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This case report describes a patient in whom debilitating lower back pain that always occurred during menses resolved when she received treatment for subclinical temporomandibular disorder (TMD). The patient was diagnosed with subclinical TMD and facial myalgia based on the results of clinical and radiographic examinations. She was treated with maxillary (nighttime) and mandibular (daytime) dental orthotics to provide stabilization and decompression of the temporomandibular joints. After 12 weeks of appliance therapy, which resulted in resolution of the TMD symptoms, the patient reported that the debilitating lower back pain she experienced during menses had ceased. Her back pain did not return after the use of the mandibular appliance was discontinued. The authors discuss how neurologic, postural, inflammatory, and qi flow changes attributed to the patient's TMD treatment may have contributed to the cessation of the patient's menses-related lower back pain.
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Dor Lombar , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Dor Lombar/terapia , Dor Lombar/complicações , Dor Facial/etiologia , Dor Facial/terapia , Dor Facial/diagnóstico , Transtornos da Articulação Temporomandibular/complicações , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/terapia , Articulação Temporomandibular , MandíbulaRESUMO
INTRODUCTION: Reports of SARS-CoV-2 coronavirus (COVID-19) vaccine-related myocarditis, particularly after mRNA vaccines, have raised concerns amongst the general public. This review examined the literature regarding myocarditis post COVID-19 vaccination, drawing from vaccine safety surveillance databases and case reports. METHODS: Combinations of search terms were used in PubMed and COVID-19-specific repositories - LitCovid and the Cochrane COVID-19 Study Register - between 1 October 2020 and 31 October 2021. Manual searches of GoogleScholar and screening of article bibliographies were also performed. RESULTS: Information was obtained from five vaccine safety surveillance databases. Fifty-two (52) case reports totalling 200 cases of possible COVID-19 vaccine-related myocarditis were summarised. Vaccine surveillance databases differed in reporting formats and vaccination rates; however, gross estimates suggested low overall incidence rates of 2-5 per million mRNA vaccines. The incidence appeared to be higher in younger male populations, with onset of symptoms within a few days, usually after the second dose. Some with prior COVID-19 infections had onset after the first dose. Cases with prior unrelated myocarditis were also noted. Almost all presented with chest pain (98.0%). Troponin elevation was universally described and cardiac magnetic resonance imaging was commonly reported based on the updated Lake Louise criteria. Clinical course was mild in the majority, with response to anti-inflammatory treatment. CONCLUSION: COVID-19 vaccine-related myocarditis is an important but rare adverse event. More research is needed into its pathogenesis and reasons for its predominance in young males, while gaps in data exist in those aged <16 years, as well as those with prior COVID-19 infections and prior myocarditis.
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COVID-19 , Miocardite , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Masculino , Miocardite/diagnóstico , Miocardite/epidemiologia , Miocardite/etiologia , SARS-CoV-2 , Vacinação/efeitos adversos , Vacinas de mRNARESUMO
BACKGROUND: Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 patients with DCM across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60 706 individuals to identify clinically interpretable genes robustly associated with dominant monogenic DCM. METHODS: We used the TruSight Cardio sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 patients with DCM and 912 healthy volunteers processed with identical sequencing and bioinformatics pipelines. We further aggregated data from 1498 patients with DCM sequenced in diagnostic laboratories and the Exome Aggregation Consortium database for replication and meta-analysis. RESULTS: Truncating variants in TTN and DSP were associated with DCM in all comparisons. Variants in MYH7, LMNA, BAG3, TNNT2, TNNC1, PLN, ACTC1, NEXN, TPM1, and VCL were significantly enriched in specific patient subsets, with the last 2 genes potentially contributing primarily to early-onset forms of DCM. Overall, rare variants in these 12 genes potentially explained 17% of cases in the outpatient clinic cohort representing a broad range of adult patients with DCM and 26% of cases in the diagnostic referral cohort enriched in familial and early-onset DCM. Although the absence of a significant excess in other genes cannot preclude a limited role in disease, such genes have limited diagnostic value because novel variants will be uninterpretable and their diagnostic yield is minimal. CONCLUSIONS: In the largest sequenced DCM cohort yet described, we observe robust disease association with 12 genes, highlighting their importance in DCM and translating into high interpretability in diagnostic testing. The other genes analyzed here will need to be rigorously evaluated in ongoing curation efforts to determine their validity as Mendelian DCM genes but have limited value in diagnostic testing in DCM at present. This data will contribute to community gene curation efforts and will reduce erroneous and inconclusive findings in diagnostic testing.
