Survival Curves Research Articles

Lower rate of ischemic events with PCSK9 inhibition in patients with atherosclerotic cardiovascular disease but without prior ischemic events

Abstract Background Individuals with atherosclerotic cardiovascular disease (ASCVD) without prior ischemic events, such as myocardial infarction (MI), ischemic stroke (IS), or unstable angina (UA) hospitalization, are at very high risk for having an event. Purpose To estimate the impact of PCSK9 inhibitor (PCSK9i) therapy on ischemic events in this population. Methods Patients with ASCVD were initially selected from the Optum Research Database during Jan 2016 to Dec 2022. For selected patients the index (time zero for follow-up) was required to be in a period of ASCVD without prior ischemic events, however patients may have ischemic events after index. Determination of ASCVD and ischemic events was based on diagnosis and procedure codes. For the PCSK9i group, index was initiation of PCSK9i and information before index was examined to ascertain ASCVD and rule out prior ischemic events. For each patient in the PCSK9i group, up to 5 matching patients in the no-PCSK9i group were chosen based on propensity score (PS) distance, with maximum allowable PS distance of 0.1. Among all possible choices for index for the no-PCSK9i patient, the selected one minimized the PS-distance. The primary endpoint was defined as the composite of nonfatal MI, nonfatal IS, and all-cause death. In order to further reduce bias and ensure causally interpretable estimation, the G-computation methodology was employed by marginalizing the conditional treatment effect (as estimated by a Cox model) over the baseline characteristics. Two effects were estimated: intention-to-treat (ITT) where only the treatment assignment at index was considered as the intervention, and per-protocol (PP) where the effect of sustained treatment with PCSK9i over time was estimated. Results A total of 15,067 and 66,470 patients met the selection criteria for the PCSK9i and no-PCSK9i groups, respectively. Baseline characteristics were well-balanced at index. G-computation analysis resulted in estimated survival curves over time in the two groups for the ITT and PP scenarios (Figures 1 and 2). For the ITT scenario, the estimated 5-year event rate was 18.7% (95% confidence interval [CI]: 17.1%–20.1%) in the PCSK9i group and 28.4% (95% CI: 27.7%–29.1%) in the no-PCSK9i group. The implied relative risk reduction (RRR) and absolute risk reduction (ARR) were 34.3% (p<0.001) and 9.7% (p<0.001), respectively, in favor of the PCSK9i group. For the PP scenario, the estimated 5-year event rate was 10.7% (95% CI: 9.7%–11.7%) in the PCSK9i group and 28.8% (95% CI: 28.3%–29.5%) in the no-PCSK9i group. The implied RRR and ARR were 62.7% (p<0.001) and 18.1% (p<0.001), respectively, in favor of the PCSK9i group. Conclusions Initiation of PCSK9i in patients with ASCVD but without prior ischemic events is associated with significantly and substantially lower risk for ischemic events.Event Rates Intention-to-Treat ScenarioEvent Rates Per-Protocol Scenario

How much does elective cardioversion increase the risk of ischaemic stroke compared to the baseline risk in atrial fibrillation? A nationwide study

Abstract Background Patients with atrial fibrillation (AF) undergoing cardioversion (CV) are exposed to an increased risk for stroke during the post-cardioversion period, but the exact magnitude of this risk after elective CV with preceding appropriate oral anticoagulant (OAC) therapy is unknown. Purpose We explored the rate of ischaemic stroke (IS) after elective CV and compared the IS rate during the post-cardioversion period with the long-term stroke rate in patients with AF using guideline-recommended OAC therapy. Methods This is a nationwide register-based study, including all AF patients undergoing their first-ever elective CV between 2012-18 in Finland. Data were collected from the Finnish health care registers covering uniquely all levels of care. Visual assessment of the survival curve identified a cut-off point in IS rate at 1 week after CV. Therefore, the follow-up time was split into two intervals, the 1-week post-cardioversion period and the subsequent period up to 360 days. Stroke rates were calculated separately for these periods. Unadjusted and adjusted incidence rate ratios were estimated with Poisson regression. Moreover, interaction between the two follow-up periods and conventional IS risk factors as well as OAC treatment was assessed. Results A total of 9625 AF patients undergoing their first elective CV were identified (mean age 67.7±9.9 years, 61.2% men, mean CHA2DS2-VASc score 2.6±1.6). Warfarin was used in 6 245 (64.9%) and non-vitamin K oral anticoagulants in 3 380 (35.1%) patients. Overall, 92 (1.0%) patients suffered an IS during the year after CV. The survival plot displayed a higher incidence of IS within the first week after CV, stabilizing thereafter to a consistent level (Figure). In the adjusted regression analyses, IS rate within the first week after elective CV was 13.6-fold (95% confidence interval [CI]: 8.6-21.5) compared the subsequent rate of IS (Table). We observed no significant interaction between any of the conventional IS risk factors or OAC treatment and the two follow-up time periods, indicating that their association with IS rate did not differ during the post-cardioversion period compared to the subsequent time period. Conclusions In this nationwide study, the rate of IS was roughly 14 times higher during the first week after elective CV compared to the subsequent follow-up time.Cumulative risk of IS after elective CVIncidence rates of IS after elective CV

