Initiation of a Robotic Program in Spinal Surgery: Experience at a Three-Site Medical Center

ObjectiveTo highlight the early experience of implementing a robotic spine surgery program at a three-site medical center, evaluating the impact of increasing experience on the operative time and number of procedures performed.Patients and MethodsA retrospective chart review of patients undergoing robotic screw placement between September 4, 2018, and October 16, 2019, was conducted. Baseline characteristics as well as intraoperative and post-operative outcomes were obtained.ResultsFor a total of 77 patients, the mean age (SD) was 55.7 years (11.5) and 49.4% (n=38) were female. A total of 402 screws were placed (384 pedicle screws, 18 cortical screws) using robotic guidance with a median of two operative levels (interquartile range [IQR], 1 to 2). Median (IQR) estimated blood loss was 100 mL (50 to 200 mL) and the median (IQR) operative time was 224 minutes (193 to 307 minutes). With accrual of surgical experience, operative time declined significantly (R=-0.39; P<.001) whereas the number of procedures performed per week increased (R=0.30; P=.05) throughout the study period. Median (IQR) length of hospital stay following surgery was 2 days (IQR, 2 to 3 days). There were two screws requiring revision intraoperatively. No postoperative revisions were required, and no complications were encountered related to screw placement.ConclusionEarly experience at our institution using a spinal robot has demonstrated no requirement for postoperative screw revisions and no complications related to screw malposition. The increased operative times were reduced as the frequency of procedures increased. Moreover, procedural times diminished over a short period with a weekly increasing number of procedures.     

Women Are Less Likely to Survive AMI Presenting With Out-of-Hospital Cardiac Arrest: A Nationwide Study

ObjectiveTo assess the impact of patient’s sex on outcomes and management of acute myocardial infarction (AMI) patients presenting with out-of-hospital cardiac arrest (OHCA).Patients and MethodsWe conducted a population-based retrospective cohort study in AMI patients admitted with OHCA between 2010 and 2017 from the Myocardial Ischaemia National Audit Project (MINAP) registry. We used multivariable logistic regression models to evaluate the role of sex as a predictor of clinical outcomes and treatment strategy.ResultsOf 16,278 patients, women constituted almost one-quarter of the population (n=3710 [22.7%]). Women were older (median age 69 [IQR, 57-79] years vs 63 [IQR, 54-72] years, P<.001), experienced longer call-to-hospital-arrival time (median, 1.2 hours vs 1.1 hours; P=.008), were less likely to present with shockable rhythm (86.8% vs 91.5%, P<.001), and less likely to receive dual antiplatelet therapy (73.8% vs 78.6%, P<.001), beta blockers (64.7% vs 72.3%, P<.001), angiotensin-converting enzyme inhibitors (49.0% vs 55.3%, P<.001), coronary angiography (73.7% vs 83.3%, P<.001), and percutaneous coronary intervention (37.5% vs. 40.7%, p 0.004). After adjusting for patient characteristics and management, women had significantly higher odds of in-hospital death compared with men (odds ratio [OR], 1.3; 95% CI, 1.1 to 1.5) and lower odds of receiving coronary angiography (OR, 0.67; 95% CI, 0.59 to 0.75) and coronary artery bypass graft (OR, 0.28; 95% CI, 0.19 to 0.40).ConclusionWomen were less likely to survive following OHCA secondary to AMI. Hospital protocols that minimize physician bias and improve women-physician communication are needed to close this gap.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

Implementation of an All-Day Artificial Intelligence–Based Triage System to Accelerate Door-to-Balloon Times