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Proteínas Reguladoras de Apoptose/genética , Cardiomiopatia Dilatada/genética , Predisposição Genética para Doença , Testes Genéticos , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Cardiomiopatia Dilatada/diagnóstico , Exoma/genética , Feminino , Heterogeneidade Genética , Humanos , Masculino , Adulto JovemRESUMO
Cardiovascular disease (CVD) is the number one cause of death in both men and women. Younger women have a lower risk for CVD, but their risk increases considerably after menopause when estrogen levels decrease. The cardiovascular protective properties of estrogen are mediated through decreasing vascular inflammation and progression of atherosclerosis, decreasing endothelial cell damage by preventing apoptosis and anti-hypertrophic mechanisms. Estrogen also regulates glucose and lipid levels, which are 2 important risk factors for CVD. Resveratrol (RES), a cardioprotective polyphenolic compound, is classified as a phytoestrogen due its capacity to bind to and modulate estrogen receptor signalling. Due to its estrogen-like property, we speculate that the cardioprotective effects of RES treatment could be sex-dependent. Based on earlier reports and more recent data from our lab presented here, we found that RES treatment may have more favourable cardiovascular outcomes in females than in males. This review will discuss estrogen- and phytoestrogen-mediated cardioprotection, with a specific focus on sex-dependent effects reported in preclinical and clinical studies.
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Cardiotônicos/farmacologia , Fitoestrógenos/farmacologia , Resveratrol/farmacologia , Caracteres Sexuais , Animais , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , HumanosRESUMO
In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague-Dawley rats, cultured for either 24 h (cardiomyocytes) or 48 h (CF) before treatments. To isolate MF, CF were trypsinized after 48 h in culture, seeded in fresh plates and cultured for 24 h prior to treatment. All three cells were then treated for a further 24 h with a range of Rsv doses. In CF and MF, cell proliferation, viability, apoptosis assays were performed with or without Rsv treatment for 24 h. In cardiomyocytes, cell viability and apoptosis assay were performed 24 h after treatment. In separate experiments, CF was pre-incubated with estrogen, tamoxifen and fulvestrant for 30 min prior to Rsv treatment. Rsv treatment decreased proliferation of both fibroblasts and myofibroblasts. Rsv treatment also increased the proportion of dead CF and MF in a dose dependent manner. However, treatment with Rsv did not induce cell death in adult cardiomyocytes. There was an increase in the percentage of cells with condensed nuclei with Rsv treatment in both CF and MF, but not in cardiomyocytes. Treatment with estrogen, tamoxifen and fulvestrant alone or in combination with Rsv did not have any additional effects on CF survival. Our results demonstrate that treatment with Rsv can inhibit cell proliferation and induce cell death in rat CF and MF, while not affecting cardiomyocyte survival. We also demonstrated that the induction of cell death in CF with Rsv treatment was independent of estrogen receptor alpha (ERα) signaling.
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Proliferação de Células/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Receptor alfa de Estrogênio/genética , Humanos , Ratos , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estilbenos/química , Tamoxifeno/farmacologia , FitoalexinasRESUMO
BACKGROUND: Bleeding is an important and common complication of left ventricular assist devices (LVADs). One of the common causes of gastrointestinal bleeding is arteriovenous malformations. However, the source of bleeding is often hard to identify. Thalidomide is efficacious in treatment of gastrointestinal (GI) bleeding in non-LVAD patients. We report our experience of the use of thalidomide in the treatment of GI bleeding in four patients with LVAD. METHOD AND RESULTS: Four patients who had recurrent GI bleeding from May 2009 to December 2014 were started on thalidomide. All of them responded to treatment and had no further gastrointestinal bleeding while on thalidomide. One patient developed constipation, requiring thalidomide to be stopped. Another patient developed symptomatic neuropathy, that resolved with reduction of dosage. CONCLUSION: Thalidomide appears safe and efficacious in LVAD patients with recurrent gastrointestinal bleeding.