Artificial intelligence-enhanced electrocardiography predicts 10-year risk of atherosclerotic cardiovascular disease

Abstract Background The ACC/AHA pooled cohort equations (PCE) calculates the 10-year primary risk of atherosclerotic cardiovascular disease (ASCVD), an indication to initiate primary prevention statin therapy in international guidelines. The validity of PCE is limited by its overestimation of risk in high-risk cohorts and an ethnic heterogeneity. Electrocardiography (ECG) has not been incorporated in current ASCVD risk estimation tools. Artificial Intelligence (AI)-based models are capable to capture patterns that are informative for cardiovascular prognosis. Purpose We explored the predictive value of a discrete-time survival model in 10-year ASCVD risk in comparison to PCE. Methods We developed an AI-ECG model to predict the 10-year ASCVD risk in an unselected secondary care population from the USA comprised of 1,163,401 ECGs from 189,539 patients. Data was split into training/validation and hold-out test sets by patient ID. Our AI-ECG model uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves, accounting for both time to event and censorship (i.e., loss to follow up). We compared the performance of out AI-ECG model using a subset of outpatient data (n=4590) of the BIDMC dataset to PCE and ASCVD risk factors including systolic blood pressure, total cholesterol, HDL cholesterol, hypertension, smoking history, diabetes mellitus, and ethnicity. Performances were evaluated using cox survival analysis. Our AI-ECG model was externally validated in the UKB Biobank (UKB), where we compared the performance of our AI-ECG model to predictions of existing AI-ECG models such as the Stanford Estimator of Electrocardiogram Risk (SEER) model. Results Our AI-ECG successfully predicted future ASCVD events in individuals (C-index 0.721 (0.719-0.723), 5-year AUC 0.761 (0.758-0.763), and differentiated between high and low risk group with an adjusted HR of 2.33 (2.26-2.41). Upon internal validation our AI-ECG model showed a superior performance (C-index 0.679 (0.651-0.708)) than PCE (0.605 (0.577-0.634)) and all risk factors combined (C index 0.642 (0.613-0.672)). When combining AI-ECG predictions with all risk factors, the model showed additional predictive value (0.686 (0.657-0.715)) (Figure 1). Our AI-ECG model showed modest predictive value within the UKB dataset (C-index 0.655 (0.637-0.673)), but significantly outperformed the SEER model (C-index 0.547 (0.527-0.567), p <0.0001 for comparison with AIRE). Conclusion We have shown the potential of AI-ECG models in predicting future ASCVD risks. AI-ECG models demonstrated accurate discrete time survival prediction and good classification performance superior to that of the SEER model, as well as PCE and ASCVD risk factors. . Accurate risk assessment of ASCVD may help prevent adverse events in high risk subjects and save unnecessary pharmacological interventios in low risk subjects.Figure 1

Prognostic values of lipoprotein(a) levels for secondary prevention of acute coronary syndrome among patients who underwent primary percutaneous coronary intervention

