OAC Group Research Articles

Structure–activity relationship study of nitrogen signaling factors

We have synthesized 10 analogs of oxylipins, which are nitrogen signaling factors (NSFs) that mediate cell-to-cell communication in the fission yeast Schizosaccharomyces pombe, and evaluated their structure–activity relationships with the aim of developing molecular probes for NSFs. We found that the OH or OAc group at C10 could be replaced with a compact amide (17) or carbamate (19). Introducing an alkyne as a detection tag at C10 led to decreased, though still sufficient, activity. Introducing an alkyne at the C18 position showed a similar trend, suggesting tolerance is relatively low even for compact functional groups such as alkynes. Although introduction of a diazirine moiety as a photoreactive group at the C5 position decreased the activity, we found that introducing diazirine at the C13 position was acceptable, and compound 38 exhibited potent NSF activity. These findings will be helpful in the development of molecular probes for NSFs.

Combined use of anticoagulant and antiplatelet on outcome after stroke in patients with nonvalvular atrial fibrillation and systemic atherosclerosis

This study aimed to investigate whether there was a difference in one-year outcome after stroke between patients treated with antiplatelet and anticoagulation (OAC + antiplatelet) and those with anticoagulation only (OAC), when comorbid atherosclerotic disease was present with non-valvular atrial fibrillation (NVAF). This was a retrospective study using a prospective cohort of consecutive patients with ischemic stroke. Patients with NVAF and comorbid atherosclerotic disease were assigned to the OAC + antiplatelet or OAC group based on discharge medication. All-cause mortality, recurrent ischemic stroke, hemorrhagic stroke, myocardial infarction, and bleeding events within 1 year after the index stroke were compared. Of the 445 patients included in this study, 149 (33.5%) were treated with OAC + antiplatelet. There were no significant differences in all outcomes between groups. After inverse probability of treatment weighting, OAC + antiplatelet was associated with a lower risk of all-cause mortality (hazard ratio 0.48; 95% confidence interval 0.23–0.98; P = 0.045) and myocardial infarction (0% vs. 3.0%, P < 0.001). The risk of hemorrhagic stroke was not significantly different (P = 0.123). OAC + antiplatelet was associated with a decreased risk of all-cause mortality and myocardial infarction but an increased risk of ischemic stroke among patients with NVAF and systemic atherosclerotic diseases.

Dirhodium(II) complex catalyzed dehydrosilylation of styrenes: theoretical investigations on the mechanism, selectivity, and ligand effects.

The dirhodium(II) complexes with bridging phosphine and OAc ligands showed high reactivity and selectivities in olefin dehydrosilylation. In order to determine the structure of the actual catalyst which cannot be determined experimentally, the geometries of the dirhodium catalyst, the detailed catalytic mechanism, and the stereo- and chemo-selectivities of the title reaction were studied using DFT calculations. The results showed that one OAc group is monodentate and the other is bidentate in the dirhodium catalyst C'. The determined catalytic cycle consists of four processes: Rh-H bond activation in C', Si-H bond activation in alkoxysilane, alkylene insertion into the Rh-Si bond, followed by β-H elimination or σ-metathesis reaction. Among them, the alkylene insertion process is the rate-determining step. The stereoselectivity of the title reaction is controlled by the steric effect and orbital interactions between the alkyene and dirhodium catalysts in the β-H elimination process. The chemoselectivity is regulated by the presence of the axial ligand in the dirhodium catalyst, when there is an axial ligand coordinated to the Rh atom, E-alkene is the main product, whereas alkane would be obtained in the absence of an axial ligand. Our work determines the structure of the actual catalyst, and provides explanations and predictions for the activity, and chemo- and stereo-selectivity control of olefin dehydrosilylation.

