First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Representativeness of the PIONEER-HF and PARAGLIDE-HF in patients hospitalized with acute heart failure.

AIMS: The PIONEER-HF and PARAGLIDE-HF trials aimed to determine the efficacy and safety of the in-hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real-world routine care is unclear. This study aimed to investigate the applicability of the PIONEER-HF and PARAGLIDE-HF trials to real-world AHF patients. METHODS AND RESULTS: We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER-HF eligible (n = 3683) and non-eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE-HF eligible (n = 5191) and non-eligible (n = 5832) patients with an LVEF >40%. Over a mean follow-up of 3.5 years, the PIONEER-HF non-eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88-1.04). No significant difference was found in the composite outcome between PARAGLIDE-HF non-eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90-1.04). CONCLUSIONS: Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril-valsartan. Yet, non-eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril-valsartan benefits in non-eligible AHF patients.

Analysis of outcomes and prognostic factor in acute type A aortic dissection complicated with preoperative shock: A single-center study.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a critical cardiovascular emergency that requires prompt surgical intervention for preserving life, particularly in patients with critical preoperative status. This retrospective study aimed to investigate the clinical features, early and late outcomes, and prognostic factors in patients undergoing aortic repair surgery for ATAAD complicated with preoperative shock. METHODS: Between April 2007 and July 2020, 694 consecutive patients underwent emergency ATAAD repair at our institution, including 162 (23.3%) presenting with preoperative shock (systolic blood pressure <90 mm Hg), who were classified into the survivor (n = 125) and non-survivor (n = 37) groups according to whether they survived to hospital discharge. The clinical demographics, surgical information, and postoperative complications were compared. Five-year survival and freedom from reoperation rates of survivors were analyzed using the Kaplan-Meier actuarial method. Multivariate logistic regression analysis was used to identify independent risk factors for in-hospital mortality. RESULTS: The in-hospital surgical mortality rate in patients with ATAAD and shock was 22.8%. The non-survivor group showed higher rates of preoperative cardiopulmonary resuscitation, acute myocardial infarction, and cerebral infarction, and was associated with longer cardiopulmonary bypass time, higher rates of total arch replacement and intraoperative extracorporeal membrane oxygenation implementation. The non-survivor group had higher blood transfusion volumes and rates of malperfusion-related complications. Multivariate analysis revealed that preoperative cardiopulmonary resuscitation, prolonged cardiopulmonary bypass time, and total arch replacement were risk factors for in-hospital mortality. For patients who survived to discharge, the 5-year cumulative survival and freedom from aortic reoperation rates were 75.6% (95% confidence interval, 67.6%-83.6%) and 82.6% (95% confidence interval, 74.2%-91.1%), respectively. CONCLUSIONS: Preoperative shock in ATAAD is associated with a high risk of in-hospital mortality, particularly in patients who undergo cardiopulmonary resuscitation and complex aortic repair procedures with extended cardiopulmonary bypass. However, late outcomes are acceptable for patients who were stabilized through surgical treatment and survived to discharge.

Acute type a aortic intramural hematoma complicated with preoperative hemopericardium: early and late surgical outcome analyses.

