Association of COPD with adverse outcomes in heart failure patients with preserved ejection fraction.

We performed a systematic review and meta-analysis to detect the impact of chronic obstructive pulmonary disease (COPD) on the prognosis of heart failure patients with preserved ejection fraction (HFpEF). We systematically screened eligible literature from three electronic databases, PubMed, EMBASE and Cochrane Library, up to April 2023. Two researchers participated in data collection independently. Risk ratios (RRs) from included studies with 95% confidence intervals (CIs) were pooled in the Review Manager version 5.40 software using a random-effects model for analysis. A total of 11 studies (3 post hoc analyses of RCTs and 8 observational studies) with 18 602 participants were included in this meta-analysis. After pooling all the data from eligible studies, our results indicated that COPD was associated with an increased risk of hospitalization (RR = 1.66, 95% CI, 1.47-1.87, P < 0.00001), mortality (RR = 1.62, 95% CI, 1.34-1.95, P < 0.00001), and the composition of hospitalization or mortality (RR = 1.84, 95% CI, 1.35-2.51, P < 0.001) in patients with HFpEF. In a subgroup analysis, the risks of cardiovascular-related mortality (RR = 1.59, 95% CI, 1.30-1.93, P < 0.00001) and post-discharge mortality risk (RR = 2.57, 1.34-4.93, P < 0.01) were increased in HFpEF patients comorbid with COPD, and these associations were also detected in HF-caused hospitalization (RR = 1.64, 95% CI, 1.44-1.87, P < 0.00001). Evidence from existing studies supported that COPD was an independent prognostic risk factor for patients with HFpEF. Developing rapid clinical diagnostic indicators and early use of novel drugs such as SGLT-2 and ARNI may improve the prognosis of this population, deserving further study.

Real-world evidence of early rhythm control in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The favorable benefits of early rhythm control (ERC) therapy in newly diagnosed patients with atrial fibrillation (AF) have been demonstrated in the EAST-AFNET 4 trial. However, the generalizability and applicability of ERC in real-world clinical settings remain inconclusive. METHODS: We conducted a systematic search of the PubMed and Embase databases to identify observational studies published between January 2020 and February 2024 that focused on real-world evidence pertaining to ERC. The effectiveness and safety outcomes in our study were analogous to those evaluated in the EAST-AFNET 4 trial. RESULTS: A total of 4 observational studies that fulfilled the inclusion criteria of EAST-AFNET 4 were included, involving 130,970 patients with AF, 30.7% of whom received ERC therapy. In our pooled analysis using the fixed-effects model, compared with rate control, ERC significantly decreased the occurrence risk of the primary composite outcome (hazard ratio [HR] 0.86, 95% confidence interval[CI] 0.82-0.91), cardiovascular death (HR 0.87, 95% CI 0.78-0.98), stroke (HR 0.80, 95% CI 0.73-0.87), and hospitalization with worsening heart failure (HR 0.91, 95% CI 0.84-0.99) or acute coronary syndrome (HR 0.72, 95% CI 0.59-0.87). In terms of safety outcomes, there were no differences in the composite safety outcome (HR 1.00, 95% CI 0.95-1.05) and all-cause death (HR 0.93, 95% CI 0.82-1.06) between the two studied groups. CONCLUSIONS: ERC therapy showed favorable effectiveness outcomes compared with rate control, whereas the safety outcomes between the two therapeutic strategies did not differ significantly, supporting the benefits of ERC therapy over rate control in selected real-world patients with AF. REGISTRATION: The study protocol was registered to PROSPERO (CRD42023443569).

Association of hypertension burden with stroke risk in patients with heart failure with preserved ejection fraction.

