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1.
Angiology ; 75(2): 182-189, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36905204

RESUMO

Currently, gender is not considered in the choice of the revascularization strategy for patients with unprotected left main coronary artery (ULMCA) disease. This study analyzed the effect of gender on the outcomes of percutaneous coronary intervention (PCI) vs coronary artery bypass grafting (CABG) in patients with ULMCA disease. Females who had PCI (n = 328) were compared with females who had CABG (n = 132) and PCI in males (n = 894) was compared with CABG (n = 784). Females with CABG had higher overall hospital mortality and major adverse cardiovascular events (MACE) than females with PCI. Male patients with CABG had higher MACE; however, mortality did not differ between males with CABG vs PCI. In female patients, follow-up mortality was significantly higher in CABG patients, and target lesion revascularization was higher in patients with PCI. Male patients had no difference in mortality and MACE between groups; however, MI was higher with CABG, and congestive heart failure was higher with PCI. In conclusion, women with ULMCA disease treated with PCI could have better survival with lower MACE compared with CABG. These differences were not evident in males treated with either CABG or PCI. PCI could be the preferred revascularization strategy in women with ULMCA disease.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Feminino , Masculino , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Mortalidade Hospitalar , Fatores de Risco
2.
Crit Pathw Cardiol ; 23(1): 12-16, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37948094

RESUMO

BACKGROUND: The use of dual antiplatelet therapy (DAPT) after coronary revascularization for left-main disease is still debated. The study aimed to characterize patients who received dual versus single antiplatelet therapy (SAPT) after coronary artery bypass grafting (CABG) for unprotected left-main disease and compare the outcomes of those patients. RESULTS: This multicenter retrospective cohort study included 551 patients who were grouped into 2 groups: patients who received SAPT (n = 150) and those who received DAPT (n = 401). There were no differences in age ( P = 0.451), gender ( P = 0.063), smoking ( P = 0.941), diabetes mellitus ( P = 0.773), history of myocardial infarction ( P = 0.709), chronic kidney disease ( P = 0.615), atrial fibrillation ( P = 0.306), or cerebrovascular accident ( P = 0.550) between patients who received SAPT versus DAPT. DAPTs were more commonly used in patients with acute coronary syndrome [87 (58%) vs. 273 (68.08%); P = 0.027], after off-pump CABG [12 (8%) vs. 73 (18.2%); P = 0.003] and in patients with radial artery grafts [1 (0.67%) vs. 32 (7.98%); P < 0.001]. While SAPTs were more commonly used in patients with low ejection fraction [55 (36.67%) vs. 61 (15.21%); P < 0.001] and in patients with postoperative acute kidney injury [27 (18%) vs. 37 (9.23%); P = 0.004]. The attributed treatment effect of DAPT for follow-up major adverse cerebrovascular and cardiac events was not significantly different from that of SAPT [ß, -2.08 (95% confidence interval (CI), -20.8-16.7); P = 0.828]. The attributed treatment effect of DAPT on follow-up all-cause mortality was not significantly different from that of SAPT [ß, 4.12 (CI, -11.1-19.32); P = 0.595]. There was no difference in bleeding between groups ( P = 0.666). CONCLUSIONS: DAPTs were more commonly used in patients with acute coronary syndrome, after off-pump CABG, and with radial artery grafts. SAPTs were more commonly used in patients with low ejection fraction and acute kidney injury. Patients on DAPT after CABG for left-main disease had comparable major adverse cerebrovascular and cardiac events and survival to patients on SAPT, with no difference in bleeding events.


Assuntos
Síndrome Coronariana Aguda , Injúria Renal Aguda , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/cirurgia , Síndrome Coronariana Aguda/induzido quimicamente , Estudos Retrospectivos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Hemorragia/induzido quimicamente , Injúria Renal Aguda/induzido quimicamente
3.
Int J Pharm ; 645: 123384, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37678472

