RESUMO
BACKGROUND: Several evidence demonstrated that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce the risk of dementia in type 2 diabetes patients by improving memory, learning, and overcoming cognitive impairment. In this study, we elucidated the molecular processes underlying the protective effect of Tirzepatide (TIR), a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP-RA)/ GLP-1RA, against learning and memory disorders. METHODS: We investigated the effects of TIR on markers of neuronal growth (CREB and BDNF), apoptosis (BAX/Bcl2 ratio) differentiation (pAkt, MAP2, GAP43, and AGBL4), and insulin resistance (GLUT1, GLUT4, GLUT3 and SORBS1) in a neuroblastoma cell line (SHSY5Y) exposed to normal and high glucose concentration. The potential role on DNA methylation of genes involved in neuroprotection and epigenetic modulators of neuronal growth (miRNA 34a), apoptosis (miRNA 212), and differentiation (miRNA 29c) was also investigated. The cell proliferation was detected by measuring Ki-67 through flow cytometry. The data were analysed by SPSS IBM Version 23 or GraphPad Prism 7.0 software and expressed as the means ± SEM. Differences between the mean values were considered significant at a p-value of < 0.05. GraphPad Prism software was used for drawing figures. RESULTS: For the first time, it was highlighted: (a) the role of TIR in the activation of the pAkt/CREB/BDNF pathway and the downstream signaling cascade; (b) TIR efficacy in neuroprotection; (c) TIR counteracting of hyperglycemia and insulin resistance-related effects at the neuronal level. CONCLUSIONS: We demonstrated that TIR can ameliorate high glucose-induced neurodegeneration and overcome neuronal insulin resistance. Thus, this study provides new insight into the potential role of TIR in improving diabetes-related neuropathy.
Assuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Inibidor Gástrico , Receptor do Peptídeo Semelhante ao Glucagon 2 , Resistência à Insulina , MicroRNAs , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo , Fator Neurotrófico Derivado do Encéfalo , Glicemia/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/farmacologiaRESUMO
Tirzepatide is a new drug targeting glucagon-like peptide 1(GLP1) and gastric inhibitory polypeptide (GIP) receptors. This drug has demonstrated great potential in improving the clinical outcomes of patients with type 2 diabetes. It can lead to weight loss, better glycemic control, and reduced cardiometabolic risk factors. GLP1 receptor agonists have been proven effective antidiabetic medications with possible cardiovascular benefits. Even though they have been proven to reduce the risk of major adverse cardiovascular events, their effectiveness in treating heart failure is unknown. Unlike traditional GLP1 receptor agonists, tirzepatide is more selective for the GIP receptor, resulting in a more balanced activation of these receptors. This review article discusses the possible mechanisms tirzepatide may use to improve cardiovascular health. That includes the anti-inflammatory effect, the ability to reduce cell death and promote autophagy, and also its indirect effects through blood pressure, obesity, and glucose/lipid metabolism. Additionally, tirzepatide may benefit atherosclerosis and lower the risk of major adverse cardiac events. Currently, clinical trials are underway to evaluate the safety and efficacy of tirzepatide in patients with heart failure. Overall, tirzepatide's dual agonism of GLP1 and GIP receptors appears to provide encouraging cardiovascular benefits beyond glycemic control, offering a potential new therapeutic option for treating cardiovascular diseases and heart failure.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Incretinas , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Animais , Resultado do Tratamento , Incretinas/uso terapêutico , Incretinas/efeitos adversos , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Biomarcadores/sangue , Medição de Risco , Receptor do Peptídeo Semelhante ao Glucagon 2 , Polipeptídeo Inibidor GástricoRESUMO
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. METHODS: A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. RESULTS: Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. CONCLUSION: Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Polipeptídeo Inibidor Gástrico , Receptor do Peptídeo Semelhante ao Glucagon 2 , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/prevenção & controle , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Hipertrofia , Hipoglicemiantes/farmacologia , Miócitos Cardíacos , Fibrose , Glucose , Receptor do Peptídeo Semelhante ao Glucagon 1RESUMO
Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.