Abstract Background Lipoprotein(a) [Lp(a)] is known to be a residual risk factor for acute coronary syndrome(ACS). However, in the current era where primary percutaneous coronary intervention (PCI) and lipid-lowering therapies have advanced, the role of Lp(a) levels in secondary prevention among ACS patients remains unclear. Purpose The purpose of this study is to determine whether Lp(a) levels play a role in secondary prevention by studying patients with ACS who underwent primary PCI and survived discharge. Methods Consecutive ACS patients who were admitted to our institution between December 2016 and March 2021, requiring primary PCI and were discharged alive were enrolled for the current study (n = 471). Of these patients, those with the following circumstances were excluded: (1) multidisciplinary treatment such as mechanical ventilation management and percutaneous cardiopulmonary support (n = 74), (2) incomplete clinical data (n = 34), (3) ACS classified as other than type 1 in the universal definition (n = 6), and (4) unknown prognosis at 6 months after discharge (n = 8). A total of 349 consecutive patients were included in the current study. They were divided into two groups according to Lp(a) levels: Lower Lp(a) group (Lp(a) < 30 mg/dL, n = 277) and Higher Lp(a) group (Lp(a) ≥ 30 mg/dL, n = 72). The primary endpoints were major adverse cardiac events (MACEs), composite of all cause death, nonfatal myocardial infarction, nonfatal stroke and congestive heart failure requiring admission. Event-free survival curves were estimated using Kaplan-Meier method and log-rank test was used to detect statistically significant differences. In addition, influence of Lp(a) levels on MACE was examined using three cox regression analyses. Model 1 was adjusted for age, gender and body mass index, model 2 was adjusted for hypertension, diabetes and chronic kidney disease (CKD), model 3 was adjusted for old myocardial infarction (OMI), smoking and multivessel disease, respectively. Results The mean age was 67.0 ± 12.8 years, and 70.5% were male. The median serum Lp(a) levels of the entire population was 14 mg/dL (interquartile range, 7 to 26). There were no significant differences about baseline patient’s characteristics, laboratory findings, and medications at discharge including statin treatment. The MACE was observed in 15.5% of the Lower Lp(a) group and 20.8% of the Higher Lp(a) group (p=0.29). No difference was observed about MACE between the two groups (log-rank p=0.45). After adjusting for cardiovascular risk factors, Lp(a) levels were not associated with MACEs in all three models. However, in model 2 and model 3, CKD and OMI were associated with MACEs (hazard ratio 4.29, 95% confidence interval 2.17 to 8.46, p < 0.001, hazard ratio 3.02, 95% confidence interval 1.39 to 6.51, p = 0.005, respectively). Conclusions In the current era, Lp(a) levels are not associated with secondary prevention among ACS patients who underwent primary PCI.

Transcatheter versus surgical aortic valve replacement in lower-risk patients: an updated meta-analysis of randomised controlled trials

Abstract Background Long-term clinical outcomes after transcatheter [TAVI] and surgical [SAVR] aortic valve replacement are of utmost importance in lower-risk patients. Event rates are diminished in lower-risk patients, therefore individual trials may be separately underpowered to assess low-frequency outcomes. New randomised data has emerged, including 4, 5 and 10-year follow-up from the Evolut Low Risk, PARTNER-3 and NOTION trials, respectively. Purpose To perform a systematic review and meta-analysis of randomised trials studying long-term outcomes in patients with severe aortic stenosis at low-surgical risk undergoing TAVI versus SAVR. Methods Trials randomising patients at lower surgical risk in trials comparing TAVI with SAVR were systematically identified. The prespecified primary endpoint was all-cause death. Key secondary endpoints included stroke, death or disabling stroke, cardiac death, new permanent pacemaker, aortic valve reintervention, and new-onset atrial fibrillation. Reconstructed individual patient data [IPD] was obtained via digitisation of Kaplan-Meier survival curves. Using these data, Cox proportional hazards regression was performed using frailty models on the primary outcome of all-cause death. To assess total lifetime lost, the restricted mean survival time [RMST] was calculated. Conventional pairwise random effects meta-analyses were also performed. This analysis was prospectively registered [CRD42023484976]. Results 4 eligible trials contributed data from 3557 patients with a weighted mean follow-up duration of approximately 4 years (47.6 months). In the reconstructed IPD pooled analyses, there was no significant difference in the hazard of death [hazard ratio 1.15, 95% CI 0.93 to 1.41, p=0.20] or RMST [Δ-0.8 months, p=0.09] (Figure 1). In pairwise meta-analyses, there was no difference between TAVI and SAVR in all-cause death [relative risk (RR) 0.94, 95% confidence interval (CI) 0.78 to 1.13, p=0.51] (Figure 2). There was also no significant difference for stroke [RR 0.94, 95% CI 0.59 to 1.50, p=0.80], or a composite of death or disabling stroke [RR 0.92, 95% CI 0.70 to 1.22, p=0.57]. There was an increase in new pacemaker implantation with TAVI [RR 2.15, 95% CI 1.50 to 3.07, p<0.001], and a reduction in new AF with TAVI [RR 0.43, 95% CI 0.26 to 0.70, p<0.001]; there was no significant difference in any other endpoint (Figure 2). Conclusions The present analysis demonstrates no difference in major clinical outcomes with TAVI or SAVR in lower-risk patients at 4-years follow-up. These results were consistent when analysed using pooled reconstructed IPD or conventional meta-analyses and there were no differences in RMST. These data are informative for lower-risk patients and clinicians, but longer-term follow-up is required to confirm whether equivalence is maintained.Kaplan-Meier plot comparing TAVI vs SAVRForest plot for key clinical endpoints

Ischemic and bleeding risk after ST-segment elevated myocardial infarction in patients with active cancer