BACKGROUND: Acute type A aortic intramural hematoma (ATAIMH) is a variant of acute type A aortic dissection (ATAAD), exhibiting an increased risk of hemopericardium and cardiac tamponade. It can be life-threatening without emergency treatment. However, comprehensive studies of the clinical features and surgical outcomes of preoperative hemopericardium in patients with ATAIMH remain scarce. This retrospective study aims to investigate the clinical features and early and late outcomes of patients who underwent aortic repair surgery for ATAIMH complicated with preoperative hemopericardium. METHODS: We investigated 132 consecutive patients who underwent emergency ATAIMH repair at this institution between February 2007 and August 2020. These patients were dichotomized into the hemopericardium (n = 58; 43.9%) and non-hemopericardium groups (n = 74; 56.1%). We compared the clinical demographics, surgical information, postoperative complications, 5-year cumulative survival rates, and freedom from reoperation rates. Furthermore, multivariable logistic regression analysis was utilized to identify independent risk factors for patients who underwent re-exploration for bleeding. RESULTS: In the hemopericardium group, 36.2% of patients presented with cardiac tamponade before surgery. Moreover, the hemopericardium group showed higher rates of preoperative shock and endotracheal intubation and was associated with an elevated incidence of intractable perioperative bleeding, necessitating delayed sternal closure for hemostasis. The hemopericardium group exhibited higher blood transfusion volumes and rates of re-exploration for bleeding following surgery. However, the 5-year survival (59.5% vs. 75.0%; P = 0.077) and freedom from reoperation rates (93.3% vs. 85.5%; P = 0.416) were comparable between both groups. Multivariable analysis revealed that hemopericardium, cardiopulmonary bypass time, and delayed sternal closure were the risk factors for bleeding re-exploration. CONCLUSIONS: The presence of hemopericardium in patients with ATAIMH is associated with an elevated incidence of cardiac tamponade and unstable preoperative hemodynamics, which could lead to perioperative bleeding tendencies and high complication rates. However, patients of ATAIMH complicated with hemopericardium undergoing aggressive surgical intervention exhibited long-term surgical outcomes comparable to those without hemopericardium.

Cancer Therapy-Related Cardiac Dysfunction in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real-world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy-related cardiac dysfunction (CT-RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of <53%. Among 421 patients undergoing ADT, LVEF declined from 66.3±11.3% to 62.5±13.6% (95% CI of mean difference: -5.0% to -2.7%) after a mean follow-up period of 1.6±0.8 years. CT-RCD occurred in 58 patients (13.7%) with a nadir LVEF of 40.3±9.1% after ADT. Lower baseline LVEF was significantly associated with CT-RCD (odds ratio, 1.07 [95% CI, 1.04-1.10]). The area under the curve of baseline LVEF for discriminating CT-RCD was 75.6%, with the corresponding optimal cutoff value of 64.5% (sensitivity, 79.3%; specificity, 67.2%). Conclusions ADT with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, and bilateral orchiectomy were associated with an increased risk of CT-RCD in patients with prostate cancer. In addition, lower baseline LVEF was a significant predictor of CT-RCD in patients with prostate cancer undergoing treatment with ADT.

Ambient Temperature Effect on Acute Myocardial Infarction by Risk Factors: Daily Data From 2000 to 2017, Taiwan.

Background: A U-shaped relationship between temperature and acute myocardial infarction (AMI) was observed, but the risk factors were rarely included. Objectives: The authors sought to examine AMI's cold and heat exposure after considering their risk groups. Methods: Daily data on ambient temperature, newly diagnosed AMI, and 6 known risk factors of AMI for the Taiwan population from 2000 to 2017 were created by linking 3 Taiwan national databases. Hierarchical clustering analysis was performed. Poisson regression was performed on the AMI rate with the clusters along with the daily minimum temperature in cold months (November-March) and the daily maximum temperature in hot months (April-October). Results: There were 319,737 patients with new-onset AMI over 109.13 billion person-days, corresponding to the incidence rate of 107.02 per 100,000 person-years (95% CI: 106.64-107.39 person-years). Hierarchical clustering analysis identified 3 distinct clusters (1: age <50 years, 2: age ≥50 years without hypertension, and 3: mainly age ≥50 years with hypertension) with AMI incidence rates of 16.04, 105.13, and 388.17 per 100,000 person-years, respectively. Poisson regression revealed that below 15 °C, cluster 3 had the highest risk of AMI per 1°C reduce in temperature (slope = 1.011) compared with clusters 1 (slope = 0.974) and 2 (slope = 1.009). However, above the 32 °C thresholds, cluster 1 had the highest risk of AMI per 1 °C increase in temperature (slope = 1.036) compared with clusters 2 (slope = 1.02) and 3 (slope = 1.025). Cross validation showed a good fit for the model. Conclusions: People ≥50 years of age with hypertension are more susceptible to cold-related AMI. However, heat-related AMI is more prominent in individuals <50 years of age.

