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1.
Phytother Res ; 36(1): 22-32, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34517426

RESUMO

This review aims to evaluate if there are clinical benefits of curcumin (CUR) in patients with polycystic ovary syndrome (PCOS). Electronic databases (PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar) were systematically searched to identify only randomized clinical trials (RCTs) that assessed CUR in patients with PCOS from inception to May 5, 2021. Five RCTs were included with a total of 296 patients, with 148 among the CUR groups and 148 patients among the control group. Revised Cochrane risk-of-bias tool for randomized trials was used to assess the risk of bias, three RCTs provided a low risk of bias and two provided a high risk of bias. Compared with the control group, CUR was associated with a statistically significant improvement in the glycemic control including fasting blood glucose (MD = -3.67; 95% CI = [-5.25, -2.08], p < .00001), insulin level (MD = -1.91; 95% CI = [-2.97, -0.84], p = .0005), homeostasis model assessment of insulin resistance (MD = -0.55; 95% CI = [-0.83, -0.27], p = .0001), and quantitative insulin sensitivity check index (MD = 0.01; 95% CI = [0.00, 0.02], p = .0005). The mean difference in total cholesterol was also statistically significant (MD = -15.55; 95% CI = [-30.33, -0.76], p < .04). The rest of the secondary outcomes, including LDL, HDL, sex hormone, body weight, and CRP, were not statistically significant. This review concluded that among patients with PCOS, the use of CUR demonstrated a significant difference from the control group for glycemic control. Those findings suggest that CUR confers clinical benefits in patients with PCOS. However, due to the limited number of the included studies, further high-quality studies are needed to establish the clinical efficacy of the CUR.


Assuntos
Curcumina , Síndrome do Ovário Policístico , Glicemia , Curcumina/uso terapêutico , Suplementos Nutricionais , Feminino , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R69-R78, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432916

RESUMO

The production of H2S and its effect on bioenergetics in mammalian cells may be evolutionarily preserved. Erythrocytes of birds, but not those of mammals, have a nucleus and mitochondria. In the present study, we report the endogenous production of H2S in chicken erythrocytes, which was mainly catalyzed by 3-mercaptopyruvate sulfur transferase (MST). ATP content of erythrocytes was increased by MST-generated endogenous H2S under normoxic, but not hypoxic, conditions. NaHS, a H2S salt, increased ATP content under normoxic, but not hypoxic, conditions. ATP contents in the absence or presence of NaHS were eliminated by different inhibitors for mitochondrial electron transport chain in chicken erythrocytes. Succinate and glutamine, but not glucose, increased ATP content. NaHS treatment similarly increased ATP content in the presence of glucose, glutamine, or succinate, respectively. Furthermore, the expression and activity of sulfide:quinone oxidoreductase were enhanced by NaHS. The structural integrity of chicken erythrocytes was largely maintained during 2-wk NaHS treatment in vitro, whereas most of the erythrocytes without NaHS treatment were lysed. In conclusion, H2S may regulate cellular bioenergetics as well as cell survival of chicken erythrocytes, in which the functionality of the electron transport chain is involved. H2S may have different regulatory roles and mechanisms in bioenergetics of mammalian and bird cells.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Eritrócitos/metabolismo , Sulfeto de Hidrogênio/farmacologia , Trifosfato de Adenosina/sangue , Animais , Galinhas , Transporte de Elétrons/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Glucose/farmacologia , Glutamina/farmacologia , Hipóxia/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ácido Succínico/farmacologia , Sulfurtransferases/metabolismo
3.
Catheter Cardiovasc Interv ; 94(2): 181-186, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30628754