RESUMO

The current work aims to design and provide a preliminary IND-enabling study of selective BMX inhibitors for cancer therapeutics development. BMX is an emerging target, more notably in oncological and immunological diseases. In this work, we have employed a predictive AI-based platform to design the selective inhibitors considering the novelty, IP prior protection, and drug-likeness properties. Furthermore, selected top candidates from the initial iteration of the design were synthesized and chemically characterized utilizing 1H NMR and LC-MS. Employing a panel of biochemical (enzymatic) and cancer cell lines, the selected molecules were tested against these assays. In addition, we used artificial intelligence to predict and evaluate several critical IND-focused physicochemical and pharmacokinetics values of the selected molecules. A secondary objective of the current work was also to validate the sole role of BMX in animal models known to be mediated by BMX. More than 50 molecules were designed in the present study employing five novel discovered scaffolds. Two molecules were nominated for further IND-focused studies. Compound II showed promising in-vitro activity against BMX in both enzymatic assays compared to other kinases and in cancer cell lines with known BMX overexpression. Interestingly, compound II showed very favorable physicochemical and pharmacokinetics properties as predicted by the used platforms. The animal study further confirmed the sole role of BMX in the disease model. The current work provides promising data on a selective BMX inhibitor as a potential lead for therapeutics development, and the asset is currently in the optimization stage. Notably, the current study shows a framework for a combined approach employing both AI and experimentation that can be used by academic labs in their research programs to more streamline programs into IND-focused to be bridged easily for further clinical development with industrial partners.

4.
Eur J Med Res ; 28(1): 210, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37393361

RESUMO

BACKGROUND: The optimal revascularization strategy in patients with left main coronary artery (LMCA) disease in the emergency setting is still controversial. Thus, we aimed to compare the outcomes of percutaneous coronary interventions (PCI) vs. coronary artery bypass grafting (CABG) in patients with and without emergent LMCA disease. METHODS: This retrospective cohort study included 2138 patients recruited from 14 centers between 2015 and 2019. We compared patients with emergent LMCA revascularization who underwent PCI (n = 264) to patients who underwent CABG (n = 196) and patients with non-emergent LMCA revascularization with PCI (n = 958) to those who underwent CABG (n = 720). The study outcomes were in-hospital and follow-up all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Emergency PCI patients were older and had a significantly higher prevalence of chronic kidney disease, lower ejection fraction, and higher EuroSCORE than CABG patients. CABG patients had significantly higher SYNTAX scores, multivessel disease, and ostial lesions. In patients presenting with arrest, PCI had significantly lower MACCE (P = 0.017) and in-hospital mortality (P = 0.016) than CABG. In non-emergent revascularization, PCI was associated with lower MACCE in patients with low (P = 0.015) and intermediate (P < 0.001) EuroSCORE. PCI was associated with lower MACCE in patients with low (P = 0.002) and intermediate (P = 0.008) SYNTAX scores. In non-emergent revascularization, PCI was associated with reduced hospital mortality in patients with intermediate (P = 0.001) and high (P = 0.002) EuroSCORE compared to CABG. PCI was associated with lower hospital mortality in patients with low (P = 0.031) and intermediate (P = 0.001) SYNTAX scores. At a median follow-up time of 20 months (IQR: 10-37), emergency PCI had lower MACCE compared to CABG [HR: 0.30 (95% CI 0.14-0.66), P < 0.003], with no significant difference in all-cause mortality between emergency PCI and CABG [HR: 1.18 (95% CI 0.23-6.08), P = 0.845]. CONCLUSIONS: PCI could be advantageous over CABG in revascularizing LMCA disease in emergencies. PCI could be preferred for revascularization of non-emergent LMCA in patients with intermediate EuroSCORE and low and intermediate SYNTAX scores.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Estudos Retrospectivos , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia
5.
Kidney Blood Press Res ; 48(1): 545-555, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37517398

RESUMO

INTRODUCTION: The evidence about the optimal revascularization strategy in patients with left main coronary artery (LMCA) disease and impaired renal function is limited. Thus, we aimed to compare the outcomes of LMCA disease revascularization (percutaneous coronary intervention [PCI] vs. coronary artery bypass grafting [CABG]) in patients with and without impaired renal function. METHODS: This retrospective cohort study included 2,138 patients recruited from 14 centers between 2015 and 2,019. We compared patients with impaired renal function who had PCI (n= 316) to those who had CABG (n = 121) and compared patients with normal renal function who had PCI (n = 906) to those who had CABG (n = 795). The study outcomes were in-hospital and follow-up major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Multivariable logistic regression analysis showed that the risk of in-hospital MACCE was significantly higher in CABG compared to PCI in patients with impaired renal function (odds ratio [OR]: 8.13 [95% CI: 4.19-15.76], p < 0.001) and normal renal function (OR: 2.59 [95% CI: 1.79-3.73]; p < 0.001). There were no differences in follow-up MACCE between CABG and PCI in patients with impaired renal function (HR: 1.14 [95% CI: 0.71-1.81], p = 0.585) and normal renal function (HR: 1.12 [0.90-1.39], p = 0.312). CONCLUSIONS: PCI could have an advantage over CABG in revascularization of LMCA disease in patients with impaired renal function regarding in-hospital MACCE. The follow-up MACCE was comparable between PCI and CABG in patients with impaired and normal renal function.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Rim/cirurgia
6.
Cardiology ; 148(3): 173-186, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36966525