Osteopontin mediation of disturbed flow-induced endothelial mesenchymal transition through CD44 is a novel mechanism of neointimal hyperplasia in arteriovenous fistulae for hemodialysis access.

In dysfunctional arteriovenous fistulae (AVF) for hemodialysis access, neointimal hyperplasia (NH) is prone to occur in the region exposed to disturbed flow. We hypothesized that disturbed flow contributes to NH in AVF by inducing endothelial mesenchymal transition (EndMT) through activation of the osteopontin/CD44 axis. In rats with aortocaval fistula, a rodent model of AVF, we demonstrated development of EndMT and expression of osteopontin and CD44 specifically in the vicinity of the arteriovenous junction using immunostaining. Duplex scan confirmed this region was exposed to a disturbed flow. A mixed ultrastructural phenotype of endothelium and smooth muscle cells was found in luminal endothelial cells of the arteriovenous junction by electron microscopy ascertaining the presence of EndMT. Endothelial lineage tracing using Cdh5-Cre/ERT2;ROSA26-tdTomato transgenic mice showed that EndMT was involved in NH of AVF since the early stage and that the endothelial-derived cells contributed to 24% of neointimal cells. In human umbilical vein endothelial cells (HUVECs) in culture, osteopontin treatment induced EndMT, which was suppressed by CD44 knockdown. Exposure to low oscillatory wall shear stress using a parallel-plate system induced EndMT in HUVECs, also suppressed by osteopontin or CD44 knockdown. In AVF of CD44 knockout mice, EndMT was mitigated and NH decreased by 35% compared to that in wild-type mice. In dysfunctional AVF of patients with uremia, expressions of osteopontin, CD44, and mesenchymal markers in endothelial cells overlying the neointima was also found by immunostaining. Thus, the osteopontin/CD44 axis regulates disturbed flow-induced EndMT, plays an important role in neointimal hyperplasia of AVF, and may act as a potential therapeutic target to prevent AVF dysfunction.

A Comparison among Nonvitamin K Antagonist Oral Anticoagulants in Asian Patients with Venous Thromboembolism: A Multi-Institutional Study.

The comparison of clinical effectiveness and safety across different nonvitamin K antagonist direct oral anticoagulants (DOACs) in Asian patients with venous thromboembolism (VTE) remains unclear. Therefore, we assessed the real-world benefits of different DOACs in these patients. A cohort of 1480 patients with VTE were identified from the Chang Gung Research Database between 1 January 2012, and 31 December 2019. The composite outcomes of recurrent VTE and major bleeding were evaluated for four DOACs. The composite outcomes of recurrent VTE and major bleeding occurred in 9.06%, 9.80%, 8.61%, and 10.86% of the apixaban, dabigatran, edoxaban, and rivaroxaban groups, respectively, within 12 months of treatment initiation. The risk of the composite outcomes was similar in the rivaroxaban group and the apixaban, dabigatran, and edoxaban groups, with a subdistribution hazard ratio (SHR) of 0.80 (95% CI, 0.49-1.29), 0.81 (95% CI, 0.34-1.95), and 0.76 (95% CI, 0.42-1.39), respectively. No significant differences in the rates of recurrent VTE or major bleeding were observed between the rivaroxaban and other DOAC groups at the 12-month follow-up. According to real-world practice in Asian patients with VTE, the DOAC type was not associated with the differences in the risk of recurrent VTE or major bleeding within 12 months of treatment initiation.

Delayed sternal closure for intractable bleeding after acute type A aortic dissection repair: outcomes and risk factors analyses.

