBPC services exhibited a lower risk of readmission for the same disease (risk reduction of 0.66, 95% CI 0.50, 0.87) and hospitalization (risk reduction of 0.58, 95% CI 0.46, 0.73) compared with those who did not use HBPC services. The annual average total medical cost was $4764 lower for older adults who used HBPC services than for those who did not (95% CI -6469.49,-3057.52). There was no significant difference in the risk of admission to long-term care hospitals or facilities. HBPC services had a positive effect on reducing 30-day readmission due to the same disease, hospitalization, and annual average total medical costs among older adults after discharge.

Comparative evaluation of negative lymph node count, positive lymph node count, and lymph node ratio in prognostication of survival following completely resection for non-small cell lung cancer: a multicenter population-based analysis

ObjectiveLung cancer is the leading cause of cancer-related mortality. Lymph node involvement remains a crucial prognostic factor in non-small cell lung cancer (NSCLC), and the TNM system is the current standard for staging. However, it mainly considers the anatomical location of lymph nodes, neglecting the significance of node count. Metrics like metastatic lymph node count and lymph node ratio (LNR) have been proposed as more accurate predictors.MethodsWe used data from the SEER 17 Registry Database (2010–2019), including 52,790 NSCLC patients who underwent lobectomy or pneumonectomy, with at least one lymph node examined. Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression models assessed the prognostic value of negative lymph node (NLN) count, number of positive lymph node (NPLN), and LNR, with cut-points determined using X-tile software. Model performance was evaluated by the Akaike information criterion (AIC).ResultsThe Cox proportional hazards model analysis revealed that NLN, NPLN, and LNR are independent prognostic factors for OS and LCSS (P &amp;lt; 0.0001). Higher NLN counts were associated with better survival (HR = 0.79, 95% CI = 0.76–0.83, P &amp;lt; 0.0001), while higher NPLN (HR = 2.19, 95% CI = 1.79–2.67, P &amp;lt; 0.0001) and LNR (HR = 1.64, 95% CI = 1.79–2.67, P &amp;lt; 0.0001) values indicated worse outcomes. Kaplan-Meier curves for all three groups (NLN, NPLN, LNR) demonstrated clear stratification (P &amp;lt; 0.0001). The NLN-based model (60,066.5502) exhibited the strongest predictive performance, followed by the NPLN (60,508.8957) and LNR models (60,349.4583), although the differences in AIC were minimal.ConclusionsNLN count, NPLN, and LNR were all identified as independent prognostic indicators in patients with NSCLC. Among these, the predictive model based on NLN demonstrated a marginally superior prognostic value compared to NPLN, with NPLN outperforming the LNR model. Notably, higher NLN counts, along with lower NPLN and LNR values, were consistently associated with improved survival outcomes. The relationship between these prognostic markers and NSCLC survival warrants further validation through prospective studies.

The relationship between dietary niacin intake and the incidence of all-cause and cardiovascular mortality among chronic kidney disease patients.

Chronic kidney disease (CKD) is a major cause of human mortality and cardiovascular disease (CVD)-related death. Niacin can treat dyslipidemia and can lower overall cardiovascular event incidence and mortality rates. The present study was designed to clarify the link between dietary consumption of niacin and cardiovascular mortality. This study enrolled subjects ≥18 years of age from the National Health and Nutrition Examination Survey 2009-2014 and excluded any individuals for whom data regarding their CKD status, dietary niacin intake, or other covariate information was unavailable. Relationships between dietary niacin intake levels and overall or CVD-related mortality among these CKD patients were assessed using univariate and multivariate Cox regression analyses. The study included 1,798 subjects and recorded 514 and 186 instances of all-cause and cardiovascular death, respectively. Males comprised 51.8% of the study cohort, and the mean age of these subjects was 65. Cox proportional hazard model analyses revealed no relationship between dietary niacin intake and all-cause or cardiovascular death risk among the overall CKD patient population (P > 0.05). However, in age-stratified analyses, those subjects <60 years of age exhibiting the highest levels of dietary niacin consumption (≥ 38 mg/day) were found to face a significantly higher risk of all-cause mortality, and this association remained intact in sensitivity analyses. These results do not support any link between the dietary intake of niacin and all-cause or cardiovascular mortality risk among patients with CKD. Age and niacin intake exhibited a significant interaction related to all-cause mortality.

