Plasma Biomarkers of Tau and Neurodegeneration During Major Cardiac and Noncardiac Surgery.
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ABSTRACT:
SUBMITTER: Feinstein I
PROVIDER: S-EPMC8453356 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Plasma Biomarkers of Tau and Neurodegeneration During Major Cardiac and Noncardiac Surgery.
Feinstein Igor I Wilson Edward N EN Swarovski Michelle S MS Andreasson Katrin I KI Angst Martin S MS Greicius Michael D MD
JAMA neurology 20211101 11
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Project description:ObjectiveTo assess the incremental contribution of preoperative stress test results toward a diagnosis of obstructive coronary artery disease (CAD), prediction of mortality, or prediction of perioperative myocardial infarction in patients considering noncardiac, nonophthalmologic surgery.Design, setting, participantsA retrospective cohort study of visits to a preoperative risk assessment and optimization clinic in a large health system between 2008 and 2018.MeasurementsTo assess diagnostic information of preoperative stress testing, we used the Begg and Greenes method to calculate test characteristics adjusted for referral bias, with a gold standard of angiography. To assess prognostic information, we first created multiply-imputed logistic regression models to predict 90-day mortality and perioperative myocardial infarction (MI), starting with two tools commonly used to assess perioperative cardiac risk, Revised Cardiac Risk Index (RCRI) and Myocardial Infarction or Cardiac Arrest (MICA). We then added stress test results and compared the discrimination for models with and without stress test results.Main resultsAmong 136,935 visits by patients without an existing diagnosis of CAD, the decision to obtain preoperative stress testing identified around 4.0% of likely new diagnoses. Stress testing increased the likelihood of CAD (likelihood ratio: 1.31), but for over 99% of patients, stress testing should not change a decision on whether to proceed to angiography. In 117,445 visits with subsequent noncardiac surgery, stress test results failed to improve predictions of either perioperative MI or 90-day mortality. Reweighting the models and adding hemoglobin improved the prediction of both outcomes.ConclusionsCardiac stress testing before noncardiac, nonophthalmologic surgery does not improve predictions of either perioperative mortality or myocardial infarction. Very few patients considering noncardiac, nonophthalmologic surgery have a pretest probability of CAD in a range where stress testing could usefully select patients for angiography. Better use of existing patient data could improve predictions of perioperative adverse events without additional patient testing.
| S-EPMC10529226 | biostudies-literature
Project description:Background/objectiveRisk-stratification tools for cardiac complications after noncardiac surgery based on preoperative risk factors are used to inform postoperative management. However, there is limited evidence on whether risk stratification can be improved by incorporating data collected intraoperatively, particularly for low-risk patients.MethodsWe conducted a retrospective cohort study of adults who underwent noncardiac surgery between 2014 and 2018 at four hospitals in the United States. Logistic regression with elastic net selection was used to classify in-hospital major adverse cardiovascular events (MACE) using preoperative and intraoperative data ("perioperative model"). We compared model performance to standard risk stratification tools and professional society guidelines that do not use intraoperative data.ResultsOf 72,909 patients, 558 (0.77%) experienced MACE. Those with MACE were older and less likely to be female. The perioperative model demonstrated an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI, 0.85-0.92). This was higher than the Lee Revised Cardiac Risk Index (RCRI) AUC of 0.79 (95% CI, 0.74-0.84; P < .001 for AUC comparison). There were more MACE complications in the top decile (n = 1,465) of the perioperative model's predicted risk compared with that of the RCRI model (n = 58 vs 43). Additionally, the perioperative model identified 2,341 of 7,597 (31%) patients as low risk who did not experience MACE but were recommended to receive postoperative biomarker testing by a risk factor-based guideline algorithm.ConclusionsAddition of intraoperative data to preoperative data improved prediction of cardiovascular complication outcomes after noncardiac surgery and could potentially help reduce unnecessary postoperative testing.
| S-EPMC7531939 | biostudies-literature
Project description:BackgroundIt remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised-compared to routine-intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery.MethodsIn this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.e. maintaining intraoperative mean arterial pressure [MAP] above preoperative baseline MAP from automated 24-h blood pressure monitoring) or routine blood pressure management (i.e. maintaining MAP above 65 mm Hg). The primary outcome was the incidence of neurocognitive disorders (composite of delayed neurocognitive recovery and delirium) between postoperative days 3 and 7.ResultsThe primary outcome, neurocognitive disorders, occurred in 18 of 147 patients (12%) assigned to personalised and 21 of 148 patients (14%) assigned to routine blood pressure management (odds ratio [OR]=0.84, 95% confidence interval [CI]: 0.40-1.75, P=0.622). Delayed neurocognitive recovery occurred in 17 of 146 patients (12%) assigned to personalised and 17 of 145 patients (12%) assigned to routine blood pressure management (OR=0.99, 95% CI: 0.45-2.17, P=0.983). Delirium occurred in 2 of 157 patients (1%) assigned to personalised and 4 of 158 patients (3%) assigned to routine blood pressure management (OR=0.50, 95% CI: 0.04-3.53, P=0.684).ConclusionsPersonalised intraoperative blood pressure management maintaining preoperative baseline MAP neither reduced the incidence of the composite primary outcome neurocognitive disorders between postoperative days 3 and 7 nor the incidences of the components of the composite primary outcome-delayed neurocognitive recovery and delirium-compared to routine blood pressure management in patients having major noncardiac surgery.Clinical trial registrationClinicalTrials.gov (NCT03442907).