BACKGROUND: Perioperative coagulopathy and intractable bleeding are severe complications in acute type A aortic dissection (ATAAD) repair surgery. Mediastinal packing with delayed sternal closure (DSC) is a commonly adapted technique to stabilize the hemorrhagic tendency. This retrospective study aims to investigate the early and late outcomes and risk factors in patients who underwent DSC procedure during ATAAD repair surgery. METHODS: This study investigated 704 consecutive patients who underwent ATAAD repair at this institution between January 2007 and September 2020. These patients were dichotomized into the DSC (n = 109; 15.5%) and primary sternal closure (PSC) groups (n = 595; 84.5%). The clinical features, surgical information, postoperative complications, 5-years cumulative survival, and freedom from reoperation rates were compared. A multivariate logistic regression analysis was used to identify the independent risk factors for patients who underwent DSC. RESULTS: The DSC group showed a higher rate of hemopericardium and preoperative malperfusion, and was associated with longer cardiopulmonary bypass and aortic clamping times and a higher rate of intraoperative extracorporeal membrane oxygenation (ECMO) support. The DSC group showed higher blood transfusion volumes and rate of reexploration for bleeding after surgery. However, the in-hospital mortality rates (17.4% vs. 13.3%; P = 0.249), 5-year survival rates (66.9% vs. 68.2%; P = 0.635), and freedom from reoperation rates (89.1% vs. 82.5%; P = 0.344) were comparable between the DSC and PSC groups. Multivariate analysis revealed that hemopericardium, preoperative malperfusion, and intraoperative ECMO support were risk factors for implementing DSC. CONCLUSIONS: DSC is an efficient life-saving technique to stabilize patients with intractable bleeding after undergoing ATAAD repair surgery, which leads to acceptable short- and long-term outcomes. Patients who were at risk for intractable bleeding should have early decision-making for implementing DSC.

Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma Treated With Targeted Therapies.

Background: The risk for major adverse cardiovascular events (MACE) with targeted therapies for patients with advanced renal cell carcinoma (RCC) in real-world practice remains unclear. Objectives: The aim of this study was to compare the risk for MACE associated with targeted cancer therapies with that associated with cytokine treatment in patients with advanced RCC. Methods: Using Taiwan's National Health Insurance Research Database, a retrospective nationwide cohort study was conducted involving patients with advanced RCC who had received targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus) or cytokine therapy (interleukin-2 or interferon gamma) from 2007 to 2018. Cox proportional hazards models were used to estimate the risk for MACE (a composite of myocardial infarction, ischemic stroke, heart failure, and cardiovascular death) in the cohort using the propensity score method of stabilized inverse probability of treatment weighting. Results: In this cohort of 2,785 patients with advanced RCC, 2,257 (81%) and 528 (19%) had received targeted and cytokine therapy, respectively. After stabilized inverse probability of treatment weighting, the incidence rates of MACE were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively (HR: 1.80; 95% CI: 1.19-2.74). Baseline history of heart failure (HR: 3.88; 95% CI: 2.25-6.71), atrial fibrillation (HR: 3.60; 95% CI: 2.16-5.99), venous thromboembolism (HR: 2.50; 95% CI: 1.27-4.92), ischemic stroke (HR: 1.88; 95% CI: 1.14-3.11), and age ≥ 65 years (HR: 1.81; 95% CI: 1.27-2.58) were independent risk factors for targeted therapy-associated MACE. Conclusions: Among patients with advanced RCC, the risk for MACE associated with targeted cancer therapy is higher than that associated with cytokine therapy.

Safety of the endovascular aneurysm repair procedure: real-world evidence using interrupted-time series analysis.