Administration colostrum in preventing mortality and morbidity in preterm infants

Background: Oropharyngeal administration of colostrum has found to play a role in preventing the Necrotizing Enterocolitis (NEC), thus reducing mortality and morbidity in preterm infants. We aimed to determine whether early oropharyngeal administration of mother’s own colostrum can reduce the rates of NEC and/or mortality in preterm infants. Methods: We conducted a randomized, placebo controlled, intervention study in Department of Neonatology, Bangabandhu Sheikh Mujib Medical University, Dhaka from 2019 to 2021. Total 92 infants were enrolled, 52 were randomized to oropharyngeal administration of colostrum group and 40 to placebo group. Oropharyngeal administration of colostrum group received maternal colostrum (0.2 ml), after 24 hours of postnatal life and were given every 3 hour for the next 3 days. Serum IgA was measured at 24 hrs and 7th day of postnatal age. Clinical data during hospitalization were collected. SPSS version 21 was used for statistical analysis. Results: Baseline characteristics were comparable and almost similar between the two groups. There was significant reduction in the incidence of NEC stage 2, 16 (30.7%) vs. 26, (65%); p = 0.001). There was significant reduction of age of achieving full enteral feeding (12.1±4.5 vs 19.5±7.5; p = 0.001), disseminated intravascular coagulation (DIC) 12 (23%) vs. 22 (55%); p=0.002, use of mechanical ventilators, 11 (21.1%) vs. 22 (55%); p = 0.001 and number of inotropes (1.2±0.3 vs. 1.61±0.4975; p = 0.002), duration of inotropes (19.7±14.2 vs. 36.5±17.5; p=0.002) in OAC group. However, there was no significant difference in probable sepsis, culture proven sepsis, survival rate and serum IgA level at 1st and 7th day in OAC group, compared to placebo. Conclusions: There was a positive effect in decreasing the incidence of NEC, but no significant effect was observed on survival rate. This intervention facilitates faster achievement of full enteral feeding, reducing the risk of DIC in preterm infants.

Oral anticoagulation therapy in atrial fibrillation patients with advanced chronic kidney disease: CODE-AF Registry

Abstract Background and objectives Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no OAC among AF patients with advanced CKD or ESRD on dialysis. Methods Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate [eGFR] &amp;lt;3 0ml/min per 1.73 m2) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC group, and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. Results During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.05 to 0.95, p=0.042). In addition, the risk of composite adverse clinical outcome (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.32, 95% CI 0.11 to 0.96, p=0.043). Conclusion Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcome compared to no OAC. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korean Healthcare Technology R&amp;D project funded by the Ministry of Health &amp; Welfare (HI15C1200, HC19C0130)

Abstract 157: Ischemic Strokes In Patients With Atrial Fibrillation On Oral Anticoagulant: The Neuro-AFib Study

Background: Ischemic stroke (IS) admissions in patients with atrial fibrillation (AF) using either direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) are commonly seen in stroke units but data on their prevalence and causes are scarce. Understanding the frequency/causes of failures of current FDA-approved preventive methods in patients with AF is important to reduce stroke risk and related death/disability. Methods: The Neuro-AFib study is a multicenter effort geared toward elucidating the causes and consequences of IS and hemorrhagic stroke in a contemporary AF cohort. Detailed clinical, laboratory and multimodal neuro- and cardiac imaging data from known AF patients consecutively admitted to 22 US academic stroke centers with an IS between 1/2018-12/2019 were used to compare characteristics of IS on vs off oral anticoagulants. Results: Out of 6443 IS patients with AF, 4898 (76%) had known AF prior to the acute stroke. Among these patients with known AF, 2204 (45%) were using oral anticoagulants [OAC= DOAC (59.3%) or VKA (40.7%)]. Patients who had IS on OAC were younger (76.8 + 11 vs 78 + 12, p=0.001), had higher mean CHA 2 DS 2 -VASc scores (4.17 + 1.5 vs 3.9 + 1.5, p&lt;0.0001), and more likely to have a past history of IS/TIA when compared to non-OAC group (35% vs 23%, p&lt;0.0001). In a multivariable logistic regression model, history of IS/TIA, diabetes, hyperlipidemia, heart failure, prosthetic heart valve, sleep apnea, permanent atrial fibrillation, left atrial dilation and ischemic arterial disease were all independently associated with IS on OAC (all p&lt;0.05). Imaging data were complete in 15% of the cohort and IS on OAC group had more acute lacunar infarcts, and extracranial and intracranial atherosclerotic disease causing 50% or more ipsilateral stenosis compared to patients with IS off OAC (all p&lt;0.05). Conclusions: Based on a large multicenter contemporary cohort of IS patients with known AF, the numbers of patients who failed OACs (and especially DOACs) are high. These patients have severe vascular risk factor loads, concurrent etiologies, and they are more likely to have recurrent ischemic events. Further detailed data focused on imaging and IS mechanisms from this contemporary cohort will be ready to be presented during ISC 2022.