Association Between the Ionized-to-Total Calcium Ratio and the Risk of Acute Kidney Injury in Patients With Severe Autoimmune Diseases: A Retrospective Analysis From the MIMIC-IV Database.

To investigate the relationship between the ionized-to-total calcium ratio and the incidence of acute kidney injury (AKI) in critically ill patients with autoimmune diseases. A retrospective study was conducted utilizing data from the Medical Information Mart for Intensive Care IV database. In-hospital AKI was the primary outcome. Patients were classified into four distinct categories depending on the calcium ratio. Cox proportional hazards model and restricted cubic spline (RCS) analysis were applied to assess the association between the calcium ratio and AKI risk. Subgroup analyses were conducted to evaluate the consistency of this association across various patient characteristics. A total of 1054 critically ill patients with autoimmune diseases were enrolled and stratified by calcium ratio quartiles into four groups (< 0.515; 0.515-0.546; 0.546-0.576; > 0.576). Cumulative incidence curves showed significant difference in AKI risk among the four groups. Patients in the highest calcium ratio quartile experienced a markedly reduced likelihood of AKI versus those in the lowest, especially in the fully adjusted model (HR = 0.66, 95% CI 0.51-0.84, p < 0.001). RCS analysis demonstrated an obvious nonlinear relationship, showing a steep decline in AKI risk with increasing calcium ratio, which eventually plateaued. This protective effect of higher calcium ratios against AKI was consistent across subgroups, except in those with chronic kidney disease at baseline. The ionized-to-total calcium ratio proves to be significantly associated with the development of AKI in critically ill patients with autoimmune diseases, with its elevation indicating a reduced AKI risk.

Redefining low-threshold buprenorphine access in an integrated mobile clinic program: Factors associated with treatment retention

IntroductionThe Spot mobile clinic provides low-threshold buprenorphine integrated with clinical and social services in Baltimore City, MD. In 2021, The Spot modified practices to improve engagement including providing extended prescriptions, reducing frequency of toxicology testing, giving up to six months to stabilize on medication, offering maximum doses (up to 32 mg total) daily, and utilizing telemedicine. This study characterizes care retention by examining both the total time in care and the percentage of time with buprenorphine prescription coverage during these practice changes, and examines factors associated with retention. MethodsThis retrospective cohort study includes patients (n = 341) who received a buprenorphine prescription who initiated care on The Spot mobile clinic from September 2021 to October 2022, with follow-up through October 2023. We utilized the Cox proportional hazards model and Kaplan-Meier survival analyses to assess differences in care retention by the factors of patient demographics and clinical characteristics. Additionally, we performed sensitivity analyses using Poisson regression to examine differences between patients with 80 % or greater time with active prescription coverage versus <80 % of time with active prescription coverage. ResultsAfter practice setting changes, retention in care at 90 days was 60 %. Patients whose maximum daily buprenorphine dose was 28 to 32 mg were 80 % less likely to discontinue treatment over the study period than those prescribed ≤16 mg (adjusted hazard ratio of discontinuation: 0.2 [95 % CI: 0.1–0.3]). Engaging in wound care or hepatitis C treatment was associated with higher retention in care, and individuals experiencing homelessness remained engaged at rates comparable to stably housed patients. ConclusionPractice changes aimed to improve access to patient-centered, low-threshold buprenorphine treatment may increase retention in care. Notably, higher doses of buprenorphine and integrated treatment with wound care and hepatitis C treatment were associated with increased retention. Due to gaps in patient care, retention metrics should incorporate total time in care as well as percentage of time with an active buprenorphine prescription.