| S-EPMC11267063 | biostudies-literature
Project description:IntroductionBlood-based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players.MethodsThe sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45-74). Plasma assays were conducted for beta-amyloid (Aβ) 40, Aβ42, hyper-phosphorylated tau (p-tau) 181+231, total tau (t-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), Aβ42/p-tau181 and Aβ42/Aβ40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES).ResultsP-tau181 and p-tau231(padj = 0.016) were higher and Aβ42/p-tau181 was lower(padj = 0.004) in football players compared to controls. Discrimination accuracy for p-tau was modest (area under the curve [AUC] = 0.742). Effects were not attributable to AD-related pathology. Younger age of first exposure (AFE) correlated with higher NfL (padj = 0.03) and GFAP (padj = 0.033). Plasma GFAP was higher in TES-chronic traumatic encephalopathy (TES-CTE) Possible/Probable (padj = 0.008).DiscussionPlasma p-tau181 and p-tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI-related neuropathologies.HighlightsFormer football players had higher plasma p-tau181 and p-tau231 and lower Aβ42/ptau-181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES-CTE possible/probable compared to TES-CTE no/suggestive.
| S-EPMC11567811 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) is a common vascular complication of non-cardiac surgery.MethodsWe evaluated national trends in perioperative in-hospital VTE incidence, management, and outcomes using a large database of hospital admissions from the United States. Patients aged ≥ 45 years undergoing major non-cardiac surgery from 2005 to 2013 were identified from the National Inpatient Sample. In-hospital perioperative VTE was defined as lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and the incidence was evaluated over time. Multivariable regression models with demographics and comorbidities as covariates were generated to estimate adjusted odds ratios (aOR).ResultsMajor non-cardiac surgery was performed in 9,431,442 hospitalizations that met inclusion criteria, and perioperative VTE occurred in 99,776 patients (1,057 per 100,000), corresponding to an annual incidence of ≈53,000 after applying sample weights. Over time, perioperative VTE per 100,000 surgeries increased by 135 (95% CI 107 - 163), from 925 in 2005 to 1,060 in 2013 (p for trend <0.001; aOR [for 2013 versus 2005] 1.22, 95% CI 1.19 - 1.26), due to increases in non-fatal VTE rates (from 840 [per 100,000 surgeries] in 2005 to 987 in 2013; p for trend <0.001). Perioperative VTE occurred most frequently in patients undergoing thoracic (2.0%) and vascular surgery (1.8%). Mortality was higher in patients with VTE than those without VTE (aOR 3.12, 95% CI 3.05 - 3.20).ConclusionsPerioperative VTE occurs in approximately 1% of patients ≥45 years undergoing major non-cardiac surgery, with increasing incidence of non-fatal VTE over time.
| S-EPMC6146393 | biostudies-literature
Project description:BackgroundPlasma-derived β-amyloid, tau, and neurodegeneration (ATN) biomarkers can accurately diagnose Alzheimer's disease (AD) and predict its progression. Few studies have investigated the relationship between plasma biomarkers and changes in plasma inflammatory markers in clinically diagnosed AD.MethodsSeventy-four participants were recruited, including 30 mild-to-moderate AD dementia patients and 44 normal controls (NC). All participants underwent neuropsychological testing and blood sampling for biomarker testing. AD was clinically diagnosed according to the National Institute on Aging-Alzheimer's Association (NIA-AA) core criteria and required age-mismatched hippocampal atrophy. We performed Single Molecule Array (Simoa), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA), to examine plasma ATN markers, including β-amyloid (Aβ) 40, Aβ42, p-tau181, total (t)-tau, neurofilament protein light chain (NfL), and inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8).ResultsThe level of the plasma Aβ42/Aβ40 ratio was significantly declined and the levels of the plasma p-tau181, NfL and TNF-α were significantly higher in the AD group than the NC group, but there was no significant difference in the levels of plasma t-tau, IL-1β, IL-6, and IL-8 between the AD and NC groups. The levels of plasma p-tau181, NfL, Aβ42/Aβ40 ratio, and TNF-α were all associated with impairments in multiple cognitive domains. Among them, the plasma Aβ42/Aβ40 ratio, and the p-tau181 and TNF-α levels were associated with impairments in global cognition, memory, and visuospatial abilities, but not with executive function, only plasma NfL level was associated with executive function. Plasma NfL showed higher diagnostic performance in AD than in NC individuals (AUC = 0.833). A combined diagnostic prediction model of plasma Aβ42/Aβ40 ratio, p-tau 181, and NfL had the highest value than each factor alone (AUC = 0.902),with a sensitivity and specificity of 0.867 and 0.886, respectively.ConclusionThe levels of plasma ATN biomarkers (Aβ42/Aβ40 ratio, p-tua181, and NfL) were significantly changed in clinically diagnosed AD patients and they all associated with different domains of cognitive impairment. Plasma ATN biomarkers better differentiate mild-to-moderate AD dementia from NC when they are incorporated into diagnostic models together rather than individually. Plasma ATN biomarkers have the potential to be a screening tool for AD. However, the expression of inflammatory factors in AD patients requires further research.