Impact of Oropharyngeal Administration of Colostrum in Preterm Newborns' Oral Microbiome.

The initial colonization of the human microbiota is of paramount importance. In this context, the oropharyngeal administration of colostrum is a safe, viable, and well-tolerated practice even by the smallest preterm infants. Therefore, this study evaluated the effects of oropharyngeal administration of colostrum on the establishment of preterm infants’ oral microbiota. A longitudinal observational study was carried out with 20 premature neonates, divided into two groups: one receiving the protocol (Oropharyngeal Administration of Colostrum; OAC) and the other one receiving Standard Caare (SC). Saliva samples were collected from the newborns weekly during the study period (from the day of birth until the 21st day of life) for analysis of oral microbiota through 16S rRNA gene sequencing. We observed that the colonization of the oral microbiota of preterm newborns preseanted a higher relative abundance of Staphylococcus on the 7th day of life, mainly in the OAC group. Additionally, an increased abundance of Bifidobacterium and Bacteroides was observed in the OAC group at the first week of life. Regarding alpha and beta diversity, time was a key factor in the oral modulation of both groups, showing how dynamic this environment is in early life.

Do oral anticoagulants impact outcomes and false lumen patency after repair of acute type A aortic dissection?

ObjectiveThe study objective was to analyze the effects of chronic oral anticoagulation on long-term outcomes after repair of type A acute aortic dissection and its influence on false lumen fate. MethodsWe studied 188 patients (median age, 62 years; 74% were male) who underwent repair of type A aortic dissection; patients receiving postoperative chronic oral anticoagulation (n = 59) were compared with those receiving antiplatelet therapy alone (n = 129). ResultsMedian age was similar: 60 years (18-79 years; OAC group) versus 64 years (22-86; no-OAC group) (P = .11); patients taking anticoagulants were more frequently male (88% vs 67%, P = .003). After a median follow-up of 8.4 years (2 months to 30 years), 58 patients died, 18 of aortic-related causes, and 37 patients underwent aortic reintervention. After multivariable adjustment, anticoagulation showed no significant effect on long-term survival (hazard ratio, 0.85; 95% confidence interval, 0.41-1.76; P = .66) or risk of reintervention (hazard ratio, 0.55; 95% confidence interval, 0.27-1.15; P = .11). Analysis of 127 postoperative computed tomography scans showed a patent false lumen in 53% of anticoagulated patients versus 38% of nonanticoagulated patients (P = .09): partially thrombosed in 8% versus 28% (P = .01) and thrombosed in 39% versus 34% (P = .63), respectively. In patients with a control computed tomography, there were 6 late aortic-related deaths, 1 among anticoagulated patients and 5 in those who were not. ConclusionsChronic anticoagulation after repair of type A acute aortic dissection favors persistent late false lumen patency, which is not a risk factor for late mortality or reoperation. Chronic anticoagulation can be administered safely to patients with repaired type A acute aortic dissection regardless of its specific indication.

Oropharyngeal administration of colostrum for preventing necrotizing enterocolitis and late-onset sepsis in preterm infants with gestational age\u2009\u2264\u200932\u2009weeks: a pilot single-center randomized controlled trial

BackgroundOropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis and improve short-term outcomes. Our objective was to evaluate the role of OAC in the early prevention of NEC and late-onset sepsis in preterm infants with gestational age (GA) ≤ 32 weeks.MethodsA pilot, single-center, 1:1 parallel randomized controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China from 1 January 2019 to 30 September 2020. Preterm infants were randomly divided into two groups with GA ≤ 32 weeks. The OAC group included preterm infants who received 0.4 ml of maternal colostrum via the oropharyngeal route every 3 h for 10 days beginning within the first 48 h after birth, and the control group included preterm infants who received normal saline instead. Data from the two groups were collected and compared.ResultsA total of 127 infants in the OAC group and 125 infants in the control group were enrolled. The incidence of NEC (Bell stage 2 or 3) and late-onset sepsis were lower in the OAC group [2.36% vs. 10.40%, relative risk (RR) 0.23 (95% confidence interval (CI) 0.07, 0.78), adjusted RR 0.23 (95% CI 0.06, 0.84); 4.72% vs. 13.60%, RR 0.35 (95% CI 0.14, 0.85), adjusted RR 0.36 (95% CI 0.14, 0.95)]. In addition, the incidence of proven sepsis and intraventricular hemorrhage (IVH) (stage 3 or 4) were lower in the OAC group [2.36% vs. 8.80%, RR 0.27 (95% CI 0.08, 0.94); 1.57% vs. 7.20%, RR 0.22 (95% CI 0.05, 0.99)], and the time to achieve full enteral feeding was shorter (23.13 ± 9.45 days vs. 28.50 ± 14.80 days). No adverse reactions were observed in either group.ConclusionsOropharyngeal administration of colostrum is a safe and simple NICU procedure that may yield a potential effect in decreasing the incidences of NEC, late-onset sepsis, and severe IVH and shorten the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks.Trial registrationChinese Clinical Trial Registry, ChiCTR1900023697, Registered 8 June 2019, retrospectively registered.

Design, synthesis and photoluminescent studies of new 1,5-benzodiazepines derivatives: Towards new ESIPT compounds

A series of novel N 1 -triazolo-4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-ones 7a-e and N 5 -triazolo-4-(2-acetoxyphenyl)-1,5-benzodiazepin-2-ones 8a-e were designed and synthesized in good yields via a Cu(I) catalyzed 1,3 -dipolar alkyne-azide coupling reaction (CuAAC) between the N 1 - and N 5 -propargyl-1,5-benzodiazepines 2 and 5 respectively and various arylazides 6a-e . Photophysical properties were investigated for all the obtained triazolo-benzodiazepine hybrids by mean of absorption and fluorescence spectral techniques. Thus, a fluorescent emission was detected for the derivatives 7a-e in aggregated state. On another hand, the O -acetylated derivatives 8a-e were found to be not emissive. Finally, we have chosen a model reaction to demonstrate that upon deprotecting the -OAc group in the N 1 , N 5 -disubstituted benzodiazepine 8d a moderate fluorescence reappeared in the obtained product 9d proving that an ESIPT process can take place as long as the hydroxyl group remains free, allowing the OH/C O proton transfer to occur. A computational study of compounds 7e and 9d in vacuo provide further details and arguments to rationalize the fluorescence of these compounds in aqueous mixtures. • A series of novel 1,5-benzodiazepin-2-ones have been designed and synthesized. • Some compounds have shown fluorescence response due to ESIPT process as long as their hydroxyl group remains free. • O-acetylation prevents emission by blocking proton transfer. • It is hypothesized that distant OH/C O proton transfer can occur leading to unexpected ESIPT mechanism in aqueous mixtures. • Computational studies provide a rationalization of proton transfer.

Oral Anticoagulation in Heart Failure with Atrial Fibrillation: Are We Taking the Right Steps Towards Guidelines?

Background Atrial fibrillation (AF) is commonly coexists with heart failure (HF) and it contributes to higher morbidity and mortality. Many studies from developed countries disclosed underuse of OAC in this population despite robust guidelines recommendations. However, there is limited data from middle eastern countries regarding this issue. So, this study sought to investigate adherence rate of physicians to ACC guidelines regarding prescribing OAC for HF patients with non-valvular AF. Methods Patients who were presented to the hospital with HF and AF were included, patientsꞌ data collected including demographics, lab results and treatment during hospitalization and at discharge. So, patients grouped into: those who were prescribed OAC versus those who were not.CHA2DS2-VASc score was calculated by the investigator for each patient. Results Ninety-one cases with HF and AF were collected, three patients with prosthetic valves were excluded. Total (88) cases were recruited with mean age of 65.4±12.9 years, females constitute 42.04% of patients. Eighty-four patients (95.45%) meet ACC class I recommendation for OAC in HF with AF (CHA2DS2-VASc ≥2) while OAC was prescribed in 25 (29.76%) of them despite no contraindications in those who were not prescribed OAC. Among total (88) patients OAC was prescribed in 27 (30.68%) patients, among whom 37.03% were prescribed direct OAC. Among OAC group, 40.74% were females versus 42.62% in Non OAC group (p˂0.001), mean age was 64.5±13.4 in OAC group versus 65.8±12.8 (p=0.6), patients in OAC group were less to be hypertensive 74.07% versus 80.32% in Non OAC group (p˂0.001) and less to have IHD 55.5% versus 72.13% (p Conclusions OAC in context of HF with AF are underutilized in practice, they were less used in females, patients with hypertension, IHD and concomitant antiplatelets while used more in patients with diabetes and stroke. Every effort should be done to bridge this practice gap by implementing quality improvement projects to improve adherence to evidence-based therapy to achieve better cardiovascular care and outcomes