Abstract Background Treatment of patients with cancer presenting with ST-elevation myocardial infarction (STEMI) is complex given the increased risk of both thrombotic and major bleeding complications. We evaluated the risk of major bleeding and re-infarction in patients with or without cancer following admission with STEMI Methods A nationally-linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project (MINAP) registry and the UK national Hospital Episode Statistics Admitted Patient Care (HES APC) registry. Cox proportional hazard models were used, and Kaplan-Meier survival and cumulative survival curves were constructed. Results A total of 322,776 STEMI indexed admissions were identified between Jan 2005 and March 2019. Of those, 7050 (2.2%) patients were diagnosed with active cancer. Cancer patients were older with more cardiovascular comorbidities. Cancer patients received invasive coronary angiography (62.2% vs 72.7%, p<0.001) and PCI (58.4% vs 69.5%) less often compared to patients without cancer and were less likely to be prescribed DAPT (85% vs 95.4%). Major bleeding rate at one year was higher in cancer patients (6.5% vs 3.5%) while re-infarction rates were similar (cancer 5.7%, no cancer 5.1%). Adjustment for differences in baseline covariates, a similar risk of re-infarction (SHR 1.10, 95% CI 0.94-1.27) and a 50% increased risk of major bleeding (SHR 1.49, 95% CI 1.30-1.71) was observed in cancer patients. Conclusion Compared to non-cancer patients, cancer patients have a higher risk of major bleeding but not of re-infarction. Mitigating bleeding risk in STEMI patients with cancer is of paramount importance to improve outcomes.bleeding risk at 1 yearRe-infarction risk at 1 year

The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center

BackgroundRecurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies.Methods40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method.ResultsThe mean IORT dose was 13.8 Gy (range 10–18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95–14.881, p = 0.059 and HR 2.165 CI 95%: 0.916–5.114, p = 0.078ConclusionsThe survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.

Recovery rate and predictors among children aged 6–59 months with severe acute malnutrition in Addis Ababa, Ethiopia: a retrospective follow-up study

IntroductionSevere acute malnutrition (SAM) is a critical public health concern in Ethiopia, contributing to high morbidity and mortality rates among children. Despite the improvement in hospital coverage and the development of standardized WHO treatment guidelines, recent reviews indicated a wide range in recovery rates (34%–88%) due to several context-specific factors. Understanding the factors influencing the recovery time can help inform targeted interventions and improve the overall management of SAM cases. Therefore, this study aimed to assess the time to recovery and predictors of children aged 6–59 months with severe acute malnutrition in Addis Ababa, Ethiopia, in 2023.MethodsAn institutional-based retrospective follow-up study was conducted among children aged 6–59 months who were admitted to Tirunesh Beijing Hospital (TBH), Addis Ababa, Ethiopia, from July 2019 to June 2023. The Kaplan–Meir estimate and survival curve were used to compare the time to recovery using a log-rank test among different characteristics. A Cox proportional hazard regression analysis model was used to identify significant predictors of time to recovery. Finally, a p-value of &amp;lt;0.05 was used to declare a significant association.ResultsThe median survival time to recovery was 17 (95% CI: 16.39–17.60) days, and the incidence rate of recovery from SAM was 37.8 per 1,000 child days. Moreover, exclusive breastfeeding [adjusted hazard ratio (aHR): 1.97, 95% CI: 1.45–2.68], amoxicillin provision (aHR = 1.62, 95% CI: 1.11–2.35), and deworming (aHR = 2.14, 95% CI: 1.48–3.09) were protective factors. However, complications at admission (aHR = 0.41, 95% CI: 0.23–0.73) and diarrhea during admission (aHR = 0.64, 95% CI: 0.45–0.91) were identified as risk factors of recovery from SAM.ConclusionThe time to recovery among the current study participants was low compared with the sphere standard. Besides, exclusive breastfeeding, complications at admission, diarrhea, amoxicillin provision, and deworming were independent predictors. Therefore, appropriate provision of routine medication and early management of medical comorbidity as per the national SAM management protocol can reduce the mortality of children with severe acute malnutrition significantly.

Comparative Analysis of Treatment Patterns in DoD Beneficiaries With Malignant Central Nervous System Tumors: A Focus on Care Setting.

