Evaluating the applicability of ivabradine in acute heart failure.

BACKGROUND: While ivabradine has demonstrated benefits in heart rate control and prognosis for chronic heart failure patients, its application in acute decompensated heart failure remains underexplored. HYPOTHESIS: For patients with acute decompensated heart failure with reduced ejection fraction (HFrEF) who are intolerant to ß-blockers or unable to further titrate their dosage, the use of ivabradine is hypothesized to be effective and safe is improving outcomes. METHODS: This retrospective, multicenter database analysis included patients with hospitalized decompensated heart failure with a left ventricular ejection fraction of ≤40% from June 1, 2015 to December 31, 2020. The exclusion criteria were a baseline heart rate of <70 bpm, previous use of ivabradine, mortality during admission, existing atrial fibrillation, or atrial flutter. The primary outcome was the composite of cardiovascular death and hospitalization for heart failure. RESULTS: Of the 4163 HFrEF patients analyzed, 684 (16.4%) were administered ivabradine during their index admission. After matching, there were 617 patients in either group. The results indicated that ivabradine use was not significantly associated with the risk of the primary composite outcome (hazard ratio: 1.10; 95% confidence interval: 0.94-1.29). Similarly, the risk of secondary outcomes and adverse renal events did not significantly differ between the ivabradine and non-ivabradine cohorts (all p > .05). CONCLUSION: For hospitalized acute decompensated heart failure patients who are intolerant to ß-blockers or cannot further titrate them, ivabradine offers a consistent therapeutic effect. No significant disparities were noted between the ivabradine and non-ivabradine groups in heart failure hospitalization and cardiovascular death.

Recent Advances in Engineering Carriers for siRNA Delivery.

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.

Creation of Chitosan-Based Nanocapsule-in-Nanofiber Structures for Hydrophobic/Hydrophilic Drug Co-Delivery and Their Dressing Applications in Diabetic Wounds.

Nanofiber meshes (NFMs) loaded with therapeutic agents are very often employed to treat hard-to-heal wounds such as diabetic wounds. However, most of the NFMs have limited capability to load multiple or hydrophilicity distinctive-therapeutic agents. The therapy strategy is therefore significantly hampered. To tackle the innate drawback associated with the drug loading versatility, a chitosan-based nanocapsule-in-nanofiber (NC-in-NF) structural NFM system is developed for simultaneous loading of hydrophobic and hydrophilic drugs. Oleic acid-modified chitosan is first converted into NCs by the developed mini-emulsion interfacial cross-linking procedure, followed by loading a hydrophobic anti-inflammatory agent Curcumin (Cur) into the NCs. Sequentially, the Cur-loaded NCs are successfully introduced into reductant-responsive maleoyl functional chitosan/polyvinyl alcohol NFMs containing a hydrophilic antibiotic Tetracycline hydrochloride. Having a co-loading capability for hydrophilicity distinctive agents, biocompatibility, and a controlled release property, the resulting NFMs have demonstrated the efficacy on promoting wound healing either in normal or diabetic rats.

Comparing angiotensin receptor-neprilysin inhibitors with sodium-glucose cotransporter 2 inhibitors for heart failure with diabetes mellitus.

BACKGROUND AND AIMS: Clinical comparisons of angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set. METHODS: We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time (n = 647 and 840, respectively) between January 1, 2016, and December 31, 2021, and with clinical outcomes of CV death, hospitalization for heart failure (HHF), composite CV outcomes, or renal outcomes. RESULTS: The HHF risk reduction conferred by SGLT2i treatment was more significant than that conferred by ARNI treatment (37.7% vs. 30.4%; 95% confidence interval [CI] 1.06-1.41). SGLT2i use conferred significantly greater renal protection against the doubling of serum creatinine (13.1% vs. 9.3%; 95% CI 1.05-1.75), an estimated glomerular filtration rate decline of > 50% (24.9% vs. 20.0%; 95% CI 1.02-1.45), and progression to end-stage renal disease (3.1% vs. 1.5%; 95% CI 1.62-5.23). The improvements in echocardiographic parameters were comparable between the groups. CONCLUSIONS: Compared with ARNI treatment, SGLT2i treatment was associated with a more significant HHF risk reduction and greater preservation of renal function in patients with HFrEF and T2DM. This study also supports the prioritization of SGLT2i use in these patients when patients' conditions or economic resources need to be considered.