Introduction: Whether the hypertension burden is associated with stroke incidence is inconclusive. In this study, we aimed to investigate the relationship between hypertension burden and stroke risk in patients with heart failure with preserved ejection fraction (HFpEF). Methods: HFpEF patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were divided into three groups (low, medium, and high risk) according to their hypertension burden values. Higher hypertension burden risk represented the longer duration of hypertension. We evaluated the association of hypertension burden with stroke risk using Fine and Gray's competing risk models. Results: A total of 3431 HFpEF patients (mean age: 68.5 ± 9.58 years, 51.6% females) were enrolled. During a median follow-up of 3.3 years, per 10-point increase in hypertension burden was associated with any stroke (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.21), new-onset stroke (HR 1.14, 95% CI 1.07-1.21), and ischemic stroke (HR 1.10, 95% CI 1.02-1.17). When hypertension burden was analyzed as a categorical variable, any stroke risk was increased in the medium- (HR 1.59, 95% CI 1.01-2.40) and high-risk (HR 3.19, 95% CI 2.05-4.97) groups when compared with the low-risk group. For the outcomes of new-onset (HR 2.92, 95% CI 1.80-4.74) and ischemic stroke (HR 2.46, 95% CI 1.41-4.29), similar results were observed in patients with high-versus low-risk hypertension burden. Conclusions: Increasing hypertension burden was associated with an increased risk of stroke, suggesting that shortening hypertension duration might appropriately minimize the stroke incidence in HFpEF patients.

Bilateral diffuse metastases in advanced lung adenocarcinoma harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKIs.

Bilateral diffuse metastatic lung adenocarcinoma (BLDM-LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co-mutation characteristics of BLDM-LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR-yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non-small-cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM-LUAD. In order to analyze the survival outcomes of BLDM-LUAD patients harboring EGFR mutations who were treated with EGFR-TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR-TKIs treatment were adjusted using propensity score-matching (PSM). The Kaplan-Meier survival curves and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The co-mutation characteristics of BLDM-LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first-line treatment of EGFR-TKIs were successfully matched. BLDM-LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM-LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co-mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia-mutated (ATM) (7.4%) and mesenchymal-epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM-LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR-TKI.

Effect of edoxaban compared with other oral anticoagulants for stroke prevention in patients with atrial fibrillation: A meta-analysis.

Background and aim: Current observational studies have compared the effectiveness and safety of edoxaban with other oral anticoagulants in patients with AF, but the results are still disputed. This meta-analysis was conducted to compare the effect of edoxaban in patients with AF. Methods: We performed systematic research from the PubMed, EMBASE, and Cochrane Library databases until November 2022 to obtain relevant observational studies. Adjusted risk ratios (RRs) and 95 % confidence intervals (CIs) of the outcomes were collected and pooled by a random-effects model. This study was prospectively registered in PROSPERO (CRD42022314222). Results: A total of 17 observational studies were included in this meta-analysis. Compared with vitamin K antagonists, edoxaban was associated with lower risks of stroke or systemic embolism (RR = 0.67, 95 % CI:0.61-0.74), major bleeding (RR = 0.54, 95 % CI:0.44-0.67), and intracranial hemorrhage (RR = 0.51, 95 % CI:0.29-0.90). Compared with dabigatran or rivaroxaban, edoxaban was associated with reduced risks of stroke or systemic embolism (dabigatran [RR = 0.76, 95 % CI:0.66-0.87]; rivaroxaban [RR = 0.81, 95 % CI:0.70-0.94]) and major bleeding (dabigatran [RR = 0.82, 95 % CI:0.69-0.98]; rivaroxaban [RR = 0.81, 95 % CI:0.70-0.94]). Compared with apixaban, edoxaban was associated with a reduced risk of stroke or systemic embolism (RR = 0.87, 95 % CI:0.79-0.97), but had similar risks of bleeding events. Conclusions: Our current evidence suggested that edoxaban might have superior effectiveness and/or safety outcomes than vitamin K antagonists, dabigatran, rivaroxaban, and apixaban for stroke prevention in patients with AF.

A simple ATTR-CM score to identify transthyretin amyloid cardiomyopathy burden in HFpEF patients.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is often found in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence regarding ATTR-CM and prognosis in HFpEF remains scarce. This study sought to determine whether the ATTR-CM burden was associated with clinical outcomes in HFpEF patients. METHODS: We evaluated the associations of baseline ATTR-CM score with adverse outcomes in HFpEF patients from the TOPCAT trial using the Cox proportional hazards model or the competing risk regression model. The discriminatory ability of the ATTR-CM score was assessed using the area under the time-dependent receiver operating characteristic curve (AUC). RESULTS: We included 870 HFpEF patients, 18.9% of which had an ATTR-CM score ≥6. Per 1 increment in the ATTR-CM score was significantly associated with an increased risk of the primary outcome (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.12-1.27) with an AUC of 0.652 (0.594-0.711), whereas patients with ATTR-CM score ≥6 presented higher risks of the primary outcome (adjusted HR 2.20, 95% CI 1.65-2.95). Similar results were observed toward the secondary outcomes. CONCLUSIONS: The simple ATTR-CM score identified an 18.9% ATTR-CM burden in HFpEF patients, and a higher ATTR-CM burden might predict adverse outcomes with moderate discriminatory abilities in HFpEF.