Malignant brain and other central nervous system tumors (MBT) are deadly and disproportionately affect younger men and women in the age range of most active-duty service members. Timely and appropriate treatment is important to both survival and quality of life of patients. Information on treatment factors across direct care (DC) and private sector care (PSC) networks may be important for provider training and staffing for the DoD. The aim of this study was to analyze treatment patterns for patients with MBT within the DoD's universal access Military Health System (MHS), comparing DC and PSC networks. The Military Cancer Epidemiology database was used to identify patients 18 years and older who were diagnosed with an MBT between 1999 and 2014 who received primary treatment. Differences in first treatment type and time from diagnosis to initial treatment between DC and PSC were assessed using chi-square and Wilcoxon-Mann-Whitney tests, respectively. Frequency of treatment initiation beyond the 28-day TRICARE Prime access standard for Specialty Care was also compared between care settings using chi-square and Fisher's exact tests. Then logistic regression models generated odds of treatment initiation beyond 28 days and 95% confidence intervals (CIs) associated with care setting. Kaplan-Meier survival curves and log-rank tests compared survival between DC and PSC. The study included 857 patients, with n = 540 treated in DC and n = 317 treated in PSC. The proportion of patients receiving each initial treatment type did not differ by care setting (P = .622). Median time from diagnosis to initial treatment (interquartile range) varied significantly between DC at 6 (0 to 25) days and PSC at 12 (0 to 37) days for all treatment types combined (P < .001). For all years combined, treatment was initiated beyond 28 days for 21% of patients using DC compared to 31% of patients using PSC (P = .001). The odds of treatment initiation beyond 28 days for a patient treated in PSC were 1.61 (95% CI, 1.11 to 2.33, P = .012) compared to patients treated in DC when controlling for demographic, military, tumor, and patient variables. Survival did not differ by care setting (P = 1.000). Based on the available data between 1999 and 2014, care setting was associated with differences in time to initial treatment and odds of treatment initiation beyond 28 days among DoD beneficiaries with MBT receiving care in the MHS. Information on these differences may help inform MHS leadership decisions on the most appropriate location for military provider training and staffing.

Validation and clinical performance of a single test, DNA based endometrial cancer molecular classifier

ObjectivesWe have previously shown that DNA based, single test molecular classification by next generation sequencing (NGS) (Proactive Molecular risk classifier for Endometrial cancer (ProMisE) NGS) is highly concordant with the...

Clinical characteristics and prognostic analysis of adult patients hospitalized with acute myocarditis

Objective: To analyze the clinical characteristics of patients hospitalized with acute myocarditis and explore the relevant factors affecting the prognosis. Methods: This study was a retrospective cohort study. Patients with acute myocarditis hospitalized in the Second Affiliated Hospital of Harbin Medical University from March 2010 to October 2022 were included and divided into severe myocarditis group and non-severe myocarditis group according to clinical diagnosis results, retrospectively. Basic clinical features were collected and followed up in both groups. The primary endpoint was cardiac death and the secondary endpoint was cardiac re-hospitalization. According to the clinical outcome, Kaplan-Meier survival curve was drawn and assessed via log-rank P test. Cox proportional risk model was established to analyze the related factors affecting the prognosis of patients with acute myocarditis. Results: A total of 235 patients with acute myocarditis were included, including 138 males (58.7%), aged (34±16) years, 102 patients (43.4%) in the severe myocarditis group and 133 patients (56.6%) in the non-severe myocarditis group. Compared with the non-severe myocarditis group, the severe myocarditis group was older and had more clinical symptoms of dyspnea, edema, and syncope. At a follow-up of 3.8 (2.8, 4.8) years, cumulative cardiac mortality and cardiac readmissions in patients with acute myocarditis were 4.2% and 9.6%, respectively. Among them, patients with severe myocarditis had a higher risk of cardiac death and cardiac readmission than those without severe myocarditis (9.3% vs. 1.0%, log-rank P=0.004; 13.4% vs. 4.2%, log-rank P=0.021). Multivariate Cox analysis showed that the independent risk factor for cardiac death in patients with acute myocarditis was elevated serum creatinine level at baseline (HR=1.016, 95%CI: 1.003-1.028, P=0.013). Independent risk factors for cardiogenic readmission were increased left ventricular end-diastolic diameter on admission (HR=1.108, 95%CI: 1.035-1.187, P=0.003) and ventricular tachycardia or fibrillation during hospitalization (HR=6.563, 95%CI: 2.138-20.142, P=0.001). Conclusions: The patients with acute myocarditis had more clinical symptoms of dyspnea, edema, and syncope. Elevated serum creatinine level on admission was an independent risk factor for cardiac death in patients with acute myocarditis; increased end-left ventricular diameter on admission and ventricular tachycardia or fibrillation during hospitalization were independently associated with cardiac rehospitalization.