Uso do fotobiomodulação no tratamento de osteoartrite de joelhos:avaliação da marcha

O objetivo do presente estudo foi avaliar uso da terapia por fotobiomodulação a LED (diodo emissor de luz) na atividade funcional da marcha em animais com OA em joelhos. Para isso, 20 ratos da linhagem Wistar, machos, com dois meses de idade e massa corpórea média de 150 g foram utilizados. A indução da OA (osteoartrite) foi realizada no joelho esquerdo de todos os animais por meio da transecção do ligamento cruzado anterior (TLCA). 4 semanas após a indução da OA os ratos foram divididos aleatoriamente em grupo OA controle (OAC): animais sem nenhuma intervenção terapêutica e grupo OA LED (OAL): animais irradiados com LED. A avaliação da marcha foi realizada antes do início do tratamento com LED e após 4 semanas de tratamento com LED (850 nm, 200 mW, 30 seg, 6 J, 3 vezes por semana). A análise da marcha não demonstrou diferença significativa entre o grupo OAC e OAL. Assim, sugere-se que a terapia por fotobiomodulação a LED não foi capaz de promover alteração da marcha em animais. O objetivo do presente estudo foi avaliar uso da terapia por fotobiomodulação a LED (diodo emissor de luz) na atividade funcional da marcha em animais com OA em joelhos. Para isso, 20 ratos da linhagem Wistar, machos, com dois meses de idade e massa corpórea média de 150 g foram utilizados. A indução da OA (osteoartrite) foi realizada no joelho esquerdo de todos os animais por meio da transecção do ligamento cruzado anterior (TLCA). 4 semanas após a indução da OA os ratos foram divididos aleatoriamente em grupo OA controle (OAC): animais sem nenhuma intervenção terapêutica e grupo OA LED (OAL): animais irradiados com LED. A avaliação da marcha foi realizada antes do início do tratamento com LED e após 4 semanas de tratamento com LED (850 nm, 200 mW, 30 seg, 6 J, 3 vezes por semana). A análise da marcha não demonstrou diferença significativa entre o grupo OAC e OAL. Assim, sugere-se que a terapia por fotobiomodulação a LED não foi capaz de promover alteração da marcha em animais.

Effectiveness of Led Photobiomodulation Therapy on Treatment With Knee Osteoarthritis

The present study aimed to evaluate the effectiveness of photobiomodulation therapy by light-emitting diode on osteoarthritis treatment in the knees of rats. Twenty male Wistar rats were randomly assigned into two experimental groups: OAC: animals subjected to induction of osteoarthritis, without therapeutic intervention and the group OAL: animals subjected to induction of osteoarthritis treated with light-emitting diode photobiomodulation therapy (850 nm, 200 mW, 6 J). The results of gait analysis showed no statistical difference between the groups. The histological findings showed that the OAL group presented abnormal chondrocyte orientation, yet with less irregularities along fibrillation and the joint tissue. Thus, it presented a lower degenerative process when evaluated by the Osteoarthritis Research Society International. Likewise, in the immunohistochemical analysis, the OAL group showed higher collagen 2 and transforming growth factor β immunoexpression when compared with the OAC group. Given the above, it is possible to suggest that the photobiomodulation therapy by light-emitting diode had positive effects on the expression of extracellular matrix proteins responsible for synthesis of articular tissue.