Assuntos
Disfunção Cognitiva , Eritropoetina , Fármacos Neuroprotetores , Insuficiência Renal Crônica , Humanos , Eritropoetina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/psicologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Animais , Proteínas Recombinantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Cognição/efeitos dos fármacosRESUMO
To date, non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease, affecting up to 70% of patients with diabetes. Currently, there are no specific drugs available for its treatment. Beyond their anti-hyperglycemic effect and the surprising role of cardio- and nephroprotection, GLP-1 receptor agonists (GLP-1 RAs) have shown a significant impact on body weight and clinical, biochemical and histological markers of fatty liver and fibrosis in patients with NAFLD. Therefore, GLP-1 RAs could be a weapon for the treatment of both diabetes mellitus and NAFLD. The aim of this review is to summarize the evidence currently available on the role of GLP-1 RAs in the treatment of NAFLD and to hypothesize potential future scenarios.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus Tipo 2/patologia , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
BACKGROUND: prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. METHODS: data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. RESULTS: there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. CONCLUSIONS: statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients.
Assuntos
Síndrome Coronariana Aguda , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio com Supradesnível do Segmento ST , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Prognóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológicoRESUMO
BACKGROUND AND AIM: Elderly patients are at increased risk of hemorrhagic and thrombotic complications after an acute coronary syndrome (ACS). Frailty, comorbidities and low body weight have emerged as conditioning the prognostic impact of dual antiplatelet therapy (DAPT). The aim of the present study was to investigate the prognostic impact of body mass index (BMI) on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study comparing low-dose (5 mg) prasugrel vs clopidogrel among elderly patients with ACS. METHODS AND RESULTS: Our population is represented by 1408 patients enrolled in the Elderly-ACS 2 trial. BMI was calculated at admission. The primary endpoint of this analysis was cardiovascular (CV) mortality. Secondary endpoints were all-cause death, recurrent MI, Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding, and re-hospitalization for cardiovascular reasons or stent thrombosis within 12 months after index admission. Patients were grouped according to median values of BMI (Assuntos
Síndrome Coronariana Aguda/terapia
, Índice de Massa Corporal
, Clopidogrel/administração & dosagem
, Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia
, Intervenção Coronária Percutânea
, Inibidores da Agregação Plaquetária/administração & dosagem
, Cloridrato de Prasugrel/administração & dosagem
, Infarto do Miocárdio com Supradesnível do Segmento ST/terapia
, Síndrome Coronariana Aguda/diagnóstico por imagem
, Síndrome Coronariana Aguda/mortalidade
, Fatores Etários
, Idoso
, Idoso de 80 Anos ou mais
, Causas de Morte
, Clopidogrel/efeitos adversos
, Comorbidade
, Feminino
, Idoso Fragilizado
, Avaliação Geriátrica
, Hemorragia/induzido quimicamente
, Hemorragia/mortalidade
, Humanos
, Itália
, Masculino
, Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem
, Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade
, Intervenção Coronária Percutânea/efeitos adversos
, Intervenção Coronária Percutânea/mortalidade
, Inibidores da Agregação Plaquetária/efeitos adversos
, Cloridrato de Prasugrel/efeitos adversos
, Recidiva
, Medição de Risco
, Fatores de Risco
, Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
, Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade
, Fatores de Tempo
, Resultado do Tratamento
RESUMO
BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.
Assuntos
Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Clopidogrel/administração & dosagem , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Cloridrato de Prasugrel/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Clopidogrel/efeitos adversos , Intervalo Livre de Doença , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Masculino , Intervenção Coronária Percutânea , Cloridrato de Prasugrel/efeitos adversos , Taxa de SobrevidaRESUMO
BACKGROUND: Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. RESULTS: Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P < 0.001, Fisher's exact test) and presented a spindle cell morphology (P = 0.002; Fisher's exact test). MC and Ki-67 index were significantly correlated (P < 0.001; R = 0.67; Spearman's rank correlation); median values were 15 (range, 0-153) and 28% (range, 1-78%), respectively. Both were significantly higher in spindle cell melanomas, in tumours lacking junctional activity and in poorly-pigmented tumours. Follow-up information was available for 33 cats (66%). Variables related with a poor clinical outcome included mucosal location, tumour size, spindle, balloon and signet ring cell histotypes, low pigmentation, MC > 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. CONCLUSIONS: Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.