OBJECTIVES: In Taiwan, endovascular aneurysm repair for treating abdominal aortic aneurysms (AAA) was introduced in 2004 and became reimbursable in February 2010. We evaluated the real-world practice and safety of endovascular aneurysm repair in Taiwan. METHODS: Patients who underwent repair operations for AAA (open or endovascular) from 2000 to 2016 were enrolled (n = 11485). Outcome statistics (during the index hospitalization: length of stay, rate of ischaemic bowel disease and 30-day mortality; after discharge: 30-day readmission rate, 2-year mortality, 2-year reintervention rate and 2-year paraplegia rate) were calculated for each half-year cohort. Propensity score-based stabilized weights were used to balance covariates among each half-year cohort. Interrupted time-series analysis was then performed. RESULTS: The elective and emergency ratio of AAA repair was 50:50 from 2000 to 2004 and became 60:40 from 2010 to 2016. The half-year rate of endovascular aneurysm repair was 0% in 2000 to 2004/06, 83.16% in 2010 and 98.1% in 2016. Interrupted time series analysis revealed that after endovascular aneurysm repair became reimbursable, both elective and emergency groups had a reduction in length of stay (-4.2 days, P < 0.0001; -1.5 days, P = 0.0928) and 30-day mortality (-5.22%, P = 0.0702; -7.76%, P = 0.0086) but a significant increase in the reintervention rate (5.05%, P = 0.0031; 4.36%, P = 0.0097). CONCLUSIONS: Endovascular aneurysm repair was predominantly used in treating AAAs after it was reimbursed in Taiwan. Endovascular aneurysm repair is efficacious regarding short-term outcomes but increased the 2-year reintervention rate in both groups.

Anti-Inflammatory Effect of Resveratrol Derivatives via the Downregulation of Oxidative-Stress-Dependent and c-Src Transactivation EGFR Pathways on Rat Mesangial Cells.

In Taiwan, the root extract of Vitis thunbergii Sieb. et Zucc. (Vitaceae, VT) is rich in stilbenes, with resveratrol (Res) and its derivatives being the most abundant. Previously, we showed that the effect of Res derivatives against tumor necrosis factor-α (TNF-α)-stimulated inflammatory responses occurs via cPLA2/COX-2/PGE2 inhibition. This study compared and explored the underlying anti-inflammatory pharmacological mechanisms. Before stimulation with TNF-α, RMCs were treated with/without pharmacological inhibitors of specific protein kinases. The expression of inflammatory mediators was determined by Western blotting, gelatin zymography, real-time PCR, and luciferase assay. Cellular and mitochondrial ROS were measured by H2DHFDA or DHE and MitoSOX™ Red staining, respectively. The RNS level was indirectly measured by Griess reagent assay. Kinase activation and association were assayed by immunoprecipitation followed by Western blotting. TNF-α binding to TNFR recruited Rac1 and p47phox, thus activating the NAPDH oxidase-dependent MAPK and NF-κB pathways. The TNF-α-induced NF-κB activation via c-Src-driven ROS was independent from the EGFR signaling pathway. The anti-inflammatory effects of Res derivatives occurred via the inhibition of ROS derived from mitochondria and NADPH oxidase; RNS derived from iNOS; and the activation of the ERK1/2, JNK1/2, and NF-κB pathways. Overall, this study provides an understanding of the various activities of Res derivatives and their pharmacological mechanisms. In the future, the application of the active molecules of VT to health foods and medicine in Taiwan may increase.

Postoperative Stroke After Type A Aortic Dissection Repair: Hemorrhage Versus Ischemia.

BACKGROUND: Postoperative stroke is a severe and potentially disabling complication following surgical intervention for acute type A aortic dissection (ATAAD). This retrospective study aims to compare the early and late outcomes between patients who had hemorrhagic and ischemic stroke after undergoing ATAAD repair surgery. METHODS: Between January 2007 and June 2020, a total of 685 consecutive patients underwent ATAAD repair at our institution. Patients who had a preoperative stroke or were unconscious at presentation were excluded from this study. Of the 656 included for analysis, 102 (15.5%) patients had a postoperative stroke confirmed by computed tomography angiography. The strokes were classified into the ischemia group (n = 83, 12.7%) and hemorrhage group (n = 19, 2.9%). Clinical features, surgical information, postoperative complications, modified Rankin Scale (mRS) scores after discharge, and 5-year cumulative survival rates were compared. RESULTS: Demographics, comorbidities, and presentations of ATAAD were similar between the two groups, except a higher rate of preoperative antithrombotic medication was found in the hemorrhage group. The hemorrhage group was associated with a higher complexity of aortic arch replacement, longer cardiopulmonary bypass, and aortic clamping times than the ischemia group. A higher in-hospital mortality rate (42.1% versus 20.5%; p = 0.048) and a higher median mRS score at the 3-month follow-up after discharge (6[3-6] versus 4[2-6]; p = 0.027) were found in the hemorrhage group. The hemorrhage group showed a lower 5-year cumulative survival rate (23.4% versus 57.8%; p = 0.003) compared with the ischemia group. CONCLUSIONS: Postoperative hemorrhagic stroke was associated with poorer neurological outcomes and lower survival rates than those with ischemic stroke. Patients who have complex arch replacement, long cardiopulmonary bypass and aortic clamping times are at risk for postoperative hemorrhagic stroke and should have intensive neurological surveillance for early diagnosis and treatment after ATAAD repair surgery.