P107 Predictors of increased d-dimer level at follow-up period after transcatheter aortic valve implantation.Is oral anticoagulation therapy better?

Abstract Background Recently, there are some reports that hypo-attenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) is incidentally detected by multi-slice computed tomography. It is believed that valve thrombosis causes HALT, because oral anticoagulation therapy (OAC) is effective for HALT regression. Furthermore, it is reported that d-dimer level increases in patients with HALT, and might be a key biomarker to detect HALT. Purpose We sought to investigate the predictors related to increased d-dimer level at 6 months after follow-up TAVI. Methods We enrolled 124 consecutive patients who underwent successful TAVI between 2016 and 2018. Study patients were classified into two groups according to antithrombotic therapy resume (OAC therapy or anti-platelet therapy).We set the primary endpoint as the d-dimer levels at 6 months after TAVI. To evaluate the risks of the primary endpoint, we employed a multivariable linear regression model, setting the primary endpoint as an objective variable and patient and clinical backgrounds as explanatory variables. Furthermore, we set the secondary endpoint as one-year bleeding event. Results The median age of patients was 83 years old (quartile 80-87). Patients who had taken OAC at 6 months follow-up after TAVI were 29.8%. The median d-dimer level at 6 months after TAVI was 1.3 (1.0-2.2) µg/ml, and OAC group had statistically lower d-dimer level at 6 months follow-up than those in non-OAC group (p = 0.020). Uni-variable liner regression model demonstrated that increased d-dimer level at follow-up had significant relationship with large effective orifice area (EOA) (p = 0.002) and low left ventricular ejection fraction (LVEF) (p = 0.048) after TAVI. Furthermore, large EOA (p = 0.003) and OAC therapy (p = 0.027) were independently associated with increased d-dimer level in multivariate analysis. Kaplan-Meier estimates revealed that there were no significant difference regarding one-year bleeding event between OAC group and non-OAC group (long-rank p = 0.167). Conclusions This study suggests that large EOA after TAVI is associated with increased d-dimer levels at 6 months after TAVI, and OAC therapy might have a potential to decrease d-dimer level after TAVI without increase of bleeding events. Abstract P107 Figure: One-year bleeding event

Delayed Time to Emergency Hip Surgery in Patients Taking Oral Anticoagulants

Abstract Introduction Surgical intervention within 48 hours of admission in patients with acute hip fractures has been associated to lower morbidity and mortality. Patients anticoagulated with Vitamin K Antagonists (VKAs) have longer time to corrective surgery than those not anticoagulated. Sparse data exists on time to surgery (TTS) in patients taking direct oral anticoagulants (DOACs). The aim of this study is to establish TTS among non-anticoagulated and anticoagulated patients taking either VKA or DOAC. Materials and Methods We conducted a retrospective cohort study of consecutive patients admitted with acute hip fracture between July 1, 2016 and December 31, 2017. Patient-, anticoagulant- and surgery-related characteristics were collected. The primary outcome was TTS calculated from time of admission. Median TTS with interquartile range (IQR) was compared among 3 groups of patients: DOAC, VKA and No OAC. Results A total of 472 patients were included: 12.5% (59/472) were anticoagulated (28/472 on VKAs and 31/472 on DOACs). Median TTS was longer in the VKA group [64 hours (IQR: 50-84)] and in the DOAC group [(61 hours; IQR: 42 to 77)] versus the No OAC group [44 hours (IQR: 28-63), p =0.0006 and p=0.003 respectively]. There was no significant difference in median TTS in the VKA group versus the DOAC group (p =0.6396). Conclusion Patients taking either VKA or DOAC have significant delays to emergency hip fracture surgery compared to those not anticoagulated. An action plan aimed at early identification and cessation of anticoagulation is warranted in this vulnerable group of patients. Keywords: Direct Oral anticoagulants, Vitamin K antagonists, Anticoagulation, Acute hip fracture, Emergency surgery Disclosures Tagalakis: BMS-Pfizer: Other: participated on ad boards; Sanofi Aventis: Other: investigator initiated grant;participated on ad boards; Pfizer: Other: participated on ad boards; Bayer: Other: participated on ad boards; Servier: Other: participated on ad boards.