RESUMO

INTRODUCTION: The aim of this study was to evaluate the effects of baseline anemia and anemia following revascularization on outcomes in patients with unprotected left main coronary artery (ULMCA) disease. METHODS: This was a retrospective, multicenter, observational study conducted between January 2015 and December 2019. The data on patients with ULMCA who underwent revascularization through percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) were stratified by the hemoglobin level at baseline into anemic and non-anemic groups to compare in-hospital events. The pre-discharge hemoglobin following revascularization was categorized into very low (<80 g/L for men and women), low (≥80 and ≤119 g/L for women and ≤129 g/L for men), and normal (≥130 g/L for men and ≥120 g/L for women) to assess impact on follow-up outcomes. RESULTS: A total of 2,138 patients were included, 796 (37.2%) of whom had anemia at baseline. A total of 319 developed anemia after revascularization and moved from being non-anemic at baseline to anemic at discharge. There was no difference in hospital major adverse cardiac and cerebrovascular event (MACCE) and mortality between CABG and PCI in anemic patients. At a median follow-up time of 20 months (interquartile range [IQR]: 27), patients with pre-discharge anemia who underwent PCI had a higher incidence of congestive heart failure (CHF) (p < 0.0001), and those who underwent CABG had significantly higher follow-up mortality (HR: 9.85 (95% CI: 2.53-38.43), p = 0.001). CONCLUSION: In this Gulf LM study, baseline anemia had no impact upon in-hospital MACCE and total mortality following revascularization (PCI or CABG). However, pre-discharge anemia is associated with worse outcomes after ULMCA disease revascularization, with significantly higher all-cause mortality in patients who had CABG, and a higher incidence of CHF in PCI patients, at a median follow-up time of 20 months (IQR: 27).


Assuntos
Anemia , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Masculino , Humanos , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Anemia/complicações , Sistema de Registros , Fatores de Risco
7.
Angiology ; 74(8): 754-764, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-35969482

RESUMO

The optimal stenting strategy for unprotected left main coronary artery (ULMCA) disease remains debated. This retrospective observational study (Gulf Left Main Registry) analyzed the outcomes of 1 vs 2 stents in patients with unprotected left main percutaneous coronary intervention (PCI). Overall, 1222 patients were evaluated; 173 had 1 stent and 1049 had 2 stents. The 2-stent group was older with more comorbidities, higher mean SYNTAX scores, and more distal bifurcation lesions. In the 1-stent group, in-hospital events were significant for major bleeding, and better mean creatinine clearance. At median follow-up of 20 months, the 1-stent group was more likely to have target lesion revascularization (TLR). Total mortality was numerically lower in the 1-stent group (.00% vs 2.10%); however, this was not statistically significant (P=.068). Our analysis demonstrates the benefits of a 2-stent approach for ULMCA patients with high SYNTAX scores and lesions in both major side branches, while the potential benefit of a 1-stent approach for less complex ULMCA was also observed. Further studies with longer follow-up are needed to definitively demonstrate the optimal approach.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Doença da Artéria Coronariana/terapia , Stents , Estudos Retrospectivos , Sistema de Registros
8.
J Cardiovasc Med (Hagerstown) ; 24(1): 23-35, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36219153