ObjectiveTo implement an all-day artificial intelligence (AI)–based system to facilitate chest pain triage in the emergency department.MethodsThe AI-based triage system encompasses an AI model combining a convolutional neural network and long short-term memory to detect ST-elevation myocardial infarction (STEMI) on electrocardiography (ECG) and a clinical risk score (ASAP) to prioritize patients for ECG examination. The AI model was developed on 2907 twelve-lead ECGs: 882 STEMI and 2025 non-STEMI ECGs.ResultsBetween November 1, 2019, and October 31, 2020, we enrolled 154 consecutive patients with STEMI: 68 during the AI-based triage period and 86 during the conventional triage period. The mean ± SD door-to-balloon (D2B) time was significantly shortened from 64.5±35.3 minutes to 53.2±12.7 minutes (P=.007), with 98.5% vs 87.2% (P=.009) of D2B times being less than 90 minutes in the AI group vs the conventional group. Among patients with an ASAP score of 3 or higher, the median door-to-ECG time decreased from 30 minutes (interquartile range [IQR], 7?59 minutes) to 6 minutes (IQR, 4?30 minutes) (P<.001). The overall performances of the AI model in identifying STEMI from 21,035 ECGs assessed by accuracy, precision, recall, area under the receiver operating characteristic curve, F1 score, and specificity were 0.997, 0.802, 0.977, 0.999, 0.881, and 0.998, respectively.ConclusionImplementation of an all-day AI-based triage system significantly reduced the D2B time, with a corresponding increase in the percentage of D2B times less than 90 minutes in the emergency department. This system may help minimize preventable delays in D2B times for patients with STEMI undergoing primary percutaneous coronary intervention.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

High-Intensity Interval Training in Cardiac Rehabilitation: Impact on Fat Mass in Patients With Myocardial Infarction

ObjectiveTo examine the effect of high-intensity interval training (HIIT) on body fat mass and distribution in patients with myocardial infarction (MI) who underwent cardiac rehabilitation (CR).Patients and MethodsWe retrospectively screened 391 consecutive patients with MI enrolled in CR between September 1, 2015, and February 28, 2018. We included 120 patients who completed 36 CR sessions and underwent pretest-posttest dual-energy x-ray absorptiometry; 90 engaged in HIIT, and 30 engaged in moderate-intensity continuous training (MICT). High-intensity interval training included 4 to 8 alternating intervals of high- (30-60 seconds at a rating of perceived exertion [RPE] of 15-17 [Borg scale range, 6-20]) and low-intensity (1-5 minutes at RPE <14), and MICT performed for 20 to 45 minutes of exercise at an RPE of 12 to 14. Body weight, fat mass, and lean mass were measured via dual-energy x-ray absorptiometry with lipid profile measured via clinical procedures.ResultsThe HIIT and MICT groups were similar in age (67 vs 67 years), sex (26.7% [24 of 90 patients in the HIIT group] vs 26.7% [8 of 30 in the MICT group), and body mass index (30.3 vs 29.5 kg/m²) at baseline. The HIIT group had greater reductions in body fat percentage (P<.001), fat mass (P<.001), abdominal fat percentage (P<.001), waist circumference (P=.01), total cholesterol (P=.002), low-density lipoprotein cholesterol (P<.001), and triglycerides (P=.006). Improvements in total body mass and body mass index were not different across groups. After matching exercise duration, exercise intensity, and energy expenditure, HIIT-induced improvements in total fat mass (P=.02), body fat percentage (P=.01), and abdominal fat percentage (P=.02) persisted.ConclusionOur data suggest that supervised HIIT results in significant reductions in total fat mass (P<.001) and abdominal fat percentage (P<.001) and improved lipid profile in patients with MI who undergo CR.     

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization

ObjectiveTo assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.MethodsFrom January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.ResultsIn multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).ConclusionRCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Prognostic Value of Cardiac Magnetic Resonance Imaging in Acute Coronary Syndrome Patients With Troponin Elevation and Nonobstructive Coronary Arteries