Delayed time to emergency hip surgery in patients taking oral anticoagulants

IntroductionSurgical intervention within 48 h of admission in patients with acute hip fractures has been associated to lower morbidity and mortality. Patients anticoagulated with vitamin K antagonists (VKAs) have longer time to corrective surgery than those not anticoagulated. Sparse data exists on time to surgery (TTS) in patients taking direct oral anticoagulants (DOACs). The aim of this study is to establish TTS among non-anticoagulated and anticoagulated patients taking either VKA or DOAC. Materials and methodsWe conducted a retrospective cohort study of consecutive patients admitted with acute hip fracture between July 1, 2016 and December 31, 2017. Patient-, anticoagulant- and surgery-related characteristics were collected. The primary outcome was TTS calculated from time of admission. Median TTS with interquartile range (IQR) was compared among 3 groups of patients: DOAC, VKA and No OAC. ResultsA total of 472 patients were included: 12.5% (59/472) were anticoagulated (28/472 on VKAs and 31/472 on DOACs). Median TTS was longer in the VKA group [64 h (IQR: 50–84)] and in the DOAC group [(61 h; IQR: 42 to 77)] versus the No OAC group [44 h (IQR: 28–63), p = 0.0006 and p = 0.003 respectively]. There was no significant difference in median TTS in the VKA group versus the DOAC group (p = 0.6396). ConclusionPatients taking either VKA or DOAC have significant delays to emergency hip fracture surgery compared to those not anticoagulated. Future studies aimed at examining this relationship more closely are warranted. In the meantime, an action plan aimed at early identification and appropriate management of anticoagulation in this vulnerable group of patients is necessary.

P2. Abstract Title: Delayed Time to Emergency Hip Surgery in Patients Taking Oral Anticoagulants

<h3>Introduction</h3> Surgical intervention within 48 hours of admission in patients with acute hip fractures has been associated to lower morbidity and mortality. Patients anticoagulated with Vitamin K Antagonists (VKAs) have longer time to corrective surgery than those not anticoagulated. Sparse data exists on time to surgery (TTS) in patients taking direct oral anticoagulants (DOACs). The aim of this study is to establish TTS among non-anticoagulated and anticoagulated patients taking either VKA or DOAC. <h3>Materials and Methods</h3> We conducted a retrospective cohort study of consecutive patients admitted with acute hip fracture between July 1, 2016 and December 31, 2017. Patient-, anticoagulant- and surgery-related characteristics were collected. The primary outcome was TTS calculated from time of admission. Median TTS with interquartile range (IQR) was compared among 3 groups of patients: DOAC, VKA and No OAC. <h3>Results</h3> A total of 472 patients were included: 12.5% (59/472) were anticoagulated (28/472 on VKAs and 31/472 on DOACs). Median TTS was longer in the VKA group [64 hours (IQR: 50–84)] and in the DOAC group [(61 hours; IQR: 42 to 77)] versus the No OAC group [44 hours (IQR: 28–63), p=0.0006 and p=0.003 respectively]. There was no significant difference in median TTS in the VKA group versus the DOAC group (p =0.6396). <h3>Conclusion</h3> Patients taking either VKA or DOAC have significant delays to emergency hip fracture surgery compared to those not anticoagulated. An action plan aimed at early identification and cessation of anticoagulation is warranted in this vulnerable group of patients.

Synthesis, Crystal Structures and Catalytic Property of Dioxomolybdenum(VI) and Nickel(II) Complexes Derived from bis-Schiff Bases