RESUMO

OBJECTIVES: This study aimed to evaluate the efficacy and safety of genotype- and phenotype-guided intensified antiplatelet therapy compared with conventional therapy in patients undergoing stent implantation. BACKGROUND: Although potent P2Y12 receptor inhibitors are recommended for percutaneous coronary intervention (PCI)-treated acute coronary syndrome, their usage is limited by a high bleeding risk. Therefore, personalized antiplatelet therapy could provide a valuable foundation for selection of antiplatelet therapy in this population. METHODS: We conducted a Bayesian network meta-analysis for all randomized clinical trials (RCTs) that evaluated genotype- and/or phenotype-guided therapy in PCI-treated coronary artery disease. RESULTS: Thirteen RCTs were included with a total of 6,845 patients. The results showed no significant differences in major adverse cardiovascular events (MACE) between the treatment options ((genotype guided vs. standard of care; OR 0.64; 95% CI: 0.38-1.05) and (phenotype vs. standard of care; OR 0.93; 95% CI: 0.54-1.37)). In addition, no significant differences were demonstrated in bleeding events ((genotype guided vs. standard of care; OR 0.73; 95% CI: 0.45-1.25) and (phenotype vs. standard of care; OR 0.90; 95% CI: 0.62-1.39)). CONCLUSIONS: In this mixed treatment meta-analysis of RCTs, neither genotype- nor phenotype-guided antiplatelet therapy in patients with PCI-treated coronary artery disease was superior to conventional therapy.


Assuntos
Doença da Artéria Coronariana/terapia , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/uso terapêutico , Medicina de Precisão , Teorema de Bayes , Tomada de Decisão Clínica , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Citocromo P-450 CYP2C19/metabolismo , Hemorragia/induzido quimicamente , Humanos , Metanálise em Rede , Seleção de Pacientes , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Testes Farmacogenômicos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
4.
Catheter Cardiovasc Interv ; 93(7): 1246-1252, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30403317

RESUMO

OBJECTIVES: This study aimed to evaluate the efficacy and safety of personalized genotype-guided selection of antiplatelet therapy versus standard of care in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Clopidogrel is the most frequently used P2Y12 receptor antagonist in patients with coronary artery disease. However, genetic variations of clopidogrel are associated with inter-individual response variability which could limit its efficacy. METHODS: Electronic databases were searched for all randomized clinical trials (RCTs) evaluating genotype-guided therapy versus standard of care in patients undergoing stent implantation. Aggregated risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS: We included 6 RCTs with a total of 2,371 patients. When compared with standard of care, the use of genotype-guided therapy did not significantly reduce major adverse cardiovascular events (MACE) (RR 0.67; 95% CI: 0.35-1.27; P = 0.22). However, MACE was significantly reduced in the subset of trials which enrolled only acute coronary syndromes (ACS) (P < 0.01). In addition, there was a significant reduction in myocardial infarction in the genotype-guided group (RR 0.44; 95% CI: 0.28-0.70; P < 0.01; I2 = 0%). Other clinical outcomes were not significantly different: cardiovascular mortality (RR 0.68; 95% CI: 0.27-1.74; P = 0.42), stroke (RR 0.62; 95% CI: 0.23-1.65; P = 0.34), stent thrombosis (RR 0.37; 95% CI: 0.13-1.06; P = 0.06), and bleeding (RR 0.68; 95% CI: 0.43-1.06; P = 0.09). CONCLUSION: In patients undergoing stent implantation, MACE with genotype-guided therapy was not significantly reduced; however, there was a signal towards reduction of MACE in ACS patients, as well as a lower rate of MI, though this will require further confirmation in adequately powered trials.


Assuntos
Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Citocromo P-450 CYP2C19/genética , Intervenção Coronária Percutânea , Testes Farmacogenômicos , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/administração & dosagem , Tomada de Decisão Clínica , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/mortalidade , Citocromo P-450 CYP2C19/metabolismo , Cálculos da Dosagem de Medicamento , Resistência a Medicamentos/genética , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Farmacogenética , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Stents , Resultado do Tratamento
5.
J Thromb Thrombolysis ; 47(2): 179-185, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30511259