ObjectiveTo define the diagnostic yield of cardiac magnetic resonance (CMR) in differentiating the underlying causes of myocardial infarction with nonobstructive coronary arteries (MINOCA) and to determine the long-term prognostic implications of such diagnoses.MethodsCardiac magnetic resonance evaluation was performed in 227 patients (mean age, 56.4±14.9 years; 120 [53%] female) with a “working diagnosis” of MINOCA as defined by presentation with a troponin-positive acute coronary syndrome (troponin I >0.04 μg/L) and nonobstructed coronary arteries between January 1, 2007, and February 28, 2013. Follow-up was performed to assess the primary composite end point of myocardial infarction, heart failure, and all-cause mortality.ResultsCardiac magnetic resonance identified nonstructural cardiomyopathies in 97 (43%) patients, myocardial infarction in 55 (24%) patients, structural cardiomyopathies in 27 (12%) patients, and pulmonary embolism in 1 patient. No CMR abnormalities were identified in the remaining patients. Kaplan-Meier analysis demonstrated the ability of a CMR diagnosis to predict the risk of the primary composite end point (P=.005) at 5-year follow-up. Worse outcomes were seen among patients with “true” MINOCA and a normal CMR image compared with those with CMR-confirmed myocardial infarction (P=.02). Use of antiplatelets (78% [37/45] vs 95% [52/55]; P=.01), beta blockers (56% [25/45] vs 82% [45/55]; P=.004), and statins (64% [29/45] vs 85% [47/55]; P=.01) was significantly lower in patients with true MINOCA with normal CMR imaging compared with those with CMR-confirmed myocardial infarction.ConclusionsCardiac magnetic resonance carries a high diagnostic yield in patients with MINOCA and predicts long-term prognosis. Patients with MINOCA with normal CMR imaging had an increased rate of major adverse cardiac events and lower use of guideline-recommended myocardial infarction therapy compared with those with CMR-confirmed myocardial infarction.     

Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients

ObjectiveTo explore the possible associations of serum 25-hydroxyvitamin D [25(OH)D] concentration with coronavirus disease 2019 (COVID-19) in-hospital mortality and need for invasive mechanical ventilation.Patients and MethodsA retrospective, observational, cohort study was conducted at 2 tertiary academic medical centers in Boston and New York. Eligible participants were hospitalized adult patients with laboratory-confirmed COVID-19 between February 1, 2020, and May 15, 2020. Demographic and clinical characteristics, comorbidities, medications, and disease-related outcomes were extracted from electronic medical records.ResultsThe final analysis included 144 patients with confirmed COVID-19 (median age, 66 years; 64 [44.4%] male). Overall mortality was 18%, whereas patients with 25(OH)D levels of 30 ng/mL (to convert to nmol/L, multiply by 2.496) and higher had lower rates of mortality compared with those with 25(OH)D levels below 30 ng/mL (9.2% vs 25.3%; P=.02). In the adjusted multivariable analyses, 25(OH)D as a continuous variable was independently significantly associated with lower in-hospital mortality (odds ratio, 0.94; 95% CI, 0.90 to 0.98; P=.007) and need for invasive mechanical ventilation (odds ratio, 0.96; 95% CI, 0.93 to 0.99; P=.01). Similar data were obtained when 25(OH)D was studied as a continuous variable after logarithm transformation and as a dichotomous (<30 ng/mL vs ≥30 ng/mL) or ordinal variable (quintiles) in the multivariable analyses.ConclusionAmong patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation. Further observational studies are needed to confirm these findings, and randomized clinical trials must be conducted to assess the role of vitamin D administration in improving the morbidity and mortality of COVID-19.     

Clinical Characteristics,Management Strategies and Outcomes of Acute Myocardial Infarction Patients With Prior Coronary Artery Bypass Grafting

ObjectiveTo investigate the management strategies, temporal trends, and clinical outcomes of patients with a history of coronary artery bypass graft (CABG) surgery and presenting with acute myocardial infarction (MI).Patients and MethodsWe undertook a retrospective cohort study using the National Inpatient Sample database from the United States (January 2004–September 2015), identified all inpatient MI admissions (7,250,768 records) and stratified according to history of CABG (group 1, CABG-naive [94%]; group 2, prior CABG [6%]).ResultsPatients in group 2 were older, less likely to be female, had more comorbidities, and were more likely to present with non-ST-elevation myocardial infarction compared with group 1. More patients underwent coronary angiography (68% vs 48%) and percutaneous coronary intervention (PCI) (44% vs 26%) in group 1 compared with group 2. Following multivariable logistic regression analyses, the adjusted odd ratio (OR) of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.98; 95% CI, 0.95 to 1.005; P=.11), all-cause mortality (OR, 1; 95% CI, 0.98 to 1.04; P=.6) and major bleeding (OR, 0.99; 95% CI, 0.94 to 1.03; P=.54) were similar to group 1. Lower adjusted odds of in-hospital major adverse cardiovascular and cerebrovascular events (OR, 0.64; 95% CI, 0.57 to 0.72; P<.001), all-cause mortality (OR, 0.45; 95% CI, 0.38 to 0.53; P<.001), and acute ischemic stroke (OR, 0.71; 95% CI, 0.59 to 0.86; P<.001) were observed in group 2 patients who underwent PCI compared with those managed medically without any increased risk of major bleeding (OR, 1.08; 95% CI, 0.94 to 1.23; P=.26).ConclusionsIn this national cohort, MI patients with prior-CABG had a higher risk profile, but similar in-hospital adverse outcomes compared with CABG-naive patients. Prior-CABG patients who received PCI had better in-hospital clinical outcomes compared to those who received medical management.     

