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1.
J Formos Med Assoc ; 123 Suppl 2: S82-S90, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37633770

RESUMO

The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hiperaldosteronismo , Hipertensão , Humanos , Adulto , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hipertensão/complicações , Programas de Rastreamento , Prevalência
2.
J Formos Med Assoc ; 123 Suppl 2: S114-S124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37202237

RESUMO

Adrenal venous sampling (AVS) is a crucial method for the lateralization of primary aldosteronism (PA). It is advised to halt the use of the patient's antihypertensive medications and correct hypokalemia prior to undergoing AVS. Hospitals equipped to conduct AVS should establish their own diagnostic criteria based on current guidelines. If the patient's antihypertensive medications cannot be discontinued, AVS can be performed as long as the serum renin level is suppressed. The Task Force of Taiwan PA recommends using a combination of adrenocorticotropic hormone stimulation, quick cortisol assay, and C-arm cone-beam computed tomography to maximize the success of AVS and minimize errors by using the simultaneous sampling technique. If AVS is not successful, an NP-59 (131 I-6-ß-iodomethyl-19-norcholesterol) scan can be used as an alternative method to lateralize PA. We depicted the details of the lateralization procedures (mainly AVS, and alternatively NP-59) and their tips and tricks for confirmed PA patients who would consider to undergo surgical treatment (unilateral adrenalectomy) if the subtyping shows unilateral disease.


Assuntos
Glândulas Suprarrenais , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/cirurgia , Aldosterona , Anti-Hipertensivos , Adosterol , Estudos Retrospectivos
3.
J Formos Med Assoc ; 123 Suppl 2: S98-S103, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37173226

RESUMO

The aldosterone-to-renin ratio (ARR) is the standard screening test for primary aldosteronism (PA). Because of the poor reproducibility of the ARR, repeat testing is recommended if the result is not compatible with the clinical condition. Various methods to measure renin are used in different hospitals in Taiwan, and the ARR cutoff values also differ among laboratories. The Task Force of Taiwan PA recommend using plasma renin activity (PRA) to calculate ARR instead of direct renin concentration (DRC) unless PRA is unavailable, because PRA is widely used in international guidelines and most studies.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Reprodutibilidade dos Testes , Hospitais , Hipertensão/etiologia
4.
J Formos Med Assoc ; 123 Suppl 2: S104-S113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37173227

RESUMO

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Hidrocortisona , Captopril
5.
J Formos Med Assoc ; 123 Suppl 2: S91-S97, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37291044

RESUMO

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding ß-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Aldosterona , Bloqueadores dos Canais de Cálcio/uso terapêutico , Renina , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico
6.
J Am Chem Soc ; 145(18): 10275-10284, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37115733

RESUMO

Formamidinium lead triiodide (FAPbI3) is the leading candidate for single-junction metal-halide perovskite photovoltaics, despite the metastability of this phase. To enhance its ambient-phase stability and produce world-record photovoltaic efficiencies, methylenediammonium dichloride (MDACl2) has been used as an additive in FAPbI3. MDA2+ has been reported as incorporated into the perovskite lattice alongside Cl-. However, the precise function and role of MDA2+ remain uncertain. Here, we grow FAPbI3 single crystals from a solution containing MDACl2 (FAPbI3-M). We demonstrate that FAPbI3-M crystals are stable against transformation to the photoinactive δ-phase for more than one year under ambient conditions. Critically, we reveal that MDA2+ is not the direct cause of the enhanced material stability. Instead, MDA2+ degrades rapidly to produce ammonium and methaniminium, which subsequently oligomerizes to yield hexamethylenetetramine (HMTA). FAPbI3 crystals grown from a solution containing HMTA (FAPbI3-H) replicate the enhanced α-phase stability of FAPbI3-M. However, we further determine that HMTA is unstable in the perovskite precursor solution, where reaction with FA+ is possible, leading instead to the formation of tetrahydrotriazinium (THTZ-H+). By a combination of liquid- and solid-state NMR techniques, we show that THTZ-H+ is selectively incorporated into the bulk of both FAPbI3-M and FAPbI3-H at ∼0.5 mol % and infer that this addition is responsible for the improved α-phase stability.