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Cardiomiopatias/cirurgia , Hemorragia Gastrointestinal/tratamento farmacológico , Coração Auxiliar/efeitos adversos , Talidomida/administração & dosagem , Idoso , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoAssuntos
COVID-19/epidemiologia , Insuficiência Cardíaca/epidemiologia , Admissão do Paciente/tendências , Saúde Pública/tendências , COVID-19/prevenção & controle , Insuficiência Cardíaca/terapia , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Saúde Pública/normas , SingapuraRESUMO
PURPOSE OF REVIEW: Hypertension is the most prevalent risk factor in heart failure with preserved ejection fraction (HFpEF) and plays a key role in the disease. The continued lack of effective therapies to improve outcomes in HFpEF underscores the knowledge gaps regarding the pathophysiology of HFpEF. This review builds on fundamental concepts in pressure overload-induced left ventricular modeling, and summarizes recent knowledge gained regarding the mechanisms underlying the transition from hypertensive heart disease to HFpEF. RECENT FINDINGS: The pathophysiology of hypertensive HFpEF extends beyond the development of left ventricular hypertrophy and diastolic dysfunction to myocardial contractile dysfunction, beyond left atrial structural dilatation to left atrial functional decline, beyond macrovascular stiffening to microvascular dysfunction, beyond central cardiac triggers to systemic endothelial inflammation, beyond fibrosis to titin changes, and beyond collagen deposition to qualitative changes in collagen. The central paradigm involves a systemic proinflammatory state triggering a downstream cascade of cardiac microvascular endothelial activation, oxidative stress, and abnormal myocardial cyclic guanosine monophosphate signaling, leading to microvascular rarefaction, chronic ischemia, fibrosis and progression to HFpEF. SUMMARY: Recent advances have provided insights into the pathophysiology of HFpEF in hypertension. Such knowledge provides novel opportunities for therapeutic strategies in the treatment of hypertensive HFpEF.
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Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Volume Sistólico/fisiologia , Humanos , Hipertrofia Ventricular Esquerda , MiocárdioRESUMO
We have previously shown that through test-tube molecular evolution, an arbitrarily chosen noncatalytic DNA sequence can be evolved into a catalytic DNA (DNAzyme) with significant RNA-cleaving activity. In this study, we aim to address the question of whether the catalytic activity of such a DNAzyme can be further optimized using in vitro selection. Several cycles of selective enrichment starting with a partially randomized DNA library have resulted in the isolation of many sequence variations that show notably improved catalytic activity. Bioinformatic analysis and activity examination of several DNAzyme-substrate constructs have led to two interesting findings about sequence mutations and the secondary structure of this DNAzyme: (1) three crucial mutations have transformed the DNAzyme into 8-17, a DNAzyme that has been discovered in multiple previous in vitro selection experiments, and (2) other mutations have allowed this special 8-17 variant to make structural fine-tuning in order to cleave an arbitrarily chosen RNA-containing substrate with a defined sequence. Our study not only showcases the combined power of directed molecular evolution and in vitro selection techniques in turning a noncatalytic nucleic acid sequence into an efficient enzyme, but it also raises the question of whether mother nature has used a similar approach to evolve natural enzymes.
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DNA Catalítico/metabolismo , Ribonucleases/metabolismo , Sequência de Bases , DNA Catalítico/química , Cinética , Conformação de Ácido Nucleico , Técnica de Seleção de AptâmerosRESUMO
Huntington disease (HD) is an adult-onset neurodegenerative disorder that is caused by a trinucleotide CAG repeat expansion in the HTT gene that codes for the protein huntingtin (HTT in humans or Htt in mice). HTT is a multi-functional, ubiquitously expressed protein that is essential for embryonic survival, normal neurodevelopment, and adult brain function. The ability of wild-type HTT to protect neurons against various forms of death raises the possibility that loss of normal HTT function may worsen disease progression in HD. Huntingtin-lowering therapeutics are being evaluated in clinical trials for HD, but concerns have been raised that decreasing wild-type HTT levels may have adverse effects. Here we show that Htt levels modulate the occurrence of an idiopathic seizure disorder that spontaneously occurs in approximately 28% of FVB/N mice, which we have called FVB/N Seizure Disorder with SUDEP (FSDS). These abnormal FVB/N mice demonstrate the cardinal features of mouse models of epilepsy including spontaneous seizures, astrocytosis, neuronal hypertrophy, upregulation of brain-derived neurotrophic factor (BDNF), and sudden seizure-related death. Interestingly, mice heterozygous for the targeted inactivation of Htt (Htt+/- mice) exhibit an increased frequency of this disorder (71% FSDS phenotype), while over-expression of either full length wild-type HTT in YAC18 mice or full length mutant HTT in YAC128 mice completely prevents it (0% FSDS phenotype). Examination of the mechanism underlying huntingtin's ability to modulate the frequency of this seizure disorder indicated that over-expression of full length HTT can promote neuronal survival following seizures. Overall, our results demonstrate a protective role for huntingtin in this form of epilepsy and provide a plausible explanation for the observation of seizures in the juvenile form of HD, Lopes-Maciel-Rodan syndrome, and Wolf-Hirschhorn syndrome. Adverse effects caused by decreasing huntingtin levels have ramifications for huntingtin-lowering therapies that are being developed to treat HD.