Long-Term Risk of Major Adverse Cardiac Events in Atrial Fibrillation Patients on Direct Oral Anticoagulants

ObjectiveTo determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).Patients and MethodsThis study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.ResultsThe mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.ConclusionDOACs are associated with a lower risk of MACE in patients with AF independently from dosage.     

Efficacy and Safety of Lower Limb Progressive Resistance Exercise for Patients With Total Knee Arthroplasty: A Meta-analysis of Randomized Controlled Trials

ObjectiveTo evaluate the efficacy and safety of progressive resistance exercise (PRE) for patients with total knee arthroplasty (TKA) in a meta-analysis.Data SourcesPubMed, MEDLINE, Cochrane’s Library, and EMBASE databases.Study SelectionRandomized controlled trials evaluating the effect of PRE on mobility and function in patients with TKA.Data ExtractionA random-effects model was applied if significant heterogeneity was detected; otherwise, a fixed-effects model was applied.Data SynthesisSeven randomized controlled trials. Compared with a rehabilitation program without PRE, physiotherapy including PRE was associated with improvements in the 6-minute walking test (weighed mean difference [WMD], 19.22m; P=.04) with a wide confidence interval (CI, 0.48～37.95). However, sensitivity analysis by omitting 1 study with preoperative rehabilitation revealed nonsignificant results (WMD, 15.15m; P=.16). Moreover, PRE did not significantly improve the maximal walking speed (WMD, 0.05m/s, 95% CI, 0.00～0.11; P=.05). However, PRE was associated with improved knee strength of extension (standardized mean difference [SMD], 0.72; 95% CI, 0.47～0.96; P<.001) and flexion (SMD, 0.47; 95% CI, 0.19～0.74; P<.001) but not self-reported physical function (SMD, ?0.17; 95% CI, ?0.37～0.03; P=.10) or changes in pain score (SMD, 0.11; 95% CI, ?0.15～0.37; P=.40). PRE did not increase the risk of adverse events (risk ratio, 1.19; 95% CI, 0.52～2.71; P=.68).ConclusionsPRE may lead to improvements in physical function among patients receiving a TKA. PRE leads to higher ultimate strength in the surgical knee and is safe to perform.     

Survival and Progression in Synucleinopathy Phenotypes With Parkinsonism: A Population-Based Study

ObjectiveTo compare survival by the presenting parkinsonism symptoms at diagnosis among patients with incident clinically diagnosed synucleinopathies.Patients and MethodsUsing the Rochester Epidemiology Project medical records–linkage system, we identified all persons residing in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from January 1, 1991, through December 31, 2010. A movement disorder specialist reviewed the complete medical records of each individual to confirm the presence of parkinsonism, determine the type of synucleinopathy, and identify the onset dates of each cardinal symptom (tremor at rest, bradykinesia, rigidity, and impaired postural reflexes). We determined the median time from age at diagnosis to death or censoring (June 30, 2015) for each presenting symptom and the age- and sex-adjusted risk of death.ResultsFrom 1991 through 2010, a total of 433 individuals had a synucleinopathy diagnosed (301 [69.5%], Parkinson disease; 68 [15.7%], dementia with Lewy bodies; 52 [12.0%], Parkinson disease dementia; and 12 [2.8%], multiple systems atrophy with parkinsonism). Overall, the risk of death in the tremor-predominant group was less than that in the bradykinesia/rigidity-only group (hazard ratio [HR], 0.59; 95% CI, 0.40-0.87; P=.007). Similarly, risk of death in the bradykinesia/rigidity-only group was significantly greater than in the tremor-predominant group (HR, 1.75; 95% CI, 1.23-2.51; P=.002) and compared with tremor before bradykinesia (HR, 1.75; 95% CI, 1.24-2.47; P=.001).ConclusionPatients with tremor as a presenting symptom have longer survival. In contrast, the presence of bradykinesia/rigidity as a presenting symptom correlates with reduced survival across all types of synucleinopathies.     