RESUMO

Patients undergoing cardiac surgery are among the most common recipients of allogeneic red blood cell (RBC) transfusions. However, whether restrictive RBC transfusion strategies for cardiac surgery achieve a similar clinical outcome in comparison with liberal strategies remains unclear. We searched electronic databases from inception to December 2017 for randomized controlled trials (RCTs). We calculated the risk ratios (RRs) and weighted-mean difference (MD) using a random-effects model. We included 9 RCTs with a total of 9005 patients. There was no significant difference in mortality between groups [RR 1.03; 95% confidence interval (CI) 0.74-1.45; P = 0.86]. In addition, there were no significant differences between groups in the clinical outcomes of infections (RR 1.09; 95% CI 0.94-1.26; P = 0.26), stroke (RR 0.98; 95% CI 0.72-1.35; P = 0.91), respiratory morbidity (RR 1.05; 95% CI 0.89-1.24; P = 0.58), renal morbidity (RR 1.02; 95% CI 0.94-1.09; P = 0.68), myocardial infarction (RR 1.00; 95% CI 0.80-1.24; P = 0.99), cardiac arrhythmia (RR 1.05; 95% CI 0.88-1.26; P = 0.56), gastrointestinal morbidity (RR 1.93; 95% CI 0.81-4.63; P = 0.14), or reoperation (RR 0.90; 95% CI 0.67-1.20; P = 0.46). There was a significant difference in the intensive care unit length of stay (h) (MD 4.29; 95% CI 2.19-6.39, P < 0.01) favoring the liberal group. However, there was no significant difference in the hospital length of stay (days) (MD 0.15; 95% CI - 0.18 to 0.48; P = 0.38). In conclusion, this meta-analysis showed that restrictive strategies for RBC transfusion are as safe as liberal strategies in patients undergoing cardiac surgery with regards to short-term clinical outcomes.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Transfusão de Eritrócitos/métodos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transfusão de Eritrócitos/efeitos adversos , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
J Thromb Thrombolysis ; 47(2): 233-247, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30511260

RESUMO

Recurrent stroke is common immediately following a transient ischemic attack (TIA) or ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than monotherapy. Electronic databases were searched for randomized clinical trials (RCTs) comparing DAPT with monotherapy in ischemic stroke/TIA. Sixteen RCTs with a total of 29,032 patients were included. Compared with monotherapy, DAPT was associated with significantly lower rates of any stroke (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.72-0.89) and ischemic stroke (RR 0.75; 95% CI 0.66-0.85) during any follow-up period. Although significant increases in intracranial bleeding (RR 1.55; 95% CI 1.20-2.01) and major bleeding (RR 1.90; 95% CI 1.33-2.72) were associated with DAPT, especially with long-term follow-up, the number needed to harm was 258 and 113, respectively. Nevertheless, short-duration DAPT (≤ 1 month) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy. In contrast, long DAPT and DAPT started later after the index event (≥ 1 month) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy. Other clinical outcomes were essentially similar between the two groups and included recurrent TIA (RR 0.88; 95% CI 0.72-1.07), myocardial infarction (RR 1.04; 95% CI 0.84-1.29), vascular death (RR 0.99; 95% CI 0.82-1.19), and any death (RR 1.12; 95% CI 0.88-1.42). Similar findings were observed in patients who presented with minor stroke/TIA. Conclusions: Among patients who presented with ischemic stroke/TIA, short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention.


Assuntos
Aspirina/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Clopidogrel/administração & dosagem , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Prevenção Secundária/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Aspirina/efeitos adversos , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Clopidogrel/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Humanos , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/diagnóstico , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do Tratamento
7.
Eur Heart J ; 39(43): 3879-3892, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-29741611

RESUMO

Aims: Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity to model, and add clarity to, HCM. Methods and results: CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-ß-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated to hPSC-CMs for high-throughput, non-subjective molecular and functional assessment using 12 approaches in 2D monolayers and/or 3D engineered heart tissues. Although immature, edited hPSC-CMs exhibited the main hallmarks of HCM (hypertrophy, multi-nucleation, hypertrophic marker expression, sarcomeric disarray). Functional evaluation supported the energy depletion model due to higher metabolic respiration activity, accompanied by abnormalities in calcium handling, arrhythmias, and contraction force. Partial phenotypic rescue was achieved with ranolazine but not omecamtiv mecarbil, while RNAseq highlighted potentially novel molecular targets. Conclusion: Our holistic and comprehensive approach showed that energy depletion affected core cardiomyocyte functionality. The engineered R453C-ßMHC-mutation triggered compensatory responses in hPSC-CMs, causing increased ATP production and αMHC to energy-efficient ßMHC switching. We showed that pharmacological rescue of arrhythmias was possible, while MHY7: MYH6 and mutant: wild-type MYH7 ratios may be diagnostic, and previously undescribed lncRNAs and gene modifiers are suggestive of new mechanisms.


