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1.
Int J Mol Sci ; 25(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892223

ABSTRACT

The high incidence of atrial fibrillation (AFib) following cardiac surgery (postoperative atrial fibrillation, POAF) relies on specific surgical features. However, in the setting of POAF, the role of the microbiome in the modulation of cardiac fibrosis is still not clear. This study aimed to analyze the effect of the microbiome and its main metabolic product (trimethylamine-N-oxide, TMAO) in the fibrosis of myocardial tissue, to investigate its role in POAF. Patients undergoing elective cardiac surgery with cardiopulmonary bypass, central atrio-caval cannulation and no history of AFib, were included. A fragment of the right atrium was analyzed for qualitative and mRNA-quantitative evaluation. A preoperative blood sample was analyzed with enzyme-linked immunosorbent assay (ELISA). A total of 100 patients have been included, with POAF occurring in 38%. Histologically, a higher degree of fibrosis, angiogenesis and inflammation has been observed in POAF. Quantitative evaluation showed increased mRNA expression of collagen-1, collagen-3, fibronectin, and transforming growth factor beta (TGFb) in the POAF group. ELISA analysis showed higher levels of TMAO, lipopolysaccharide and TGFb in POAF, with similar levels of sP-selectin and zonulin. TMAO ≥ 61.8 ng/mL (odds ratio, OR 2.88 [1.35-6.16], p = 0.006), preoperative hemoglobin < 13.1 g/dL (OR 2.37 [1.07-5.24], p = 0.033) and impaired right ventricular function (OR 2.38 [1.17-4.83], p = 0.017) were independent predictors of POAF. Also, TMAO was significantly associated with POAF by means of increased fibrosis. Gut microbiome product TMAO is crucial for myocardial fibrosis, which is a key factor for POAF. Patients in preoperative sinus rhythm who will develop POAF have increased genetic expression of pro-fibrotic genes and enhanced fibrosis in histological staining. Elevated TMAO level (≥61.8 ng/mL) is an independent risk factor for POAF.


Subject(s)
Atrial Fibrillation , Fibrosis , Gastrointestinal Microbiome , Myocardium , Humans , Atrial Fibrillation/etiology , Atrial Fibrillation/metabolism , Atrial Fibrillation/pathology , Male , Female , Aged , Middle Aged , Myocardium/metabolism , Myocardium/pathology , Postoperative Complications/etiology , Postoperative Complications/microbiology , Methylamines/blood , Methylamines/metabolism
2.
Neurohospitalist ; 14(2): 157-165, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38666284

ABSTRACT

As the population has aged and as aortic valve therapies have evolved, the use of trans-catheter aortic valve replacement (TAVR) has grown dramatically over the past decade. A well-known complication of percutaneous cardiac intervention is embolic phenomena, and TAVR is among the highest risk procedures for clinical and subclinical stroke. As indications for TAVR expand to lower-risk and ultimately younger patients, the long-term consequences of stroke are amplified. Cerebral embolic protection (CEP) devices have taken a on unique preventative role following the Food and Drug Administration approval of the SentinelTM Cerebral Protection System (CPS). More recently, the PROTECTED TAVR study has spurred extensive debate in the neuro-cardiac community. In this review we describe the contemporary literature regarding stroke risk associated with TAVR, the history and role of CEP devices, a PROTECTED TAVR sub-group analysis, and implications for next steps in the field. Lastly, we explore the unique need for CEP in a younger TAVR population, as well as directions for future research.

3.
Biochem Biophys Res Commun ; 706: 149746, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38461646

ABSTRACT

Polyglycine hydrolases are fungal effectors composed of an N-domain with unique sequence and structure and a C-domain that resembles ß-lactamases, with serine protease activity. These secreted fungal proteins cleave Gly-Gly bonds within a polyglycine sequence in corn ChitA chitinase. The polyglycine hydrolase N-domain (PND) function is unknown. In this manuscript we provide evidence that the PND does not directly participate in ChitA cleavage. In vitro analysis of site-directed mutants in conserved residues of the PND of polyglycine hydrolase Es-cmp did not specifically impair protease activity. Furthermore, in silico structural models of three ChitA-bound polyglycine hydrolases created by High Ambiguity Driven protein-protein DOCKing (HADDOCK) did not predict significant interactions between the PND and ChitA. Together these results suggest that the PND has another function. To determine what types of PND-containing proteins exist in nature we performed a computational analysis of Foldseek-identified PND-containing proteins. The analysis showed that proteins with PNDs are present throughout biology as either single domain proteins or fused to accessory domains that are diverse but are usually proteases or kinases.