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease.

BACKGROUND: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. METHODS: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. RESULTS: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

Preparation of CO2 -Based Cationic Polycarbonate/Polyacrylonitrile Nanofibers with an Optimal Fibrous Microstructure for Antibacterial Applications.

Utilizing CO2 as one of the monomer resources, poly(vinylcyclohexene carbonates) (PVCHCs) are used as the precursor for preparing cationic PVCHCs (CPVCHCs) via thiol-ene click functionalization. Through the functionalization, CPVCHC-43 with a tertiary amine density of 43% relative to the backbone is able to display a significantly antibacterial ability against Staphylococcus aureus (S. aureus). Blending CPVCHC-43 with polyacrylonitrile (PAN), CPVCHC/PAN nanofiber meshes (NFMs) have been successfully prepared by electrospinning. More importantly, two crucial fibrous structural factors including CPVCHC/PAN weight ratio and fiber diameter have been systematically investigated for the effects on the antibacterial performance of the NFMs. Sequentially, a quaternization treatment has been employed on the NFMs with an optimal fibrous structure to enhance the antibacterial ability. The resulting quaternized NFMs have demonstrated the great biocidal effects against Gram-positive and Gram-negative bacteria. Moreover, the excellent biocompatibility of the quaternized NFMs have also been thoroughly evaluated and verified.

Tumor endothelial marker 1 is upregulated in heart after cardiac injury and participates in cardiac remodeling.

Tumor endothelial marker 1 (TEM1) is a transmembrane glycoprotein that appears on mesenchymal lineage-derived cells during embryogenesis, but its expression greatly reduces after birth. Re-upregulation of TEM1 is found in tumor angiogenesis, organ fibrosis and wound healing indicating its potential role in tissue remodeling and repair. The expression level and function of TEM1 in adult heart are unknown. In explanted hearts from heart failure (HF) patients received cardiac transplantation, immunofluorescence staining showed TEM1 was expressed in cardiomyocytes (CMs) and cardiac fibroblasts. Bioinformatics analysis showed TEM1 upregulation in mouse heart after coronary ligation. Cardiac TEM1 expression was reconfirmed in mouse HF induced by coronary ligation or doxorubicin injection. TEM1 expression increased in cultured CMs stimulated with mechanical stretch, doxorubicin and hypoxia. Further studies showed recombinant TEM1 (rTEM1) was a functional protein that influenced cell behaviors of CMs. It directly activated Erk and Akt through interaction with PDGF receptor. TEM1lacZ/lacZ mice had less collagen deposition and worse cardiac function than wild type mice. These results indicate that TEM1 expression increases in the heart after cardiac injury and works as a functional protein that participates in cardiac remodeling.

Carbon Dioxide-Derived Biodegradable and Cationic Polycarbonates as a New siRNA Carrier for Gene Therapy in Pancreatic Cancer.

Pancreatic cancer is an aggressive malignancy associated with poor prognosis and a high tendency in developing infiltration and metastasis. K-ras mutation is a major genetic disorder in pancreatic cancer patient. RNAi-based therapies can be employed for combating pancreatic cancer by silencing K-ras gene expression. However, the clinical application of RNAi technology is appreciably limited by the lack of a proper siRNA delivery system. To tackle this hurdle, cationic poly (cyclohexene carbonate) s (CPCHCs) using widely sourced CO2 as the monomer are subtly synthesized via ring-opening copolymerization (ROCOP) and thiol-ene functionalization. The developed CPCHCs could effectively encapsulate therapeutic siRNA to form CPCHC/siRNA nanoplexes (NPs). Serving as a siRNA carrier, CPCHC possesses biodegradability, negligible cytotoxicity, and high transfection efficiency. In vitro study shows that CPCHCs are capable of effectively protecting siRNA from being degraded by RNase and promoting a sustained endosomal escape of siRNA. After treatment with CPCHC/siRNA NPs, the K-ras gene expression in both pancreatic cancer cell line (PANC-1 and MiaPaCa-2) are significantly down-regulated. Subsequently, the cell growth and migration are considerably inhibited, and the treated cells are induced into cell apoptotic program. These results demonstrate the promising potential of CPCHC-mediated siRNA therapies in pancreatic cancer treatment.

Progressive tricuspid regurgitation and elevated pressure gradient after transvenous permanent pacemaker implantation.