7.
J Formos Med Assoc ; 122(5): 393-399, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36813699

RESUMO

PURPOSE: Mineralocorticoid receptor antagonists are the first-line treatment for bilateral adrenal hyperplasia (BAH) with primary aldosteronism (PA), while unilateral adrenalectomy is the standard treatment for aldosterone-producing adenoma (APA). In this study, we investigated the outcomes of patients with BAH after unilateral adrenalectomy and compared them with those of patients with APA. METHODS: From January 2010 to November 2018, 102 patients with a diagnosis of PA confirmed by adrenal vein sampling (AVS) and available NP-59 scans were enrolled. All patients underwent unilateral adrenalectomy based on the lateralization test results. We prospectively collected the clinical parameters over 12 months and compared the outcomes of BAH and APA. RESULTS: A total of 102 patients were enrolled in this study: 20 (19.6%) had BAH and 82 (80.4%) had APA. Significant improvements in serum aldosterone-renin ratio (ARR), potassium level, and reduction of antihypertensive drugs were observed in both groups at 12 months after surgery (all p < 0.05). Patients with APA showed a significant decrease in blood pressure after surgery (p < 0.001) than those with BAH. Additionally, multivariate logistic regression analysis indicated that APA was associated with biochemical success (odds ratio: 4.32, p = 0.024) compared to BAH. CONCLUSION: Patients with BAH had a higher failure rate in clinical outcomes, and APA was associated with biochemical success after unilateral adrenalectomy. However, significant improvements in ARR, hypokalemia, and a decreased use of antihypertensive drugs were noted in patients with BAH after surgery. Unilateral adrenalectomy is feasible and beneficial in selected patients, and could potentially serve as a treatment option.


Assuntos
Adrenalectomia , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/cirurgia , Aldosterona , Hiperplasia , Anti-Hipertensivos/uso terapêutico
8.
Acta Cardiol Sin ; 39(6): 817-830, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38022428

RESUMO

Background: The optimal strategy of percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated with cardiogenic shock (CS) remains controversial. We aimed to elucidate the renal and cardiovascular impact of culprit-only (C) revascularization versus additional interventions on non-infarct-related arteries. Methods: PubMed, Embase, MEDLINE, and Cochrane Library were searched for relevant literature. A total of 96,812 subjects [C-PCI: 69,986; multi-vessel (MV)-PCI: 26,826] in nine studies (one randomized control trial; eight observational cohort studies) were enrolled. Results: MV-PCI was associated with a higher kidney event rate [relative risk (RR): 1.29, 95% confidence interval (CI): 1.12-1.49; p < 0.001]. However, the all-cause mortality rate was comparable both during admission (RR: 1.07, 95% CI: 0.94-1.22; p = 0.30) and at one year (RR: 0.96, 95% CI: 0.79-1.16; p = 0.65). MV-PCI was associated with a greater risk of stroke (RR: 1.19, 95% CI: 1.08-1.32; p < 0.001) and bleeding events (RR: 1.27, 95% CI: 1.07-1.51; p = 0.006), but reduced risk of recurrent MI (RR: 0.89, 95% CI: 0.82-0.97; p = 0.009) and repeat revascularization (RR: 0.34, 95% CI: 0.16-0.71; p = 0.004). No increased risk of coronary artery bypass grafting was present (RR: 1.09, 95% CI: 0.38-3.17; p = 0.87). Conclusions: C-PCI was associated with a lower rate of renal dysfunction but not all-cause mortality in patients with CS complicating acute MI.

9.
Acta Cardiol Sin ; 39(4): 511-543, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37456934

RESUMO

Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

10.
Acta Cardiol Sin ; 39(4): 619-627, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37456942

RESUMO

Background: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown. Objectives: This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment. Methods: We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment. Results: Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m2, and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement. Conclusions: The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement.