Subject(s)
Peptide Hydrolases , Peptides , Peptides/chemistry , Peptide Hydrolases/metabolism , Endopeptidases/metabolism , Proteolysis
4.
ACS Appl Mater Interfaces ; 16(10): 12873-12885, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38437591

ABSTRACT

Organic field-effect transistors (OFETs) were fabricated using three high-surface area and flexible expanded-poly(tetrafluoroethylene) (ePTFE) membranes in gate dielectrics, along with the semiconducting polymer poly[2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione-3,6-diyl)-alt-(2,2':5',2″:5″,2‴-quaterthiophen-5,5‴-diyl)] (PDPP4T). The transistor behavior of these devices was investigated following annealing at 50, 100, 150, and 200 °C, all sustained for 1 h. For annealing temperatures above 50 °C, the OFETs displayed improved transistor behavior and a significant increase in output current while maintaining similar magnitudes of Vth shifts when subjected to static voltage compared to those kept at ambient temperature. We also tested the response to NO2 gas for further characterization and for possible applications. The ePTFE-PDPP4T interface of each membrane was characterized via scanning electron microscopy for all four annealing temperatures to derive a model for the hole mobility of the ePTFE-PDPP4T OFETs that accounts for the microporous structure of the ePTFE and consequently adjusts the channel width of the OFET. Using this model, a maximum hole mobility of 1.8 ± 1.0 cm2/V s was calculated for the polymer in an ePTFE-PDPP4T OFET annealed at 200 °C, whereas a PDPP4T OFET using only the native silicon wafer oxide as a gate dielectric exhibited a hole mobility of just 0.09 ± 0.03 cm2/V s at the same annealing condition. This work demonstrates that responsive semiconducting polymer films can be deposited on nominally nonwetting and extremely bendable membranes, and the charge carrier mobility can be significantly increased compared to their as-prepared state by using thermally durable polymer membranes with unique microstructures as gate dielectrics.

5.
World J Surg ; 48(4): 779-790, 2024 04.
Article in English | MEDLINE | ID: mdl-38423955

ABSTRACT

BACKGROUND: Previous meta-analyses combining randomized and observational evidence in cardiac surgery have shown positive impact of enhanced recovery protocols after surgery (ERAS) on postoperative outcomes. However, definitive data based on randomized studies are missing, and the entirety of the ERAS measures and pathway, as recently systematized in guidelines and consensus statements, have not been captured in the published studies. The available literature actually focuses on "ERAS-like" protocols or only limited number of ERAS measures. This study aims at analyzing all randomized studies applying ERAS-like protocols in cardiac surgery for perioperative outcomes. METHODS: A meta-analysis of randomized controlled trials (RCTs) comparing ERAS-like with standard protocols of perioperative care was performed (PROSPERO registration CRD42021283765). PRISMA guidelines were used for abstracting and assessing data. RESULTS: Thirteen single center RCTs (N = 1704, 850 in ERAS-like protocol and 854 in the standard care group) were selected. The most common procedures were surgical revascularization (66.3%) and valvular surgery (24.9%). No difference was found in the incidence of inhospital mortality between the ERAS and standard treatment group (risk ratio [RR] 0.61 [0.31; 1.20], p = 0.15). ERAS was associated with reduced intensive care unit (standardized mean difference [SMD] -0.57, p < 0.01) and hospital stay (SMD -0.23, p < 0.01) and reduced rates of overall complications when compared to the standard protocol (RR 0.60, p < 0.01) driven by the reduction in stroke (RR 0.29 [0.13; 0.62], p < 0.01). A significant heterogeneity in terms of the elements of the ERAS protocol included in the studies was observed. CONCLUSIONS: ERAS-like protocols have no impact on short-term survival after cardiac surgery but allows for a faster hospital discharge while potentially reducing surgical complications. However, this study highlights a significant nonadherence and heterogeneity to the entirety of ERAS protocols warranting further RCTs in this field including a greater number of elements of the framework.