BACKGROUND: The association of postimplant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. HYPOTHESIS: This study aimed to explore the clinical outcomes of progressive postimplant TR after permanent pacemaker (PPM) implantation. METHODS: A total of 1670 patients who underwent a single ventricular or dual-chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, history of HF, and baseline abnormal TR and TRPG were excluded. Finally, a total of 1075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and TRPG of >30 mmHg after implant. RESULTS: In 198 (18.4%) patients (group 1) experienced progressive postimplant TR and elevated TRPG, whereas 877 patients (group 2) did not have progressive postimplant TR. Group 1 had larger change in postimplant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p < .001) than group 2. Group 1 had a higher incidence of HF hospitalization compared to group 2 (13.6% vs. 4.7%; p < .001). Preimplant TRPG (HR: 1.075; 95% confidence interval [CI]: 1.032-1.121; p = .001) was an independent predictor of progressive postimplant TR. CONCLUSIONS: After a transvenous ventricular-based PPM implantation, 18.4% of patients experienced progressive postimplant TR and elevated TRPG. Higher preimplant TRPG was an independent predictor of progressive postimplant TR.

Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs at a Higher Risk of Acute Coronary Syndrome.

Background Cardiovascular disease is the most common cause of death in patients with rheumatoid arthritis. It is believed that using disease-modifying antirheumatic drugs (DMARDs) to control inflammation can reduce the risk of cardiovascular disease. In this study, we investigated whether patients who responded differently to DMARDs might sustain different cardiovascular events. Methods and Results We designed a cohort study using the Chang Gung Research Database. We identified 7114 patients diagnosed with rheumatoid arthritis. After strict exclusion criteria, we collected 663 individuals as an inadequate response to DMARDs group. Then, 2034 individuals were included as the control group. The end point was composite vascular outcomes, including acute coronary syndrome or ischemic stroke. We used the inverse probability of treatment weighting to keep the covariates between these 2 groups well balanced. We compared the risk of these outcomes using the Cox proportional hazards model. The mean follow-up time was 4.7 years. During follow-up, there were 7.5% and 6.4% of patients with composite vascular outcomes in the DMARD-inadequate response and control groups, respectively. There was no significant difference in the risk of composite vascular outcomes (95% CI, 0.94-1.41) and ischemic stroke (95% CI, 0.84-1.36). The risk of acute coronary syndrome was significantly higher in the DMARD-inadequate response group (hazard ratio, 1.45; 95% CI, 1.02-2.05). Conclusions Patients with DMARD-inadequate response rheumatoid arthritis have a higher risk of developing acute coronary syndrome than those whose disease can be controlled by DMARDs.

Group 2 innate lymphoid cells contribute to IL-33-mediated alleviation of cardiac fibrosis.

Rationale: The major cause of heart failure is myocardium death consequent to detrimental cardiac remodeling and fibrosis following myocardial infarction. The cardiac protective cytokine interleukin (IL)-33, which signals by ST2 receptor binding, is associated with group 2 innate lymphoid cell (ILC2) activation and regulates tissue homeostasis and repair following tissue injury in various tissues. However, the distribution and role of IL-33-responsive ILC2s in cardiac fibrosis remain unclear. In this study, we elucidated the roles of IL-33-responsive cardiac-resident ILC2s and IL-33-mediated immunomodulatory functions in cardiac fibrosis. Methods: We examined the distribution of cardiac ILC2s by using flow cytometry. The roles of IL-33-mediated ILC2 expansion in cardiac fibrosis was evaluated in the mouse model of catecholamine-induced cardiac fibrosis. ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice were implemented to determine the contribution of endogenous ILC in the progression of cardiac fibrosis. Histopathological assessments, speckle tracking echocardiography, and transcriptome profile analysis were performed to determine the effects of IL-33-mediated cardiac protective functions. Results: We identified the resident cardiac ILC2s, which share similar cell surface marker and transcriptional factor expression characteristics as peripheral blood and lung tissue ILC2s. IL-33 treatment induced ILC2 expansion via ST2. In vivo, ILC-deficient Rag2‒/‒IL2Rγc‒/‒ mice developed exacerbated cardiac fibrosis following catecholamine-induced stress cardiac injury. IL-33 treatment expanded cardiac ILC2s and revealed protective effects against cardiac tissue damage with reduced cardiomyocyte death, immune cell infiltration, tissue fibrosis, and improved myocardial function. Transcriptome analysis revealed that IL-33 attenuated extracellular matrix synthesis- and fibroblast activation-associated gene expressions. IL13-knockout or epidermal growth factor receptor (EGFR) inhibition abolished IL-33-mediated cardiac protective function, confirming IL-13 and EGFR signaling as crucial for IL-33-mediated cardioprotective responses. Moreover, ILC2-produced BMP-7 served as a novel anti-fibrotic factor to inhibit TGF-ß1-induced cardiac fibroblast activation. Conclusion: Our findings indicate the presence of IL-33-responsive ILC2s in cardiac tissue and that IL-33-mediated ILC2 expansion affords optimal cardioprotective function via ILC2-derived factors. IL-33-mediated immunomodulation is thus a promising strategy to promote tissue repair and alleviate cardiac fibrosis following acute cardiac injury.