Continuous Renal Replacement Therapy Liberation and Outcomes of Critically Ill Patients With Acute Kidney Injury

ObjectiveTo examine the association between continuous renal replacement therapy (CRRT) liberation and clinical outcomes among patients with acute kidney injury (AKI) requiring CRRT.MethodsThis single-center, retrospective cohort study included adult patients admitted to intensive care units with AKI and treated with CRRT from January 1, 2007, to May 4, 2018. Based on the survival and renal replacement therapy (RRT) status at 72 hours after the first CRRT liberation, we classified patients into liberated, reinstituted, and those who died. We observed patients for 90 days after CRRT initiation to compare the major adverse kidney events (MAKE₉₀).ResultsOf 1135 patients with AKI, 228 (20%), 437 (39%), and 470 (41%) were assigned to liberated, reinstituted, and nonsurvival groups, respectively. The MAKE₉₀, mortality, and RRT independence rates of the cohort were 62% (707 cases), 59% (674 cases), and 40% (453 cases), respectively. Compared with reinstituted patients, the liberated group had a lower MAKE₉₀ (29% vs 39%; P=.009) and higher RRT independence rate (73% vs 65%; P=.04) on day 90, but without significant difference in 90-day mortality (26% vs 33%; P=.05). After adjustments for confounders, successful CRRT liberation was not associated with lower MAKE₉₀ (odds ratio, 0.71; 95% CI, 0.48 to 1.04; P=.08) but was independently associated with improved kidney recovery at 90-day follow-up (hazard ratio, 1.81; 95% CI, 1.41 to 2.32; P<.001).ConclusionOur study demonstrated a high occurrence of CRRT liberation failure and poor 90-day outcomes in a cohort of AKI patients treated with CRRT.     

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban,Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism

ObjectiveTo compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE).Patients and MethodsConsecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB).ResultsIn the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37).ConclusionApixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer.Trial RegistrationClinicalTrials.gov identifier: NCT03504007.     

Inability of Radioiodine Remnant Ablation to Improve Postoperative Outcome in Adult Patients with Low-Risk Papillary Thyroid Carcinoma

ObjectiveTo determine whether radioiodine remnant ablation (RRA) reduces cause-specific mortality (CSM) or tumor recurrence (TR) rate after bilateral lobar resection (BLR).Patients and MethodsThere were 2952 low-risk adult papillary thyroid cancer (LRAPTC) patients (with MACIS scores <6) who underwent potentially curative BLR during 1955-2014. During 1955-1974, 1975-1994, and 1995-2014, RRA was administered in 3%, 49%, and 28%. Statistical analyses were performed using SAS software.ResultsDuring 1955-1974, the 20-year CSM and TR rates after BLR alone were 1.0% and 6.8%; rates after BLR+RRA were 0% (P=.63) and 5.9% (P=.82). During 1975-1994, post-BLR 20-year rates for CSM and TR were 0.3% and 7.5%; after BLR+RRA, rates were higher at 0.9% (P=.31) and 12.8% (P=.01). When TR rates were examined separately for 448 node-negative and 317 node-positive patients, differences were nonsignificant. In 1995-2014, post-BLR 20-year CSM and TR rates were 0% and 9.2%; rates after BLR+RRA were higher at 1.4% (P=.19) and 21.0% (P<.001). In 890 pN0 cases, 15-year locoregional recurrence rates were 3.4% after BLR and 3.7% after BLR+RRA (P=.99). In 740 pN1 patients, 15-year locoregional recurrence rates were 10% higher after BLR+RRA compared with BLR alone (P=.01). However, this difference became nonsignificant when stratified by numbers of metastatic nodes.ConclusionRRA administered to LRAPTC patients during 1955-2014 did not reduce either the CSM or TR rate. We would therefore not recommend RRA in LRAPTC patients undergoing BLR with curative intent.     

