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1.
Biogerontology ; 24(6): 845-866, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37439885

RESUMO

Human ageing is a complex, multifactorial process characterised by physiological damage, increased risk of age-related diseases and inevitable functional deterioration. As the population of the world grows older, placing significant strain on social and healthcare resources, there is a growing need to identify reliable and easy-to-employ markers of healthy ageing for early detection of ageing trajectories and disease risk. Such markers would allow for the targeted implementation of strategies or treatments that can lessen suffering, disability, and dependence in old age. In this review, we summarise the healthy ageing scores reported in the literature, with a focus on the past 5 years, and compare and contrast the variables employed. The use of approaches to determine biological age, molecular biomarkers, ageing trajectories, and multi-omics ageing scores are reviewed. We conclude that the ideal healthy ageing score is multisystemic and able to encompass all of the potential alterations associated with ageing. It should also be longitudinal and able to accurately predict ageing complications at an early stage in order to maximize the chances of successful early intervention.


Assuntos
Envelhecimento Saudável , Humanos , Envelhecimento , Biomarcadores
2.
J Cancer Educ ; 38(4): 1157-1162, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36701024

RESUMO

Chronic sun exposure and sunburns are the main preventable causes of skin cancer. Due to the nature of their work, physical education teachers are at high risk for occupational skin cancer. This descriptive, cross-sectional study analyzes primary and secondary physical education teachers in Andalusia, Spain. All participants were invited to monitor their ultraviolet (UV) radiation exposure using individual biologic dosimeters and record their photoprotection practices over 3 workdays. The teachers spent an average of 2.7 h outdoors and the mean personal UV radiation exposure was 309.9 J/m2 per day, a value three times higher than international recommendations. Based on the photoprotection diary, it was determined that classes held outdoors were not scheduled outside the hours with the highest UV index and that the percentage of participants who followed the photoprotective practices of remaining in the shade or wearing a hat during outdoor lessons were less than 20% and 60%, respectively. The results on sun exposure and photoprotection practices show a need for organizational and educational intervention strategies to mitigate sun exposure and increase compliance with photoprotection measures to reduce skin cancer risk among these workers and promote early diagnosis of the disease.


Assuntos
Neoplasias Cutâneas , Luz Solar , Humanos , Luz Solar/efeitos adversos , Educação Física e Treinamento , Espanha , Estudos Transversais , Instituições Acadêmicas , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Protetores Solares/uso terapêutico
3.
Sleep Breath ; 26(3): 1281-1286, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34671911

RESUMO

BACKGROUND: Sleep-disordered breathing (SDB) is prevalent in heart failure (HF). Yet, scarce data exist on sleep-patterns in acute HF and differences in specific subgroups. Our goal was to assess SDB prevalence in hospitalized patients with decompensated HF across the entire spectrum of left ventricle ejection fraction (LVEF). METHODS: Single-center retrospective study enrolling patients admitted for acute HF between 2013 and 2018. All patients were screened for SDB with an ApneaLink™ Plus device before discharge while euvolemic and receiving oral therapy. Those with a sleep study time < 3 h were excluded. HF with reduced, moderately reduced, and preserved LVEF (HFrEF, HFmrEF, and HFpEF) was defined by a LVEF < 40%, 40-49%, and ≥ 50%, respectively. SDB was defined by an apnea-hypopnea index (AHI) ≥ 5/h. RESULTS: Overall, 221 patients were included (mean age 75 ± 11 years). Seventy-two (33%) had HFrEF, 26 (11%) HFmrEF, and 123 (56%) HFpEF. In total, 176 (80%) met the criteria for mild SDB, while 59% and 38% had an AHI ≥ 15/h or ≥ 30/h, respectively. SDB prevalence was high and similar between HFrEF, HFmrEF, and HFpEF. Yet, SDB was often more severe in HFrEF when compared to HFpEF. HFmrEF had intermediate characteristics, with an AHI closer to HFrEF. CONCLUSION: In a cohort of patients admitted for acute HF, SDB was highly prevalent in all subgroups, including HFmrEF. The pervasiveness and severity of SDB was particularly noted in HFrEF. These findings suggest that routine SDB screening may be warranted following acute HF.