RESUMO

AIMS: The impact of left ventricular dysfunction on clinical outcomes following revascularization is not well established in patients with unprotected left main coronary artery disease (ULMCA). In this study, we evaluated the impact of left ventricular ejection fraction (LVEF) on clinical outcomes of patients with ULMCA requiring revascularization with percutaneous coronary intervention (PCI) compared with coronary artery bypass graft (CABG). METHODS: The details of the design, methods, end points, and relevant definitions are outlined in the Gulf Left Main Registry: a retrospective, observational study conducted between January 2015 and December 2019 across 14 centres in 3 Gulf countries. In this study, the data on patients with ULMCA who underwent revascularization through PCI or CABG were stratified by LVEF into three main subgroups; low (l-LVEF <40%), mid-range (m-LVEF 40-49%), and preserved (p-LVEF ≥50%). Primary outcomes were hospital major adverse cardiovascular and cerebrovascular events (MACCE) and mortality and follow-up MACCE and mortality. RESULTS: A total of 2137 patients were included; 1221 underwent PCI and 916 had CABG. During hospitalization, MACCE was significantly higher in patients with l-LVEF [(10.10%), P = 0.005] and m-LVEF [(10.80%), P = 0.009], whereas total mortality was higher in patients with m-LVEF [(7.40%), P = 0.009] and p-LVEF [(7.10%), P = 0.045] who underwent CABG. There was no mortality difference between groups in patients with l-LVEF. At a median follow-up of 15 months, there was no difference in MACCE and total mortality between patients who underwent CABG or PCI with p-LVEF and m-LVEF. CONCLUSION: CABG was associated with higher in-hospital events. Hospital mortality in patients with l-LVEF was comparable between CABG and PCI. At 15 months' follow-up, PCI could have an advantage in decreasing MACCE in patients with l-LVEF.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Volume Sistólico , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Função Ventricular Esquerda , Resultado do Tratamento , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Sistema de Registros
9.
Cardiovasc Revasc Med ; 46: 52-61, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35961856

RESUMO

BACKGROUND: Real-world data for managing patients with diabetes and left main coronary artery (LMCA) disease are scarce. We compared percutaneous coronary intervention (PCI) outcomes versus coronary artery bypass grafting (CABG) in diabetes and LMCA disease patients. METHODS: We retrospectively studied patients with LMCA presented to 14 centers from 2015 to 2019. The study included 2138 patients with unprotected LMCA disease; 1468 (68.7 %) had diabetes. Patients were grouped into; diabetes with PCI (n = 804) or CABG (n = 664) and non-diabetes with PCI (n = 418) or CABG (n = 252). RESULTS: In diabetes, cardiac (34 (5.1 %) vs. 22 (2.7 %); P = 0.016), non-cardiac (13 (2 %) vs. 6 (0.7 %); P = 0.027) and total hospital mortality (47 (7.1 %) vs. 28 (3.5 %); P = 0.0019), myocardial infarction (45 (6.8 %) vs. 11 (1.4 %); P = 0.001), cerebrovascular events (25 (3.8 %) vs. 12 (1.5 %); P = 0.005) and minor bleeding (65 (9.8 %) vs. 50 (6.2 %); P = 0.006) were significantly higher in CABG patients compared to PCI; respectively. The median follow-up time was 20 (10-37) months. In diabetes, total mortality was higher in CABG (P = 0.001) while congestive heart failure was higher in PCI (P = 0.001). There were no differences in major adverse cerebrovascular events and target lesion revascularization between PCI and CABG. Predictors of mortality in diabetes were high anatomical SYNTAX, peripheral arterial disease, chronic kidney disease, and cardiogenic shock. CONCLUSIONS: In this multicenter retrospective study, we found no significant difference in clinical outcomes during the short-term follow-up between PCI with second-generation DES and CABG except for lower total mortality and a higher rate of congestive heart failure in PCI group of patients. Randomized trials to characterize patients who could benefit from each treatment option are needed.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Insuficiência Cardíaca , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Estudos Retrospectivos , Intervenção Coronária Percutânea/efeitos adversos , Revascularização Miocárdica , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/etiologia , Resultado do Tratamento
10.
Curr Probl Cardiol ; 48(1): 101424, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167223

RESUMO

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in revascularization of left main coronary artery (LMCA) disease has been evaluated in previous studies. However, there has been minimal study of the relationship between co-existing non-coronary atherosclerosis (NCA) and LMCA disease revascularization. We aim to examine this relationship. The Gulf-LM study is a retrospective analysis of unprotected LMCA revascularization cases undergoing PCI with second generation drug-eluting stent vs CABG across 14 centers within 3 Gulf countries between January 2015 and December 2019. A total of 2138 patients were included, 381 with coexisting NCA and 1757 without. Outcomes examined included major adverse cardiovascular and cerebrovascular events (MACCE), cardiac and non-cardiac death, and all bleeding. In patients with NCA, preexisting myocardial infarction and congestive heart failure were more common, with PCI being the most common revascularization strategy. A statistically significant reduction in in-hospital MACCE and all bleeding was noted in patients with NCA undergoing PCI as compared to CABG. At a median follow-up of 15 months, MACCE and major bleeding outcomes continued to favor the PCI group, though no such difference was identified between revascularization strategies in patients without NCA.In this multicenter retrospective study of patients with and without NCA who require revascularization (PCI and CABG) for unprotected LMCA disease, PCI demonstrated a better clinical outcome in MACCE both in-hospital and during the short-term follow-up in patients with NCA. However, no such difference was observed in patients without NCA.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/etiologia , Sistema de Registros , Aterosclerose/etiologia , Fatores de Risco , Estudos Multicêntricos como Assunto
11.
BMC Med Educ ; 22(1): 377, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35581587