A new mononuclear dioxomolybdenum(VI) complex, [MoO2L1], and a new linear trinuclear nickel(II) complex, [NiNiL2(?1-?1:?0-OAc)(?2-?1:?1-OAc)2]·H2O, where L1 is the dianionic form of N,N'-bis(5-fluorosalicylidene)-1,3-propanediamine (H2L1), L2 is the dianionic form of N,N'-bis(5-fluoro-2-hydroxybenzylidene)-2-hydroxy-1,3-propanediamine (H2L2), have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray determination. The Mo atom in the molybdenum complex is coordinated by four donor atoms of the Schiff base ligand, and two oxo groups, forming an octahedral coordination. In the nickel complex, there are three bridges across the Ni-Ni atom pairs, involving two phenolate O atoms of a Schiff base ligand, and an O-C-O moiety of a ?2-?1:?1-OAc group. The central Ni atom is located on an inversion center and has octahedral coordination involving four bridging O atoms from two Schiff base ligands in the equatorial plane and two O atoms from two ?2-?1:?1-OAc ligands in the axial positions. The coordination around the terminal Ni atoms is also octahedral, with two imino N and two phenolate O atoms from a Schiff base ligand defining the equatorial plane, and with two O atoms respectively from a ?1-?1:?0-OAc and a ?2-?1:?1-OAc ligands occupying the axial positions. The molybdenum complex has excellent catalytic property for sulfoxidation reactions.

Outcomes of Micra leadless pacemaker implantation with uninterrupted anticoagulation.

Implantation of the MICRA Leadless pacemaker requires the use of a 27 French introducer, blunt delivery system and device fixation to the myocardium via nitinol tines. While prior studies have proven its safety, it is unclear whether performing this procedure with uninterrupted anticoagulation exposes patients to increased risks. We sought to investigate the feasibility and safety of continuing therapeutic anticoagulation during the periprocedural period. We evaluated all patients undergoing MICRA placement at our institution between April 2014 and August 2018 with complete follow-up data (n = 170). Patients were stratified into two groups: those on active anticoagulation (OAC, n = 26), defined as having an International normalized ratio >2.0 or having continued a direct oral anticoagulant, and those not anticoagulated (Off-OAC, n = 144). We evaluated for a composite outcome of all major complications, including access site complications and pericardial effusion. OAC and Off-OAC groups had similar mean age (74 ± 13 vs 75 ± 13 years; P = .914). The OAC group had a nonsignificantly lower prevalence of end-stage renal disease (8% vs 17%; P = .375) and aspirin use (27% vs 47%; P = .131). Those in the OAC group were more likely to be on warfarin than those in the Off-OAC group (81% vs 30%; P < .001). The rate of the composite endpoint was similar between the OAC and Off-OAC groups (3.8 % vs 1.4%, respectively; P = .761). Length of stay was similar between groups (1.3 ± 2.6 vs 2.3 ± 3.4 days; P = 0.108). Continuation of therapeutic anticoagulation during MICRA implantation appears to be feasible, safe and associated with shorter hospitalization among appropriately selected individuals.

Percutaneous Left Atrial Appendage Closure Following Transcatheter Aortic Valve Replacement: Results from The ATTRACTIVE Study

ABSTRACT Background: To study the safety and efficacy of percutaneous left atrial appendage closure (LAAC) in combination with transcatheter aortic valve replacement (TAVR) as treatment option for patients with severe aortic stenosis (AS), atrial fibrillation (AF) and high bleeding risk. Methods: During a 14-month period, 308 patients underwent TAVR. Of these, 118 patients (38%) were known to have AF and 20 patients with a high bleeding risk were treated with LAAC (TAVR + LAAC group) vs. 98 patients who were continued on medical therapy for stroke prevention (TAVR + medical group). In case of combined TAVR + LAAC, TAVR was performed first, followed by LAAC 4−10 days later. Clinical 1-year follow-up data were available for all patients. In the TAVR + LAAC group, both TAVR and LAAC procedures were performed successfully without any major procedural complication. Following LAAC, all patients, except one, received double anti-platelet therapy (DAPT) for a period of 3 months, followed by single anti-platelet therapy (SAPT). Results: At 1-year follow-up, there were no reports of stroke, thromboembolism (TE) or major bleeding in the TAVR + LAAC population, whereas in the TAVR + (N)OAC group, a stroke/TE was reported in four patients (5%; p = 0.236) and a major bleeding was noted in eight patients (10%; p = 0.036). Conclusions: Treatment of patients with severe AS, AF, and a high bleeding risk with combined TAVR and LAAC is feasible and safe with no procedural complications. Medium-term safety and efficacy outcomes are promising. Large-scale studies and longer-term follow-up are warranted to confirm these findings.