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A reduced incidence of various forms of cancer has been reported in Huntington's disease patients and may be due to pro-apoptotic effects of mutant huntingtin. We tested this hypothesis by assessing the effects of huntingtin protein overexpression on survival in two murine cancer models. We generated YAC HD mice containing human huntingtin transgenes with various CAG tract lengths (YAC18, YAC72, YAC128) on either an Msh2 or p53 null background which have increased cancer incidence. In both mouse models of cancer, the overexpression of either mutant or wild-type huntingtin had no significant effect on overall survival. These results do not support the hypothesis that mutant huntingtin expression is protective against cancer.
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Doença de Huntington , Neoplasias , Camundongos , Animais , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/metabolismo , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares , Modelos Animais de Doenças , Neoplasias/genéticaRESUMO
BACKGROUND: As the primary burden of treating COVID-19 patients began to ease in the United Kingdom, ophthalmology clinic volume within the National Health Service has since recovered. Alarmingly, the rate of non-attendance remains higher than the pre-pandemic level. PURPOSE: The purpose was to assess how the perceived risk of contracting coronavirus disease 2019 (COVID-19) influences the willingness of individuals with sight-threatening macular conditions to attend intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection appointments during the second wave of the pandemic. METHODS: This prospective cross-sectional survey was conducted at the Macular Treatment Centre, Manchester Royal Eye Hospital. Patients who missed their appointment in January 2021 were invited to complete an anonymous survey over the telephone. The survey consisted of two parts: (1) a 23-item questionnaire aiming to assess fear of contracting COVID-19 in different hospital-related settings; and (2) the validated COVID-19 Anxiety Syndrome Scale (C-19ASS) to evaluate COVID-19-related anxiety. RESULTS: A total of 104 patients agreed to participate in the survey. Only a small proportion of patients believed COVID-19 vaccination (23 out of 88, 26.1%) had influenced their willingness to attend injection appointments. Majority of patients felt concerned about contracting COVID-19 during hospital appointments (n = 63, 60.6%). Only a minority of patients (n = 36, 34.6%) agreed with the hospital guidance on minimising clinical examinations during clinic visit. The C-19ASS was significantly higher in female patients, those older than 70 years and those with mobility issues. Higher C-19ASS, older age and living alone were predictors of clinic nonattendance. CONCLUSION: COVID-19 anxiety and fear of viral exposure could adversely affect patient adherence to clinic appointments during the pandemic. Particular attention should be provided to older patients, those who live alone and patients with impaired mobility. This is particularly relevant as hospital eye services across the world are in the process of restarting.
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BACKGROUND: There have been conflicting data regarding the risk of sudden cardiac death (SCD) in Asian population with reduced left ventricular ejection fraction (LVEF). We aim to study mortality outcome and its risk predictors in patients with reduced LVEF who declined an implantable cardioverter defibrillator (ICD) implantation and assess whether current ICD guidelines for primary prevention are applicable to the population in Singapore. METHODS: This prospective observational study involved 240 consecutive patients who fulfilled the ACC/AHA/HRS criteria for ICD implantation for primary prevention of SCD but declined ICD implantation. Baseline characteristics and mortality outcomes through May 2017 were collected via case-note review after a mean follow-up of 44.8 ± 16.6 months. RESULTS: Majority of our patients were Chinese (71.3%), followed by Malays (16.2%) and Indians (10.8%). Mean age (±SD) was 61 ± 10 years, and 84% were male. Majority were in New York Heart Association (NYHA) functional classes I (46.7%) and II (46.3%). Over a mean follow-up of 44.8 ± 16.6 months, all-cause mortality rate was 34.6%. Diabetes mellitus (HR = 1.57; 95% CI, 1.01-2.44; P = 0.047) and chronic kidney disease (CKD; HR = 1.95; 95% CI, 1.17-3.23; P = 0.010) were independent predictors of mortality. Patients in NYHA classes II (HR = 2.15; 95% CI, 1.32-3.50; P = 0.002) and III (HR = 2.82; 95% CI, 1.34-5.96; P = 0.007) showed higher risk of death. CONCLUSION: The mortality rate was comparable with major primary prevention trials. ICD guideline recommendations for primary prevention may thus be applicable to our local population. Patients with diabetes, CKD, and poorer NYHA status exhibited higher mortality rates.
