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AIMS: Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. METHODS AND RESULTS: We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. CONCLUSION: Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.
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Fibrilación Atrial , Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Insuficiencia Cardíaca , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Accidente Cerebrovascular , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Estudios de Cohortes , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Insuficiencia Cardíaca/epidemiología , Glucosa , Sodio , Hipoglucemiantes , Estudios RetrospectivosRESUMEN
BACKGROUND: Strokes are a longstanding complication of acute type A aortic dissection (ATAAD) repair. Understanding the neuroanatomy, mechanism, and severity of stroke will facilitate efforts to improve prediction, prevention, and treatment strategies. METHODS: Retrospective review of patients who sustained stroke from a consecutive series of patients undergoing ATAAD repair. Neuroimaging was interpreted by two stroke neurologists blinded to clinical results. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS). Residual disability at 30 days was assessed using the modified Rankin Scale (mRS). RESULTS: Twenty percent (38/189) of patients undergoing repair for ATAAD had stroke (unilateral 58%, bi-hemispheric 42% [p = .33]). All strokes were ischemic. No significant lateralization (right vs. left) was noted with unilateral strokes (26% vs. 32%, p = .67). Etiology of stroke was embolic (58%), hypoperfusion (26%), mixed (11%), and unknown (5%). There were no intraoperative variables that correlated with the neuroanatomy or mechanism of stroke. Preoperative carotid dissection was seen in 40% (n = 15), while postoperatively 10% (n = 4) sustained intracranial large vessel occlusion (LVO). Strokes were moderate or severe (NIHSS ≥ 9) in 97% of cases, with 66% incidence of moderate residual disability (mRS ≥ 3) at 1 month postoperatively. CONCLUSIONS: Strokes associated with ATAAD are severe at presentation resulting in significant disability. One in 10 strokes is due to LVO and potentially amenable to endovascular treatment. Heterogeneity in both location and etiology of stroke makes prevention challenging. Future trials may evaluate the role of early neuroimaging and simultaneous treatment of stroke given advancements in endovascular therapy.
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Disección Aórtica , Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Disección Aórtica/complicaciones , Isquemia Encefálica/etiología , Humanos , Neuroanatomía , Neuroimagen , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases affecting joints with a prevalence of one in a thousand children. There is a growing body of literature examining the use of mesenchymal stem/progenitor cells (MPCs) for the treatment of adult and childhood arthritis, however, we still lack a clear understanding of how these MPC populations are impacted by arthritic disease states and how this could influence treatment efficacy. In the current study we examined the immunophenotyping, self-renewal ability and chondrogenic capacity (in vitro and in vivo) of synovial derived MPCs from normal, JIA and RA joints. Synovial MPCs from JIA patients demonstrated reduced self-renewal ability and chondrogenic differentiation capacity. Furthermore, they did not induce cartilage regeneration when xenotransplanted in a mouse cartilage injury model. Synovial MPCs from JIA patients are functionally compromised compared to MPCs from normal and/or RA joints. The molecular mechanisms behind this loss of function remain elusive. Further study is required to see if these cells can be re-functionalized and used in cell therapy strategies for these JIA patients, or if allogenic approaches should be considered.
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Artritis Juvenil , Células Madre Mesenquimatosas , Animales , Artritis Juvenil/terapia , Diferenciación Celular , Condrogénesis , Ratones , Líquido SinovialRESUMEN
OBJECTIVES: Extended-arch techniques offer the potential to comprehensively treat acute type-A aortic dissection (ATAAD), but add surgical complexity compared to the standard hemiarch technique. This study describes both perioperative and mid-term outcomes following the introduction of an extended-arch technique for ATAAD. METHODS: Ours is a retrospective single-centre observational study of 95 consecutive patients with ATAAD from 2011 to 2016. The decision to perform extended-arch or hemiarch repair was individualized based on clinical and radiological features. Extended-arch repair was defined as replacement of the ascending aorta and arch with reimplantation of head vessels with or without distal endovascular extension. Clinical follow-up was 100% complete. Cross-sectional double-oblique measurements were performed for aortic remodelling analysis. RESULTS: Extended-arch (n = 28) and hemiarch (n = 67) repair resulted in a in-hospital mortality of 10% (n = 3) and 10%, (n = 7), and permanent neurological deficit rate of 7% and 12%, respectively. At a mean imaging follow-up duration of 2.7 ± 1.5 years, false lumen thrombosis was achieved in 57% and 9% of patients undergoing extended-arch and hemiarch repair, respectively. Rate of growth in the proximal descending aorta was 0.7 ± 2.3 mm/year in the extended-arch group vs 2.7 ± 3.9 mm/year in the hemiarch group. At a mean clinical follow-up time of 3.0 ± 1.6 years, open surgical aortic reoperation was 0% in the extended-arch group and 22% in the hemiarch group. CONCLUSIONS: Extended-arch repair of ATAAD can be introduced in the acute setting without increase in perioperative mortality or morbidity. At mid-term follow-up, extended-arch for ATAAD improves aortic remodelling and reduces the need for open surgical reoperation.
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Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Enfermedad Aguda , Adulto , Anciano , Disección Aórtica/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
Advances in open and endovascular techniques have resulted in novel approaches to repair of acute Type A aortic dissection. Hybrid arch procedures involve open arch resection and stent grafting of the descending aorta with stent graft insertion in one of two ways: Frozen or Staged. In this article, pros and cons of the two different paradigms of emerging hybrid arch techniques for acute Type A aortic dissections are discussed.
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Potential benefits of extending the distal extent of repair for acute type A aortic dissection beyond hemiarch has prompted the exploration of various total arch repair approaches. A zone 2 arch is advocated by some surgeons but the nomenclature and technique have not been described.
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Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Procedimientos Endovasculares/métodos , Enfermedad Aguda , Prótesis Vascular , HumanosRESUMEN
BACKGROUND: Resident macrophages in OA synovial tissue contribute to synovitis through pro-inflammatory mediators driving cartilage loss. What remains unknown is how these macrophages interact with synovial mesenchymal progenitor cells (sMPCs) in the joint. sMPCs have the potential to undergo chondrogenesis, but for yet unknown reasons, this ability is decreased in OA patients. In this study, we sought to identify if alteration of macrophage activity regulates the chondrogenic capacity of sMPCs. METHODS: An explant model was developed using human synovium obtained from normal individuals and OA patients. These explants were subjected to macrophage depletion and/or cytokine stimulation in order to regulate/deplete the residing macrophage population. Supernatant was collected following a 12-day treatment phase and subjected to inflammatory secretome analysis. sMPCs from the explants were subsequently placed under 21-day chondrogenic differentiation and levels of type II collagen (Col2a), Aggrecan (Acan), and Sox9 gene expression was quantified. RESULTS: Inflammatory secretome analysis from OA patients revealed the presence of pro-inflammatory analytes following pro- and anti-inflammatory cytokine stimulation and/or macrophage depletion. Additionally, chondrogenic differentiation of sMPCs was heterogeneously impacted across all OA patients following pro-/anti-inflammatory cytokine stimulation and/or macrophage depletion. CONCLUSION: Tissue resident synovial macrophages can regulate the chondrogenic differentiation of sMPCs after cytokine stimulation in a patient specific manner. The secretion profile of OA synovium was also responsive to cytokine stimulation and/or macrophage depletion as observed by the largely pro-inflammatory milieu upregulated following cytokine stimulation.