Baseline Risk Factors Research Articles

Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial.

BackgroundAnti‐drug antibodies (ADAb) frequently form early in the treatment course of infliximab and other tumour necrosis factor (TNF) inhibitors, leading to treatment failure and adverse events.ObjectiveTo identify risk factors for ADAb in the early phase of infliximab treatment.MethodsPatients (n = 410) with immune‐mediated inflammatory diseases who initiated infliximab treatment were included in the 38‐week Norwegian Drug Monitoring Trial (NOR‐DRUM) A and randomised 1:1 to therapeutic drug monitoring (TDM) or standard therapy. Serum levels of infliximab and ADAb were measured at each infusion. Possible risk factors for ADAb formation were assessed using logistic regression, adjusting for potential confounders.ResultsADAb were detected in 78 (19%) patients. A diagnosis of rheumatoid arthritis (RA) (odds ratio [OR], 1.9 [95% confidence interval [CI] 1.0–3.6]) and lifetime smoking (OR, 2.0 [CI 1.1–3.6]) were baseline risk factors, while baseline use of concomitant immunosuppressors (OR, 0.4 [CI 0.2–0.8]) and a diagnosis of spondyloarthritis (SpA) (OR, 0.4 [CI 0.2–0.8]) reduced the risk of ADAb. Higher disease activity during follow‐up (OR, 1.1 [CI 1.0–1.1]) and “drug holidays” of more than 11 weeks (OR, 4.1 [CI 1.2–13.8]) increased the risk of ADAb, whereas higher infliximab doses (OR, 0.1 [CI 0.0–0.3) and higher serum infliximab concentrations (OR, 0.7 [CI 0.6–0.8]) reduced the risk of immunogenicity.ConclusionSeveral risk factors for ADAb formation during early‐phase infliximab treatment were identified. This knowledge provides a basis for treatment strategies to mitigate the formation of ADAb and identify patients in whom these measures are of particular importance.

Longitudinal trajectories of prescription opioid misuse in adolescents

BackgroundAdolescent misuse of prescription opioids is hazardous. This study aimed to generate data on prescription opioid misuse trajectories across adolescence and identify risk factors and mechanisms for more dangerous use trajectories. MethodsUsing a prospective longitudinal cohort repeated measures design, baseline (Fall 2013) and seven semiannual assessments were administered through Spring 2017 in 10 public high schools in Los Angeles, CA. Frequency of past 30-day prescription opioid misuse was captured. Trajectory groups were identified using growth mixture modeling and multinomial logistic regression identified associations between baseline risk factors with membership in each trajectory group. ResultsOverall, 3395 students were evaluated (53.4% female, Mean [SD] age at baseline=14.58[0.40]; range=12.83–16.29). Four discrete misuse trajectories were identified among 1062 students: (1) Minimal/Experimental (infrequent time-limited use; range of estimated mean number of days using prescription opioid across waves=0.0–0.6 days]; N = 705[20.8%]); (2) Low Deescalating (range=2.0–0.7 days; N = 189[5.6%]); (3) Moderate Escalating (range=0.7–3.6 days; N = 108[3.2%]); and (4) Frequent Persistent (range=4.7–9.4 days; N = 60[1.8%]). Students reporting tobacco, cannabis, alcohol use, or impulsivity in 9th grade were more likely to demonstrate membership in the Moderate Escalating trajectory class when compared to 2333 (68.7%) students reporting sustained abstinence. Female sex, peer opioid misuse, alcohol use, other substance use, impulsivity, or delinquent behavior reported in 9th grade was associated with membership in the Frequent Persistent trajectory class. ConclusionsPrescription opioid misuse in adolescence appears to follow 4 discrete trajectories, including the potentially problematic Moderate Escalating and Frequent Persistent trajectories. Female sex, peer influences, substance use, and intrapersonal risk factors were associated with membership in these classes.