Subject(s)
Cardiac Surgical Procedures , Enhanced Recovery After Surgery , Humans , Postoperative Complications/etiology , Randomized Controlled Trials as Topic , Perioperative Care/methods , Cardiac Surgical Procedures/adverse effects , Length of Stay , Meta-Analysis as Topic , Systematic Reviews as Topic
6.
J Cardiothorac Surg ; 19(1): 87, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38342923

ABSTRACT

BACKGROUND: Negative pressure wound therapy (NPWT) is traditionally used to treat postoperative wound infections. However, its use in closed wound sternotomy post cardiac surgery in high-risk patients has become increasingly popular. The potential preventive benefit of reducing sternal wound infections has been recently acknowledged. Bilateral internal mammary artery (BIMA) grafts are used in coronary artery bypass grafting but have been associated with an increased risk of sternal wound infections (SWIs). OBJECTIVES: This systematic analysis examines whether NPWT can reduce the incidence of SWI following BIMA grafts, leading to more patients benefiting from the better survival outcome associated with BIMA grafting. METHOD: A comprehensive systematic search and meta-analysis were performed to identify studies on the use of NPWT in closed wound sternotomy. Ovid MEDLINE (in-process and other nonindexed citations and Ovid MEDLINE 1990 to present), Ovid EMBASE (1990 to present), and The Cochrane Library (Wiley), PubMed, and Google Scholar databases were searched from their inception to May 2022 using keywords and MeSH terms. Thirty-four articles from 1991 to May 2022 were selected. RESULT: Three studies reported on the outcome of NPWT following BIMA grafting. The pooled analysis did not show any significant difference in the incidence of sternal wound infection between NPWT and standard dressing (RR 0.48 95% CI 0.17-1.37; P = 0.17) with substantial heterogeneity (I2 65%). Another seven studies were found comparing the outcome of SWI incidence of negative pressure closed wound therapy with conventional wound therapy in patients undergoing adult cardiac surgery. The pooled analysis showed that NPWT was associated with a low risk of SWIs compared to conventional dressing (RR 0.47 95% CI 0.36-0.59; P < 0.00001), with low heterogeneity (I2 1%). CONCLUSION: The literature identified that NPWT significantly decreased the incidence of sternal wound complications when applied to sutured sternotomy incisions in high-risk patients, and in some cases, it eliminated the risk. However, the inadequate number of randomized controlled trials assessing the effectiveness of NPWT in BIMA grafting emphasizes the need for further, robust studies.


Subject(s)
Mammary Arteries , Negative-Pressure Wound Therapy , Adult , Humans , Wound Healing , Surgical Wound Infection/prevention & control , Surgical Wound Infection/epidemiology , Surgical Wound Dehiscence/prevention & control
7.
Nat Chem Biol ; 20(6): 732-741, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38321209

ABSTRACT

Glycosylation is a critical post-translational protein modification that affects folding, half-life and functionality. Glycosylation is a non-templated and heterogeneous process because of the promiscuity of the enzymes involved. We describe a platform for sequential glycosylation reactions for tailored sugar structures (SUGAR-TARGET) that allows bespoke, controlled N-linked glycosylation in vitro enabled by immobilized enzymes produced with a one-step immobilization/purification method. We reconstruct a reaction cascade mimicking a glycosylation pathway where promiscuity naturally exists to humanize a range of proteins derived from different cellular systems, yielding near-homogeneous glycoforms. Immobilized ß-1,4-galactosyltransferase is used to enhance the galactosylation profile of three IgGs, yielding 80.2-96.3% terminal galactosylation. Enzyme recycling is demonstrated for a reaction time greater than 80 h. The platform is easy to implement, modular and reusable and can therefore produce homogeneous glycan structures derived from various hosts for functional and clinical evaluation.