Assuntos
Insuficiência Cardíaca , Síndromes da Apneia do Sono , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
4.
Cardiology ; 146(2): 201-206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33524984

RESUMO

BACKGROUND: In patients with heart failure (HF) and reduced ejection fraction (HFrEF) with or without type 2 diabetes mellitus, the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was recently shown to reduce the risk of worsening HF or death from cardiovascular causes in the dapagliflozin in patients with heart failure and reduced ejection fraction (DAPA-HF) trial. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF enrolment criteria. METHODS: This is a single-center retrospective study enrolling consecutive, unselected patients followed up in an HF clinic from 2013 to 2019. Key DAPA-HF inclusion criteria (i.e., left ventricular ejection fraction [LVEF] ≤40% and NT-proBNP ≥600 pg/mL [or ≥900 pg/mL if atrial fibrillation]) and exclusion criteria (estimated glomerular filtration rate [eGFR] <30 mL/kg/1.73 m2 and systolic blood pressure [SBP] <95 mm Hg) were considered. RESULTS: Overall, 479 patients (age 76 ± 13 years; 50.5% male; 78.9% hypertensive; 45.1% with an eGFR <60 mL/min/1.73 m2; 36.5% with TD2M; and 33.5% with ischaemic HF) were assessed. The median SBP was 128.5 (112.0-146.0) mm Hg, mean eGFR was 50.8 ± 23.7 mL/min/1.73 m2, and median NT-proBNP was 2,183 (IQR 1,010-5,310) pg/mL. Overall, 155 (32.4%) patients had LVEF ≤40%. According to the DAPA-HF trial key criteria, 90 patients (18.8%) would be eligible for dapagliflozin. The remainder would be excluded due to LVEF >40% (67.6%), eGFR <30 mL/min/1.73 m2 (19.4%), NT-proBNP below the cutoff (16.7%), and/or SBP <95 mm Hg (6.5%). If we center the analysis to those with LVEF ≤40%, 58.1% would be eligible for dapagliflozin. The remainder would be excluded due to an eGFR <30 mL/min/1.73 m2 (20%), NT-proBNP below the cutoff (16.1%), and/or SBP <95 mm Hg (8.4%). CONCLUSION: Roughly half of our real-world HFrEF cohort would be eligible for dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was an eGFR <30 mL/min/1.73 m2. However, two-thirds of patients had LVEF >40%. These findings show that dapagliflozin is a promising complementary new drug in the therapeutic armamentarium of most patients with HFrEF, while highlighting the urgent need for disease-modifying drugs in mid-range and preserved LVEF and the need to assess the efficacy and safety of SLGT2i in advanced kidney disease patients. The results of ongoing SGLT2i trials in these LVEF subgroups are eagerly awaited.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Idoso , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Glucosídeos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
5.
Pacing Clin Electrophysiol ; 42(10): 1400-1407, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31433493

RESUMO

Vasovagal reflex is the most common cause of syncope. Pacemaker with rate drop response (RDR) or closed-loop stimulation (CLS) anti-syncope algorithms have been studied in recurrent vasovagal syncope (VVS), with conflicting results. We aim to investigate the role of pacemaker therapy and anti-syncope pacing mode in cardioinhibitory recurrent VVS. MEDLINE, Cochrane Library and registered clinical trials were searched for single or double-blind randomized controlled trials on pacing as a treatment for recurrent VVS. Five studies were eligible, overall enrolling 228 patients. After pooling data from all trials, pacemaker therapy showed a 63% reduction in syncope recurrence compared to control [Risk Ratio (RR): 0.37; 95% CI: 0.14-0.98; I2  = 67%)]. Subgroup analyses suggested that the effect was greater in single-blind studies (RR: 0.07; 95% CI: 0.01-0.52, I2  = 0%). When comparing pacing algorithms, the results from RDR versus no pacing trials (n = 2) did not show a significant reduction in syncope recurrence (RR: 0.73; 95% CI: 0.25-2.16, I2 60 = 75%). In contrast, the data from the CLS versus standard pacing trials (n = 3) evidenced a statistically meaningful reduction in syncopal burden (RR: 0.18; 95% CI: 0.07-0.47, I2  = 0%). It is unclear whether pacemaker therapy reduces syncopal burden in cardioinhibitory recurrent VVS. However, our results suggest effectiveness of CLS pacing mode.