Assuntos
Arritmias Cardíacas/genética , Cardiomiopatia Hipertrófica/genética , Contração Miocárdica/genética , Miócitos Cardíacos/fisiologia , Células-Tronco Pluripotentes/fisiologia , Sistemas CRISPR-Cas/genética , Células Cultivadas , Edição de Genes , Humanos , Modelos Cardiovasculares
8.
Pacing Clin Electrophysiol ; 41(12): 1577-1582, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30362185

RESUMO

BACKGROUND: Ventricular arrhythmias (VAs) are independently related to mortality risk in patients with heart failure (HF). The wide availability of implantable cardioverter defibrillators and cardiac resynchronization therapy devices now offers an opportunity to clinically correlate the two disease processes. We hypothesized that there is an association between changes in the intrathoracic impedance and episodes of VA. METHODS: Nonconcurrent prospective study of adults (age >20 years) with known HF with reduced ejection fraction (<35%). The OptiVol threshold was categorized as follows: 0-30 Ω-days, 31-60 Ω-days, 61-90 Ω-days, 91-120 Ω-days, and >120 Ω-days. Patients with OptiVol values at 0-30 Ω-days were used as the reference group. Receiver operating characteristic analysis was used to estimate the sensitivity and specificity at each threshold. RESULTS: Of the 87 eligible patients, 65.5% were males. The mean age of the sample was 73.3 years (±12.7). Compared to patients in the 0-30 Ω-days category, those in the 31-60, 61-90, 91-120, and >120 Ω-days groups had, on average, 1.48, 1.64, 2.24, and 1.6 more VAs, respectively (P = 0.002, 0.009, 0.010 and 0.009, respectively). The sensitivity and specificity of each threshold were as follows: 82.6% and 61.7% at 31-60 Ω-days, 43.5% and 78.3% at 61-90 Ω-days, 30.4% and 85.0% at 91-120 Ω-days, and 21.7% and 88.3% at >121 Ω-days. CONCLUSION: Our study found a significant positive relationship between changes in intrathoracic impedance and episodes of VAs in patients with HF.


Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Impedância Elétrica , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Volume Sistólico
9.
J Thromb Thrombolysis ; 46(4): 440-450, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30117036

RESUMO

Tenecteplase is a genetically mutated variant of alteplase with superior pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety in acute ischemic strokes are limited. Hence, we conducted a study to evaluate the efficacy and safety of tenecteplase compared with alteplase in acute ischemic stroke. Electronic databases were searched for randomized clinical trials (RCTs) comparing tenecteplase with alteplase in acute ischemic stroke patients eligible for thrombolysis. We evaluated various efficacy and safety outcomes using random-effects models for both pairwise and Bayesian network meta-analyses along with meta-regression analyses. We included 5 RCTs with a total of 1585 patients. Compared with alteplase, tenecteplase treatment was associated with significantly greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval [CI] 1.04-3.87; p = 0.04) and early neurological improvement (OR 1.43; 95% CI 1.01-2.03; p = 0.05). There were no differences between the two thrombolytics in terms of excellent recovery (modified Rankin Scale [mRS] 0-1; OR 1.17; 95% CI 0.95-1.44; p = 0.13), functional independence (mRS 0-2; OR 1.24; 95% CI 0.78-1.98), poor recovery (mRS 4-6; OR 0.78; 95% CI 0.49-1.25; p = 0.31), complete/partial recanalization (OR 1.51; 95% CI 0.70-3.26; p = 0.30), any intracerebral hemorrhage (OR 0.81; 95% CI 0.56-1.17; p = 0.26), symptomatic intracerebral hemorrhage (OR 0.98; 95% CI 0.52-1.83; p = 0.94), or mortality (OR 0.83; 95% CI 0.54-1.26; p = 0.38). In network meta-analysis, there were better efficacy and imaging-based outcomes with tenecteplase 0.25 mg/kg without increased risk of safety outcomes. Our results demonstrate that in acute ischemic stroke, thrombolysis with tenecteplase is at least as effective and safe as alteplase.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Tenecteplase , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
10.
J Thromb Thrombolysis ; 46(3): 299-303, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29934940