Assuntos
Antígeno Ki-67/metabolismo , Melanoma/veterinária , Neoplasias Bucais/veterinária , Neoplasias Cutâneas/veterinária , Animais , Doenças do Gato/patologia , Doenças do Gato/terapia , Gatos , Feminino , Masculino , Melanoma/patologia , Melanoma/terapia , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Pigmentação , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/terapiaRESUMO
Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia.
Assuntos
Antineoplásicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Gerenciamento Clínico , Prova Pericial , Imidazóis/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piridazinas/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Ensaios Clínicos como Assunto/métodos , Prova Pericial/métodos , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding. STUDY DESIGN: The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score). CONCLUSION: The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503).
Assuntos
Síndrome Coronariana Aguda/terapia , Aspirina/uso terapêutico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Clopidogrel , Quimioterapia Combinada , Intervenção Médica Precoce , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Mortalidade , Infarto do Miocárdio/epidemiologia , Readmissão do Paciente , Recidiva , Acidente Vascular Cerebral/epidemiologia , Ticlopidina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Recurrent ST-segment elevations in acute coronary syndromes have been attributed to coronary cyclic flow variations (CCFVs) possibly due to coronary vasospasm and unstable platelet aggregation in partially occluded arteries. METHODS: We describe the case of a patient with an acute myocardial infarction, recurrent ST-segment elevations and diffuse disease of the left anterior descending artery. RESULTS: The post-angiography 12-lead continuous ECG monitoring revealed cyclic anterior ST-segment elevations that were completely abolished with continuous intravenous infusion of low-dose isosorbide-dinitrate. CONCLUSION: The complete and sustained response to low-dose nitrate suggests that vasoconstriction plays a crucial role to provoke CCFVs. This case underlines the importance of continuous 12-lead ECG monitoring with ST-segment trend analysis in the CCU.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Circulação Coronária/efeitos dos fármacos , Eletrocardiografia , Nitroglicerina/administração & dosagem , Vasodilatadores/administração & dosagem , Síndrome Coronariana Aguda/diagnóstico , Idoso de 80 Anos ou mais , Angiografia Coronária , Circulação Coronária/fisiologia , Humanos , Masculino , Inibidores da Agregação Plaquetária/administração & dosagemRESUMO
Pulmonary artery dissection is a rare and fatal disease. Diagnosis is mainly made during autopsy because most patients die suddenly due to pulmonary artery dissection in the pericardium resulting in pericardial tamponade. The optimum management is not clearly defined because of the paucity of cases in the literature. We describe the case of an 81-year-old man, affected by rheumatoid arthritis and with history of aortic valve replacement surgery, who attended an emergency department for non-specific symptoms, started complaining of chest pain rapidly deteriorated into cardiac shock. Computed tomography scan, performed on suspicion of an acute aortic pathology and/or a pulmonary embolism, allowed the identification of pulmonary artery dissection associated with aorto-pulmonary fistula. Despite early diagnosis in the emergency department, the outcome was unfortunately fatal.
Assuntos
Dissecção Aórtica , Artéria Pulmonar , Humanos , Idoso de 80 Anos ou mais , Masculino , Dissecção Aórtica/cirurgia , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Evolução Fatal , Tomografia Computadorizada por Raios X , Fístula Vascular/cirurgia , Fístula Vascular/diagnóstico , Fístula Vascular/diagnóstico por imagemRESUMO
BACKGROUND: This case report outlines the presentation of an emerging complication arising from left bundle branch area pacing (LBBAP). CASE SUMMARY: A 43-year-old male with no history of cardiac problems experienced recurrent episodes of syncope with no prodromal symptoms. During monitoring in the emergency department, the patient underwent an episode of asystole, leading to LBBAP implantation. The procedure encountered technical challenges, resulting in an interventricular septal hematoma and subsequent ventricular arrhythmias. Despite initial concerns, conservative management led to resolution, demonstrated through echocardiographic follow-ups. DISCUSSION: This report underscores the significance of ventricular arrhythmias as indicators of interventricular septal hematoma, providing insights into its diagnosis, management, and implications for LBBAP procedures.