Assuntos
Estimulação Cardíaca Artificial/métodos , Síncope Vasovagal/terapia , Algoritmos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Síncope Vasovagal/fisiopatologia
6.
Sleep Breath ; 22(3): 749-755, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29344749

RESUMO

PURPOSE: ApneaLink is a portable device for the screening of sleep apnea, a prevalent and underdiagnosed comorbidity in heart failure patients. A prospective cross-sectional study in patients with chronic heart failure was carried out to assess the sensitivity and specificity of apnea-hypopnea index (AHI) measurements using ApneaLink against the standard polysomnography test. METHODS: Adult patients with a prior hospitalization in an acute heart failure hospital unit were recruited for the study. All participants were tested for sleep apnea using ApneaLink and polysomnography simultaneously during an overnight stay at a sleep laboratory. Global sleep apnea was evaluated according to the AHI, which was analyzed and compared. Subpopulation comparison based on ejection fraction was not realized due to population size. RESULTS: Thirty-five patients with stable chronic heart failure completed the study (mean age 70.9 ± 10.5 years and body mass index 30.0 ± 4.7 kg/m2). Two patients were excluded due to insufficient study duration. ApneaLink had a sensitivity greater than 80% for all AHI measurements, and a specificity greater than 80% for all AHI measurements, except for AHI ≥ 5 events/h (61.5%). The results showed higher sensitivities and specificities at AHI values of ≥ 10 events/h (sensitivity 81.3% and specificity 84.2%) and ≥ 15 events/h (sensitivity 83.3% and specificity 91.3%). Correlation analysis showed that AHI measurements using ApneaLink and polysomnography had a strong and significant correlation (r = 0.794; P < 0.001). CONCLUSIONS: Our results suggest that ApneaLink could be used in clinical practice to identify heart failure patients with high (AHI ≥ 15 events/h) and low (AHI < 5 events/h) probability of having sleep apnea, sparing the need for a diagnostic polysomnography and thus potentially impacting prognosis by providing a more cost-effective and timely diagnosis of this non-cardiac comorbidity.


Assuntos
Insuficiência Cardíaca/complicações , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Idoso , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
Eur J Haematol ; 99(6): 505-513, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28885736

RESUMO

OBJECTIVES: To assess prevalence, predictive factors, and prognostic impact on in-hospital mortality of anemia, iron deficiency anemia (IDA), iron deficiency with or without anemia (ID), and iron deficiency without anemia (IDWA) in patients admitted to an internal medicine ward. METHODS: This 1-year prospective study collected data on demographics, medical history, and blood tests in 771 consecutive patients on admission. RESULTS: Most patients were ≥65 years old (80%) and had hypertension (63%), moderate chronic kidney disease (CKD) (43%), and heart failure (41%). Prevalence of anemia, IDA, ID, and IDWA was 67%, 41%, 58%, and 18%, respectively. Anemia was independently associated with age ≥65 years (OR 1.76, 95% CI 1.15-2.70), active cancer (OR 2.44, 95% CI 1.42-4.39), and moderate CKD (OR 1.65, 95% CI 1.12-2.43). ID was independently associated with female gender (OR 2.29, 95% CI 1.64-3.22), heart failure (OR 1.65, 95% CI 1.16-2.37), and moderate CKD (OR 2.95, 95% CI 2.04-4.30). Incidence of in-hospital mortality was 21% and independently associated with anemia (RR 1.82, 95% CI 1.21-2.74). CONCLUSIONS: Anemia and iron deficiency were highly prevalent in internal medicine patients. As anemia negatively impacts on in-hospital mortality, awareness should be raised for effective diagnosis and management of these comorbidities in hospitalized patients.


Assuntos
Anemia Ferropriva/epidemiologia , Anemia/epidemiologia , Hospitalização , Medicina Interna , Idoso , Idoso de 80 Anos ou mais , Anemia/diagnóstico , Anemia/etiologia , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/etiologia , Biomarcadores , Feminino , Humanos , Incidência , Ferro/sangue , Ferro/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Prognóstico , Estudos Prospectivos
11.
Neurosignals ; 21(1-2): 1-13, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22378242

RESUMO

Nitric oxide (NO) is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP) and the cGMP-dependent kinase (PKG) are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ) were used. We observed that long-term exposure to the NO donor (24 h), NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h) increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner.