Correction: Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.

[This corrects the article DOI: 10.18632/oncotarget.20382.].

The Interrelationship between Ventilatory Inefficiency and Left Ventricular Ejection Fraction in Terms of Cardiovascular Outcomes in Heart Failure Outpatients.

The relationship between left ventricular ejection fraction (LVEF) and cardiovascular (CV) outcome is documented in patients with low LVEF. Ventilatory inefficiency is an important prognostic predictor. We hypothesized that the presence of ventilatory inefficiency influences the prognostic predictability of LVEF in heart failure (HF) outpatients. In total, 169 HF outpatients underwent the cardiopulmonary exercise test (CPET) and were followed up for a median of 9.25 years. Subjects were divided into five groups of similar size according to baseline LVEF (≤39%, 40-58%, 59-68%, 69-74%, and ≥75%). The primary endpoints were CV mortality and first HF hospitalization. The Cox proportional hazard model was used for simple and multiple regression analyses to evaluate the interrelationship between LVEF and ventilatory inefficiency (ventilatory equivalent for carbon dioxide (VE/VCO2) at anaerobic threshold (AT) >34.3, optimized cut-point). Only LVEF and VE/VCO2 at AT were significant predictors of major CV events. The lower LVEF subgroup (LVEF ≤ 39%) was associated with an increased risk of CV events, relative to the LVEF ≥75% subgroup, except for patients with ventilatory inefficiency (p = 0.400). In conclusion, ventilatory inefficiency influenced the prognostic predictability of LVEF in reduced LVEF outpatients. Ventilatory inefficiency can be used as a therapeutic target in HF management.

Incidence and risk factors of colonoscopic post-polypectomy bleeding and perforation in patients with end-stage renal disease.

BACKGROUND AND AIMS: Colonoscopic polypectomy in end-stage renal disease (ESRD) patients are at risks of post-polypectomy bleeding and perforation, but evidences are limited. This study aimed to determine the incident polypectomy complications among ESRD patients. METHODS: In the nationwide ESRD cohort, a propensity score matched case-control study design was conducted to assess risk associated with post-polypectomy bleeding and perforation using the Taiwanese National Health Insurance Research Database from 1997 to 2013 for adults aged 40 years and older; 7011 ESRD and 19 118 non-ESRD patients met the study criteria. A total of 5302 patients in each group were matched for further analyses. The primary endpoint was post-polypectomy bleeding or bowel perforation in 30 days. The secondary endpoint was mortality and length of hospital stay for the bleeding complications requiring hospitalization. RESULTS: Overall incidences of post-polypectomy bleeding or perforation in patients with ESRD was higher than the non-ESRD group (5.83% vs 1.78%, P < 0.0001) in the matched cohort. High risk of adverse outcomes was associated with ESRD (adjusted odds ratio [aOR], 2.38, 95% confidence interval [CI], 1.85-3.05), female patient (aOR, 1.7, 95% CI, 1.37-2.11), history of acute myocardial infarction (aOR, 1.91, 95% CI, 1.1-3.32), liver disease (aOR, 1.79, 95% CI, 1.37-2.34), diabetes (aOR, 1.45, 95% CI, 1.16-1.82), cancer (aOR, 1.4, 95% CI, 1.09-1.81), inpatient setting (aOR, 13.19, 95% CI, 9.73-17.88), and prior use of clopidogrel (aOR, 1.61, 95% CI, 1.03-2.52) and warfarin (aOR, 2.03, 95% CI, 1.21-3.41). CONCLUSIONS: End-stage renal disease was associated with approximately twofold higher risk of colonoscopic post-polypectomy bleeding or perforation and should be cautiously performed in this special population cohort.

