ABSTRACT
BACKGROUND: The efficacy of different nucleos(t)ide analogs in the treatment of chronic hepatitis B virus (CHB) with severe acute exacerbation (SAE) remained unclear. Thus, this study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients having CHB with SAE. METHODS: We analyzed consecutive patients with treatment-naive CHB receiving TDF (nâ =â 36) or ETV (nâ =â 65) for SAE. The primary endpoint was overall mortality or receipt of liver transplantation (LT) by 24 weeks. The secondary endpoints are the comparison of ETV vs. TDF influences on renal function and virological and biochemical responses at 4, 12, 24, and 48 weeks. RESULTS: The baseline characteristics were comparable between the two groups. By 24 weeks, 8 (22%) patients in the TDF group and 10 (15%) patients in the ETV group had either died (nâ =â 15) or received LT (nâ =â 3) ( P â =â 0.367). Cox-regression multivariate analysis revealed age ( P â =â 0.003), baseline international normalized ratio of prothrombin time ( Pâ =â 0.024), and early presence of hepatic encephalopathy ( P â =â 0.003) as independent factors associated with mortality or LT. The two groups of patients achieved comparable biochemical and virological responses at 48 weeks. No significant difference was found in the estimated glomerular filtration rate (eGFR) between the TDF and the ETV groups. However, a significant reduction in the eGFR at 48 weeks, as compared with the baseline, was found in each group. CONCLUSION: TDF and ETV achieved similar short-term clinical outcomes and treatment responses in CHB patients with SAE.
Subject(s)
Antiviral Agents , Guanine , Hepatitis B, Chronic , Tenofovir , Humans , Guanine/analogs & derivatives , Guanine/therapeutic use , Guanine/adverse effects , Female , Male , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/mortality , Tenofovir/therapeutic use , Antiviral Agents/therapeutic use , Antiviral Agents/adverse effects , Middle Aged , Adult , Treatment Outcome , Liver Transplantation , Retrospective Studies , Disease Progression , Severity of Illness Index , Glomerular Filtration Rate/drug effects , DNA, Viral/blood , Viral Load , Time Factors , Hepatitis B virus/drug effects , Hepatitis B virus/genetics , Proportional Hazards ModelsABSTRACT
BACKGROUND: The existing literature lacks studies examining the epidemiological link between scrub typhus and deep vein thrombosis (DVT) or pulmonary embolism (PE), and the long-term outcomes. The objective of this study is to explore the potential association between scrub typhus and the subsequent risk of venous thromboembolism, and long-term mortality. METHOD: This nationwide cohort study identified 10,121 patients who were newly diagnosed with scrub typhus. Patients with a prior DVT or PE diagnosis before the scrub typhus infection were excluded. A comparison cohort of 101,210 patients was established from the general population using a propensity score matching technique. The cumulative survival HRs for the two cohorts were calculated by the Cox proportional hazards model. RESULT: After adjusting for sex, age, and comorbidities, the scrub typhus group had an adjusted HR (95% CI) of 1.02 (0.80-1.30) for DVT, 1.11 (0.63-1.93) for PE, and 1.16 (1.08-1.25) for mortality compared to the control group. The post hoc subgroup analysis revealed that individuals younger than 55 years with a prior scrub typhus infection had a significantly higher risk of DVT (HR: 1.59; 95% CI: 1.12-2.25) and long-term mortality (HR: 1.75; 95% CI, 1.54-1.99). CONCLUSION: The scrub typhus patients showed a 16% higher risk of long-term mortality. For those in scrub typhus cohort below 55 years of age, the risk of developing DVT was 1.59 times higher, and the risk of mortality was 1.75 times higher. Age acted as an effect modifier influencing the relationship between scrub typhus and risk of new-onset DVT and death.