Assuntos
Proliferação de Células , Proteínas Quinases Dependentes de GMP Cíclico/fisiologia , Guanilato Ciclase/fisiologia , Células-Tronco Neurais/fisiologia , Óxido Nítrico/fisiologia , Transdução de Sinais/fisiologia , Animais , Carbazóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Guanilato Ciclase/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Transdução de Sinais/efeitos dos fármacos
12.
Cureus ; 15(8): e42952, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37667694

RESUMO

Aortoenteric fistulas (AEFs) are a rare and deadly cause of gastrointestinal bleeding that can be easily overlooked, leading to massive bleeding. Secondary AEFs are more common than primary AEFs. An example of a secondary cause of anemia is postoperative hemorrhage due to a surgically placed aortic graft or after endovascular aneurysm repair. This report aims to increase the awareness of AEF as a differential diagnosis when anemia is detected. The clinical report presents a case of anemia in a 79-year-old man due to a secondary AEF, which occurred in a patient who had undergone abdominal aortic aneurysm surgery 10 years before. Surgical repair is considered the gold standard for AEF treatment; however, in this case, the patient was managed with medical therapy and discharged after two months.

13.
Antioxidants (Basel) ; 12(8)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37627556

RESUMO

Ras are a family of small GTPases that function as signal transduction mediators and are involved in cell proliferation, migration, differentiation and survival. The significance of Ras is further evidenced by the fact that Ras genes are among the most mutated oncogenes in different types of cancers. After translation, Ras proteins can be targets of post-translational modifications (PTM), which can alter the intracellular dynamics of the protein. In this review, we will focus on how S-nitrosylation of Ras affects the way these proteins interact with membranes, its cellular localization, and its activity. S-Nitrosylation occurs when a nitrosyl moiety of nitric oxide (NO) is covalently attached to a thiol group of a cysteine residue in a target protein. In Ras, the conserved Cys118 is the most surface-exposed Cys and the preferable residue for NO action, leading to the initiation of transduction events. Ras transduces the mitogen-activated protein kinases (MAPK), the phosphoinositide-3 kinase (PI3K) and the RalGEF cellular pathways. S-Nitrosylation of elements of the RalGEF cascade remains to be identified. On the contrary, it is well established that several components of the MAPK and PI3K pathways, as well as different proteins associated with these cascades, can be modified by S-nitrosylation. Overall, this review presents a better understanding of Ras S-nitrosylation, increasing the knowledge on the dynamics of these proteins in the presence of NO and the underlying implications in cellular signaling.

14.
Eur J Case Rep Intern Med ; 10(11): 004061, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920229

RESUMO

Primary hepatic lymphoma (PHL) is extremely rare, accounting for less than 1% of all lymphomas, and is limited to the liver without extrahepatic involvement. A 30-year-old male was admitted in the Emergency Department complaining of weakness, fever, night sweats, significant weight loss, discrete ring alopecia, hepatomegaly, right axillary adenopathy and oedema of both legs. Laboratory evaluation showed normocytic normochromic anaemia, thrombocytosis, hyperbilirubinemia, cholestasis and increased international normalised ratio (INR). A computed tomography (CT) scan found an enlarged liver with a heterogeneous structure and moderate ascites. After admission in our ward further investigation revealed increased sedimentation velocity, ferritin and serum lactate dehydrogenase. A hepatic biopsy was performed which confirmed the diagnosis as a nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). The patient was transferred to a haematological ward and underwent chemotherapy with six cycles of R-CHOP. He is in complete remission after a year and half since the beginning of treatment. NLPHL, a very rare lymphoma, is more common in men between the third and fifth decades of life. Usually, the symptoms are very unspecific; a few patients have B symptoms at admission. This kind of presentation is also common in infectious, metabolic and autoimmune diseases, which were excluded in this case. Due to technical issues the final diagnosis was only possible due to the liver biopsy. Treatment with standard Hodgkin lymphoma protocols leads to complete remission in more that 95% of patients with NLPHL. LEARNING POINTS: Differential diagnosis of fever, especially in young patients, is very complex and complete investigation takes time, which can delay the diagnosis of malignancies such as primary hepatic lymphoma (PHL).PHL is very rare, and overlapping symptoms with other liver diseases can make the diagnosis very challenging.When the suspicion of PHL is very high, only the hepatic biopsy can lead to the correct diagnosis because the disease has no extrahepatic involvement.

15.
Acta Med Port ; 36(3): 193-201, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36762993

RESUMO

Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute heart failure are caused by congestive conditions, not all patients have a congestive phenotype, reflecting the complexity of a process with multiple pathophysiological pathways. The use of diuretics, usually loop diuretics, is the mainstay of treatment for congestion. However, many patients develop resistance, thus constituting a challenge with no consensual solution to date, despite extensive debate over the years. Despite its frequent use in clinical practice, the co-administration of albumin and furosemide remains controversial in the management of patients with acute heart failure, hypoalbuminemia, and diuretic resistance. This review addresses the pathophysiological mechanisms of congestion in patients with acute heart failure and explores the theoretical basis that supports the co-administration of albumin and furosemide in this clinical context. It is intended to clarify the potential benefit of the combined approach in this specific population and identify possible gaps in the literature that could be the subject of future studies.