Cemented Femoral Fixation in a High-Risk Cohort Diminishes Risk of Early Postoperative Periprosthetic Fracture

BackgroundEarly periprosthetic fractures (PPFx) following primary total hip arthroplasty (THA) create significant morbidity. Established risk factors for early PPFx include age, gender, body mass index, surgical approach, and implant fixation. We investigated the role of femoral fixation on early PPFx (<90 days postoperatively) in a high-risk cohort undergoing direct anterior approach (DAA) THA. MethodsThe final cohort comprised 344 consecutive patients (390 hips) with risk factors for PPFx (age >68 years and body mass index <25 kg/m2) who underwent primary DAA THA between May 4, 2009 and December 31, 2019 and had 90-day follow-up. Noncemented fixation was used in 229-hips, while cemented fixation was used in 161 hips. The primary outcome was early PPFx. Fisher’s exact test was used for categorical variables, while t-tests were used to compare continuous variables. ResultsWe observed 8 early PPFx (2.1%), all fractures occurring in the noncemented group. Baseline demographics were similar but not equal, with the cemented group being older (78.0 versus 76.3 years; P = .004) with a greater proportion of females (91.9% versus 69.4%; P < .001). The rate of early PPFx was significantly higher with noncemented fixation compared to cemented fixation (3.5% versus 0.0%; P = .023). A post hoc power analysis confirmed sufficient power (1−β = 0.81). ConclusionAlthough baseline risk factors for early PPFx are not easily modifiable, surgical factors can be modified. Cemented fixation has the potential to markedly reduce the risk of early PPFx in high-risk patients undergoing DAA THA.

The Relationships of Fibrinogen and C-Reactive Protein With Gait Performance: A 20-Year Longitudinal Study.

BackgroundGait speed, a central marker of aging, has been linked to various health outcomes, such as cognitive and physical functions in middle-aged adults. Although long-term systemic low-grade inflammation is considered a mechanism underlying a variety of aging-related risk factors, the longitudinal associations between inflammation markers and gait speed are yet to be fully investigated.ObjectiveTo explore the associations of CRP and fibrinogen levels, measured two decades ago, with gait speed among community dwelling adults, considering the contribution of cardio-metabolic factors and cognition.MethodsStudy participants took part in two phases of the of the “Kibbutzim Family Study” (i.e., Phase II, 1999–2000 and Phase III, 2017–2019). Blood samples collected in Phase II (baseline) were used to determine level of inflammatory markers. Gait speed was assessed under single-task (ST) and dual-task (DT) conditions in Phase III. Demographic, anthropometric and clinical data were collected in both phases. Linear regression models were used to assess the adjusted associations of inflammation and gait speed.ResultsA total of 373 individuals aged 34–99 (mean 64 ± 13 years) in Phase III were included in the study. Gait speed under ST was negatively associated with baseline levels of fibrinogen (b per standard deviation (SD) = −0.053, p = 0.0007) and CRP (b per SD = −0.043, p = 0.010), after adjusting for baseline and concurrent cardiometabolic risk factors. Accounting for executive functions, associations of fibrinogen with gait under ST were somewhat attenuated, yet associations remained statistically significant (p < 0.05). Associations with CRP were attenuated to the null. In contrast, there were no associations between inflammation markers and gait under DT.ConclusionOur findings demonstrate that in a sample including younger to older adults, higher systemic inflammatory activity was linked with gait 20 years later, beyond age and cardiometabolic health, and to a certain extent, beyond executive functions. Thus, systemic inflammation may serve as an early marker to identify individuals at risk for gait decline.

Association between use of enhanced recovery after surgery protocols and postoperative complications in colorectal surgery in Europe: The EuroPOWER international observational study