Statins reduce new-onset atrial fibrillation after acute myocardial infarction: A nationwide study.

Atrial fibrillation (AF) is an important complication of acute myocardial infarction (AMI). The association between AF and serum lipid profile is unclear and statin use for lowering the incidence of new-onset AF remains controversial. The objective of this study was to investigate whether statins confer a beneficial effect on AF after AMI.Data available in the Taiwan National Health Insurance Research Database on 32886 AMI patients between 2008 and 2011 were retrospectively analyzed. Total 27553 (83.8%) had complete 1-yr follow-up data. Cardiovascular outcomes were analyzed based on the baseline characteristics and AF type (existing, new-onset, or non-AF). AF groups had significantly higher incidence of heart failure (HF), stroke, all-cause death, and major adverse cardiac and cerebrovascular event (MACCE) after index AMI (all P < .05). In contrast, myocardial re-infarction (re-MI) was not significantly different among the three groups (P = .95). Statin use tended to be associated with lower risk of new-onset AF after AMI (HR: 0.935; 95% confidence interval (CI): 0.877-0.998; P = .0427).Existing AF and new-onset AF subgroups had similar cardiovascular outcomes after AMI and were both inferior to the non-AF group. Statin tended to reduce new-onset AF after AMI.

The role of antibiotics in upper gastrointestinal bleeding among cirrhotic patients without major complications after endoscopic hemostasis.

BACKGROUND AND AIM: Antibiotic prophylaxis should be instituted for cirrhotic patients with upper gastrointestinal bleeding (UGIB), but the benefit on compensated patients remains undetermined. We aimed to compare the clinical outcomes between cirrhotic patients without major complications with UGIB with and without antibiotic prophylaxis. METHODS: We conducted this population-based cohort study by using Taiwanese Longitudinal Health Insurance Database 2000 (LHID2000, between 1997 to 2013), aged 18 years or older with a hospital discharge diagnosis of cirrhosis (n = 64,506), UGIB (n = 7,784), and endoscopic therapy (n = 2,292). After strict exclusions, 1205 patients were enrolled and were divided into antibiotic exposure (n = 558) and non-exposure (n = 647) groups. The outcomes were rebleeding and mortality. RESULTS: After completing the analysis adjusted by death, the rebleeding rates within 4 weeks were significantly lower in patients with antibiotic prophylaxis (3.05% versus 6.03%, P = 0.0142) and those with endoscopic therapy (0.72% vs 3.09%, P = 0.0033) but not significant after 3 months and onwards. Male patients aged > 55, high CCI score â‰§ 4, and UGIB of variceal etiologies were benefited from rebleeding. The use of antibiotics did not significantly impact 6-week mortality (adjusted hazard ratio: 1.07, 95%CI: 0.41~2.75; P = 0.8943). Old age, multiple comorbidities, and UGIB of variceal etiologies were risk factors of all-cause mortality. CONCLUSIONS: The current study suggested that cirrhotic patients without major complications who suffered from UGIB were benefited by the use of antibiotics to prevent rebleeding within 4 weeks after endoscopic treatment of UGIB especially for those with age > 55, high CCI score â‰§ 4, and UGIB of variceal etiologies.

Risk of Recurrent Peptic Ulcer Disease in Patients Receiving Cumulative Defined Daily Dose of Nonsteroidal Anti-Inflammatory Drugs.