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BACKGROUND: Gastrointestinal bleeding (GIB) is a complication reported in patients post left ventricular assist device (LVAD) implantation that is associated with high mortality rates. Thalidomide is an anti-angiogenic compound that may offer a potential option for management of refractory LVAD-related GIB. METHODS: A single-center, retrospective review was conducted from January 2009 to October 2016 at a tertiary cardiology center. It included LVAD patients initiated on thalidomide for refractory GIB. RESULTS: All patients (n = 11) were started on thalidomide 50 mg nocte and there was resolution of GIB in all patients except one (90.9%) during initial thalidomide treatment.The median duration of thalidomide therapy was 98 days (interquartile range: 34-215). The dose of thalidomide was reduced for 2 patients due to adverse effects. Thalidomide therapy was discontinued in 6 patients due to cessation of GIB (n = 4) and adverse effects (n = 2). Reported adverse effects included LVAD thrombosis (n = 2), somnolence (n = 1), neuropathy (n = 1), constipation (n = 1), and transaminitis (n = 1).Recurrent GIB occurred in 4 patients (45.4%) post-discontinuation of thalidomide therapy, which led to the re-initiation of therapy. CONCLUSIONS: Thalidomide appears to be a safe and effective option for management of refractory LVAD-related GIB. Monitoring for recurrent GIB should be performed closely following cessation of thalidomide therapy.
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Inibidores da Angiogênese/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Idoso , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in â¼1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease.
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Cardiomiopatia Dilatada/genética , Conectina/genética , Variação Genética/genética , Coração/fisiologia , Animais , Cardiomiopatia Dilatada/patologia , Estudos de Casos e Controles , Estudos de Coortes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , RatosRESUMO
INTRODUCTION: Diuretics are the mainstay of therapy for restoring the euvolaemic state in patients with decompensated heart failure. However, diuretic resistance remains a challenge. METHODS: We conducted a retrospective cohort study to examine the efficacy and safety of ultrafiltration (UF) in 44 hospitalised patients who had decompensated heart failure and diuretic resistance between October 2011 and July 2013. RESULTS: Among the 44 patients, 18 received UF (i.e. UF group), while 26 received diuretics (i.e. standard care group). After 48 hours, the UF group achieved lower urine output (1,355 mL vs. 3,815 mL, p = 0.0003), greater fluid loss (5,058 mL vs. 1,915 mL, p < 0.0001) and greater weight loss (5.0 kg vs. 1.0 kg, p < 0.0001) than the standard care group. The UF group also had a shorter duration of hospitalisation (5.0 days vs. 9.5 days, p = 0.0010). There were no differences in the incidence of 30-day emergency department visits and rehospitalisations for heart failure between the two groups. At 90 days, the UF group had fewer emergency department visits (0.2 vs. 0.8, p = 0.0500) and fewer rehospitalisations for heart failure (0.3 vs. 1.0, p = 0.0442). Reduction in EQ-5D™ scores was greater in the UF group, both at discharge (2.7 vs. 1.4, p = 0.0283) and 30 days (2.5 vs. 0.3, p = 0.0033). No adverse events were reported with UF. CONCLUSION: UF is an effective and safe treatment that can improve the health outcomes of Asian patients with decompensated heart failure and diuretic resistance.
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Diuréticos/uso terapêutico , Insuficiência Cardíaca/terapia , Ultrafiltração , Idoso , Resistência a Medicamentos , Serviço Hospitalar de Emergência , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Device therapy is efficacious in preventing sudden cardiac death (SCD) in patients with reduced ejection fraction. However, few who need the device eventually opt to undergo implantation and even fewer reconsider their decisions after deliberation. This is due to many factors, including unresolved patient barriers. This study identified the factors that influenced patients' decision to decline implantable cardioverter defibrillator (ICD) implantation, and those that influenced patients who initially declined an implant to reconsider having one. METHODS: A single-centre survey was conducted among 240 patients who had heart failure with reduced ejection fraction and met the ICD implantation criteria, but had declined ICD implantation. RESULTS: Participants who refused ICD implantation were mostly male (84%), Chinese (71%), married (72%), currently employed (54%), and had up to primary or secondary education (78%) and monthly income of < SGD 3,000 (51%). Those who were more likely to reconsider their decision were aware that SCD was a consequence of heart failure with reduced ejection fraction, knowledgeable of the preventive role of ICDs, currently employed and aware that their doctor strongly recommended the implant. Based on multivariate analysis, knowledge of the role of ICDs for primary prophylaxis was the most important factor influencing patient decision. CONCLUSION: This study identified the demographic and social factors of patients who refused ICD therapy. Knowledge of the role of ICDs in preventing SCD was found to be the strongest marker for reconsidering ICD implantation. Measures to address this information gap may lead to higher rates of ICD implantation.