Study objectiveAssess the relationship between the Enhanced Recovery After Surgery (ERAS®) pathway and routine care and 30-day postoperative outcomes. DesignProspective cohort study. SettingEuropean centers (185 hospitals) across 21 countries. PatientsA total of 2841 adult patients undergoing elective colorectal surgery. Each hospital had a 1-month recruitment period between October 2019 and September 2020. InterventionsRoutine perioperative care. MeasurementsTwenty-four components of the ERAS pathway were assessed in all patients regardless of whether they were treated in a formal ERAS pathway. A multivariable and multilevel logistic regression model was used to adjust for baseline risk factors, ERAS elements and country-based differences. ResultsA total of 1835 patients (65%) received perioperative care at a self-declared ERAS center, 474 (16.7%) developed moderate-to-severe postoperative complications, and 63 patients died (2.2%). There was no difference in the primary outcome between patients who were or were not treated in self-declared ERAS centers (17.1% vs. 16%; OR 1.00; 95%CI, 0.79–1.27; P = 0.986). Hospital stay was shorter among patients treated in self-declared ERAS centers (6 [5–9] vs. 8 [6–10] days; OR 0.82; 95%CI, 0.78–0.87; P < 0.001). Median adherence to 24 ERAS elements was 57% [48%–65%]. Adherence to ERAS-pathway quartiles (≥65% vs. <48%) suggested that patients with the highest adherence rates experienced a lower risk of moderate-to-severe complications (15.9% vs. 17.8%; OR 0.71; 95%CI, 0.53–0.96; P = 0.027), lower risk of death (0.3% vs. 2.9%; OR 0.10; 95%CI, 0.02–0.42; P = 0.002) and shorter hospital stay (6 [4–8] vs. 7 [5–10] days; OR 0.74; 95%CI, 0.69–0.79; P < 0.001). ConclusionsTreatment in a self-declared ERAS center does not improve outcome after colorectal surgery. Increased adherence to the ERAS pathway is associated with a significant reduction in overall postoperative complications, lower risk of moderate-to-severe complications, shorter length of hospital stay and lower 30-day mortality.

Reproducible disease phenotyping at scale: Example of coronary artery disease in UK Biobank.

A lack of internationally agreed standards for combining available data sources at scale risks inconsistent disease phenotyping limiting research reproducibility. To develop and then evaluate if a rules-based algorithm can identify coronary artery disease (CAD) sub-phenotypes using electronic health records (EHR) and questionnaire data from UK Biobank (UKB). Case-control and cohort study. Prospective cohort study of 502K individuals aged 40-69 years recruited between 2006-2010 into the UK Biobank with linked hospitalization and mortality data and genotyping. We included all individuals for phenotyping into 6 predefined CAD phenotypes using hospital admission and procedure codes, mortality records and baseline survey data. Of these, 408,470 unrelated individuals of European descent had a polygenic risk score (PRS) for CAD estimated. CAD Phenotypes. Association with baseline risk factors, mortality (n = 14,419 over 7.8 years median f/u), and a PRS for CAD. The algorithm classified individuals with CAD into prevalent MI (n = 4,900); incident MI (n = 4,621), prevalent CAD without MI (n = 10,910), incident CAD without MI (n = 8,668), prevalent self-reported MI (n = 2,754); prevalent self-reported CAD without MI (n = 5,623), yielding 37,476 individuals with any type of CAD. Risk factors were similar across the six CAD phenotypes, except for fewer men in the self-reported CAD without MI group (46.7% v 70.1% for the overall group). In age- and sex- adjusted survival analyses, mortality was highest following incident MI (HR 6.66, 95% CI 6.07-7.31) and lowest for prevalent self-reported CAD without MI at baseline (HR 1.31, 95% CI 1.15-1.50) compared to disease-free controls. There were similar graded associations across the six phenotypes per SD increase in PRS, with the strongest association for prevalent MI (OR 1.50, 95% CI 1.46-1.55) and the weakest for prevalent self-reported CAD without MI (OR 1.08, 95% CI 1.05-1.12). The algorithm is available in the open phenotype HDR UK phenotype library (https://portal.caliberresearch.org/). An algorithmic, EHR-based approach distinguished six phenotypes of CAD with distinct survival and PRS associations, supporting adoption of open approaches to help standardize CAD phenotyping and its wider potential value for reproducible research in other conditions.

A Prospective, Matched Comparison of Health-Related Quality of Life in Bariatric Patients following Truncal Body Contouring.