Clinical outcomes of Sacubitril/Valsartan in patients with acute heart failure: A multi-institution study.

BACKGROUND: The effectiveness and safety of initiating sacubitril/valsartan therapy among patients who are hospitalized for acute heart failure (HF) is unclear. METHODS: A cohort of 3736 patients with HF with reduced ejection fraction (HFrEF) hospitalized for acute HF was identified from Chang Gung Research Database between January 1, 2016 and August 31, 2019. The risks of rehospitalization for HF and death associated with sacubitril/valsartan therapy compared to angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy were evaluated. We used stabilized inverse probability of treatment weighting to balance the baseline covariates. The risks of fatal and non-fatal outcomes between the groups were compared using a Cox proportional hazard model and Fine and Gray subdistribution hazard model, respectively. FINDINGS: The composite of rehospitalization for HF and death occurred in 22.9% of the patients in the sacubitril/valsartan group compared to 32.6% in the ACEI/ARB group (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52-0.97) after a mean follow-up period of 11.8 months. The sacubitril/valsartan group had a lower risk of rehospitalization for HF (subdistribution HR 0.83, 95% CI 0.74-0.92) and all-cause death (HR 0.51, 95% CI 0.27-0.94). There were no significant differences in the rates of worsening renal function or severe hyperkalemia between the two groups. INTERPRETATION: In real-world practice, initiating sacubitril/valsartan therapy among patients with HFrEF who were hospitalized for acute HF was associated with a lower rate of rehospitalization for HF and death compared with ACEI/ARB therapy. FUNDING: This study was supported by Novartis Pharmaceuticals.

Gonadotropin-releasing hormone antagonist associated with lower cardiovascular risk compared with gonadotropin-releasing hormone agonist in prostate cancer: A nationwide cohort and in vitro study.

BACKGROUND: We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and those who receive GnRH antagonist therapy. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score-matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional-hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase-9 (MMP-9) expression and invasion ability in THP-1 differentiated macrophages. RESULTS: GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90) than GnRHa therapy, with a mean follow-up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06-0.70) and all-cause mortality (HR, 0.77; 95% CI, 0.61-0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP-9 activity and the invasive ability of THP-1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively. CONCLUSION: GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.

Surgical outcomes of DeBakey type I and type II acute aortic dissection: a propensity score-matched analysis in 599 patients.