Body mass index and clinical outcomes in patients with heart failure with preserved ejection fraction mediated by diastolic blood pressure status?

Background: The "obesity paradox" has been elucidated in patients with heart failure (HF). Current guidelines introduce a target diastolic blood pressure (DBP) < 80 mmHg but >70 mmHg in HF patients. Due to reduced coronary perfusion, low DBP has a deleterious impact on cardiovascular outcomes. This present study aimed to assess the relationship between BMI and adjudicated clinical outcomes in HFpEF patients according to the status of DBP. Methods: We analyzed the data in 1749 HFpEF patients from the Americas of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) Trial. The population was stratified by DBP (<70 mmHg, and ≥70 mmHg) and BMI strata (normal weight, overweight, and obesity). Cox proportional hazards models and competing-risks regression analysis were performed. Results: At baseline, the median BMI and DBP were 32.9 kg/m2 (interquartile range 28.0-38.5 kg/m2) and 70 mmHg (interquartile range 62-80 mmHg), respectively. In the multivariable analysis, obesity was associated with better survival rates in the total HFpEF population (all-cause death: HR = 0.439, 95% CI 0.256-0.750; and cardiovascular death: HR = 0.378, 95% CI 0.182-0.787). In patients with DBP<70 mmHg, obesity was not significantly associated with reduced risks for all-cause death (HR = 0.531, 95% CI: 0.263-1.704) and cardiovascular death (HR = 0.680, 95% CI: 0.254-1.819). However, multivariate analyses for cardiovascular death (HR = 0.339, 95% CI: 0.117-0.983) and all-cause death (HR = 0.389, 95% CI: 0.156-0.969) were significant in patients with DBP≥70 mmHg. Nevertheless, there were no interactions between DBP and BMI. Conclusions: The obesity paradox was observed in patients with HFpEF, regardless of DBP strata (<70 mmHg, and ≥70 mmHg).

Comparison of induction chemotherapy combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in Lymph-Node-Stage III nasopharyngeal carcinoma based on propensity score-matching.

PURPOSE: To explore the role of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients diagnosed with N3 nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: A total of 787 patients with newly diagnosed N3 NPC treated with IC + CCRT or CCRT alone were included. Progression-free survival (PFS) was the primary endpoint. We balanced variables using propensity score matching (PSM). Kaplan-Meier curves with log-rank tests were applied to evaluate the survival condition of each group. Independent prognostic factors were identified using the Cox regression analysis. RESULTS: PSM assigned 228 patients to IC + CCRT and CCRT alone groups. Survival analysis for the matched data set showed that IC + CCRT achieved better survival outcomes compared with CCRT alone, and significant difference was observed in 5-year PFS [74.8% (95%CI 69.2 âˆ¼ 80.9%) vs 65.4% (95%CI 59.4 âˆ¼ 72.0%), P = 0.008], 5-year OS [(77.4%(95%CI 71.9 âˆ¼ 83.3%) vs66.3%(95%CI 60.3 âˆ¼ 72.9%), P = 0.005)] and 5-year distant metastasis-free survival (DMFS)[(81.8%(95%CI 76.7 âˆ¼ 87.2%) vs72.4%(95%CI 66.7 âˆ¼ 78.7%), P = 0.007)] between the two treatment groups. In multivariate analysis, IC + CCRT remained an independent protective factor for PFS (adjusted HR, 0.603; 95% CI, 0.433-0.841; P = 0.003), OS (adjusted HR, 0.568; 95% CI, 0.406-0.793; P < 0.001), and DMFS (adjusted HR, 0.541; 95% CI, 0.364-0.805; P = 0.002). CONCLUSION: More chemotherapy should be considered in patients with N3 NPC because of its ability to improve survival time. This could be from the use of IC or adjuvant metronomic chemotherapy.