Massive weight loss after bariatric surgery can lead to excess skin associated with functional and aesthetic sequelae. Access to the benefit provided by body contouring procedures may be limited by insurance approval, which does not consider health-related quality of life. The aim of this study was to quantify the benefit in health-related quality of life for patients who undergo body contouring procedures after massive weight loss. Patients evaluated for postbariatric body contouring procedures were systematically identified and prospectively surveyed using the BODY-Q. Health-related quality-of-life change for each functional scale was compared between those who underwent body contouring procedures (operative group, preoperatively versus postoperatively) and those who did not (nonoperative group, preoperatively versus resurvey) using t tests. Propensity score matching allowed the authors to balance baseline demographics, comorbidities, physical symptoms, and risk factors between cohorts. Fifty-seven matched patients were analyzed (34 operative versus 23 nonoperative). No significant difference in age, body mass index, time between surveys, or preoperative BODY-Q scores existed between cohorts. The surgical group demonstrated a significant improvement in 10 out of 11 BODY-Q functional scales. The nonoperative group realized no improvements and, in the interim, had a significant deterioration in four BODY-Q scales. Postbariatric body contouring procedures represent a critical and final step in the surgical weight loss journey for patients and are associated with significant improvements in health-related quality of life. Further deterioration in psychosocial and sexual health-related quality of life occurs in patients who do not undergo body contouring procedures following bariatric surgery. This study provides prospective comparative data that validate the field's standard intervention and justification for insurance approval. Therapeutic, II.

331 A Machine Learning-based Pharmacogenomic Association Study of Major Adverse Cardiovascular Events (MACEs) in Caribbean Hispanic Patients on Clopidogrel

OBJECTIVES/GOALS: To summarize baseline characteristics and risk factors for major adverse cardiovascular events (MACEs) and develop a prediction model by testing the association between genetic variants and MACEs in Caribbean Hispanic patients on clopidogrel using machine-learning (ML) techniques. METHODS/STUDY POPULATION: This is a secondary analysis of available clinical and genomic data from an existing database of 600 Caribbean Hispanic cardiovascular (CV) patients on clopidogrel. MACEs is defined as the composite of all-cause death, myocardial infarction, stroke and stent thrombosis over 6 months. Dataset is divided into training (60%) and testing (40%) sets, respectively. Two different supervised ML approaches (i.e. multiclass classification and regression algorithms) are applied to the study dataset using Python v3.5 and WEKA, and tested by receiver operating curve (ROC) analysis. A case-control association analysis between MACEs at 6 months and genotypes is performed by using chi-squared test. RESULTS/ANTICIPATED RESULTS: Average age of participants was 68 years-old, 55% males, with high prevalence of risk factors (i.e., overweight: 28.4 kg/m2; hypertension: 83.8%; hypercholesterolemia: 71.9% and diabetes: 54.8%). MACEs rate is 13.8%, with 33.5% resistant to clopidogrel. Logistic regression, KNN and gradient boosting showed the best performance, as suggested by ROC analysis and AUC CV scores of 0.6-0.7. A significant association between MACE occurrence and ≥3 risk alleles was found (OR=8.17; p=0.041). We anticipate that these genetic variants (CYP2C19*2, rs12777823, PON1-rs662, ABCB1-rs2032582, PEAR1-rs12041331) will uniquely contribute to clopidogrel resistance and MACEs in Caribbean Hispanics. DISCUSSION/SIGNIFICANCE: Our findings help address in part the long-standing problem of excluding minorities from research, which entails a gap of knowledge about clopidogrel pharmacogenomics in Puerto Ricans. This study provides a possible ML model that integrates clinical and pharmacogenomics for MACE risk estimation.