BACKGROUND: The DeBakey classification divides Stanford acute type A aortic dissection (ATAAD) into DeBakey type I (D1) and type II (D2) according to the extent of acute aortic dissection (AAD). This retrospective study aimed to compare the early and late outcomes of D1-AAD and D2-AAD through a propensity score-matched analysis. METHODS: Between January 2009 and April 2020, 599 consecutive patients underwent ATAAD repair at our institution, and were dichotomized into D1 (n = 543; 90.7%) and D2 (n = 56; 9.3%) groups. Propensity scoring was performed with a 1:1 ratio, resulting in a matched cohort of 56 patients per group. The clinical features, postoperative complications, 5-year cumulative survival and freedom from reoperation rates were compared. RESULTS: In the overall cohort, the D1 group had a lower rate of preoperative shock and more aortic arch replacement with longer cardiopulmonary bypass time. The D1 group had a higher in-hospital mortality rate than the D2 group in overall (15.8% vs 5.4%; P = 0.036) and matched cohorts (19.6% vs 5.4%; P = 0.022). For patients that survived to discharge, the D1 and D2 groups demonstrated similar 5-year survival rates in overall (77.0% vs 85.2%; P = 0.378) and matched cohorts (79.1% vs 85.2%; P = 0.425). The 5-year freedom from reoperation rates for D1 and D2 groups were 80.0% and 97.1% in overall cohort (P = 0.011), and 93.6% and 97.1% in matched cohort (P = 0.474), respectively. CONCLUSIONS: Patients with D1-AAD had a higher risk of in-hospital mortality than those with D2-AAD. However, for patients who survived to discharge, the 5-year survival rates were comparable between both groups.

Multidrug resistance: The clinical dilemma of refractory Helicobacter pylori infection.

This study investigated the antimicrobial resistance of isolates from patients with refractory Helicobacter pylori. The resistance rate was 34.1% for amoxicillin, 92.7% for clarithromycin, 65.9% for metronidazole, 85.4% for levofloxacin, and 29.3% for rifabutin. Dual resistance to both clarithromycin and levofloxacin was found in 73.2%. The antimicrobial resistance rate of refractory H. pylori was extremely high, which had become a major consideration in therapeutic challenge.

Comparison Between Non-vitamin K Antagonist Oral Anticoagulants and Low-Molecular-Weight Heparin in Asian Individuals With Cancer-Associated Venous Thromboembolism.

Importance: It is unclear whether the clinical benefits associated with non-vitamin K antagonist oral anticoagulants (NOACs) are similar to those associated with low-molecular-weight heparins (LMWHs) in Asian individuals with cancer and acute venous thromboembolism (VTE). Objective: To compare the risk of recurrent thromboembolic events and bleeding associated with use of a NOAC vs use of the LMWH enoxaparin in Asian individuals with cancer-associated VTE. Design, Setting, and Participants: This cohort study was conducted using data from the Chang Gung Research Database, a multi-institutional electronic medical records database in Taiwan. A cohort of 1109 patients with cancer-associated VTE were identified between January 1, 2012, and January 31, 2019. Data were analyzed from March 2019 through December 2020. Exposures: Receiving a NOAC (including rivaroxaban, apixaban, edoxaban, or dabigatran) or the LMWH enoxaparin. Main Outcomes and Measures: The primary outcomes were composite recurrent VTE or major bleeding. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. We compared risks of recurrent VTE or major bleeding between groups using Cox proportional hazards models. In addition, we conducted an analysis using a Fine and Gray subdistribution hazard model that considered death as a competing risk. Results: Among 1109 patients with cancer and newly diagnosed VTE, 578 (52.1%) were women and the mean (SD) age at index date was 66.0 (13.0) years; 529 patients (47.7%) received NOACs and 580 patients (52.3%) received the LMWH enoxaparin. Composite recurrent VTE or major bleeding occurred in 75 patients (14.1%) in the NOAC group and 101 patients (17.4%) in the enoxaparin group (weighted hazard ratio [HR], 0.77; 95% CI, 0.56-1.07; P = .11). The groups had similar risk of VTE recurrence (HR, 0.62; 95% CI, 0.39-1.01; P = .05) and major bleeding (HR, 0.80; 95% CI, 0.52-1.24; P = .32) at 12 months of follow-up. However, taking a NOAC was associated with a significantly lower risk of gastrointestinal bleeding compared with receiving enoxaparin (10 patients [1.9%] vs 41 patients [7.1%]; HR, 0.29; 95% CI, 0.15-0.59; P < .001). Findings for both primary outcomes were consistent with competing risk analyses (recurrent VTE: HR, 0.68; 95% CI, 0.45-1.01; P = .05; major bleeding: HR, 0.77; 95% CI, 0.51-1.16; P = .21). Conclusions and Relevance: This cohort study found that in real-world practice, among Asian patients with cancer-associated VTE, use of a NOAC was associated with a similar risk for recurrent VTE or major bleeding compared with use of the LMWH enoxaparin. Nonetheless, use of a NOAC was associated with a significantly lower rate of gastrointestinal bleeding. Further prospective studies are needed to confirm these findings.