Assuntos
Furosemida , Insuficiência Cardíaca , Humanos , Furosemida/uso terapêutico , Diuréticos/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Albuminas/uso terapêutico
16.
Mech Ageing Dev ; 214: 111854, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37579530

RESUMO

The unprecedented rise in life expectancy observed in the last decades is leading to a global increase in the ageing population, and age-associated diseases became an increasing societal, economic, and medical burden. This has boosted major efforts in the scientific and medical research communities to develop and improve therapies to delay ageing and age-associated functional decline and diseases, and to expand health span. The establishment of induced pluripotent stem cells (iPSCs) by reprogramming human somatic cells has revolutionised the modelling and understanding of human diseases. iPSCs have a major advantage relative to other human pluripotent stem cells as their obtention does not require the destruction of embryos like embryonic stem cells do, and do not have a limited proliferation or differentiation potential as adult stem cells. Besides, iPSCs can be generated from somatic cells from healthy individuals or patients, which makes iPSC technology a promising approach to model and decipher the mechanisms underlying the ageing process and age-associated diseases, study drug effects, and develop new therapeutic approaches. This review discusses the advances made in the last decade using iPSC technology to study the most common age-associated diseases, including age-related macular degeneration (AMD), neurodegenerative and cardiovascular diseases, brain stroke, cancer, diabetes, and osteoarthritis.


Assuntos
Células-Tronco Adultas , Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Humanos , Diferenciação Celular , Envelhecimento
17.
Biomater Sci ; 11(18): 6060-6081, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37525590

RESUMO

Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (Ambystoma mexicanum) are capable of regenerating whole organs and even limbs, most mammals heal their wounds via fibrotic scarring. Recently, the African spiny mouse (Acomys sp.) has been shown to be injury resistant and capable of regenerating several tissue types. A major focal point of research with Acomys has been the identification of drivers of regeneration. In this search, the matrisome components related to the extracellular matrix (ECM) are often overlooked. In this review, we compare Acomys and axolotl skin wound healing and blastema-mediated regeneration by examining their wound healing responses and comparing the expression pattern of matrisome genes, including glycosaminoglycan (GAG) related genes. The goal of this review is to identify matrisome genes that are upregulated during regeneration and could be potential candidates for inclusion in pro-regenerative biomaterials. Research papers describing transcriptomic or proteomic coverage of either skin regeneration or blastema formation in Acomys and axolotl were selected. Matrisome and GAG related genes were extracted from each dataset and the resulting lists of genes were compared. In our analysis, we found several genes that were consistently upregulated, suggesting possible involvement in regenerative processes. Most of the components have been implicated in regulation of cell behavior, extracellular matrix remodeling and wound healing. Incorporation of such pro-regenerative factors into biomaterials may help to shift pro-fibrotic processes to regenerative responses in treated wounds.


Assuntos
Ambystoma mexicanum , Murinae , Humanos , Animais , Murinae/fisiologia , Proteômica , Cicatrização/genética , Regeneração , Materiais Biocompatíveis
18.
Rev Port Cardiol ; 42(9): 797-803, 2023 09.
Artigo em Inglês, Português | MEDLINE | ID: mdl-36948455

RESUMO

Acute heart failure (HF) decompensation generally manifests with signs and symptoms of congestion that strongly predict poor poor patient outcome. Loop diuretics are the cornerstone of therapy to counteract fluid overload and are widely used for acute management and chronic stabilization of HF. However, a diminished response to loop diuretics is a common problem, affecting the patient's clinical course and potentially prolonging hospitalization. Diuretic resistance is defined as failure to decongest despite appropriate and escalating loop diuretic therapy. We propose a protocol for the management of diuretic resistance. The initial approach should include an assessment of causes of pseudo-diuretic resistance. Adjustments to loop diuretic therapy, such as increasing doses and frequency of administration and sequential nephron blockade, may be successful. For hospitalized patients with progressive disease there are more invasive methods for fluid removal. Switching from oral to intravenous loop diuretics is essential to avoid variable absorption and for symptomatic relief. Extracorporeal ultrafiltration is also an option since this technique is highly effective at removing plasma fluid from blood. While extracorporeal ultrafiltration is an invasive solution, peritoneal dialysis is a home-based, intermittent therapeutic option that can enable efficient management of fluid overload, preventing HF-related hospital admission, and improving quality of life. As a last resort for fluid removal, a peritoneal dialysis regimen should fully exploit its decongestive properties and should be tailored to the patient's characteristics and clinical needs.