Predictive value of myocardial contrast echocardiography in evaluating myocardial perfusion and prognosis after percutaneous coronary intervention in patients with acute myocardial infarction

Objective: To evaluate myocardial microcirculation perfusion with myocardial contrast echocardiography (MCE) in patients with acute myocardial infarction after percutaneous coronary intervention (PCI), and to explore the prognostic value of different types of myocardial microcirculation perfusion. Methods: This is a prospective cohort study. Patients with acute myocardial infarction who underwent successful PCI in Nanfang Hospital of Southern Medical University and Kanghua Hospital of Dongguan City from October 2019 to June 2021 were selected. All the enrolled patients completed MCE examination within 72 hours after PCI. According to the examination results, the patients were divided into normal microcirculation perfusion group, delayed microcirculation perfusion group, and blocked microcirculation perfusion group. Adverse cardiovascular events including all-cause death, cardiovascular death, and angina re-hospitalization were followed up, and left ventricular ejection fraction (LVEF) review results were collected at six months to one year after surgery. Kaplan-Meier survival curve was used to investigate the difference in the incidence of adverse cardiovascular events in different myocardial perfusion groups, and Cox regression analysis was used to evaluate the effect of myocardial perfusion on adverse cardiovascular events. Results: A total of 113 patients with acute myocardial infarction were included, aged (56.3±11.5) years, with 88(78%) males. There were 31 cases in the normal microcirculation perfusion group, 43 cases in the delayed microcirculation perfusion group and 39 cases in the blocked microcirculation perfusion group. LVEF was reviewed in 49 patients, and LVEF in the delayed microcirculation perfusion group was significantly improved compared with baseline at follow-up ((63.3±1.2) % vs. (58.6±1.8) %, P=0.043), and there was no statistically significant difference between the other two groups (all P>0.05). The median follow-up time was 473 days, during follow-up period 30 adverse cardiovascular events occurred. Kaplan-Meier survival curve analysis showed that there was a statistically significant difference in the incidence of adverse cardiovascular events among the three groups (Plog-rank=0.029). Cox regression analysis showed that abnormal microcirculation perfusion (defined as delayed and blocked microcirculation perfusion) was an independent predictor of adverse cardiovascular events in patients with acute myocardial infarction after PCI (HR=1.90, 95%CI1.16-3.12, P=0.011). Conclusions: Microcirculatory perfusion decrease or lost is common in patients with acute myocardial infarction after PCI. Timely restoration of blood flow reconstruction can save heart function when microcirculatory perfusion decreases. Microcirculatory perfusion is a predictor of adverse cardiovascular events in patients with acute myocardial infarction, and patients with poor myocardial perfusion are more likely to experience adverse cardiovascular events.

Impact of atrial high-rate episodes on new onset of atrial fibrillation and all-cause mortality in elderly patients over 90 years old with dual-chamber pacemaker implantation

Objective: To investigate the impacts of atrial high-rate episodes (AHRE) on the risks of new onset of atrial fibrillation and all-cause mortality in elderly patients over 90 years old after cardiac dual-chamber pacemaker implantation. Methods: This study was a retrospective study. Patients aged 90 years and above who were implanted with cardiac dual-chamber pacemakers and followed up in the People's Liberation Army General Hospital from January 2017 to June 2022 were enrolled and divided into AHRE≥6 h group and AHRE<6 h group according to the onset time of AHRE. The primary endpoint was new onset of atrial fibrillation, and the secondary endpoints were all-cause mortality and cardiovascular mortality. Kaplan-Meier survival curve was poltted, and log-rank test was used to compare the differences in the incidence of new onset of atrial fibrillation, all-cause death and cardiovascular death between AHRE≥6 h and AHRE<6 h groups. Multivariate Cox survival analysis was used to investigate the factors affecting new onset of atrial fibrillation, all-cause death and cardiovascular death in elderly patients aged 90 years and above with dual-chamber pacemaker implantation. Results: A total of 169 patients were enrolled, aged (93.95±3.28) years, including 18 females (11%). The median follow-up time was 28.9 months. There were 87 and 82 patients in AHRE≥6 h group and AHRE<6 h group, respectively. Kaplan-Meier survival curve analysis showed that the incidence of new onset of atrial fibrillation (log-rank P<0.001), all-cause death (log-rank P=0.004) and cardiovascular death (log-rank P=0.026) in AHRE≥6 h group was significantly higher than that in AHRE<6 h group.After adjusting for traditional risk factors, multivariate Cox survival analysis showed that AHRE≥6 h was an independent risk factor for new onset of atrial fibrillation (HR=4.046, 95%CI 2.402-6.814, P<0.001) and all-cause mortality (HR=1.668, 95%CI 1.119-2.487, P=0.012) in elderly patients over 90 years old with cardiac dual-chamber pacemaker implantation. However, AHRE≥6 h had no effect on cardiovascular mortality (P>0.05). Anemia (HR=3.098, 95%CI 1.342-7.153, P=0.008) and heart failure with reduced ejection fraction (HR=3.028, 95%CI 1.181-7.763, P=0.021) were both independently associated with cardiovascular mortality. Conclusions: AHRE is common in cardiac dual-chamber pacemakers recipients aged 90 years and above, and AHRE≥6 h can be used as a predictor of new onset of atrial fibrillation or all-cause mortality in these patients.