The relationship between composite inflammatory indicators and short-term outcomes in patients with heart failure

BackgroundInflammatory markers are considered reliable indicators for predicting adverse outcomes of cardiovascular disease. However, the prognostic significance of composite inflammatory indicators such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and inflammatory prognosis index (IPI), in predicting mortality among heart failure (HF) patients remains unknown. MethodsWe analyzed data from 1981 patients with HF. The composite inflammatory indicators were calculated based on laboratory test. The endpoint of the study was mortality within six months of follow-up. Cox proportional hazards model and restricted cubic spline analysis were used to assess the association between inflammatory markers and outcomes. The incremental predictive value of composite inflammatory indicators was evaluated using C-index, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). ResultsSII, SIRI, and IPI were linearly associated with the risk of death. Compared to the first tertile, the hazard ratios and 95 % confidence intervals (CIs) for mortality in patients in the third tertile for SII, SIRI, and IPI were 2.32 (1.15–4.67), 3.59 (1.56–8.26), and 4.16 (1.20–14.41), respectively. Incorporating composite inflammatory indicators into the basic model significantly enhanced outcome prediction, with IPI showing the greatest incremental predictive value, as indicated by an increase in C-index (0.042, 95 % CI: 0.004–0.095), a continuous NRI of 0.712 (95 % CI: 0.360–1.063, P < 0.001), and an IDI of 0.010 (95 % CI: 0.001–0.019, P = 0.030). ConclusionsAmong patients with HF, elevated levels of SII, SIRI, and IPI were significantly associated with an increased risk of six-month mortality, with IPI providing the greatest incremental predictive value.

Impact of preoperative clinical and imaging factors on post-pericardiectomy outcomes in chronic constrictive pericarditis patients

The present study was designed to identify the preoperative clinical and imaging findings influencing adverse clinical outcomes in patients with chronic constrictive pericarditis after pericardiectomy. Patients with constrictive pericarditis who underwent pericardiectomy between January 2009 and September 2023 were retrospectively analyzed. Preoperative evaluations included assessments of clinical symptoms, comorbidities, laboratory tests, cardiac computed tomography (CT), and transthoracic echocardiography. The volume of pericardial calcifications was quantified on calcium scoring CT. Adverse clinical events were defined as cardiovascular death or hospitalization due to cardiac causes, and all-cause mortality was assessed. Univariable and multivariable Cox proportional hazard model analysis were performed to find factors associated with adverse clinical events. Among the 91 patients with available preoperative CT scans, 26 (28.6%) experienced adverse clinical events after pericardiectomy, with 19 (20.9%) experiencing cardiovascular deaths. On multivariable Cox analysis, larger pericardial calcium volume hazard ratio [HR], 1.004 (95% confidence interval [CI], 1.001–1.006) per 1cm3 increase; p = 0.005), higher E/E’ ratio (HR, 1.059, 95% CI, 1.015–1.105, p = 0.008), and lower albumin level (HR, 0.476, 95% CI, 0.229–0.986, p = 0.046) were significant factors associated with the adverse clinical events after pericardiectomy. The amount of pericardial calcification could be associated with the efficacy of pericardiectomy and potentially have implications for postoperative outcomes. Additionally, a high E/E ratio on echocardiography is indicative of unfavorable postoperative prognosis.

Development and Evaluation of Automated Artificial Intelligence-Based Brain Tumor Response Assessment in Patients with Glioblastoma.

To develop and evaluate an automated, AI-based, volumetric brain tumor MRI response assessment algorithm on a large cohort of patients treated at a high-volume brain tumor center. We retrospectively analyzed data from 634 patients treated for glioblastoma at a single brain tumor center over a 5-year period (2017-2021). The mean age was 56 +/-13 years. 372/634 (59%) patients were male, and 262/634 (41%) patients were female. Study data consisted of 3,403 brain MRI exams and corresponding standardized, radiologist-based brain tumor response assessments (BT-RADS). An artificial intelligence (AI)-based brain tumor response assessment algorithm was developed using automated, volumetric tumor segmentation. AI-based response assessments were evaluated for agreement with radiologist-based response assessments and ability to stratify patients by overall survival. Metrics were computed to assess the agreement using BTRADS as the ground-truth, fixed-time point survival analysis was conducted to evaluate the survival stratification, and associated P-values were calculated. For all BT-RADS categories, AI-based response assessments showed moderate agreement with radiologists' response assessments (F1 = 0.587-0.755). Kaplan-Meier survival analysis revealed statistically worse overall fixed time point survival for patients assessed as image worsening equivalent to RANO progression by human alone compared to by AI alone (log-rank P=0.007). Cox proportional hazard model analysis showed a disadvantage to AI-based assessments for overall survival prediction (P=0.012). AI-based volumetric glioblastoma MRI response assessment following BT-RADS criteria yielded moderate agreement for replicating human response assessments and slightly worse stratification by overall survival. GBM＝ Glioblastoma; RANO＝ Response Assessment in Neuro-Oncology; BTRADS＝ Brain Tumor Reporting and Data System; NLP = Natural Language Processing.

MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study

BackgroundMesenchymal epithelial transition factor (MET) variant is an independent prognostic factor for worse prognosis in patients with lung cancer or gastroesophageal adenocarcinoma. MET gene variants can be regarded as a subtype of melanoma but there is a lack of studies regarding the frequency of MET genetic alterations and the efficacy of immunotherapy in melanoma patients. The purpose of this study is to explore potential therapeutic strategies for melanoma subtypes with MET alterations.MethodsA total of 1751 malignant melanomas were analyzed to illustrate the landscape of MET mutations. We collected 55 melanoma cases from multicenter for a retrospective cohort from 2010 to 2023. We analyzed the impact of MET amplification on the efficacy of immunotherapy in the retrospective cohort after propensity score matching (PSM) and a pancancer cohort. CIBERSORT was used to evaluate the immune infiltration.ResultsThere were no instances of MET 14 exon skipping, and only instances of MET amplification were found in the 1751 melanomas and our retrospective cohort. Cox proportional hazards model analysis showed that MET amplification (P = 0.006) was significantly associated with poorer overall survival (OS) in patients who received immunotherapy as the first-line treatment. Compared with patients with MET amplification, patients in the negative control (NC) group had a significantly better OS (P = 0.022) after PSM. Analysis of 1661 pancancer cases with the MSK-IMPACT assay showed that patients receiving immunotherapy in the MET amplification group had a trend toward worse OS than those without MET amplification (P = 0.025).ConclusionsThis database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

Clinical characteristics and prognostic factors of epidermal growth factor receptor-mutated non-small cell lung cancer transformed into small-cell lung cancer after treatment

Objective: To analyze the clinical characteristics and prognostic factors of non-small cell lung cancer (NSCLC) patients with sensitive epidermal growth factor receptor (EGFR) mutations who developed small cell lung cancer (SCLC) transformation after treatment with EGFR tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective collection of clinical data for 21 patients with advanced EGFR mutant NSCLC who developed SCLC transformation after EGFR-TKI treatment at Beijing Chest Hospital, Capital Medical University from January 2015 to December 2021. The clinical characteristics were summarized and the prognosis analysis was conducted. Patients were followed up until February 2024. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in survival time (OS) between limited stage and extensive stage in transformed SCLC patients. Cox proportional hazards model was used to analyze the influencing factors of survival after SCLC transformation. Results: Among the 21 patients, there were 5 males and 16 females, with an age range of 33-74 years old [(58.9±2.6) years old]. All 21 patients were adenocarcinoma with sensitive EGFR mutations. There were 18 cases (85.7%) with EGFR gene 19del mutation, including 1 case of 19del+anaplastic lymphoma kinase (ALK) mutation, and 3 cases of L858R mutation. Among the transformed SCLC, there were 11 cases of pure SCLC and 10 cases of mixed SCLC (coexisting of adenocarcinoma and small cell carcinoma components). The median time from diagnosis of NSCLC to SCLC transformation was 12.0 months (95%CI: 7.6-16.3 months). Among the 21 cases of SCLC transformation, there were 13 cases with the extensive stage and 8 cases with the limited stage. Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS. Five cases had partial remission, 5 cases were stable, 3 cases had disease progression, and 3 cases cloud not be evaluated. The median progression free survival time (PFS) was 4.8 months (95%CI: 2.8-6.8 months). The median survival time (OS) after SCLC transformation in 21 patients was 10.6 months (95%CI: 7.0-14.2 months), with a median OS of 8.8 months (95%CI: 6.3-11.4 months) for patients with the extensive stage and 27.5 months (95%CI: 9.6-34.4 months) for patients with the limited stage, with statistically significant differences (P=0.002). Cox proportional hazards model analysis showed that the limited stage after SCLC transformation was a protective factor for OS (HR=0.32, 95%CI: 0.12-0.73, P=0.010). The median OS of 21 patients from the diagnosis of lung cancer was 24.9 months (95%CI: 13.0-36.7 months). Conclusions: NSCLC patients with SCLC transformation are all adenocarcinomas, and the proportion of EGFR19del mutations is relatively high. After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