Subject(s)
Enzymes, Immobilized , Galactosyltransferases , Glycosylation , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Humans , Galactosyltransferases/metabolism , Galactosyltransferases/chemistry , Polysaccharides/metabolism , Polysaccharides/chemistry , Protein Processing, Post-Translational
8.
J Stroke Cerebrovasc Dis ; 33(5): 107618, 2024 May.
Article in English | MEDLINE | ID: mdl-38402694

ABSTRACT

INTRODUCTION: The use of Left Atrial Appendage (LAA) occluder devices has been on the rise in patients with atrial fibrillation. Studies regarding the long-term risks of occluder devices remain sparse. MATERIALS & METHODS: In this brief report, we discuss the unusual case of an 85-year-old female with long-term complication from Left Atrial Appendage (LAA) closure: Device-Related Thrombus (DRT) about two years after insertion. RESULTS: Compared to the expected stroke rate without anticoagulation, patients with DRT on their LAAO device still had a 28 % relative reduction in ischemic stroke. This suggests that these strokes may have emanated from alternate etiologies other than the DRT. CONCLUSIONS: Patients with active or known history of cancer appears to have a higher risk of DRT. More data is needed on this topic to augment awareness and understanding of LAAO complications and DRT management strategies.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Stroke , Thrombosis , Female , Humans , Aged, 80 and over , Left Atrial Appendage Closure , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/therapy , Stroke/diagnostic imaging , Stroke/etiology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Atrial Fibrillation/complications , Atrial Appendage/diagnostic imaging , Treatment Outcome
9.
Heart Rhythm ; 21(6): 771-779, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38296011

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) patients at high risk for stroke and for bleeding may be unsuitable for either oral anticoagulation or endocardial left atrial appendage (LAA) occlusion. However, minimally invasive, epicardial left atrial appendage exclusion (LAAE) may be an option. OBJECTIVE: The purpose of this study was to evaluate outcomes of LAAE in high-risk AF patients not receiving oral anticoagulation. METHODS: A retrospective analysis of Medicare claims data was conducted to evaluate thromboembolic events in AF patients who underwent LAAE compared to a 1:4 propensity score-matched group of patients who did not receive LAAE (control). Neither group was receiving any oral anticoagulation at baseline or follow-up. Fine-Gray models estimated hazard ratios and evaluated between-group differences. Bootstrapping was applied to generate 95% confidence intervals (CIs). RESULTS: The LAAE group (n = 243) was 61% male (mean age 75 years). AF was nonparoxysmal in 70% (mean CHA2DS2-VASc score 5.4; mean HAS-BLED score 4.2). The matched control group (n = 972) had statistically similar characteristics. One-year adjusted estimates of thromboembolic events were 7.3% (95% CI 4.3%-11.1%) in the LAAE group and 12.1% (95% CI 9.5%-14.8%) in the control group. Absolute risk reduction was 4.8% (95% CI 0.6%-8.9%; P = .028). Adjusted hazard ratio for thromboembolic events for LAAE vs non-LAAE was 0.672 (95% CI 0.394-1.146). CONCLUSION: In AF patients not taking oral anticoagulation who are at high risk for stroke and for bleeding, minimally invasive, thoracoscopic, epicardial LAAE was associated with a lower rate of thromboembolic events.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Minimally Invasive Surgical Procedures , Stroke , Humans , Atrial Fibrillation/surgery , Atrial Fibrillation/complications , Atrial Appendage/surgery , Male , Female , Aged , Retrospective Studies , Stroke/prevention & control , Stroke/etiology , Stroke/epidemiology , Minimally Invasive Surgical Procedures/methods , Pericardium/surgery , United States/epidemiology , Propensity Score , Follow-Up Studies , Cardiac Surgical Procedures/methods , Risk Factors , Thromboembolism/prevention & control , Thromboembolism/etiology , Thromboembolism/epidemiology , Incidence , Risk Assessment/methods , Treatment Outcome
10.
J Am Heart Assoc ; : e030272, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37982263