11.
Acta Cardiol Sin ; 39(2): 213-241, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36911549

RESUMO

Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide. Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment. Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus. Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.

12.
Acta Cardiol Sin ; 39(3): 361-390, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37229331

RESUMO

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

13.
J Cell Physiol ; 237(4): 2140-2154, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35019151

RESUMO

We present a mechanism for how ornithine decarboxylase (ODC) regulates the crosstalk between autophagy and apoptosis. In cancer cells, low-intensity ultraviolet B (UVBL ) induces autophagy while high-intensity UVB (UVBH ) induces apoptosis. Overexpression of ODC decreases UVBL -induced autophagy by inhibiting Atg5-Atg12 conjugation and suppressing the expression of autophagy markers LC3, Atg7, Atg12, and BECN1 proteins. In contrast, when ODC-overexpressing cells are exposed to UVBH radiation, the levels of LC3-II, Atg5-Atg12 conjugate, BECN1, Atg7, and Atg12 increase, while the apoptosis marker cleaved-PARP proteins decrease, indicating that ODC overexpression induced UVBH -induced autophagy but inhibited UVBH -induced cellular apoptosis. Additionally, when exposed to UVBH radiation, silencing BECN1, Atg5, and Atg12 genes results in a decrease in the level of LC3-II proteins but an increase in the level of cleaved-PARP proteins, and apoptotic bodies were significantly increased while autophagosomes were significantly decreased. These findings imply that ODC inhibits apoptosis in cells via the autophagy pathway. The role of Atg12 in ODC-overexpressing cells exposed to UVBH radiation is investigated using site-directed mutagenesis. Our results indicate that the Atg12-D111S mutant has increased cell survival. The Atg12-ΔG186 mutant impairs autophagy and enhances apoptosis. We demonstrate that when ODC-overexpressing cells are silenced for the Atg12 protein, autophagy and apoptosis are strongly affected, and ODC-induced autophagy protects against UVBH -induced apoptosis via the Atg12 protein.


Assuntos
Ornitina Descarboxilase , Lesões por Radiação , Apoptose/genética , Autofagia/genética , Proteína 12 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Humanos , Ornitina Descarboxilase/genética , Raios Ultravioleta
14.
Nat Mater ; 20(9): 1248-1254, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33888905

RESUMO

Electronic doping of organic semiconductors is essential for their usage in highly efficient optoelectronic devices. Although molecular and metal complex-based dopants have already enabled significant progress of devices based on organic semiconductors, there remains a need for clean, efficient and low-cost dopants if a widespread transition towards larger-area organic electronic devices is to occur. Here we report dimethyl sulfoxide adducts as p-dopants that fulfil these conditions for a range of organic semiconductors. These adduct-based dopants are compatible with both solution and vapour-phase processing. We explore the doping mechanism and use the knowledge we gain to 'decouple' the dopants from the choice of counterion. We demonstrate that asymmetric p-doping is possible using solution processing routes, and demonstrate its use in metal halide perovskite solar cells, organic thin-film transistors and organic light-emitting diodes, which showcases the versatility of this doping approach.