Assuntos
Diuréticos , Insuficiência Cardíaca , Humanos , Diuréticos/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Ultrafiltração/métodos , Qualidade de Vida , Insuficiência Cardíaca/tratamento farmacológico
19.
Aging (Albany NY) ; 15(8): 3191-3217, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37086262

RESUMO

The World Health Organization predicts that by 2050, 2.1 billion people worldwide will be over 60 years old, a drastic increase from only 1 billion in 2019. Considering these numbers, strategies to ensure an extended "healthspan" or healthy longevity are urgently needed. The present study approaches the promotion of healthspan from an epigenetic perspective. Epigenetic phenomena are modifiable in response to an individual's environmental exposures, and therefore link an individual's environment to their gene expression pattern. Epigenetic studies demonstrate that aging is associated with decondensation of the chromatin, leading to an altered heterochromatin structure, which promotes the accumulation of errors. In this review, we describe how aging impacts epigenetics and how nutrition and physical exercise can positively impact the aging process, from an epigenetic point of view. Canonical histones are replaced by histone variants, concomitant with an increase in histone post-translational modifications. A slight increase in DNA methylation at promoters has been observed, which represses transcription of previously active genes, in parallel with global genome hypomethylation. Aging is also associated with deregulation of gene expression - usually provided by non-coding RNAs - leading to both the repression of previously transcribed genes and to the transcription of previously repressed genes. Age-associated epigenetic events are less common in individuals with a healthy lifestyle, including balanced nutrition, caloric restriction and physical exercise. Healthy aging is associated with more tightly condensed chromatin, fewer PTMs and greater regulation by ncRNAs.


Assuntos
Envelhecimento , Histonas , Humanos , Histonas/metabolismo , Envelhecimento/genética , Epigênese Genética , Cromatina , Metilação de DNA , RNA não Traduzido/metabolismo , Exercício Físico
20.
Cureus ; 15(2): e35611, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37007323

RESUMO

Introduction Recurrent hospitalizations for worsening heart failure (WHF) represent a major global public health concern, resulting in significant individual morbimortality and socioeconomic costs. This real-life study aimed to determine the rate and predictors of readmission for WHF in a cohort of outpatients with chronic heart failure (CHF) followed in a heart failure clinic (HFC) at a university hospital. Methods We conducted a longitudinal, observational, and retrospective study of all consecutive CHF patients seen at the HFC of the São Francisco Xavier Hospital, Lisbon, by a multidisciplinary team in 2019. The patients were followed for one year and were on optimized therapy. The inclusion criteria for the study were patients who had been hospitalized and subsequently discharged at least three months prior to their enrollment. Patient demographics, heart failure (HF) characterization, comorbidities, pharmacological treatment, treatments of decompensated HF in the day hospital (DH), hospitalizations for WHF, and death were recorded. We applied logistic regression analysis to assess predictors of hospital readmission for HF. Results A total of 351 patients were included: 90 patients (26%) had WHF requiring treatment with intravenous diuretics in the DH; 45 patients (mean age: 79.1 ± 9.0 years) were readmitted for decompensated HF within one year (12.8%) with no gender difference, while 87.2% of the patients (mean age: 74.9 ± 12.1 years) were never readmitted. Readmitted patients were significantly older than those who were not (p=0.031). Additionally, they had a higher New York Heart Association (NYHA) functional classification (p<.001), were on a higher daily dose of furosemide (p=0.008) at the time of the inclusion visit, were more frequently affected by the chronic obstructive pulmonary disease (COPD) (p=0.004); had been treated more often in the DH for WHF (p<.001) and had a higher mortality rate (p<.001) at one year. Conclusions This study aimed to determine WHF patient readmission rates and predictors. According to our results, a higher NYHA class, the need for treatment in the DH for WHF, a daily dose of furosemide equal to or greater than 80 mg, and COPD were predictors of readmission for WHF. CHF patients continue to experience WHF and recurrent hospitalizations despite therapeutic advances and close follow-up in the HFC with the multidisciplinary team. Besides COPD, the HF readmission risk factors found were mainly related to advanced disease. Furthermore, the structured and multidisciplinary approach of our disease management program likely contributed to our relatively low rate of readmissions.

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