Variability Across Implanting Centers in Short and Long-Term Mortality and Adverse Events in Patients on HeartMate 3 Support: A Momentum 3 Secondary Analysis

<h3>Purpose</h3> We aimed to characterize center-specific variability in HeartMate 3 (HM3) patient survival within the MOMENTUM 3 studies and to examine the correlation between implanting center survival and major adverse events (AEs). <h3>Methods</h3> Center HM3 implant volume during the MOMENTUM 3 pivotal (n=515) and continued access protocol (n=1685) trials were tallied. Centers implanting ≤16 HM3 patients (25^th percentile) were excluded. De-identified center variability in mortality was assessed at 90 days and 2 years using direct adjusted survival while accounting for key baseline risk factors. The 90-day frequency and 2-year rates of stroke, bleeding, and infection were compared across centers and correlations between survival and event rate variability were assessed. <h3>Results</h3> Among 48 centers, 1957 HM3 patients were included in this analysis with site implants ranging between 17 to 103 patients. Patient cohorts differed across the sites by age (average 52-68 years), sex (60-95% male), destination therapy intent (25-100%), and %INTERMACS profile 1-2 (2-81%). At 90 days, center adjusted median mortality was 6.5%, nadiring at ≤3.2% (25^th percentile) and peaking at ≥10.5% (75^th percentile). Median 2-year center adjusted mortality was 18.6%, nadiring at ≤14.0% and peaking at ≥25.2% (figure A). AEs were also highly variable across centers; centers with low mortality tended to have lower AE rates at 2 years (figure B). <h3>Conclusion</h3> Patient characteristics and outcomes were highly variable across MOMENTUM 3 centers despite trial preoperative inclusion/exclusion criteria. Many centers had exemplary risk-adjusted HM3 patient outcomes. Studies are needed to improve our understanding of top performing centers' best practices as they relate to HM3 care in the pre, interoperative, and chronic support stages in an effort to further improve HM3 LVAD-associated clinical outcomes.

Decreased progression to systemic lupus erythematosus in patients with cutaneous lupus erythematosus under European League Against Rheumatism/American College of Rheumatology criteria

To the Editor: Patients with cutaneous lupus erythematosus (CLE) are at the risk of developing systemic lupus erythematosus (SLE). Most studies have used the 1982 American College of Rheumatology (ACR) criteria to identify patients with CLE who progress to SLE, reporting progression rates of 12% to 17%.1,2 We found a lower progression rate with the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria than with the ACR criteria in our patient cohort.3 Because the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria is yet to be utilized for studying CLE-to-SLE progression, we sought to compare the progression rates, baseline risk factors, and criteria gained among all 3 criteria.

Predictors of failure to achieve minimal clinical important difference for pain and disability after mechanical diagnosis and therapy (MDT)-based multimodal rehabilitation for neck pain: a retrospective analysis of 4998 patients.

To determine predictors of failure to achieve minimal clinical important difference (MCID) for pain and disability at discharge after mechanical diagnosis and therapy (MDT)-based multimodal rehabilitation for neck pain (NP). Pre- and post-treatment numerical pain rating scale (NPRS) and neck disability index (NDI) in patients with mechanical NP were analysed in this retrospective study. Multivariate analysis was performed to investigate the effect of covariates such as age, gender, lifestyle, body mass index, presentation, diabetes, osteoporosis, response to repeated movement testing, treatment sessions, compliance rate, and pre-treatment NPRS and NDI scores on failure to achieve MCID of ≥ 30% for NPRS and NDI scores post-treatment. In the 4998 patients analysed for this study, 7% and 14.5% of patients failed to achieve MCID for NPRS and NDI scores, respectively, at the end of treatment. Age > 70years, diabetes, osteoporosis, partial or non-response to repeated movements, lesser treatment sessions, and lower compliance rate were associated with increased risk for failure to achieve MCID for NPRS and NDI scores. A higher pre-treatment NDI score was associated with failure to achieve MCID for NPRS score, whereas lower pre-treatment NPRS and NDI scores were associated with failure to achieve MCID for NDI score. Although MDT-based multimodal rehabilitation helped to achieve significant reduction in pain and disability in mechanical NP, several baseline risk factors were associated with failure to achieve MCID for pain and disability after treatment. Identifying and modifying these factors as part of rehabilitation treatment may help to achieve better outcomes in mechanical NP.