Reverse remodelling and clinical outcomes in patients with chagas cardiomyopathy with reduced ejection fraction

Abstract Introduction Chagas disease affects around 8 million individuals globally and about 30% develop cardiac manifestations and, in time, heart failure with reduced ejection fraction (HFrEF). Chagas cardiomyopathy (CC) patients often have a poorer prognosis compared to other causes of HFrEF, owing to a higher rate of ventricular arrhythmias and thromboembolic conditions. Reverse remodelling (RR) has been linked to enhanced mortality and morbidity outcomes in HFrEF due to non-Chagas causes, but the effect of RR on CC prognosis is still unclear. Methods This retrospective study assessed 1043 patients diagnosed with CC via positive serology for Trypanosoma cruzi infection coupled with cardiopathy and ventricular dysfunction [left ventricular ejection fraction (LVEF) &amp;lt; 40%] during the follow-up period from January 2006 to September 2021. The primary outcome measured included overall mortality and heart transplantation in relation to RR status. Propensity score matching was utilised to adjust for confounding factors. Positive reverse remodelling (PRR) was characterised as patients displaying improved LVEF, and negative reverse remodelling (NRR) as those with persistent ventricular dysfunction during follow-up. Results Initially, 221 (21.2%) were categorised as PRR and 822 (78.8%) as NRR. Participants in the PRR group were predominantly female (51.6% versus 41.4%; p &amp;lt; 0.001), older [59 years (53 – 66) versus 56 years (47 – 64); p = 0.007], more prone to hypertension (43.4% versus 35.8%; p = 0.036), and presented with higher initial heart rates [70 bpm (60 – 80) versus 65 bpm (60 – 75); p = 0.002], systolic blood pressure [120 mmHg (110 – 130) versus 110 mmHg (100 – 120); p &amp;lt; 0.001], diastolic blood pressure [80 mmHg (69 – 82) versus 70 mmHg (60 – 80); p &amp;lt; 0.001], and LVEF [30.0% (26.0 – 35.0) versus 29% (25.0 – 34.0); p &amp;lt; 0.001] compared to the NRR group. Moreover, the PRR group had a lower intake of beta-blockers (BB) (76.6% versus 87.0%; p = 0.004), spironolactone (38.5% versus 59.5%; p &amp;lt; 0.001), and triple therapy (30.9% versus 50.4%; p &amp;lt; 0.001). Following propensity score matching, 200 patients remained for the final analysis, with 100 in each group. Cox proportional hazards model analysis revealed PRR as an independent predictor [hazard ratio (HR): 0.367; 95% confidence interval (CI) 0.218 – 0.616; p &amp;lt; 0.001] of mortality from all causes or heart transplantation. The PRR group exhibited a longer event-free survival duration than the NRR group (10.332 years; 95% CI 9.557 – 11.107 versus 7.348 years; 95% CI 6.606 – 8.089; p &amp;lt; 0.001). Discussion This study suggests a positive association between the PRR and increased survival in patients with CHD and HFrEF. Previously published studies didn’t demonstrate this association, possibly due to the small number of patients included. Conclusion PRR predicts a better long-term survival free from all-cause mortality and cardiac transplantation in Chagas cardiomyopathy with LVEF &amp;lt; 40%.Kaplan-Meier event-free survival curve

AI-based cluster analysis enables outcomes prediction among patients with increased LVM