ABSTRACT

BACKGROUND: Guideline-based hypertension management is integral to the prevention of stroke. We examine trends in antihypertensive medications prescribed after stroke and assess how well a prescriber's blood pressure (BP) medication choice adheres to clinical practice guidelines (BP-guideline adherence). METHODS AND RESULTS: The FSR (Florida Stroke Registry) uses statewide data prospectively collected for all acute stroke admissions. Based on established guidelines, we defined optimal BP-guideline adherence using the following hierarchy of rules: (1) use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as first-line antihypertensive among diabetics; (2) use of thiazide-type diuretics or calcium channel blockers among Black patients; (3) use of beta blockers among patients with compelling cardiac indication; (4) use of thiazide, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or calcium channel blocker class as first line in all others; (5) beta blockers should be avoided as first line unless there is a compelling cardiac indication. A total of 372 254 cases from January 2010 to March 2020 are in the FSR with a diagnosis of acute ischemic stroke, hemorrhagic stroke, transient ischemic attack, or subarachnoid hemorrhage; 265 409 with complete data were included in the final analysis. Mean age was 70±14 years; 50% were women; and index stroke subtypes were 74% acute ischemic stroke, 11% intracerebral hemorrhage, 11% transient ischemic attack, and 4% subarachnoid hemorrhage. BP-guideline adherence to each specific rule ranged from 48% to 74%, which is below quality standards of 80%, and was lower among Black patients (odds ratio, 0.7 [95% CI, 0.7-0.83]; P<0.001) and those with atrial fibrillation (odds ratio, 0.53 [95% CI, 0.50-0.56]; P<0.001) and diabetes (odds ratio, 0.65 [95% CI, 0.61-0.68]; P<0.001). CONCLUSIONS: This large data set demonstrates consistently low rates of BP-guideline adherence over 10 years. There is an opportunity for monitoring hypertensive management after stroke.

11.
Prev Vet Med ; 220: 106053, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37865010

ABSTRACT

Johne's Disease (JD) is an infectious ruminant disease that can cause economic loss for famers through reduced milk yields and infertility and has negative implications for animal welfare. JD is endemic in the dairy populations of many countries and there has been significant effort by governments and industry to try and control it. However, these efforts have had limited success. Many studies look at individual control programmes or the adoption of Johne's control measures; however a wider perspective on what drives farmer participation Johne's control does not currently exist. This study seeks to fill this gap by conducting a systematic review informed by the PRISMA statement. The results suggest that psychological factors such as participation fatigue, cognitive dissidence over animal welfare and not having first-hand experience of the disease act as barriers to Johne's control. To better promote Johne's control, this review emphasises that control programmes need to engage farmers, advisers, and supply chain actors in their design and delivery of control programmes to account for differing attitudes and levels of knowledge.


Subject(s)
Cattle Diseases , Paratuberculosis , Cattle , Animals , Humans , Farmers/psychology , Dairying/methods , Cattle Diseases/epidemiology , Animal Welfare
12.
Stroke ; 54(10): 2552-2561, 2023 10.
Article in English | MEDLINE | ID: mdl-37675611

ABSTRACT

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.


Subject(s)
Ischemic Stroke , Stroke , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Platelet Aggregation Inhibitors/therapeutic use , Aspirin/therapeutic use , Clopidogrel/therapeutic use , Cohort Studies , Cross-Sectional Studies , Stroke/drug therapy , Stroke/epidemiology , Stroke/chemically induced , Ischemic Stroke/drug therapy , Drug Therapy, Combination , Treatment Outcome
13.
Neurohospitalist ; 13(3): 256-265, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37441203