Risk Factors for Failure of Tube Shunt Surgery: A Pooled Data Analysis

To identify the risk factors associated with failure of tube shunt surgery. Pooled analysis of 3 prospective multicenter, randomized clinical trials. A total of 621 patients with medically uncontrolled glaucoma were enrolled, including 276 from the Ahmed Baerveldt Comparison Study, 238 from the Ahmed Versus Baerveldt Study, and 107 from the tube group of the Tube Versus Trabeculectomy Study. Patients were randomized to treatment with an Ahmed glaucoma valve (model FP7) or Baerveldt glaucoma implant (model 101-350). The associations between baseline risk factors and tube shunt failure were assessed using a Cox proportional hazards regression model. The primary outcome measure was the rate of surgical failure defined as intraocular pressure (IOP) > 21 mmHg or reduced <20% from baseline, IOP ≤ 5 mmHg, loss of light perception vision, reoperation for glaucoma, or removal of implant. The cumulative probability of failure after tube shunt surgery was 38.3% after 5 years. In multivariable analyses, baseline factors that predicted tube shunt failure included preoperative IOP (≤ 21 mmHg compared to IOP > 21 and ≤ 25 mmHg; HR, 2.34; 95% CI, 1.52-3.61; P < .001), neovascular glaucoma (HR, 1.79; 95% CI, 1.28-2.52; P = .001), randomized treatment (for Ahmed glaucoma valve; HR, 1.36; 95% CI, 1.04-1.78; P = .025), and age (for 10 year decrease in age; HR, 1.19; 95% CI, 1.09-1.31; P < .001). Lower preoperative IOP, neovascular glaucoma, Ahmed implantation, and younger age were predictors of tube shunt failure. This Study provides the largest prospectively collected dataset on tube shunt surgery.

Midterm Outcomes of One-Stage Hybrid Aortic Arch Repair for Stanford Type A Aortic Dissection: A Single Center's Experience

This study sought to identify the midterm outcomes of one-stage hybrid aortic arch repair (HAAR) in patients with Stanford type A aortic dissection (TAAD). Between January 2010 and December 2015, 75 consecutive patients with TAAD involving the aortic arch who underwent one-stage type Ⅱ HAAR at our institution were identified. During this period, 496 consecutive patients with TAAD underwent traditional total aortic arch replacement (TAR) with frozen elephant trunk. The preoperative, perioperative, and postoperative data of all patients were compared. A propensity score-matching analysis was applied to adjust for baseline risk factors. Five hundred and seventy-one patients were included for analysis (428 men; mean age, 48.9 ± 11.1 years). For all patients, the mean follow-up time was 41.1 ± 22.1 months, in-hospital mortality was 4.7%, and the 5-year survival rate was 89.5%. Midterm outcomes between the propensity-matched groups were compared (59 HAAR vs TAR pairs). HAAR group showed shorter cardiopulmonary bypass time (105-159 minutes vs 158-230 minutes, P < 0.001), aortic cross-clamping time, postoperative ventilation time, and intensive care unit stays (33-108 hours vs 45-131 hours, P = 0.010) than the TAR group. There were no significant differences in in-hospital mortality, rate of stroke and rate of paraplegia between the 2 groups, however, better 5-year survival rate was found in HAAR group (94.9% vs 75.8%, Log-rank P = 0.005). As compared to propensity matched cohort of TAR patients, HAAR shows good midterm outcomes for patients with TAAD. Further randomized study was needed to clarify the optimal management strategy of TAAD.

Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

BackgroundStudies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.ObjectivesTo compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants...

Prospective Cardiovascular Surveillance of Immune Checkpoint Inhibitor-Based Combination Therapy in Patients With Advanced Renal Cell Cancer: Data From the Phase III JAVELIN Renal 101 Trial.