Subject(s)
Scrub Typhus , Venous Thromboembolism , Humans , Scrub Typhus/complications , Scrub Typhus/epidemiology , Scrub Typhus/mortality , Male , Female , Middle Aged , Aged , Adult , Venous Thromboembolism/epidemiology , Venous Thromboembolism/mortality , Venous Thromboembolism/etiology , Risk Factors , Cohort Studies , Proportional Hazards Models , Aged, 80 and over , Pulmonary Embolism/mortality , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Young AdultABSTRACT
BACKGROUND: The long-term outcome on patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been ideal after standard medical treatment. However, good outcome for patients with CTEPH after interventions such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) has been reported recently. The aim of this study was to evaluate the impact of PEA or BPA on long-term outcomes for CTEPH patients in Han-Chinese population. METHODS: This was a multicenter, prospective case-control study. Patients with CTEPH were enrolled between January, 2018 and March, 2020. They were divided into two groups, including intervention (PEA or BPA) and conservative groups. The followed-up period was 26 months after treatment. The endpoints were all-cause mortality and CTEPH mortality. RESULTS: A total of 129 patients were enrolled and assigned to receive PEA/BPA (N = 73), or conservative therapy (N = 56). Overall, the 26-month survival rate of all-cause mortality was significantly higher in intervention group compared to that in conservative group (95.89% vs 80.36%; log-rank p = 0.0164). The similar trend was observed in the 26-month survival rate of CTEPH mortality (97.26% vs 85.71%; log-rank p = 0.0355). Regarding Cox proportional-hazard regression analysis, the hazard ratios (HRs) on patients with CTEPH receiving intervention in the outcome of all-cause mortality and CTEPH mortality were statistically significant (HR = 0.07 and p = 0.0141 in all-cause mortality; HR = 0.11 and p = 0.0461 in CTEPH mortality). CONCLUSION: This multicenter prospective case-control study demonstrated that intervention such as PEA and BPA increased the long-term survival rate for patient with CTEPH significantly. Intervention was an independent factor in long-term outcome for patients with CTEPH, including all-cause mortality and CTEPH mortality.
Subject(s)
Angioplasty, Balloon , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Hypertension, Pulmonary/surgery , Pulmonary Embolism/complications , Pulmonary Embolism/surgery , Case-Control Studies , Chronic Disease , Angioplasty, Balloon/adverse effects , Endarterectomy/adverse effects , Pulmonary Artery/surgeryABSTRACT
BACKGROUND: This study aimed to evaluate the impact of end-stage kidney disease (ESKD) on mortality in patients with first-time acute myocardial infarction (AMI). METHODS: This was a retrospective nationwide cohort study. Patients diagnosed with first-time AMI between January 1, 2000, and December 31, 2012, were included. All patients were followed-up until death or December 31, 2012, whichever occurred first. A one-to-one propensity score matching technique was used to match patients with ESKD to those without ESKD of similar sex, age, comorbidities, and coronary intervention (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). Kaplan-Meier cumulative survival curves were constructed to compare AMI patients with and without ESKD. RESULTS: A total of 186 112 patients were enrolled and 8056 patients with ESKD were identified. Propensity score matched 8056 patients without ESKD were included in the comparison. Overall, the 12-year mortality rate was significantly higher in patients with ESKD than in those without ESKD (log-rank p < 0.0001), including the sex, age, and PCI and CABG subgroups. In Cox proportional-hazard regression analysis, ESKD was an independent risk factor for mortality after patients suffered from first-time AMI (hazard ratio, 1.77; 95% CI, 1.70-1.84; p < 0.0001). A forest plot for subgroup analysis revealed that in AMI patients, ESKD had a higher impact on mortality in male; younger age; without comorbidities such as hypertension, diabetes mellitus, peripheral vascular disease, heart failure, cerebrovascular accident, and chronic obstructive pulmonary disease; and receiving PCI and CABG subgroups. CONCLUSION: ESKD significantly increases the mortality risk in patients with first-time AMI, including both sexes, different ages, and whether PCI or CABG was performed. In patients with AMI, ESKD has a high impact on mortality in male, younger age, without comorbidities, and those undergoing PCI and CABG.
Subject(s)
Coronary Artery Disease , Kidney Failure, Chronic , Myocardial Infarction , Percutaneous Coronary Intervention , Female , Humans , Male , Percutaneous Coronary Intervention/methods , Cohort Studies , Retrospective Studies , Treatment Outcome , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapyABSTRACT
Introduction: Lipopolysaccharide (LPS) is widely used to induce experimental animals. However, its effects on cardiac contraction is controversial. Although LPS probably induces its influence in vivo both directly and indirectly, we focused on the direct effects of LPS in this report. Material and methods: Isolated ventricular myocytes mounted on a Langendorff apparatus were perfused with LPS. The changes in cultured H9c2 cells incubated with LPS over a 3-h exposure were compared with the changes after a 24-h incubation. Apoptosis was identified using flow cytometry and Western blotting. The mRNA levels were also determined. Results: LPS directly stimulated cardiac contractility at low doses, although it produced inhibition at higher doses. The TLR4-coupled JAK2/STAT3 pathway was identified in H9c2 cells after LPS treatment, with an increase in intracellular calcium levels. LPS dose-dependently activated hypertrophic signals in H9c2 cells and induced apoptosis at the high dose. However, apoptosis was observed in H9c2 cells after a 24-h exposure to LPS, even at low doses. This observation appears to be associated with the level of paracrine cytokines. Changes in H9c2 cells by LPS were diminished by NPS2390, an inhibitor of the calcium-sensing receptor (CaSR). LPS also promoted CaSR mRNA expression in H9c2 cells, which may be unrelated to the changes in cytokine expression influenced by an inflammasome inhibitor. Conclusions: In contrast to the isolated hearts, LPS activated hypertrophic signals prior to apoptotic signals in cardiac cells. Thus, LPS injury appears to be associated with CaSR, which was not markedly influenced by an inflammasome inhibitor.