Abstract Background The traditional classification of left ventricular hypertrophy (LVH) solely based on left ventricular geometry disregards associated comorbidities and clinical characteristics. We aimed to identify unique clinical phenotypes of LVH using unsupervised cluster analysis and explore their association with clinical outcomes. Methods From UK Biobank (UKBB) participants with available left ventricular mass (LVM) estimations, we identified those meeting CMR-based criteria for increased LVM: LVM index ≥ 72 g/m2 for males and LVM index ≥ 55 g/m2 for females. Baseline demographic, clinical, and laboratory data were collected. Using Ward's method, patients were clustered based on 27 variables. The primary outcome was a composite of all-cause mortality with heart failure (HF) admissions, ventricular arrhythmia, and atrial fibrillation (AF). Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results Among CMR-assessed UKBB participants, 4,255 individuals exhibited increased LVM, with an average age of 64 ± 7 years; 2,447 (58%) were females. Cluster analysis identified four distinct subgroups. Over a median 5-year follow-up (IQR: 4-6), 100 patients (2%) died, 118 (2.8%) were hospitalized due to HF, 29 (0.7%) were hospitalized due to VA, and 208 (5%) were hospitalized due to AF. Univariate Cox analysis revealed that compared to the 1st cluster (n=1,578), patients in the 2nd (n=1,296), 3rd (n=824) and 4th (n=557) clusters had 60%, 104%, and 164% increased risk of a major event, respectively (95% CI 1.2-2.16, p&amp;lt;.001 for cluster 2; 95% CI 1.49-2.78, p&amp;lt;.001 for cluster 3; 95% CI 1.92-3.62, p&amp;lt;.001 for cluster 4). Each cluster manifested different phenotypes: cluster 2 comprised mainly overweight females, with the highest prevalence of chronic lung disease; cluster 3, predominantly composed of males, had the highest burden of comorbidities and cardiovascular risk factors; and cluster 4, mostly males, presented with the most abnormal cardiac measures, including left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF). Conclusions Unsupervised cluster analysis identified four subgroups among patients with increased LVM. These subgroups bear notable relevance to overall mortality risk and clinical outcomes. This phenotypic classification holds promise in offering valuable insights regarding clinical course and outcomes in LVH patients.

Effect of physical activity level on the association of LBBB, heart failure, and mortality

Abstract Background The beneficial effect of physical activity (PA) on adverse cardiovascular outcomes in patients with heart failure (HF) and left bundle branch block (LBBB) is well established. Yet, the impact of PA on individuals with LBBB without evident HF remains unexplored. Our objective is to investigate how PA modifies the outcomes of new-onset LBBB patients concerning HF-related hospitalizations and mortality. Methods Among the UK Biobank participants without a diagnosis of HF, we identified individuals with new-onset LBBB and available PA quantification. Patients were dichotomized into normal QRS and LBBB groups, following by stratification according to summed minutes of PA per week. The primary outcome was all-cause mortality, and HF-related hospitalizations. Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results The final cohort comprised 367,934 individuals, with a mean age of 56.6±8.2 years and 47% male. Among them, 3,427 (0.9%) developed new-onset LBBB, characterized by advanced age, male predominance, and higher rates of comorbidities. Median summed PA minutes per week were 100 (IQR: 125-180), with no significant difference between normal QRS and LBBB patients. Over a median follow-up of 13.8 years (IQR: 13-14.5), 26,304 patients (7.15%) died. Kaplan-Meier analysis revealed higher mortality risk with reduced PA level and/or LBBB (log-rank p&amp;lt;0.001 for both). Multivariate Cox analysis adjusted for age, sex, and comorbidities showed LBBB patients had over 3.5-fold increased risk of death (HR 3.67, 95% CI 3.39-3.97, p&amp;lt;0.001) compared to normal QRS. The association of LBBB with mortality was modified by weekly PA minutes; those with &amp;lt;150 minutes had nearly 40% higher risk compared to those with ≥150 minutes (HR 3.78, 95% CI 3.43–4.15, p&amp;lt;0.001; HR 3.4, 95% CI 2.93–3.95, p&amp;lt;0.001; p for interaction=0.035). The protective effect of PA was 6% among normal QRS patients, compared to 22% among individuals with LBBB (HR 0.94, 95% CI 0.91 – 0.96, p&amp;lt;0.001 vs. HR 0.78, 95% CI 0.66 – 0.93, p=0.004). Similar findings were observed for HF hospitalizations. Conclusions Although the correlation between LBBB and adverse cardiovascular outcomes remained consistent across both levels of physical activity (PA), it was more pronounced among patients with low PA levels. When assessing the risk in patients with newly diagnosed LBBB, particular attention should be directed towards their PA status.