A rare case report of recurrent atypical meningioma with multiple metastases treated with anti-PD-1 and anti-VEGF therapy.

BACKGROUND: Meningioma is the most common type of primary intracranial tumor with 0.1-1% of all primary meningiomas have been reported to develop into metastases. However, there is no proven therapeutic strategy for multiple metastases of meningiomas. CASE PRESENTATION: A 60-year-old female accepted total tumor resection of a right frontal lobe meningioma in September 2018, In October 2021, the patient was admitted to hospital because of cough and shortness of breath and diagnosed with metastatic meningiomas. The computed tomography (CT) scan revealed the presence of large masses in the right thoracic and abdominal cavity. After two cycles of anti-PD-1 and anti-VEGF treatment, the symptoms were relieved and the tumor was necrotic. Follow up to June 21, 2022, the patient has been given eleven cycles of the treatment every 3 weeks without tumor progression. CONCLUSIONS: This case showed combined anti-PD-1 and anti-VEGF treatment stimulates peripheral blood immune cells to kill metastatic meningioma cells. Whether combined immunotherapy is more effective for metastatic meningioma needs further exploration.

Overexpression of Karyopherin α2 in small cell carcinoma of the cervix correlates with poor prognosis.

BACKGROUND: Cervical small cell carcinoma (SCCC) is uncommon and little is known about its molecular markers. Karyopherin α2 (KPNA2) has been demonstrated in a variety of malignancies. Our objective was to determine whether the KPNA2 level is predictive of clinical outcome in patients with SCCC. METHODS: We detected KPNA2 expression by immunohistochemistry in SCCC tumors from 62 patients. The staining results were evaluated by H-score. The correlation among KPNA2 expression level, clinical characteristics, and prognosis was analyzed. RESULTS: KPNA2 expression was detected in tumor tissue from 55 patients with SCCC (55/62, 89%). High KPNA2 expression correlated significantly with International Federation of Gynecology and Obstetrics staging (P=0.035), tumor size (P=0.019), poorer overall survival (OS) (P=0.008), and poorer disease-free survival (P=0.004) compared to low KPNA2 expression. Multivariate analysis showed that KPNA2 expression level (P=0.037) and tumor size (P=0.046) were independent prognostic factors of OS. CONCLUSIONS: KPNA2 may be a molecular marker and indicator of prognosis in SCCC.

Patient with EGFR-mutant lung cancer harboring de novo MET amplification successfully treated with gefitinib combined with crizotinib.

While 50% of lung adenocarcinoma patients in Asia have mutations in the epidermal growth factor receptor (EGFR) site, there are few patients with the EGFR mutation accompanied by de novo mesenchymal-epithelial transition (MET) amplification. Due to the low incidence rate, there is no consensus regarding treatment. Here, a case of a 62-year-old never smoker presented with EGFR Exon19del and de novo MET amplification. A radiographic examination and computed tomography (CT) imaging were conducted on the chest and middle abdomen. A pulmonary puncture was performed and a sample of the lung tissue was used for pathologic diagnosis. Immunohistochemistry was performed for the expression of CK, P40, P63, ttf-1, NapsinA, alk-d5f3, and ki-67 on the cancer cells. Craniocerebral magnetic resonance and whole body bone imaging were completed. Second-generation gene sequencing (next-generation sequencing [NGS]) and fluorescence in situ hybridization examination were also performed to further characterize the cancer cells. A radiographic examination was performed and revealed space-occupying lesions in the lungs. CT results revealed a mass in the upper lobe of the left lung. The pathologic diagnosis was non-small cell carcinoma T3N2M1a. Second-generation gene sequencing (NGS) indicated EGFR Exon 19del (p.E746_A750del, mutant abundance: 13.99%) with de novo MET amplification (CHR: q31.2, CN = 4.0). Fluorescence in situ hybridization examination confirmed MET amplification. Targeted therapy with gefitinib combined with crizotinib was administered as treatment. Four weeks later, the CT results revealed a substantial reduction in the lesion size. The patient was followed up with favorable complete recovery and no tumor-related symptoms. Although crizotinib is efficacious when used alone in follow-up treatment; however, these results of this case and others indicate that it is likely safe to use both drugs together in the case of drug resistance.