| S-EPMC9433929 | biostudies-literature
Project description:Background Cardiac complications are associated with perioperative mortality, but perioperative adverse cardiac events (PACEs) that are associated with long-term mortality have not been clearly defined. We identified PACE as a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, or stroke during the 30-day postoperative period and we compared mortality according to PACE occurrence. Methods and Results From January 2011 to June 2019, a total of 203 787 consecutive adult patients underwent noncardiac surgery at our institution. After excluding those with 30-day mortality, mortality during a 1-year follow-up was compared. Machine learning with the extreme gradient boosting algorithm was also used to evaluate whether PACE was associated with 1-year mortality. After excluding 1203 patients with 30-day mortality, 202 584 patients were divided into 7994 (3.9%) patients with PACE and 194 590 (96.1%) without PACE. After an adjustment, the mortality was higher in the PACE group (2.1% versus 7.7%; hazard ratio [HR], 1.90; 95% CI, 1.74-2.09; P<0.001). Results were similar for 7839 pairs of propensity-score-matched patients (4.9% versus 7.9%; HR, 1.64; 95% CI, 1.44-1.87; P<0.001). PACE was significantly associated with mortality in the extreme gradient boostingmodel. Conclusions PACE as a composite outcome was associated with 1-year mortality. Further studies are needed for PACE to be accepted as an end point in clinical studies of noncardiac surgery.
| S-EPMC9238468 | biostudies-literature
Project description: Not available
| S-EPMC8689147 | biostudies-literature
Project description:ImportanceMajor adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following noncardiac surgery.ObjectiveTo evaluate national trends in perioperative cardiovascular outcomes and mortality after major noncardiac surgery and to identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions.Design, setting, participantsPatients who underwent major noncardiac surgery from January 2004 to December 2013 were identified using the National Inpatient Sample.Main outcomes and measuresPerioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time.ResultsAmong 10 581 621 hospitalizations (mean [SD] patient age, 65.74 [12.32] years; 5 975 798 female patients 56.60%]) for major noncardiac surgery, perioperative MACCE occurred in 317 479 hospitalizations (3.0%), corresponding to an annual incidence of approximately 150 000 events after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (P for trend <.001; adjusted odds ratio [aOR], 0.95; 95% CI, 0.94-0.97) driven by a decline in frequency of perioperative death (aOR, 0.79; 95% CI, 0.77-0.81) and AMI (aOR, 0.87; 95% CI, 0.84-0.89) but an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (P for trend <.001; aOR 1.79; CI 1.73-1.86).Conclusions and relevancePerioperative MACCE occurs in 1 of every 33 hospitalizations for noncardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major noncardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing noncardiac surgery.
| S-EPMC5563847 | biostudies-literature
Project description:ObjectiveFrailty is an emerging risk factor for adverse outcomes. However, perioperative frailty assessments derived from electronic health records have not been studied on a large scale. We aim to estimate the prevalence of frailty and the associated incidence of major adverse cardiovascular events (MACE) among adults hospitalized for noncardiac surgery.MethodsAdults aged ≥45 years hospitalized for noncardiac surgery from 2004-2014 were identified from the National Inpatient Sample. The validated Hospital Frailty Risk Score (HFRS) derived from International Classification of Diseases codes was used to classify patients as low (HFRS <5), medium (5-10), or high (>10) frailty risk. The primary outcome was MACE, defined as myocardial infarction, cardiac arrest, and in-hospital mortality. Multivariable logistic regression was used to estimate the adjusted odds of MACE stratified by age and HFRS.ResultsA total of 55,349,978 hospitalizations were identified, of which 81.0%, 14.4%, and 4.6% had low, medium, and high HFRS, respectively. Patients with higher HFRS had more cardiovascular risk factors and comorbidities. MACE occurred during 2.5% of surgical hospitalizations and was common among patients with high frailty scores (high HFRS: 9.1%, medium: 6.9%, low: 1.3%, P < .001). Medium (adjusted odds ratio [aOR] 2.05; 95% confidence interval [CI], 2.02-2.08) and high (aOR 2.75; 95% CI, 2.70-2.79) HFRS were associated with greater odds of MACE vs low HFRS, with the greatest odds of MACE observed in younger individuals 45-64 years (interaction P value < .001).ConclusionsThe HFRS may identify frail surgical inpatients at risk for adverse perioperative cardiovascular outcomes.
| S-EPMC10038881 | biostudies-literature