Comparison of survival outcomes and safety between early and late initiation of niraparib maintenance in newly diagnosed advanced epithelial ovarian cancer

ObjectiveThis multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between early and late initiation of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer.MethodsWe...

Unsupervised Clustering of Adult Spinal Deformity Patterns Predicts Surgical and Patient-Reported Outcomes.

Retrospective cohort study. To evaluate whether different radiographic clusters of adult spinal deformity identified using artificial intelligence-based clustering are associated with distinct surgical outcomes. Patients were classified based on the results of a previously conducted analysis that examined clusters of deformity, including Moderate Sagittal (Mod Sag), Severe Sagittal (Sev Sag), Coronal, and Hyper-Thoracic Kyphosis (Hyper-TK). The surgical data, HRQOL, and complication outcomes of these clusters were then compared. The final analysis included 1062 patients. Similar to published results on a different patient sample, Mod Sag and Sev Sag patients were older, more likely to have a history of previous spine surgery, and more disabled. By 2-year, all clusters improved in HRQOL and reached a similar rate of minimal clinically important difference (MCID).The Sev Sag cluster had the highest rate major complications (53% vs 34-40%), and complications leading to reoperation (29% vs 17-23%), implant failures (20% vs 8-11%), and operative complications (27% vs 10-17%). Coronal patients had the highest rate of pulmonary complications (9% vs 3-6%) but the lowest rate of X-ray imbalance (10% vs 19-21%). No significant differences were found in neurological complications, infection rate, gastrointestinal, or cardiac events (all P > .1). Kaplan-Meier survival curves demonstrated a lower time to first complications for the Sev Sag cluster. All clusters of adult spinal deformity benefit similarly from surgery as they all achieved similar rates of MCID. Although the rates of complications varied among the clusters, the types of complications were not significantly different.

Population structure and dynamic characteristics of Taxus cuspidata in Baishilazi National Nature Reserve, China

Taxus cuspidata is listed as a first-class national key protected plant in the northeast region, with scarce individuals in the wild and significant conservation value. We conducted a systematic field survey to explore the population structure and dynamic characteristics of T. cuspidata in the Baishilazi National Nature Reserve. A total of 313 T. cuspidata were recorded, displaying a spatially clustered distribution. Young individuals made up 33 % of the population, and the population's diameter class structure indicated a decreasing trend in population size. The population's survival curve closely resembled the Deevey-II type. These results suggest that the proportion of young individuals and strong potential for self-renewal. Geographic analysis revealed that north-facing slopes with moderate gradients were the primary habitat for T. cuspidata in the reserve. Interspecific analysis identified Acer ukurunduense and A. komarovii as the species with the highest interspecific associations with T. cuspidata. The population is projected to continue growing. The nature reserve is effectively fostering the natural renewal and recovery of T. cuspidata populations. These findings offer valuable insights for the conservation management of T. cuspidata in Baishilazi National Nature Reserve, supporting the sustainable development of endangered species populations.

Predicting the prognosis of patients with renal cell carcinoma based on the systemic immune inflammation index and prognostic nutritional index

The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P < 0.05), and low PNI group was significantly lower than those in high PNI group (43.4% vs. 87.9%; p < 0.05). There were significant differences between preoperative SII and CRP, NLR, PLR, LMR, postoperative recurrence, pathological type and AJCC stage (P < 0.05). There were significant differences between preoperative PNI and BMI, platelet, NLR, PLR, LMR, postoperative recurrence, surgical mode and Fuhrman grade (P < 0.05). The ROC curve analysis showed that the AUC of PNI (AUC = 0.736) was higher than that of other inflammatory indicators, followed by the AUC of SII (0.718), and the difference in AUC area between groups was statistically significant (P < 0.05). The results from multivariate Cox regression analysis showed that SII, PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade were independent risk factors for postoperative death of patients with RCC. According to the results of Cox regression analysis, a prediction model for the prognosis of RCC patients was established, and the C-index (0.918) showed that the model had good calibration and discrimination. The subject’s operating characteristic curve indicates that the nomogram has good prediction efficiency (the AUC = 0.953). Preoperative SII and PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade are closely related to the postoperative prognosis of patients with renal cell carcinoma. The nomogram model based on SII, PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade has good accuracy, discrimination and clinical prediction efficiency.