Prognostic Interplay Between Coronary Artery Calcium Scoring and Cardiorespiratory FItness: The CAC-FIT Study

ObjectiveTo assess the incremental prognostic role of coronary artery calcium score (CACS) and exercise capacity (EC), two independent prognostic tests in the assessment of patients with coronary artery disease.MethodsThe cohort consisted of patients who had clinically indicated exercise stress testing and CACS assessment from January 1, 2015, to September 30, 2021, with a median of 27 days between each other. Exercise capacity was defined by peak metabolic equivalents of task (METs) achieved during exercise stress test. The CACS was determined by the Agatston method. Patients were observed from the latest test date to incident major adverse cardiac events (inclusive of all-cause death, nonfatal myocardial infarction, late revascularization, and admission for heart failure).ResultsThere were a` total of 1932 patients in the study population (mean age, 56±12 years; 42% female, 48% hypertension, 21% diabetes, 48% dyslipidemia). Peak METs below 6 was achieved in 8% of patients, and the median (interquartile range) CACS was 9 (0-203). In multivariable Cox regression models, both CACS (1 unit increase in log CACS: hazard ratio, 1.19; 95% CI, 1.06 to 1.34; P=.003;) and EC (1 unit increase in peak METs: hazard ratio, 0.89; 95% CI, 0.81 to 0.97; P=.01) were independently associated with outcomes. Using CACS+EC added incremental prognostic value over clinical and fitness models (C index increase from 0.68 to 0.75; P=.015). Incident event rates increased across categories of CACS and EC.ConclusionOur analysis found that CACS and EC have complementary risk-stratifying roles in coronary artery disease.     

Arthritis Prediction of Advanced Hepatic Fibrosis in HFE Hemochromatosis

ObjectiveTo evaluate whether arthritis predicts the likelihood of advanced hepatic fibrosis in HFE hemochromatosis.Patients and MethodsWe conducted a retrospective, cross-sectional analysis of 112 well-characterized patients with HFE hemochromatosis and liver biopsy–validated fibrosis staging recruited between January 1, 1983, and December 31, 2013. Complete clinical, biochemical, hematologic, and noninvasive serum biochemical indices (aspartate aminotransferase to platelet ratio index [APRI] and fibrosis 4 index [FIB4]) were available. Scheuer fibrosis stages 3 and 4, APRI greater than 0.44, or FIB4 greater than 1.1 were used to define advanced hepatic fibrosis. Comparisons between groups were performed using categorical analysis, unpaired or paired t test.ResultsMale (n=76) and female (n=36) patients were similar in age. Nineteen patients had advanced hepatic fibrosis, and 47 had hemochromatosis arthritis. Arthritis was significantly associated with the presence of advanced hepatic fibrosis as determined by liver biopsy (sensitivity, 84%, [95% CI, 62% to 95%]; negative predictive value, 95% [95% CI, 87% to 99%]; relative risk, 7.4 [95% CI, 2.5 to 23]; P<.001), APRI (sensitivity, 75% [95% CI, 55% to 88%]; negative predictive value, 91% [95% CI, 81% to 96%]; relative risk, 4.5 [95% CI, 2.0 to 10.2]; P<.001), or FIB4 (sensitivity, 61% [95% CI, 41% to 78%]; negative predictive value, 67% [95% CI, 68% to 90%]; relative risk, 2.2 [95% CI, 1.1 to 4.6]; P=.03). Mean cell volume values were significantly higher pretreatment in patients with F3-4 fibrosis (96.7±1.1 fL) compared with F0-2 fibrosis (93.4±0.5 fL; P=.004) and declined following treatment (F3-4, 93.2±0.9 fL, P=.01; F0-2, 91.7±0.6 fL, P=.01).ConclusionAdvanced hepatic fibrosis is strongly associated with arthritis in HFE hemochromatosis. The absence of arthritis predicts a low likelihood of advanced hepatic fibrosis, supporting its use as a clinical marker for advanced hepatic fibrosis in HFE hemochromatosis.     

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y₁₂ inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y₁₂ inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y₁₂ inhibitors and clopidogrel in patients with AMI-CA/CS.ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y₁₂ cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y₁₂ inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.