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Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Insuficiência Cardíaca/terapia , Prevenção Primária/métodos , Volume Sistólico/fisiologia , Estudos Transversais , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Singapura/epidemiologia , Taxa de Sobrevida/tendênciasRESUMO
Mitochondria are the nexus of energy metabolism, and consequently their dysfunction has been implicated in the development of metabolic complications and progression to insulin resistance and type 2 diabetes. The unique tetra-acyl phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane, where it maintains mitochondrial integrity. Here we show that knockdown of Tafazzin (TAZ kd), a CL transacylase, in mice results in protection against the development of obesity, insulin resistance, and hepatic steatosis. We determined that hypermetabolism protected TAZ kd mice from weight gain. Unexpectedly, the large reduction of CL in the heart and skeletal muscle of TAZ kd mice was not mirrored in the liver. As a result, TAZ kd mice exhibited normal hepatic mitochondrial supercomplex formation and elevated hepatic fatty acid oxidation. Collectively, these studies identify a key role for hepatic CL remodeling in regulating susceptibility to insulin resistance and as a novel therapeutic target for diet-induced obesity.
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Cardiolipinas/biossíntese , Cardiolipinas/metabolismo , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Obesidade/metabolismo , Aciltransferases , Animais , Western Blotting , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Feminino , Hepatócitos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipogênese/fisiologia , Fígado/patologia , Masculino , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Obesidade/etiologia , Obesidade/genética , Oxirredução , Fatores de Transcrição/deficiência , Fatores de Transcrição/metabolismo , Aumento de Peso/genética , Aumento de Peso/fisiologiaRESUMO
OBJECTIVES: 1. To assess the reproducibility of eye movement velocity measurement using two methods: traditional electro-oculography (EOG) and infrared video-oculography (VOG) and, 2. Determine whether the normal values for unilateral weakness and bilateral reduction of caloric responses vary according to method employed. BACKGROUND: Vestibular testing frequently involves measurement of eye movements. EOG has been the standard method for decades, but VOG and other methods have recently become popular. The assumption has been that all methods measure eye movements equally and accurately but this assumption has not been validated. In this paper we examine this assumption. METHODS: Eye movements were recorded simultaneously with commercially available EOG and VOG methods to evaluate differences in results for nineteen normal subjects undergoing caloric tests with warm and cold water. Examination of the records permitted identification and simultaneous measurement of 840 nystagmus beats. RESULTS: EOG and VOG measurements were correlated but the correlation was not strong (Spearman rho = 0.529, p < 0.01). Eye velocities recorded by the VOG system were greater than that for the EOG system. The mean VOG/EOG ratio was 1.71. Normal values used at our centre were adjusted to accommodate the use of video technology to account for the differences in sensitivity between EOG and VOG methods. CONCLUSION: The traditional EOG-based normal value for bilateral reduction of caloric response, 30 degree per second (d/s) based on traditional EOG measurements should be revised to 50 d/s for modern VOG testing in our lab. Normal values for vestibular testing may need to be re-evaluated when new technology is introduced. Each lab should verify normal values for their own methods and equipment.
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Eletronistagmografia/métodos , Eletroculografia/métodos , Raios Infravermelhos , Gravação em Vídeo/métodos , Testes Calóricos/métodos , Humanos , Valor Preditivo dos Testes , Valores de ReferênciaRESUMO
Takayasu arteritis is a chronic inflammatory large vessel vasculitis affecting the aorta and its main branches. It can present in various forms, and thereby may lead to a delay in diagnosis. We present a patient with Takayasu arteritis, diagnosed at our center when she presented with severe aortic regurgitation. We also review the current knowledge base with respect to Takayasu arteritis.