PURPOSEBoth immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for advanced renal cell carcinoma treatment and can cause cardiovascular events (CVs); thus, combination therapy could lead to major adverse CV events (MACE). Cardiac serum biomarker assessment and imaging, including left ventricular ejection fraction (LVEF) monitoring, can be used to evaluate MACE.METHODSTo our knowledge, the JAVELIN Renal 101 trial, assessing avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma, is the first randomized study of ICI plus VEGFR inhibitor treatment to include prospective serial cardiac monitoring of LVEF and serum cardiac biomarkers.RESULTSMACE (defined as grade ≥ 3 CV AEs) occurred in 31 patients (7.1%) in the combination arm and 17 patients (3.9%) in the sunitinib arm. Patients in the combination arm who had high baseline troponin T values were at higher risk of MACE versus patients with low values (MACE in 6/35 v 7/135, respectively; relative risk, 3.31; 95% CI, 1.19 to 9.22). This association was not observed in patients treated with sunitinib. Other CV baseline risk factors and serum cardiac biomarkers were not significantly predictive for MACE, although a trend toward an association with dyslipidemia was seen in the combination arm. No clinical value of on-treatment routine monitoring of LVEF in relation to MACE was observed. Although LVEF decline was significantly more frequent in the combination arm, most patients recovered, and decline was not associated with other significant cardiac events or symptoms.CONCLUSIONPatients with high baseline troponin T levels receiving ICI and VEGFR combinations may need to be monitored more closely for MACE. Routine monitoring of LVEF in asymptomatic patients is not recommended.

Sex Differences in Baseline Characteristics Do Not Predict Early Outcomes after Percutaneous Coronary Intervention: Results from the Australian GenesisCare Cardiovascular Outcomes Registry (GCOR).

Objective: The effect of baseline differences between men and women on early outcomes after percutaneous coronary intervention (PCI). Design, setting, participants: This is an observational study of all participants in the GenesisCare Cardiovascular Outcomes Registry, undergoing PCI. The registry holds data for both emergency and elective procedures. Data was collected on 10,989 consecutive patients from 12 Australian Private Hospitals, including baseline demographics, co-morbidities, risk factors, PCI procedures, and lesion characteristics. Main outcome measures: Outcome was measured for complications (in-hospital death, peri-procedural myocardial infarctions, and bleeding events), at discharge and at 30-days for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiac events (MACE), and unplanned readmissions. Results: Women represented 23% of the study population, were significantly older, with a higher rate of hypertension and hyperlipidaemia. Heart failure was more common in women and was associated with a significantly higher average ejection fraction than in men. Women had a lower rate of pre-existing coronary artery disease (CAD), had less complex CAD, and needed fewer stents. Periprocedural complications were similar, but major bleeding was more common in women. The 30-day outcome was similar between men and women for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiovascular events (MACE), and unplanned readmissions. Conclusions: Although significant differences were observed between women and men in both clinical presentation and complexity of disease, the 30-day outcome was similar for death and MACE. Women had a higher rate of major bleeding events, and lower adherence to statins and dual antiplatelet therapy (DAPT).

Big data insights into predictors of acute compartment syndrome

BackgroundThere remain gaps in knowledge regarding the pathophysiology, initial diagnosis, treatment, and outcome of acute compartment syndrome (ACS). Most reported clinical outcomes are from smaller studies of heterogeneous patients. For a disease associated with a financial burden to society that represents billions of dollars worldwide the literature does not currently establish baseline diagnostic parameters and risk factors that may serve to predict treatment and outcomes. MethodsThis study looks at a very large cohort of trauma patients obtained from four recent years of the Trauma Quality Programs data from the American College of Surgeons. From 3,924,127 trauma cases - 203,500 patients with tibial fractures were identified and their records examined for demographic information, potential risk factors for compartment syndrome, an associated coded diagnosis of muscle necrosis, and presence of other outcomes associated with compartment syndrome. A recurrent multiple logistic regression model was used to identify factors predictive of fasciotomy. The results were compared to the reported results from the literature to validate the findings. ResultsThe rate of fasciotomy treatment for ACS was 4.3% in the cohort of identified patients. The analysis identified several clinical predictors of fasciotomy. Proximal and midshaft tibial fractures (P <0.0001) showed highest increases in the likelihood of ACS. Open fractures were twice (O.R [2.20–2.42]) as likely to have ACS. Having a complex fracture (P<0.0001), substance abuse disorder (P<0.0002), cirrhosis (P = 0.002) or smoking (P<0.0051) all increased the likelihood of ACS. Age decreased the likelihood by 1% per year (OR= [0.99–0.993]). Crush and penetrating injuries showed an important increase in the likelihood of ACS (O.R of 1.83 and 1.37 respectively). Additionally, sex, BMI, cirrhosis, tobacco smoking and fracture pattern as defined by OTA group and OTA subgroup had predictive value on actual myonecrosis. Fasciotomies for open tibial fractures were more likely to uncover significant muscle necrosis compared to closed fractures. Amputation resulted after 5.4% of fasciotomies. ConclusionThis big data approach shows us that ACS is primarily linked to the extent of soft tissue damage. However, newfound effect of some comorbidities like cirrhosis and hypertension on the risk of ACS imply other mechanisms.