ABSTRACT

Introduction: Breakthrough acute ischemic stroke (AIS) in patients with known, nonvalvular Atrial Fibrillation (AF), on Direct Oral Anticoagulants (DOAC), is an ongoing clinical conundrum. Switching anticoagulants was shown to be ineffective in preventing recurrent AIS. Systematic, patient-level chart review of so-called "DOAC failures" may offer insight into this phenomenon. Methods: We conducted an IRB-approved, 6-year, retrospective study of AIS admissions, already prescribed DOAC for known AF. We sought plausible, alternative reasons for the AIS using a novel classification schema, CLAMP: C for Compliance concerns, L for Lacunes (small-vessel disease), A for Arteriopathy (atherosclerosis, web, or vasculitis), M for Malignancy, and P for Patent Foramen Ovale (PFO). These categories were labeled as DOAC "Pseudo-failures." Conversely, absence of CLAMP variables were labeled as DOAC "Crypto-failures" conceivably from AF itself ("atriopathy") or pharmacokinetic/pharmacogenomic dysfunction (ie, altered DOAC absorption, clearance, metabolism, or genetic polymorphisms). Forward logistic regression analysis was performed on prespecified DOAC subgroups. Results: Of 4890 AIS admissions, 606 had AF, and 87 were previously prescribed DOAC (14.4% overall DOAC failure rate, 2.4% annualized over 6 years). Pseudo-failures comprised 77%: Compliance concerns (48.9%), Lacunes (5.7%), Arteriopathy (17.0%), Malignancy (26.1%), and PFO (2.3%). Crypto-failures comprised 23%, had lower CHADSVASc scores (AOR = .65, P = .013), and occurred more with rivaroxaban (41%) than apixaban (16%) or dabigatran (5.6%). Conclusion: In AIS patients with known AF, DOAC Pseudo-failures, with identified alternate etiologies, are 3 times more likely than DOAC Crypto-failures. The CLAMP schema represents a novel approach to diagnostic classification and therapeutic adjustments in patients already prescribed DOAC for AF.

14.
Crit Care Explor ; 5(7): e0934, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37378082

ABSTRACT

Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined. DESIGN: Observational study (2008-2021). SETTING: Florida Stroke Registry (152 hospitals). PATIENTS: Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST. Patients who had WLST were older (77 vs 70 yr), more women (57% vs 49%), White (76% vs 67%), with greater stroke severity on the National Institutes of Health Stroke Scale greater than or equal to 5 (29% vs 19%), more likely hospitalized in comprehensive stroke centers (52% vs 44%), had Medicare insurance (53% vs 44%), and more likely to have impaired level of consciousness (38% vs 12%). Most predictors associated with the decision to WLST in AIS were age, stroke severity, region, insurance status, center type, race, and level of consciousness (RF AUC of 0.93 and LR AUC of 0.85). Predictors in ICH included age, impaired level of consciousness, region, race, insurance status, center type, and prestroke ambulation status (RF AUC of 0.76 and LR AUC of 0.71). Factors in SAH included age, impaired level of consciousness, region, insurance status, race, and stroke center type (RF AUC of 0.82 and LR AUC of 0.72). Despite a decrease in the rates of early WLST (< 2 d) and mortality, the overall rates of WLST remained stable. CONCLUSIONS: In acute hospitalized stroke patients in Florida, factors other than brain injury alone contribute to the decision to WLST. Potential predictors not measured in this study include education, culture, faith and beliefs, and patient/family and physician preferences. The overall rates of WLST have not changed in the last 2 decades.

15.
PLoS One ; 18(6): e0285478, 2023.
Article in English | MEDLINE | ID: mdl-37310957

ABSTRACT

Many publications lack sufficient background information (e.g. location) to be interpreted, replicated, or reused for synthesis. This impedes scientific progress and the application of science to practice. Reporting guidelines (e.g. checklists) improve reporting standards. They have been widely taken up in the medical sciences, but not in ecological and agricultural research. Here, we use a community-centred approach to develop a reporting checklist (AgroEcoList 1.0) through surveys and workshops with 23 experts and the wider agroecological community. To put AgroEcoList in context, we also assessed the agroecological community's perception of reporting standards in agroecology. A total of 345 researchers, reviewers, and editors, responded to our survey. Although only 32% of respondents had prior knowledge of reporting guidelines, 76% of those that had said guidelines improved reporting standards. Overall, respondents agreed on the need of AgroEcolist 1.0; only 24% of respondents had used reporting guidelines before, but 78% indicated they would use AgroEcoList 1.0. We updated AgroecoList 1.0 based on respondents' feedback and user-testing. AgroecoList 1.0 consists of 42 variables in seven groups: experimental/sampling set-up, study site, soil, livestock management, crop and grassland management, outputs, and finances. It is presented here, and is also available on github (https://github.com/AgroecoList/Agroecolist). AgroEcoList 1.0 can serve as a guide for authors, reviewers, and editors to improve reporting standards in agricultural ecology. Our community-centred approach is a replicable method that could be adapted to develop reporting checklists in other fields. Reporting guidelines such as AgroEcoList can improve reporting standards and therefore the application of research to practice, and we recommend that they are adopted more widely in agriculture and ecology.