RESUMO
BACKGROUND: high-sensitive cardiac TroponinI (hs-cTnI) is widely used for diagnosis of acute coronary syndromes. The latest recommendation for hs-cTnI determination is the protocol 0-1 h finalized to improve the rule out accuracy of the test. A Point of Care Testing able to guarantee these performances could be very useful due to reducing the turnaround time and ruling out patients suspected of ACS, especially by using biological matrices that are not required for centrifuge. The aim of our work is to compare the results for hs-cTnI obtained using different biological matrices and anticoagulants, obtained between Atellica® VTLi hs-cTnI POCT and Access AccuTnI+3 DxI800 performances, in order to establish a possible bias derived directly from these pre-analytical conditions. METHODS: Li-heparinized pool samples were primary employ for hs-cTnI with Atellica® VTLi as whole blood, then centrifuged and tested on Atellica® VTLi and DxI800. K3EDTA pool samples were centrifuged and measured on DxI800 too. A comparison of methods was performed according to CLSI_EP-09A2 protocol. Constant and proportional errors were investigated with Deming regression. Bias between methods was evaluated with the Bland Altman test. RESULTS: comparing whole blood lithium heparin results obtained with Atellica versus lithium heparin and K3EDTA plasma tested on DxI 800, the Deming regression revealed a proportional error, whereas in both cases Bland Altman highlighted a minimal underestimation. A similar performance was revealed when considering plasma lithium heparin tested on Atellica versus lithium heparin and K3EDTA plasma obtained with DxI800, confirming the same underestimation. Considering values close to the cut off, no significant differences were found. CONCLUSIONS: in the laboratory, the estimation of the bias of two different analyzers is pivotal. Once more this is crucial when different biological matrices and anticoagulants are employed for the analysis. Our study demonstrates that no significant differences among the two matrices are present when comparing Atellica and DxI800 performances.
RESUMO
BACKGROUND: Anopheles sacharovi, a member of the Anopheles maculipennis complex, was a historical malaria vector in Italy, no longer found since the last report at the end of 1960s. In September 2022, within the Surveillance Project for the residual anophelism, a single specimen of An. maculipennis sensu lato collected in Lecce municipality (Apulia region) was molecularly identified as An. sacharovi. This record led to implement a targeted entomological survey in September 2023. METHODS: Investigation was conducted in the areas around the first discovery, focusing on animal farms, riding stables and potential breeding sites. Adult and immature mosquitoes were collected, using active search or traps, in several natural and rural sites. Mosquitoes belonging to An. maculipennis complex were identified morphologically and molecularly by a home-made routine quantitative polymerase chain reaction (qPCR) assay, developed specifically for the rapid identification of An. labranchiae, and, when necessary, by amplification and sequencing of the ITS-2 molecular marker. RESULTS: Out of the 11 sites investigated, 6 were positive for Anopheles presence. All 20 An. maculipennis s.l. (7 adults, 10 larvae and 3 pupae) collected in the areas were identified as An. sacharovi by ITS-2 sequencing. CONCLUSIONS: The discovery of An. sacharovi, considered to have disappeared from Italy for over 50 years, has a strong health relevance and impact, highlighting an increase in the receptivity of the southern areas. As imported malaria cases in European countries are reported every year, the risk of Plasmodium introduction by gametocyte carriers among travellers from endemic countries should be taken into greater consideration. Our findings allow rethinking and building new models for the prediction and expansion of introduced malaria. Furthermore, to prevent the risk of reintroduction of the disease, the need to strengthen the surveillance of residual anophelism throughout the South should be considered.