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Introduction: Thymoquinone (TQ) is one of the principal bioactive ingredients proven to exhibit anti-diabetic effects. Recently, glucagon-like peptide-1 (GLP-1) has been found to be involved in antidiabetic effects in rats. The aim of this study was to evaluate the mediation of GLP-1 in the antidiabetic effect of TQ and to understand the possible mechanisms. Material and methods: NCI-H716 cells and CHO-K1 cells were used to investigate the effects of TQ on GLP-1 secretion in vitro. In type 1 diabetic rats, the changes in plasma glucose and GLP-1 levels were evaluated with TQ treatment. Results: The direct effect of TQ on imidazoline receptors (I-Rs) was identified in CHO-K1 cells overexpressing I-Rs. Additionally, in the intestinal NCI-H716 cells that may secrete GLP-1, TQ treatment enhanced GLP-1 secretion in a dose-dependent manner. However, these effects of TQ were reduced by ablation of I-Rs with siRNA in NCI-H716 cells. Moreover, these effects were inhibited by BU224, the imidazoline I2 receptor (I-2R) antagonist. In diabetic rats, TQ increased plasma GLP-1 levels, which were inhibited by BU-224 treatment. Functionally, TQ-attenuated hyperglycemia is also evidenced through GLP-1 using pharmacological manipulations. Conclusions: This report demonstrates that TQ may promote GLP-1 secretion through I-R activation to reduce hyperglycemia in type-1 diabetic rats.
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BACKGROUND: Percutaneous coronary interventions (PCI) in very small vessel lesions represent an intriguing aspect of coronary artery disease (CAD). Uncertainty still exists in stent implantation in very small caliber vessels. This study aimed to evaluate the long-term outcomes of patients treated with 2.0-mm drug-eluting stent (DES). METHOD: This retrospective observational study included 134 patients undergoing PCI with 2.0-mm zotarolimus DES from December 2016 to May 2020. The primary endpoint was major adverse cardiovascular events (MACE) at 2-year follow-up, which was composed of all-cause mortality, target vessel myocardial infarction, and ischemia-driven target lesion revascularization. Multiple logistic regression analysis was used to identify the independent predictors of MACE, and odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULT: The lesions were diffuse (mean length 20.9 ± 5.51 mm) and belong to type B2/C lesions (90.3%). On follow-up, the MACE rate was 20.1% and mostly driven by late lumen loss demanding revascularization (11.9%). In multivariable analysis, chronic kidney disease (CKD) (OR: 4.291, 95% CI: 1.574-11.704, p = 0.004) and calcified lesions (OR: 3.688, 95% CI: 1.311-10.371, p = 0.013) were the independent predictors of subsequent cardiovascular events, whereas statin was associated with better outcomes (OR: 0.335, 95% CI: 0.119-0.949, p = 0.040). CONCLUSION: 2.0-mm DES is a feasible option for treating very small vessel CAD in complex lesions. Patients with CKD and calcified lesions carry the hazard of worse outcomes, and careful consideration should be taken before stenting in this high-risk population.
Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Renal Insufficiency, Chronic , Humans , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Stents , Risk Factors , Prosthesis DesignABSTRACT
AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a powerful low density lipoprotein cholesterol (LDL-C)-lowering therapy, but this drug is expensive. This study aimed to describe the real-world treatment conditions in patients initiating PCSK9 inhibitor in Taiwan. METHODS: This was a multicenter, retrospective, and observational study. The clinical characteristics, baseline lipid-lowering therapy, and changes in the lipid profile of patients receiving PCSK9 inhibitor treatment were obtained from 11 major teaching hospitals in Taiwan. RESULTS: A total of 296 patients (age 57±13 years, male 73%) who received PCSK9 inhibitor treatments (73.3% alirocumab and 26.7% evolocumab) from 2017 to 2021 were included. Among the patients, 62.8% had history of coronary artery disease, and 27.7% had myocardial infarction. High intensity statin (HIS) monotherapy or HISï¼ezetimibe treatment was used in 32.5% when initiating PCSK9 inhibitor treatment. Among alirocumab users, 21.2% received 75 mg every 3 to 4 weeks, whereas among evolocumab users, 8.9% received 140 mg every 3 to 4 weeks. Almost all the non-standard-dosing PCSK9 inhibitors were paid by the patients themselves but were not reimbursed by the Taiwan National Health Insurance. Overall, the LDL-C levels at baseline and 12 weeks after treatment were 147.4±67.4 and 69.7±58.2 mg/dL (pï¼0.01), corresponding to a 49.6%±31.8% LDL-C reduction. CONCLUSIONS: In the real-world practice in Taiwan, the LDL-C reduction efficacy of PCSK9 inhibitors was slightly lower than that reported in the clinical trials. The use of non-standard-dosing PCSK9 inhibitors was not uncommon in Taiwan.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Proprotein Convertase 9 , Humans , Male , Adult , Middle Aged , Aged , Cholesterol, LDL , Antibodies, Monoclonal/therapeutic use , Retrospective Studies , Taiwan/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SubtilisinsABSTRACT
Background: A significant proportion of acute coronary syndrome (ACS) patients experience high on-treatment platelet reactivity (HPR) on clopidogrel-based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Objectives: This study assessed key independent risk factors associated with significant HPR risk on clopidogrel, but not prasugrel, in the Switch Study cohort of 200 Taiwanese ACS patients who switched from clopidogrel to low-dose prasugrel for maintenance DAPT after PCI. Methods: Univariate analysis and stepwise multivariate logistic regression analysis were conducted to identify key independent risk factors for HPR on clopidogrel, but not prasugrel. Results: A HANC [H: low hemoglobin (< 13 g/dL for men and < 12 g/dL for women); A: age ≥ 65 years; N: non-ST elevation myocardial infarction; C: chronic kidney disease as defined by estimated glomerular filtration rate < 60 mL/min] risk stratification score was developed, and demonstrated optimal sensitivity and specificity at a cutoff score of ≥ 2. The HANC score compared favorably against the recently validated ABCD score in the full Switch Study cohort (n = 200), and the ABCD-GENE score in a genotyped cohort (n = 102). Conclusions: The HANC score may serve to alert clinicians to patients at potentially higher HPR risk on clopidogrel, but not prasugrel. Further research to validate this score and assess its correlation with clinical outcomes is warranted.
ABSTRACT
BACKGROUND/PURPOSE: Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet. METHODS: CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients. RESULTS: Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel. CONCLUSION: Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.
Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Clopidogrel , Cytochrome P-450 CYP2C19 , Humans , Platelet Aggregation Inhibitors , Prasugrel Hydrochloride , TiclopidineABSTRACT
Methods: Between 2015 and 2018, 580 men undergoing PCI at a tertiary referral hospital were divided into low (<3.25 ng/mL) and normal (≥3.25 ng/mL) testosterone groups. Major adverse cardiovascular event (MACE) was defined as the composite outcome of CV death, myocardial infarction, and target lesion revascularization/target vessel revascularization (TLR/TVR) during up to 48 months follow-up after PCI. Results: There were 111 and 469 patients in the low and normal testosterone groups, respectively, with the overall MACE rate of the former being higher than the latter (26.13% vs. 13.01%, p = 0.0006). Moreover, the overall TLR/TVR (20.72% vs. 11.73%, p = 0.0125) and myocardial infarction (3.6% vs. 0.85%, p = 0.0255) rates were significantly higher in those with low serum testosterone who also had a shorter average event-free survival analysis of MACE (25.22 ± 0.88 months) than those with normal testosterone levels (35.09 ± 0.47 months, log-rank p = 0.0004). Multiple logistic regression demonstrated an association between low serum testosterone (<3.25 ng/mL) and a higher MACE rate [odds ratio: 2.06, 95% confidence interval (CI) 1.21-3.51, p = 0.0081]. After adjusting for variables in a Cox regression model, hazard ratios (HRs) for MACE (HR: 1.88, 95% CI: 1.20-2.95, p = 0.0058) and TLR/TVR (HR: 1.73, 95% CI: 1.06-2.83, p = 0.0290) rates were higher in the low testosterone group than those in the normal testosterone group. Conclusion: Low serum testosterone concentrations were associated with a higher risk of MACE and TLR/TVR after PCI than those with normal testosterone levels.
ABSTRACT
The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean - 18.2 ± 48.1; 95% confidence interval - 24.9 to - 11.5, p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.
Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/surgery , Aged , Clopidogrel/adverse effects , Female , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Prasugrel Hydrochloride/adverse effects , Ticlopidine/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Acute myocardial infarction (AMI) and atrial fibrillation (AF) are risk factors for stroke. The risk of stroke after AMI may differ between patients with and without AF. The aim of this study was to evaluate the impact of AF on stroke in patients after the first AMI. METHODS: This was a retrospective, nationwide cohort study. Patients with a primary diagnosis of a first AMI between 2000 and 2012 were included. All patients were followed up until ischemic stroke or transient ischemic attack (TIA), or December 31, 2012, whichever occurred first. Kaplan-Meier cumulative survival curves were constructed to compare ischemic stroke or TIA between AMI patients with and without AF. RESULTS: A total of 170 472 patients were enrolled in this study. Among them, 8530 patients with AF were identified. The propensity score matching technique was used to match 8530 patients without AF of similar ages and sexes. Overall, the 12-year stroke rate was significantly higher in patients with AF than in those without AF (log-rank p < 0.001), including different sexes, ages, and interventional therapy subgroups. Patients with pre-existing AF had higher stroke rates than those with newly diagnosed AF in male sex, age below 65 years, and those receiving interventional therapy subgroups. In Cox proportional-hazard regression analysis, AF was an independent risk factor for stroke after the first AMI (hazard ratio, 1.67; 95% CI: 1.5-1.87). CONCLUSION: AF significantly increases stroke risk after the first AMI. In patients with AF, those with pre-existing AF have higher stroke risks in male sex, age below 65 years, and those with interventional therapy than those with newly diagnosed AF.
Subject(s)
Atrial Fibrillation , Myocardial Infarction/complications , Stroke/etiology , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Risk AssessmentABSTRACT
The oral glucose tolerance test (OGTT) has been widely used both in clinics and in basic research for a long time. It is applied to diagnose impaired glucose tolerance and/or type 2 diabetes mellitus in individuals. Additionally, it has been employed in research to investigate glucose utilization and insulin sensitivity in animals. The main aim of each was quite different, and the details are also somewhat varied. However, the time or duration of the OGTT was the same, using the 2-h post-glucose load glycemia in both, following the suggestions of the American Diabetes Association. Recently, the use of 30-min or 1-h post-glucose load glycemia in clinical practice has been recommended by several studies. In this review article, we describe this new view and suggest perspectives for the OGTT. Additionally, quantification of the glucose curve in basic research is also discussed. Unlike in clinical practice, the incremental area under the curve is not suitable for use in the studies involving animals receiving repeated treatments or chronic treatment. We discuss the potential mechanisms in detail. Moreover, variations between bench and bedside in the application of the OGTT are introduced. Finally, the newly identified method for the OGTT must achieve a recommendation from the American Diabetes Association or another official unit soon. In conclusion, we summarize the recent reports regarding the OGTT and add some of our own perspectives, including machine learning and others.
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Pulmonary arterial hypertension (PAH) is an incurable chronic and progressive debilitating disease associated with significant morbidity and mortality. The World Health Organization functional class (WHO FC) at diagnosis and at follow-up remains one of the strongest predictors of survival in PAH. Studies have shown improved long-term outcomes in PAH patients who received PAH-specific treatment, as monotherapy or as combination therapy, early in their disease course. Studies have also shown that without treatment, PAH rapidly deteriorates even in patients with less advanced (low risk) disease state. In this article, we review evidence from randomized controlled clinical trials to support our position on the importance of early PAH management in WHO FC II patients. The growing importance of combination therapy in the early treatment of PAH and recommendations by the most recent guidelines for the diagnosis and treatment of pulmonary hypertension are also discussed in this article.
ABSTRACT
BACKGROUND: Adropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed. MATERIALS AND METHODS: Rats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasis-associated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting. RESULTS: In diabetic rats, the serum concentrations of adropin were increased in the vehicle-treated group and decreased in the insulin- or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs. CONCLUSION: STAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.
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Few reports discussed the issue of the relationship between the stent fracture and the formation of coronary artery aneurysms. We reported a case about the stent fracture associated with dissected flaps and one giant coronary artery aneurysms.
Subject(s)
Aortic Dissection/etiology , Coronary Aneurysm/etiology , Drug-Eluting Stents , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Prosthesis Failure , Aortic Dissection/diagnostic imaging , Aortic Dissection/therapy , Coronary Aneurysm/diagnostic imaging , Coronary Aneurysm/therapy , Female , Humans , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Prosthesis Design , Retreatment , Treatment OutcomeABSTRACT
Background: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia. Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9-39 (Ex 9-39) were separately administered to TQ- or vehicle-treated diabetic rats. Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9-39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects. Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.