Subject(s)
Agriculture , Checklist , Animals , Soil , Knowledge , Livestock
16.
J Neuropsychiatry Clin Neurosci ; 35(4): 361-367, 2023.
Article in English | MEDLINE | ID: mdl-37151036

ABSTRACT

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. METHODS: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. RESULTS: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. CONCLUSIONS: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.


Subject(s)
Ethnicity , Stroke , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , Puerto Rico/epidemiology , Florida/epidemiology , Depression/epidemiology , Registries , Minority Groups , Stroke/complications , Stroke/epidemiology
17.
J Clin Med ; 12(9)2023 May 07.
Article in English | MEDLINE | ID: mdl-37176767

ABSTRACT

BACKGROUND: Postoperative bleeding requiring re-exploration in cardiac surgery has been associated with complications impacting short-term outcomes and perioperative survival. Many aspects of decision-making for re-exploration still remain controversial, especially in hemodynamically stable patients with significant but not acutely cumulating chest drain output. We investigated the impact of re-exploratory surgery on short-term outcomes in a "borderline population" of CABG patients who experienced significant non-acute bleeding, but that were not in critically hemodynamic unstable conditions. METHODS: A prospectively collected database of 8287 patients undergoing primary isolated elective CABG was retrospectively interrogated. A population of hemodynamically stable patients experiencing significant non-acute or rapidly cumulating bleeding (>1000 mL of blood loss in 12 h, <200 mL per hour in the first 5 h) with normal platelet and coagulation tests was identified (N = 1642). Patients belonging to this group were re-explored (N = 252) or treated conservatively (N = 1390) based on the decision of the consultant surgeon. Clinical outcomes according to the decision-making strategy were compared using a propensity score matching (PSM) approach. RESULTS: After PSM, reoperated patients exhibited significantly higher overall blood product consumption (88.4% vs. 52.6% for red packed cells, p = 0.001). The reoperated group experienced higher rates of respiratory complications (odds ratio 5.8 [4.29-7.86] with p = 0.001 for prolonged ventilation), prolonged stay in intensive care unit (coefficient 1.66 [0.64-2.67] with p = 0.001) and overall length of stay in hospital (coefficient 2.16 [0.42-3.91] with p = 0.015) when compared to conservative management. Reoperated patients had significantly increased risk of multiorgan failure (odds ratio 4.59 [1.37-15.42] with p = 0.014) and a trend towards increased perioperative mortality (odds ratio 3.12 [1.08-8.99] with p = 0.035). CONCLUSIONS: Conservative management in hemodynamically stable patients experiencing significant but non-critical or emergency bleeding might be a safe and viable option and might be advantageous in terms of reduction of postoperative morbidities and hospital stay.

18.
Int J Stroke ; 18(7): 864-872, 2023 08.
Article in English | MEDLINE | ID: mdl-36907985

ABSTRACT

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.


Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , Humans , Stroke/complications , Prospective Studies , Ischemic Stroke/drug therapy , Anticoagulants/adverse effects , Randomized Controlled Trials as Topic , Hemorrhage/chemically induced , Atrial Fibrillation/complications , Administration, Oral
19.
Stroke ; 54(3): 733-742, 2023 03.
Article in English | MEDLINE | ID: mdl-36848428

ABSTRACT

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.


Subject(s)
Punctures , Time-to-Treatment , Humans , Female , Male , Cerebral Hemorrhage , Florida , Hospital Mortality
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