Surgical outcomes analysis in patients with uncomplicated acute type A aortic dissection: a 13-year institutional experience.

This retrospective study aimed to clarify the short-term and mid-term outcomes of and prognostic factors for patients who underwent surgical repair for uncomplicated acute type A aortic dissection (ATAAD). Between January 2007 and June 2019, 603 consecutive patients underwent ATAAD repair at our institution. According to patients' preoperative presentations and imaging studies, uncomplicated ATAAD was found in 276 (45.8%) patients by excluding preoperative complicated factors. Patients with uncomplicated ATAAD were classified into the survivor (n = 243) and non-survivor (n = 33) groups. Clinical features, surgical information, and postoperative complications were compared. Three-year survival and freedom from reoperation rates for survivors were analyzed using the Kaplan-Meier actuarial method. The in-hospital surgical mortality rate of uncomplicated ATAAD patients was 11.9%. The non-survivor group had a higher rate of postoperative malperfusion-related complications, and a multivariate analysis revealed that repeat surgery, retrograde cerebral perfusion, and intraoperative extracorporeal membrane oxygenation support were predictors of in-hospital mortality. In the survivor group, 3-year cumulative survival and freedom from aortic reoperation rates were 89.6% (95% confidence interval [CI] 84.8-92.9%) and 83.1% (95% CI 76.8-87.7%), respectively. In conclusion, uncomplicated and complicated ATAAD rates were similar; the short-term and mid-term surgical outcomes in patients with uncomplicated ATAAD were generally acceptable.

Surgical results in acute type A aortic dissection with preoperative cardiopulmonary resuscitation: Survival and neurological outcome.

BACKGROUND: Acute type A aortic dissection (ATAAD) is a life-threatening disease that requires emergent surgical intervention. This retrospective study aimed to clarify the individual characteristics, short-term and mid-term outcomes, and prognostic factors of patients who underwent surgical repair of ATAAD with preoperative cardiopulmonary resuscitation (CPR). METHODS: Between January 2007 and January 2020, 656 consecutive patients underwent ATAAD repair at our institution; 22 (3.4%) of these patients underwent CPR prior to surgery. Patients who underwent preoperative CPR were classified as the survivor group (n = 9) and non-survivor group (n = 13), according to whether they survived to hospital discharge. Clinical features, surgical information, and postoperative complications were analyzed and compared. Three-year cumulative survival rates and cerebral performance categories (CPC) scores are presented. RESULTS: In patients undergoing CPR prior to ATAAD surgery, the in-hospital mortality rate was 59.1%. A total of 72.7% of patients underwent concomitant surgical resuscitation procedures during CPR such as emergent subxiphoid pericardiotomy and/or emergent cardiopulmonary bypass. The survivor group had a higher rate of return of spontaneous heartbeat (ROSB) compared to the non-survivor group (100% versus 53.8%; P = 0.017). The 3-year cumulative survival rates were 35.1% (95% confidence interval [CI], 27.6%-42.6%) and 85.7% (95% CI, 81.9%-88.8%) for overall patients and for survivors, respectively. As for the neurological outcome, 77.8% (7/9) of patients had full cerebral performance (CPC-1) at the 3-month follow-up examination after discharge. CONCLUSIONS: Patients with ATAAD undergoing preoperative CPR, especially those without ROSB after CPR, are at high risk for in-hospital mortality. However, the short-term and mid-term outcomes, including the cerebral performance after discharge and 3-year survival rate, are promising for patients who survived to discharge.