RESUMO

Dual antiplatelet therapy with aspirin and clopidogrel are recommended as adjuncts to fibrinolytic-treated patients with ST-elevation myocardial infarction (STEMI). However, the role of switching to ticagrelor within 24 h of fibrinolytics compared with clopidogrel continuation in this setting is uncertain. Hence, we conducted a comprehensive search of electronic databases for all randomized clinical trials (RCTs) that evaluated the safety and efficacy of ticagrelor versus clopidogrel after fibrinolytic therapy in patients with STEMI. A random-effects model was used to calculate the risk ratios (RRs) and 95% confidence intervals (CIs). A total of 5 RCTs that evaluated the efficacy of ticagrelor post-fibrinolysis were identified. We included 3 RCTs with 3999 total patients for our meta-analysis. The results showed similar short-term clinical outcomes between ticagrelor and clopidogrel with regard to rates of Bleeding Academic Research Consortium (BARC) type ≥ 2 bleeding (RR 0.94; 95% CI 0.56-1.60; P = 0.83), major adverse cardiovascular events (RR 0.87; 95% CI 0.49-1.52; P = 0.62), mortality (RR 0.92; 95% CI 0.53-1.59; P = 0.77), myocardial infarction (RR 0.76; 95% CI 0.43-1.36; P = 0.36), and stroke (RR 0.93; 95% CI 0.50-1.73; P = 0.82). Our results demonstrate that in STEMI patients treated with fibrinolytic therapy, switching to ticagrelor was associated with similar bleeding and ischemic outcomes compared with clopidogrel continuation.


Assuntos
Clopidogrel/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ticagrelor/uso terapêutico , Doenças Cardiovasculares/etiologia , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Acidente Vascular Cerebral/etiologia , Análise de Sobrevida , Terapia Trombolítica , Ticagrelor/efeitos adversos
11.
Mol Pharmacol ; 85(3): 397-407, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24342771

RESUMO

TASK3 (TWIK-related acid-sensitive K(+) channel 3) potassium channels are members of the two-pore-domain potassium channel family. They are responsible for background leak potassium currents found in many cell types. TASK3 channels are genetically imprinted, and a mutation in TASK3 (G236R) is responsible for Birk Barel mental retardation dysmorphism syndrome, a maternally transmitted developmental disorder. This syndrome may arise from a neuronal migration defect during development caused by dysfunctional TASK3 channels. Through the use of whole-cell electrophysiologic recordings, we have found that, although G236R mutated TASK3 channels give rise to a functional current, this current is significantly smaller in an outward direction when compared with wild-type (WT) TASK3 channels. In contrast to WT TASK3 channels, the current is inwardly rectifying. Furthermore, the current through mutated channels is differentially sensitive to a number of regulators, such as extracellular acidification, extracellular zinc, and activation of Gαq-coupled muscarinic (M3) receptors, compared with WT TASK3 channels. The reduced outward current through mutated TASK3_G236R channels can be overcome, at least in part, by both a gain-of-function additional mutation of TASK3 channels (A237T) or by application of the nonsteroidal anti-inflammatory drug flufenamic acid (FFA; 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid). FFA produces a significantly greater enhancement of current through mutated channels than through WT TASK3 channels. We propose that pharmacologic enhancement of mutated TASK3 channel current during development may, therefore, provide a potentially useful therapeutic strategy in the treatment of Birk Barel syndrome.