Identification of Biomarkers and Molecular Pathways Implicated in Smoking and COVID-19 Associated Lung Cancer Using Bioinformatics and Machine Learning Approaches

Lung cancer (LC) is a significant global health issue, with smoking as the most common cause. Recent epidemiological studies have suggested that individuals who smoke are more susceptible to COVID-19. In this study, we aimed to investigate the influence of smoking and COVID-19 on LC using bioinformatics and machine learning approaches. We compared the differentially expressed genes (DEGs) between LC, smoking, and COVID-19 datasets and identified 26 down-regulated and 37 up-regulated genes shared between LC and smoking, and 7 down-regulated and 6 up-regulated genes shared between LC and COVID-19. Integration of these datasets resulted in the identification of ten hub genes (SLC22A18, CHAC1, ROBO4, TEK, NOTCH4, CD24, CD34, SOX2, PITX2, and GMDS) from protein-protein interaction network analysis. The WGCNA R package was used to construct correlation network analyses for these shared genes, aiming to investigate the relationships among them. Furthermore, we also examined the correlation of these genes with patient outcomes through survival curve analyses. The gene ontology and pathway analyses were performed to find out the potential therapeutic targets for LC in smoking and COVID-19 patients. Moreover, machine learning algorithms were applied to the TCGA RNAseq data of LC to assess the performance of these common genes and ten hub genes, demonstrating high performances. The identified hub genes and molecular pathways can be utilized for the development of potential therapeutic targets for smoking and COVID-19-associated LC.

Time to recovery from necrotizing enterocolitis and its predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar, Ethiopia: A retrospective follow up study, 2022.

Necrotizing enterocolitis is one of the most common, life-threatening, gastrointestinal disorders in neonates. The recovery time for neonates with NEC varies depending on disease severity, prompt diagnosis, and effective treatment. Therefore, this study was intended to assess the time to recover from necrotizing enterocolitis and its' predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar City, Ethiopia. An institution-based retrospective follow-up study design was employed. A sample of 361 medical records of neonates with necrotizing enterocolitis was selected using systematic random sampling. Diagnosis of NEC in this study required clinical, laboratory and radiographic findings. The survival function was described using Kaplan Meier survival curve and log-rank test. Bivariate and multivariate Cox-proportional hazard (Cox-PH) regression models were used for analysis. The median recovery time from necrotizing enterocolitis for neonates in the neonatal intensive care unit was 12 days. The multivariable Cox-PH model showed that neonates classified as Stage III NEC (AHR: 0.42, 95% CI = 0.23-0.77) and those exposed to perinatal asphyxia (AHR: 0.51, 95% CI: 0.35-0.74) had a negative impact on NEC recovery time. However, neonates with a birth weight of 1500-2499gm (AHR: 1.65, 95% CI: 1.05-2.58) and a platelet count greater than 150,000 (AHR: 1.75, 95% CI: 1.24-2.48) had a positive effect on NEC recovery time. The recovery time for neonates in the neonatal intensive care unit with necrotizing enterocolitis was longer. Comorbidities and advanced stage of NEC were associated with prolonged recovery time from NEC. However, neonates with better platelet count and birth weight greater than 1500mg had shorter recovery time from NEC.

Matched oligoclonal bands: Diagnostic utility and clinical characteristics.

To describe patient clinical characteristics associated with matched oligoclonal bands (OCB). A retrospective review at the University of Utah examined patients with matched OCB from 2015 to 2020. Clinical data, diagnosis, and outcomes were collected. Patients were classified with either multiple sclerosis (MS), other inflammatory neurologic disorder (other-IND), or noninflammatory neurologic disorder (NIND). Of 539 identified patients, 436 (53.4% female) were matched-only, while 103 (43.7% female) were matched + unique. Patients with matched-only bands were older (57.4 ± 16 vs. 52 ± 14.2, p < 0.001) and more likely to have a history of autoimmune disease (40.1% vs. 28.2%, p = 0.024) and/or cancer (28.7% vs. 16.5%, p = 0.012). Patients with matched + unique bands were more likely to have CSF pleocytosis (52.4% vs. 25.9%, p < 0.001), high IgG index (52.2% vs. 7.6%, p < 0.001), and an abnormal MRI (86.9% vs. 63.1%, p < 0.001). More than two-thirds of matched-only patients had NIND, while 33% and 41.7% of matched + unique patients had MS and other-IND, respectively. Patients exhibiting matched-only bands and a high IgG index demonstrated a significantly higher incidence of other-IND compared to those with matched-only bands and a normal IgG index (55.6% vs. 30.4%, p = 0.013). While Kaplan-Meier survival curves demonstrated higher mortality in the matched-only cohort compared to the matched + unique cohort (p = 0.02), multivariable Cox regression analysis showed this difference was not statistically significant when adjusting for various factors. A history of cancer was the significant predictor of increased mortality risk (Hazard ratio = 3.147, 95% CI [2.196, 4.51]). Patients with matched only versus matched + unique OCB have distinct clinical profiles.