RESUMO

BACKGROUND: Most of the medical schools in Saudi Arabia are currently evolving their curricula in accordance with the most recognized medical education trends worldwide. Undergraduate medical school's curriculum should be compatible with community health needs. Therefore, the study aims to explore the current contents of Saudi undergraduate medical curricula and to check if the core topics that were internationally recognized were implemented in their curriculum. METHODOLOGY: An online questionnaire was designed and sent to 37 deans of medical schools in Saudi Arabia. The deans or the vice-deans in charge of the curriculum were asked to complete the pre-designed questionnaire, which assessed the status of inclusion of the core topics in the curriculum of their affiliated schools. Each listed core topic was evaluated according to five options for each subject: not included, separate required course, part of the required course, separate elective course, and part of an elective course. RESULTS: Twenty four out of 37 (65%) Saudi medical schools completed the survey questionnaire. Almost all core topics, such as communication skills, evidence-based medicine, patient safety, professionalism were included in the curricula of Saudi medical schools as separate required courses or as part of required courses or elective courses. Complementary and alternative medicine and the history of medicine were the topics least taught in Saudi medical colleges, as 25% of the schools did not include them in their curricula. CONCLUSION: The majority (65%) of the internationally recognized core topics were included in the Saudi undergraduate medical curricula. Evidence-based medicine, complementary medicine, the Saudi healthcare system, patient safety, and professionalism/medical ethics should be part of compulsory credited courses in all Saudi undergraduate medical curricula.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Currículo , Humanos , Arábia Saudita , Faculdades de Medicina , Inquéritos e Questionários
12.
Curr Probl Cardiol ; 47(10): 101002, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34587490

RESUMO

Coronary artery bypass surgery (CABG) has been the standard of care for revascularization for patients with obstructive unprotected left main coronary disease (ULMCA). There have been multiple randomized and registry data demonstrating the technical and clinical efficacy of PCI in certain patients with ULMCA. The purpose of this study is to evaluate clinical outcomes of ULMCA PCI as compared to CABG in patients requiring revascularization in three Gulf countries. All ULMCA cases treated by PCI with DES versus CABG were retrospectively identified from 14 centers in 3 Arab Gulf countries (KSA, UAE, and Bahrain) from January 2015 to December 2019. In total, 2138 patients were included: 1222 were treated with PCI versus 916 with CABG. Patients undergoing PCI were older, and had higher comorbidities and mean European System for Cardiac Operative Risk Evaluation (EuroSCORE). Aborted cardiac arrest and cardiogenic shock were reported more in the PCI group at hospital presentation. In addition, lower ejection fractions were reported in the PCI group. In hospital mortality and major adverse cardiovascular and cerebrovascular events (MACCE) occurred more in patients undergoing CABG than PCI. At median follow-up of 15 months (interquartile range, 30), no difference was observed in freedom from revascularization, MACCE, or total mortality between those treated with PCI and CABG. While findings are similar to Western data registries, continued follow-up will be needed to ascertain whether this pattern continues into latter years.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Ponte de Artéria Coronária , Humanos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
Mol Pharm ; 18(3): 986-1002, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33496597

RESUMO

RNAi is a biological process that utilizes small interfering RNA (siRNA) to prevent the translation of mRNA to protein. This mechanism could be beneficial in preventing the overexpression of proteins in cancer. However, the cellular delivery of siRNA has proven to be challenging due to its inherent negative charge and relative instability. Here, we designed a multicomponent delivery system composed of a specifically designed peptide (linear or cyclic fatty acyl peptide conjugates and hybrid cyclic/linear peptides) and several lipids (DOTAP, DOPE, cholesterol, and phosphatidylcholine) to form a nanoparticle, which we have termed as peptide lipid-associated nucleic acids (PLANAs). Five formulations were prepared (a formulation with no peptide, which was named lipid-associated nucleic acid or LANA, and PLANA formulations A-D) using a mini extruder to form uniform nanoparticles around 100 nm in size with a slightly positive charge (less than +10 mv). Formulations were evaluated for peptide incorporation, siRNA encapsulation efficiency, release profile, toxicity, cellular uptake, and protein silencing. Our experiments showed effective encapsulation of siRNA (>95%), a controlled release profile, and negligible toxicity in formulations that did not contain a positively charged lipid. The results also revealed that PLANAs C and D exhibited optimum cellular uptake (with 80-90% siRNA-positive cells for most of the formulations). PLANA D formulation was selected to silence two model proteins (Src and RPS6KA5) in the triple-negative human breast cancer cell line MDA-MB-231, with promising silencing efficiency, which diminished the expression of RPS6KA5 and Src to approximately 29 and 38% compared to naïve cells, respectively. Many approaches have been investigated for safe and efficient delivery of nucleic acids in the last 20 years; however, many have failed due to the multifaceted challenges to overcome. Our results show a promising potential for a multicomponent design that incorporates different components for a variety of delivery tasks, which warrants further investigation of PLANAs in vivo.


Assuntos
Lipídeos/genética , Ácidos Nucleicos Peptídicos/genética , Peptídeos/genética , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Inativação Gênica/fisiologia , Técnicas de Transferência de Genes , Humanos , Lipídeos/química , Nanopartículas/química , Ácidos Nucleicos Peptídicos/química , Peptídeos/química , Interferência de RNA/fisiologia
14.
Curr Probl Cardiol ; 46(3): 100484, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31610953

RESUMO

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome and sudden cardiac death. The triggers for SCAD often do not include traditional atherosclerotic risk factors. The most commonly reported triggers are extreme physical or emotional stress. The current study compared in-hospital and follow-up events in patients with SCAD with and without reported stress. Data from 83 patients with a confirmed diagnosis of SCAD were collected retrospectively from 30 centers in 4 Arab Gulf countries (KSA, UAE, Kuwait, and Bahrain) from January 2011 to December 2017. In-hospital myocardial infarction (MI), percutaneous coronary intervention (PCI), ventricular tachycardia/ventricular fibrillation, cardiogenic shock, death, ICD placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) events were compared between those with and without reported stress. Emotional and physical stress was defined as new or unusually intense stress, within 1 week of their initial hospitalization. The median age of patients in the study was 44 (37-55) years. Foty-two (51%) were women. Stress (emotional, physical, and combined) was reported in 49 (59%) of all patients. Sixty-two percent of women with SCAD reported stress, and 51 % of men with SCAD reported stress. Men more commonly reported physical and combined stress. Women more commonly reported emotional stress (P < 0.001). The presence or absence of reported stress did not impact on overall adverse cardiovascular events (P = 0.8). In-hospital and follow-up events were comparable in patients with SCAD in the presence or absence of reported stress as a trigger.


Assuntos
Anomalias dos Vasos Coronários , Intervenção Coronária Percutânea , Angústia Psicológica , Estresse Fisiológico , Doenças Vasculares , Árabes , Angiografia Coronária , Anomalias dos Vasos Coronários/etiologia , Anomalias dos Vasos Coronários/psicologia , Vasos Coronários , Dissecação , Humanos , Estudos Retrospectivos , Doenças Vasculares/etiologia , Doenças Vasculares/psicologia
15.
Curr Probl Cardiol ; 46(3): 100656, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32839042

RESUMO

The COVID-19 pandemic had significant impact on health care worldwide which has led to a reduction in all elective admissions and management of patients through virtual care. The purpose of this study is to assess changes in STEMI volumes, door to reperfusion, and the time from the onset of symptoms until reperfusion therapy, and in-hospital events between the pre-COVID-19 (PC) and after COVID-19 (AC) period. All acute ST-segment elevation myocardial infarction (STEMI) cases were retrospectively identified from 16 centers in the Kingdom of Saudi Arabia during the COVID-19 period from January 01 to April 30, 2020. These cases were compared to a pre-COVID period from January 01 to April 30, 2018 and 2019. One thousand seven hundred and eighty-five patients with a mean age 56.3 (SD ± 12.4) years, 88.3% were male. During COVID-19 Pandemic the total STEMI volumes was reduced (28%, n = 500), STEMI volumes for those treated with reperfusion therapy was reduced too (27.6%, n= 450). Door to balloon time < 90 minutes was achieved in (73.1%, no = 307) during 2020. Timing from the onset of symptoms to the balloon of more than 12 hours was higher during 2020 comparing to pre-COVID 19 years (17.2% vs <3%, respectively). There were no differences between the AC and PC period with respect to in-hospital events and the length of hospital stay. There was a reduction in the STEMI volumes during 2020. Our data reflected the standard of care for STEMI patients continued during the COVID-19 pandemic while demonstrating patients delayed presenting to the hospital.


Assuntos
COVID-19 , Aceitação pelo Paciente de Cuidados de Saúde , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Tempo para o Tratamento/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2 , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Arábia Saudita/epidemiologia , Índice de Gravidade de Doença , Padrão de Cuidado/organização & administração
16.
Angiology ; 72(1): 32-43, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32787614

RESUMO

Data on spontaneous coronary artery dissection (SCAD) is based on European and North American registries. We assessed the prevalence, epidemiology, and outcomes of patients presenting with SCAD in Arab Gulf countries. Patients (n = 83) were diagnosed with SCAD based on angiographic and intravascular imaging whenever available. Thirty centers in 4 Arab Gulf countries (Kingdom of Saudi Arabia, United Arab Emirates, Kuwait, and Bahrain) were involved from January 2011 to December 2017. In-hospital (myocardial infarction [MI], percutaneous coronary intervention, ventricular tachycardia/fibrillation, cardiogenic shock, death, implantable cardioverter-defibrillator placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) cardiac events were recorded. Median age was 44 (37-55) years, 42 (51%) were females and 28.5% were pregnancy-associated (21.4% were multiparous). Of the patients, 47% presented with non-ST-elevation acute coronary syndrome, 49% with acute ST-elevation myocardial infarction, 12% had left main involvement, 43% left anterior descending, 21.7% right coronary, 9.6% left circumflex, and 9.6% multivessel; 52% of the SCAD were type 1, 42% type 2, 3.6% type 3, and 2.4% multitype; 40% managed medically, 53% underwent percutaneous coronary intervention, 7% underwent coronary artery bypass grafting. Females were more likely than males to experience overall (in-hospital and follow-up) adverse cardiovascular events (P = .029).


Assuntos
Anomalias dos Vasos Coronários/epidemiologia , Doenças Vasculares/congênito , Adulto , Angiografia Coronária , Ponte de Artéria Coronária/estatística & dados numéricos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/terapia , Terapia Antiplaquetária Dupla , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/epidemiologia , Intervenção Coronária Percutânea/estatística & dados numéricos , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/terapia , Prevalência , Sistema de Registros , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Tomografia de Coerência Óptica , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/epidemiologia , Doenças Vasculares/terapia
17.
Crit Pathw Cardiol ; 20(1): 36-43, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657974

RESUMO

BACKGROUND: Atherosclerotic coronary plaque dissection (ACPD) is one cause of acute coronary syndrome (ACS) caused by underlying atherosclerosis. Spontaneous coronary artery dissection (SCAD) occurs outside the setting of atherosclerosis among young women and individuals with few or no conventional atherosclerotic risk factors, and has emerged as an important cause of ACS, and sudden death. A comparison between ACPD and SCAD has not been previously addressed in the literature. Our study will compare ACPD and SCAD. METHODS: Patients with confirmed diagnosis of SCAD and ACPD were retrospectively identified from 30 centers in 4 Arab Gulf countries between January 2011 and December 2017. In-hospital (ventricular tachycardia/ventricular fibrillation, myocardial infarction (MI), percutaneous coronary intervention, dissection extension, cardiogenic shock, death, implantable cardioverter-defibrillator placement) and follow-up (MI, de novo SCAD, spontaneous superior mesenteric artery dissection, death) events were compared between them. RESULTS: Eighty-three cases of SCAD and 48 ACPD were compared. ACPD patients were more frequently male (91.67% vs. 49.40%, P < 0.001) and older (58.5 vs. 44, P < 0.001). Cardiovascular risk factors were more prevalent in patients with ACPD, including diabetes mellitus (60.4% vs. 25.3%), dyslipidemia (62.5% vs. 38.5%), and hypertension (62.5% vs. 31.3%), P < 0.001. Hospital presentation of ST-elevation MI was diagnosed in 48% of SCAD versus 27% of ACPD patients (P = 0.012). SCAD patients received medical-only treatment in 40% of cases and ACPD in 21% (P = 0.042). In-hospital and follow-up events were comparable in both groups (P = 0.25). CONCLUSIONS: Despite a completely different pathophysiology of ACS between SCAD and ACPD, in-hospital and follow-up events were comparable.


Assuntos
Anomalias dos Vasos Coronários , Angiografia Coronária , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico , Anomalias dos Vasos Coronários/epidemiologia , Dissecação , Feminino , Humanos , Masculino , Estudos Retrospectivos
18.
Curr Cardiol Rev ; 17(3): 328-339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33109062

RESUMO

BACKGROUND: Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome (ACS) and sudden cardiac death. Physical or emotional stressors are the most commonly reported triggers for SCAD. Unemployment has been identified as a source of emotional stress and is linked to poor mental and physical health. OBJECTIVE: To examine the association between employment status and in-hospital and follow-up adverse cardiovascular events in patients with SCAD. METHODS: We conducted a retrospective, multi-center, observational study of patients undergoing coronary angiography for ACS between January 2011 and December 2017. The total number of patients enrolled was 198,000. Patients were diagnosed with SCAD based on angiographic and intravascular imaging modalities whenever available. There were 83 patients identified with SCAD from 30 medical centers in 4 Arab gulf countries. In-hospital (myocardial infarction, percutaneous intervention, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, death, internal cardioverter/ defibrillator placement, dissection extension) and follow-up (myocardial infarction, de novo SCAD, death, spontaneous superior mesenteric artery dissection) cardiac events were compared among those who were employed and those who were not. RESULTS: The median age of patients in the study was 44 (37- 55) years. There were 42 (50.6%) female patients, and 41 (49.4) male patients. Of the cohort, 50 (60%) of the patients were employed and the remaining 33 (40%) were unemployed. 66% of all men were employed and 76% of all women were unemployed. After adjusting for gender unemployment was associated with worse in- -hospital and follow-up cardiac events (adjusted OR 7.1, [1.3, 37.9]), p = 0.021. CONCLUSION: Adverse cardiovascular events were significantly worse for patients with SCAD who were unemployed.


Assuntos
Anomalias dos Vasos Coronários/epidemiologia , Desemprego/tendências , Doenças Vasculares/congênito , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Doenças Vasculares/epidemiologia
19.
Adv Med Educ Pract ; 10: 273-278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191074

RESUMO

Background: The SaudiMEDs framework was founded and adopted by the Saudi Deans' Committee in 2011 to ensure that Saudi medical graduates learned core competencies. Meanwhile, CanMEDs was established by the Canadian Royal College of Physicians and Surgeons in 1996 and aimed to establish the abilities and skills of all aspects of medical practice, as well as to ensure the acquisition of basic knowledge related to medical education. The main purpose of this study was to explore the similarities and differences between both frameworks. Methods: In March and April 2017, 15 researchers conducted an extensive review of both the SaudiMEDs and CanMEDs frameworks using a semi-quantitative evaluation with color codes to determine the following: the exact similarities in both frameworks, the close similarities, and the unique differences. Results: According to the coloring system, most of the frameworks were similar. For example, Leadership, Communication and Professionalism were almost identical in both frameworks. There was some degree of similarity between both frameworks in "Collaborator". Furthermore, the SaudiMEDs framework had a unique input which involved the most essential skills that undergraduate medical students must acquire. Conclusion: SaudiMEDs has great potential to improve the quality of Saudi medical graduates in a manner that fits our current and future needs. CanMEDs focuses mainly on outcomes and processes, while SaudiMEDs focuses more on outcomes. SaudiMEDs was not created to provide a copy-and-paste curriculum. The ultimate goal was to create an outcome-based curriculum that ensures the quality of Saudi medical school graduates.

20.
Polymers (Basel) ; 11(4)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999603

RESUMO

A number of amphiphilic cyclic peptides-[FR]4, [WR]5, and [WK]5-containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 with lipid DOPE significantly enhanced the efficiency of siRNA delivery by up to ~2-fold compared to peptide alone. Based on the data indicating the efficiency of [WR]5 in siRNA delivery, peptides containing arginine residues on the ring and tryptophan residues on the side chain, [R6K]W6 and [R5K]W5, were also evaluated, and demonstrated improved delivery of siRNA. The presence of DOPE again enhanced the siRNA delivery in most cases. [WR]5, [R5K]W5, and [R6K]W6 did not show any significant toxicity in MDA-MB-231, MDA-MB-468, and AU565 WT cells at N/P ratios of 20:1 or less, in the presence and absence of DOPE. Silencing of kinesin spindle protein (KSP) and Janus kinase 2 (JAK2) was evaluated in MDA-MB-231 cells in the presence of the peptides. The addition of DOPE significantly enhanced the silencing efficiency for all selected peptides. In conclusion, peptides containing tryptophan and arginine residues were found to enhance siRNA delivery and to generate silencing of targeted proteins in the presence of DOPE.

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