Assuntos
Anormalidades Craniofaciais/genética , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Mutação/genética , Canais de Potássio de Domínios Poros em Tandem/genética , Canais de Potássio/genética , Linhagem Celular , Anormalidades Craniofaciais/metabolismo , Células HEK293 , Humanos , Deficiência Intelectual/metabolismo , Potenciais da Membrana/genética , Hipotonia Muscular/metabolismo , Canais de Potássio/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Zinco/metabolismo
13.
Cureus ; 16(1): e51902, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38333489

RESUMO

Although phrenic nerve and esophageal injury are commonly known risks associated with cryoablation, there is limited literature regarding coronary artery spasm (CAS), a serious and potentially fatal complication of cryoablation. We report the case of a 68-year-old Caucasian female who developed a left main CAS with a significant hemodynamic compromise during cryoablation. The patient, with a history of hyperlipidemia, hypertension, and symptomatic persistent atrial fibrillation, was admitted for elective catheter ablation for atrial fibrillation. During the ablation of the left superior pulmonary vein (LSPV), the patient developed severe hypotension and bradycardia. The patient's monitor revealed ST elevation, confirmed by a 12-lead ECG. Immediate coronary angiography revealed the left main coronary spasm, which improved with nitroglycerine administration with resolution of ST elevation and return of the patient's hemodynamics to stability. The patient's left main CAS was induced by cryoablation of LSPV. Literature on atrial fibrillation ablation-induced CAS is scant, but a Japanese study has shown that it occurs more commonly in cryoablation than in radiofrequency, hot balloon, or laser ablation. The study showed LSPV as the most common site of ablation right before the spasms happened. Further studies about this topic are needed to delineate further the risk factors and the precautions that could prevent CAS. In the meantime, prompt recognition and appropriate intervention are critical for a good patient outcome.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38459202

RESUMO

BACKGROUND: Transvenous lead removal (TLR) is associated with increased mortality and morbidity. This study sought to evaluate the impact of TLR on in-hospital mortality and outcomes in patients with and without CIED infection. METHODS: From January 1, 2017, to December 31, 2020, we utilized the nationally representative, all-payer, Nationwide Readmissions Database to assess patients who underwent TLR. We categorized TLR as indicated for infection, if the patient had a diagnosis of bacteremia, sepsis, or endocarditis during the initial admission. Conversely, if none of these conditions were present, TLR was considered sterile. The impact of infective vs sterile indications of TLR on mortality and major adverse events was studied. RESULTS: Out of the total 25,144 patients who underwent TLR, 14,030 (55.8%) received TLR based on sterile indications, while 11,114 (44.2%) received TLR due to device infection, with 40.5% having systemic infection and 59.5% having isolated pocket infection. TLR due to infective indications was associated with a significant in-hospital mortality (5.59% vs 1.13%; OR = 5.16; 95% CI 4.33-6.16; p < 0.001). Moreover, when compared with sterile indications, TLR performed due to device infection was associated with a considerable risk of thromboembolic events including pulmonary embolism and stroke (OR = 3.80; 95% CI 3.23-4.47, p < 0.001). However, there was no significant difference in the conversion to open heart surgery (1.72% vs. 1.47%, p < 0.111), and infection was not an independent predictor of cardiac (OR = 1.12; 95% CI 0.97-1.29) or vascular complications (OR = 1.12; 95% CI 0.73-1.72) between the two groups. CONCLUSION: Higher in-hospital mortality and rates of thromboembolic events associated with TLR resulting from infective indications may warrant further pursuing this diagnosis in patients.

17.
J ECT ; 28(1): 7-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21983759

RESUMO

OBJECTIVES: This study aimed to describe the practice of an unmodified electroconvulsive therapy (ECT) in a typical urban hospital setting in Pakistan. METHODS: This is a retrospective naturalistic study of patients who received ECT at Rawalpindi General Hospital between June 2000 and June 2008 by chart review. All useful data that could be retrieved from the charts were recorded. RESULTS: The process of administering ECT at the hospital is described. During the study period, of a total of 5240 patients who were admitted to the hospital, 1520 (29%) were administered ECT. Of these, 1352 (88.9%) did not get any kind of anesthesia during the procedure. The mean age of patients was 34.89 years, and the leading diagnoses were depression (60.8%), bipolar disorder (17.8%), and schizophrenia (9.1%). The mean number of ECTs received for these diagnoses were 5.78, 5.52, and 6.34, respectively. A total of 249 (16.7%) patients discontinued ECT against medical advice. CONCLUSIONS: In countries with limited resources, ECT is practiced in a markedly different way from more developed countries; although administering ECT without anesthesia is not desirable, in the face of severe economic constraints, it is often necessary.


Assuntos
Eletroconvulsoterapia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia/estatística & dados numéricos , Agendamento de Consultas , Atenção à Saúde , Eletroconvulsoterapia/economia , Eletroconvulsoterapia/instrumentação , Feminino , Hospitais Públicos , Humanos , Masculino , Serviços de Saúde Mental , Pessoa de Meia-Idade , Paquistão , Equipe de Assistência ao Paciente , Pacientes Desistentes do Tratamento , Pobreza , Estudos Retrospectivos , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-35711406

RESUMO

Ischemic stroke associated with rare clinical syndromes represents less than 5% of etiologic factors. From those syndromes are Holt-Oram syndrome and Left ventricular non-compaction syndrome. We report a case of a 66 years old male with genetically confirmed Holt-Oram syndrome due to TBX5 mutation who presented with cryptogenic stroke most likely due to cardioembolic etiology. The patient has a history of moderate nonischemic cardiomyopathy due to an atypical pattern of left ventricular non-compaction confirmed by Cardiac Magnetic Resonance Imaging. The patient was treated appropriately with thrombolytic therapy and catheter-directed mechanical thrombectomy with minimal residual stroke symptoms. Holt-Oram syndrome is a genetic condition with variable clinical phenotypes, including cardiac manifestations. Left ventricular non-compaction syndrome is rare congenital cardiomyopathy defined as prominent left ventricular trabeculae, deep intertrabecular recesses, and a thin compacted layer. And only a few cases were reported with both conditions. Therefore, patients with the Holt-Oram Syndrome should get a comprehensive cardiac evaluation to exclude non-compaction cardiomyopathy, which may have significant prognostic implications.

19.
Clin Case Rep ; 10(6): e5976, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35734186

RESUMO

A 54-year-old male patient with history of anabolic androgenic steroid (AAS) misuse presented to the emergency department with new-onset atrial fibrillation and severely reduced ejection fraction. Cardiac catheterization revealed normal coronaries. He underwent cryo-balloon ablation with subsequent conversion to sinus rhythm. After appropriate guideline-directed medical management, ejection fraction improved on follow-up.

20.
Proc (Bayl Univ Med Cent) ; 35(2): 184-189, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35261447

RESUMO

We aimed to evaluate the clinical benefits of dexmedetomidine (DEX) in comparison with the standard of care (SOC) sedation in critically ill, septic patients. Electronic databases (PubMed, EMBASE, Cochrane Central, Scopus, and Google Scholar) were systematically searched to identify only randomized clinical trials performed up until February 12, 2021. The primary outcomes were 28-day mortality, 90-day mortality, and intensive care unit (ICU) length of stay (LOS). We calculated risk ratios (RRs), 95% confidence intervals (CIs) for dichotomous data, and weighted mean differences (WMDs) for continuous data using a random-effects model. Seven randomized clinical trials were included, with a total of 529 patients in the DEX group and 520 patients in the SOC group. Compared with SOC, DEX was associated with a nonstatistically significant reduced 28-day mortality (RR = 0.76; 95% CI [0.51, 1.14]; P = 0.19), 90-day mortality (RR = 0.94; 95% CI [0.75, 1.18]; P = 0.60), and ICU LOS (WMD = -0.85; 95% CI [-2.60, 0.90]; P = 0.34). We conclude that among septic patients on sedation, the use of DEX in the ICU demonstrated no significant difference from SOC sedation protocols with respect to 28-day mortality, 90-day mortality, and total ICU LOS. Our findings suggest that DEX does not confer clinical benefit over SOC sedation in critically ill patients with sepsis.

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