The purpose of this population-based case-control study was to clarify the impact of cumulative dosage of nonsteroidal anti-inflammatory drugs (NSAIDs) on recurrent peptic ulcers among chronic users after Helicobacter pylori (H. pylori) eradication. We analyzed data of 203,407 adult peptic ulcer disease (PUD) patients from the National Health Insurance Research Database in Taiwan entered between 1997 and 2013. After matching for age/gender frequencies and the length of follow-up time in a ratio of 1:1, the matched case-control groups comprised 1150 patients with recurrent PUD and 1150 patients without recurrent PUD within 3 years of follow-up. More recurrent PUDs occurred in NSAID users than in the control group (75.30% versus 69.74%; p = 0.0028). Independent risk factors for recurrent PUD included patients using NSAIDs (adjusted OR (aOR): 1.34, p = 0.0040), H. pylori eradication (aOR: 2.73; p < 0.0001), concomitant H2 receptor antagonist (aOR: 1.85; p < 0.0001) and anti-coagulant (aOR: 4.21; p = 0.0242) use. Importantly, in the initial subgroup analysis, the risk ratio of recurrent PUD did not increase in NSAID users after H. pylori eradication compared with that in non-users (p = 0.8490) but a higher risk for recurrent PUD with the increased doses of NSAIDs without H. pylori eradication therapy (aOR: 1.24, p = 0.0424; aOR: 1.47, p = 0.0074; and aOR: 1.64, p = 0.0152 in the groups of ≤28, 29-83, and ≥84 cumulative defined daily doses, respectively). The current study suggested that H. pylori eradication therapy could decrease the risk of recurrent PUD among patients with high cumulative doses of NSAIDs.

Additional cavotricuspid isthmus block ablation may not improve the outcome of atrial fibrillation ablation.

AIMS: Pulmonary vein isolation (PVI) is an effective procedure for atrial fibrillation (AF). The role of additional cavotricuspid isthmus (CTI) block ablation remains controversial in AF patients without atrial flutter (AFL). Therefore, this study aimed to explore the clinical outcome of additional CTI block ablation in patients without AFL. METHODS: Between January 2013 and December 2017, a total of 139 patients who did not have documented AFL and who underwent catheter ablation for AF were recruited. Fifty-seven patients were classified in additional CTI block ablation group and 82 patients were classified in without CTI group. The incidence of early-onset and late-onset atrial arrhythmia recurrence was compared between the two groups. RESULTS: The additional CTI group had a higher prevalence of persistent or long-standing AF and larger left atrial volume. The additional CTI group had a higher incidence of late-onset atrial arrhythmia recurrence (38.6% vs 12.2%; P < .001). When compared to without CTI group, additional CTI therapy did not have a better outcome in terms of freedom of atrial arrhythmia in subgroup analysis. The incidence of early-onset and late-onset atrial arrhythmia recurrence did not differ between additional CTI group and without CTI group in paroxysmal AF patients and nonparoxysmal AF patients after propensity scoring matching. CONCLUSION: CTI block ablation in addition to PVI for AF patients without a history of AFL or inducible AFL during ablation may not improve the clinical outcome of AF ablation in the patients with larger LA volume, nonparoxysmal AF, or post-PVI inducible AF.

Calcitriol Attenuates Doxorubicin-Induced Cardiac Dysfunction and Inhibits Endothelial-to-Mesenchymal Transition in Mice.

Doxorubicin (Dox) is an effective anti-neoplasm drug, but its cardiac toxicity limits its clinical use. Endothelial-to-mesenchymal transition (EndMT) has been found to be involved in the process of heart failure. It is unclear whether EndMT contributes to Dox-induced cardiomyopathy (DoIC). Calcitriol, an active form Vitamin D3, blocks the growth of cancer cells by inhibiting the Smad pathway. To investigate the effect of calcitriol via inhibiting EndMT in DoIC, C57BL/6 mice and endothelial-specific labeled mice were intraperitoneally administered Dox twice weekly for 4 weeks (32 mg/kg cumulative dose) and were subsequently treated with or without calcitriol for 12 weeks. Echocardiography revealed diastolic dysfunction at 13 weeks following the first Dox treatment, accompanied by increased myocardial fibrosis and up-regulated pro-fibrotic proteins. Calcitriol attenuated Dox-induced myocardial fibrosis, down-regulated pro-fibrotic proteins and improved diastolic function. Endothelial fate tracing revealed that EndMT-derived cells contributed to Dox-induced cardiac fibrosis. In vitro, human umbilical vein endothelial cells and mouse cardiac fibroblasts were treated with Transforming growth factor (TGF)-ß with or without calcitriol. Morphological, immunofluorescence staining, and Western blot analyses revealed that TGF-ß-induced EndMT and fibroblast-to-myofibroblast transition (FMT) were attenuated by calcitriol by the inhibition of the Smad2 pathway. Collectively, calcitriol attenuated DoIC through the inhibition of the EndMT and FMT processes.

Diabetes Mellitus: An Independent Risk Factor of In-Hospital Mortality in Patients with Infective Endocarditis in a New Era of Clinical Practice.

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17%-25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p < 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p < 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p < 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.