Assuntos
Anopheles , Malária , Animais , Malária/epidemiologia , Anopheles/genética , Mosquitos Vetores , Itália/epidemiologia , Europa (Continente)RESUMO
Hypercholesterolemia plays a crucial role in the formation of lipid plaques, particularly with elevated low-density lipoprotein (LDL-C) levels, which are linked to increased risks of cardiovascular disease, cerebrovascular disease, and peripheral arterial disease. Controlling blood cholesterol values, specifically reducing LDL-C, is widely recognized as a key modifiable risk factor for decreasing the morbidity and mortality associated with cardiovascular diseases. Historically, statins, by inhibiting the enzyme ß-hydroxy ß-methylglutaryl-coenzyme A (HMG)-CoA reductase, have been among the most effective drugs. However, newer non-statin agents have since been introduced into hypercholesterolemia therapy, providing a viable alternative with a favorable cost-benefit ratio. This paper aims to delve into the latest therapies, shedding light on their mechanisms of action and therapeutic benefits.
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Diabetes mellitus, a metabolic condition affecting around 537 million individuals worldwide, poses significant challenges, particularly among the elderly population. The etiopathogenesis of type 2 diabetes (T2D) depends on a combination of the effects driven by advancing age, genetic background, and lifestyle habits, e.g. overnutrition. These factors influence the development of T2D differently in men and women, with an obvious sexual dimorphism possibly underlying the diverse clinical features of the disease in different sexes. More recently, environmental pollution, estimated to cause 9 million deaths every year, is emerging as a novel risk factor for the development of T2D. Indeed, exposure to atmospheric pollutants such as PM2.5, O3, NO2, and Persistent Organic Pollutants (POP)s, along with their combination and bioaccumulation, is associated with the development of T2D and obesity, with a 15â¯% excess risk in case of exposure to very high levels of PM2.5. Similar data are available for plasticizer molecules, e.g. bisphenol A and phthalates, emerging endocrine-disrupting chemicals. Even though causality is still debated at this stage, preclinical evidence sustains the ability of multiple pollutants to affect pancreatic function, promote insulin resistance, and alter lipid metabolism, possibly contributing to T2D onset and progression. In addition, preclinical findings suggest a possible role also for plastic itself in the development of T2D. Indeed, pioneeristic studies evidenced that micro- or nanoplastics (MNP)s, particles in the micro- or nano- range, promote cellular damage, senescence, inflammation, and metabolic disturbances, leading to insulin resistance and impaired glucose metabolism in animal and/or in vitro models. Here we synthesize recent knowledge relative to the association between air-related or plastic-derived pollutants and the incidence of T2D, discussing also the possible mechanistic links suggested by the available literature. We then anticipate the need for future studies in the field of candidate therapeutic strategies limiting pollution-induced damage in preclinical models, such as SGLT-2 inhibitors. We finally postulate that future guidelines for T2D prevention should consider pollution and sex an additional risk factors to limit the diabetes pandemic.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Fatores de Risco , Feminino , Masculino , Poluição Ambiental/efeitos adversos , Animais , Exposição Ambiental/efeitos adversos , Fatores Sexuais , Caracteres SexuaisRESUMO
A 20-yr-old African fur seal (Arctocephalus pusillus) presented with a slowly growing mass located on the dorsum at the level of the last thoracic vertebrae. The mass was hard, 10 cm in diameter, and not adherent to the underlying tissues. Multiple biopsies were collected for histopathology and revealed extensive areas of necrosis, small nodules of malignant mesenchymal proliferation with areas of chondroid metaplasia, and atypical cells in vessel walls. The morphologic diagnosis was suggestive of malignant mesenchymal neoplasia originating from the vascular wall. The mass was removed 1 mo later due to ulceration and infection. Histologically, based on the World Health Organization's classification of neoplastic processes in domestic animals, the tumor was consistent with malignant mesenchymoma. The margins of resection revealed the presence of neoplastic cells. Based on these results, the particular species involved, the high local invasiveness, and the high metastatic index of this malignant tumor in domestic mammals and humans, the prognosis was poor. The animal died 6 mo later with metatastic disease.
Assuntos
Otárias , Mesenquimoma/veterinária , Neoplasias Vasculares/veterinária , Animais , Masculino , Invasividade Neoplásica , Neoplasias Vasculares/patologiaRESUMO
Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones.