RESUMEN
The dysfunction of microtubules (α/ß-tubulin polymers) underlies a wide range of nervous system genetic abnormalities. Defects in TBCD, a tubulin-folding cofactor, cause diseases highlighted with early-onset encephalopathy with or without neurodegeneration, intellectual disability, seizures, microcephaly and tetraparaperesis. Utilizing various molecular methods, we describe nine patients from four unrelated families with two novel exon 18 variants in TBCD exhibiting the typical neurological phenotype of the disease. Interestingly, all the investigated patients had previously unreported hematological findings in the form of neutropenia and mild degree of anemia and thrombocytopenia. In addition to delineating the neurological phenotype in several patients with TBCD variants, our study stresses on the new association of neutropenia, in particular, with the disease.
Asunto(s)
Encefalopatías/sangre , Encefalopatías/genética , Proteínas Asociadas a Microtúbulos/genética , Mutación Missense , Adulto , Anemia/etiología , Encefalopatías/complicaciones , Encefalopatías/diagnóstico por imagen , Niño , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Neutropenia/etiología , Linaje , Trombocitopenia/etiología , Adulto JovenRESUMEN
Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.
Asunto(s)
Enfermedades del Tejido Conjuntivo/genética , Heterogeneidad Genética , Marcadores Genéticos/genética , Anomalías Cutáneas/genética , Secuencia de Aminoácidos , Estudios de Cohortes , Enfermedades del Tejido Conjuntivo/patología , Exoma/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Fenotipo , Homología de Secuencia de AminoácidoRESUMEN
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.
Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Estudios Retrospectivos , Intervención Coronaria Percutánea/efectos adversos , Revascularización Miocárdica , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca/etiología , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Humanos , Volumen Sistólico , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Función Ventricular Izquierda , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Sistema de RegistrosRESUMEN
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.
Asunto(s)
Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Puente de Arteria Coronaria , Humanos , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The Coronavirus Disease 2019 (COVID-19) outbreak has affected all regions and countries with varying impacts based on infection rates and the associated fatalities. This study aimed to assess knowledge, attitude, and practices (KAP) toward the COVID-19 pandemic among Saudi Arabians. METHODS: The study utilized a cross-sectional research design. Web-based questionnaires' link was sent via emails and social media and sample was 5483 respondents. Purposive sampling ensured only those participants that met the inclusion criteria. Validity and reliability were checked. RESULTS: Most respondents, 67.9%, were aged between 18 and 35 years and highest level of education university. The findings based on the study objectives indicated a high level of knowledge about COVID-19, which indicated early detection can improve treatment by 4701 (85.7%), the disease can be treated at home 84.6%, the disease can be prevented and avoided when precautions are taken 96.8%. Moreover, 37.2% of the respondents still used herbal products to prevent and treat the disease, and 72.1% indicating immediate visit the physician when there are symptoms. CONCLUSION: Promoting public knowledge about COVID-19 by the Ministry of Health is paramount in defeating this disease. Providing more education and awareness for public to comply with WHO's recommendation is recommended.
Asunto(s)
COVID-19 , Pandemias , Adolescente , Adulto , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Reproducibilidad de los Resultados , SARS-CoV-2 , Arabia Saudita/epidemiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
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).
Asunto(s)
Anomalías de los Vasos Coronarios/epidemiología , Enfermedades Vasculares/congénito , Adulto , Angiografía Coronaria , Puente de Arteria Coronaria/estadística & datos numéricos , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Anomalías de los Vasos Coronarios/terapia , Terapia Antiplaquetaria Doble , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Medio Oriente/epidemiología , Infarto del Miocardio sin Elevación del ST/epidemiología , Intervención Coronaria Percutánea/estadística & datos numéricos , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Complicaciones Cardiovasculares del Embarazo/terapia , Prevalencia , Sistema de Registros , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/epidemiología , Tomografía de Coherencia Óptica , Enfermedades Vasculares/diagnóstico por imagen , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/terapiaRESUMEN
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%, nâ¯=â¯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%, noâ¯=â¯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.