15.
Int J Urol ; 29(8): 831-837, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35474521

RESUMO

OBJECTIVES: Decreased glomerular filtration rate has been reported in patients with primary aldosteronism after unilateral adrenalectomy. Glomerular hyperfiltration has been assumed to mask the preoperative subtle renal impairment. In this study, we investigated predictors for decreased estimated glomerular filtration rate after adrenalectomy in patients with primary aldosteronism. METHODS: From January 2006 through September 2018, 328 patients with confirmatory diagnoses of primary aldosteronism received unilateral laparoscopic adrenalectomy and subsequent follow-up for 12 months. We prospectively collected related parameters of the clinical outcomes and renal function to identify predictors of renal function impairment at 12 months after surgery. RESULTS: Patients were stratified into three groups by preoperative estimated glomerular filtration rate level: 144 (43.9%) with estimated glomerular filtration rate ≥90, 130 (39.6%) with estimated glomerular filtration rate within 60-89.9, and 54 (16.5%) with estimated glomerular filtration rate <60 mL/min/1.73 m2 . The estimated glomerular filtration rate decreased significantly at the 6th month and remained stable at the 12th month, postoperatively. Patients with estimated glomerular filtration rate ≥90 had better clinical outcome with 59.6% success rate (P = 0.006) among three groups. Multivariate logistic regression analysis indicated that preoperative estimated glomerular filtration rate (odds ratio 1.012, P = 0.02) and hypokalemia (odds ratio 2.018, P = 0.024) were associated with renal impairment at 12th month after adrenalectomy. Multivariate linear regression analysis revealed high preoperative estimated glomerular filtration rate (ß = 0.261, P < 0.001), high preoperative systolic blood pressure (ß = 0.168, P = 0.003), high level of microalbuminuria (ß = 0.024, P = 0.001), and low level of serum potassium (ß = -4.883, P = 0.007) were associated with estimated glomerular filtration rate percentage decline at 12th month after adrenalectomy. CONCLUSIONS: Estimated glomerular filtration rate declined significantly after adrenalectomy in patients with estimated glomerular filtration rate ≥90. The study provided important information to identify primary aldosteronism patients with higher risk of estimated glomerular filtration rate decline after adrenalectomy and might help to adopt early interventions to improve the outcomes.


Assuntos
Hiperaldosteronismo , Insuficiência Renal , Adrenalectomia/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/cirurgia , Rim/fisiologia , Rim/cirurgia , Insuficiência Renal/etiologia , Estudos Retrospectivos
16.
Int J Mol Sci ; 24(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36614054

RESUMO

Altered metabolism is a hallmark of aging. The tricarboxylic acid cycle (TCA cycle) is an essential metabolic pathway and plays an important role in lifespan regulation. Supplementation of α-ketoglutarate, a metabolite converted by isocitrate dehydrogenase alpha-1 (idha-1) in the TCA cycle, increases lifespan in C. elegans. However, whether idha-1 can regulate lifespan in C. elegans remains unknown. Here, we reported that the expression of idha-1 modulates lifespan and oxidative stress tolerance in C. elegans. Transgenic overexpression of idha-1 extends lifespan, increases the levels of NADPH/NADP+ ratio, and elevates the tolerance to oxidative stress. Conversely, RNAi knockdown of idha-1 exhibits the opposite effects. In addition, the longevity of eat-2 (ad1116) mutant via dietary restriction (DR) was reduced by idha-1 knockdown, indicating that idha-1 may play a role in DR-mediated longevity. Furthermore, idha-1 mediated lifespan may depend on the target of rapamycin (TOR) signaling. Moreover, the phosphorylation levels of S6 kinase (p-S6K) inversely correlate with idha-1 expression, supporting that the idha-1-mediated lifespan regulation may involve the TOR signaling pathway. Together, our data provide new insights into the understanding of idha-1 new function in lifespan regulation probably via DR and TOR signaling and in oxidative stress tolerance in C. elegans.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Isocitrato Desidrogenase , Longevidade , Estresse Oxidativo , Animais , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Longevidade/genética
17.
Acta Cardiol Sin ; 38(6): 751-764, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36440250

RESUMO

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.

18.
Acta Cardiol Sin ; 38(6): 700-713, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36440253

RESUMO

Background: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF. Methods: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month. Results: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable. Conclusions: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

19.
Acta Cardiol Sin ; 38(3): 225-325, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35673334

RESUMO

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], ß-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

20.
J Formos Med Assoc ; 120(10): 1811-1820, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33906783

RESUMO

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.


Assuntos
Hiperaldosteronismo , Hipertensão , Adrenalectomia , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona , Taiwan
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