Analysis of risk factors for early death in patients with acute promyelocytic leukaemia treated with arsenic trioxide.

To date, no specific studies have evaluated early death (ED) in patients with acute promyelocytic leukaemia (APL) homogeneously treated with arsenic trioxide induction therapy and investigated according to the white blood cell (WBC) count at onset. Such patients were retrospectively analysed in this study, including 314 patients with a WBC count ≤ 10 × 109/L (standard-risk (SR) group) and 144 with a WBC count > 10 × 109/L (high-risk (HR) group). The baseline clinical characteristics and risk factors for ED were compared between the two groups. The incidence of fibrinogen < 1.0g/L and elevated serum uric acid, aspartate aminotransferase and creatinine levels were higher in the HR group than in the SR group (P = 0.001; P < 0.001; P < 0.001; P = 0.044, respectively). The ED rate was significantly higher in the HR group than in the SR group (29.17% vs. 10.83%, P < 0.001). The main cause of ED was bleeding, followed by infection and differentiation syndrome (DS) in the HR group, while it was bleeding, followed by DS and infection in the SR group. Male sex, age > 50years old, and fibrinogen < 1.0g/L were independent risk factors for ED in the SR group. Increased serum creatinine levels, decreased albumin levels, and fibrinogen < 1.0g/L were independent risk factors for ED in the HR group. Overall, the incidence of ED was higher in the HR group, and the baseline clinical characteristics, causes, times, and predictors of ED in the HR group differed from those in the SR group.

Abstract P1-14-02: Phase II study of adjuvant endocrine therapy with CDK 4/6 inhibitor, ribociclib, for localized ER+/HER2- breast cancer (LEADER, part 1)

Abstract Background: CDK 4/6 inhibitors have demonstrated substantial efficacy in treating ER+/HER2- metastatic breast cancer. Therefore, there is great interest in exploring their ability to reduce recurrence risk in early breast cancer. However, conflicting results were observed in the large adjuvant phase 3 clinical trials investigating combination of endocrine therapy and CDK 4/6 inhibitor (PALLAS, MONARCH-E). While these adjuvant clinical trials evaluated upfront use of CDK 4/6 inhibitor, the optimal timing of adding CDK 4/6 inhibitor for HR+/HER2- breast cancer remains unknown. We conducted a prospective phase II clinical trial to evaluate the addition of a CDK 4/6 inhibitor, ribociclib, in patients who were already on adjuvant endocrine therapy. Methods: In part 1 of the clinical trial, eligibility included patients with localized stage I-III ER+ (≥ 10%), HER2- breast cancer; completed surgery; and were on adjuvant endocrine therapy (any number of years) with at least one year or more of treatment remaining. Patients were randomized to two different ribociclib schedules: continuous (400 mg daily of 28-day cycle; arm 1) or intermittent (600 mg daily on days 1-21 of 28-day cycle; arm 2) for one year. Patients were concurrently treated with an aromatase inhibitor (plus GnRH agonist if premenopausal). Tolerance was evaluated via CTCAE version 4.03 and proportion of subjects who discontinued CDK 4/6 treatment early. Stratification factors for statistical analysis included: disease stage (III vs lower), duration of prior endocrine therapy (within 2 years; 2-5 years vs &amp;gt; 5 years), and whether the patient received prior chemotherapy or not. Baseline characteristics and risk factors for recurrence and for early discontinuation were compared between the arms of the study using Pearson's chi-squared test. Actuarial analysis of time to recurrence was done using the Kaplan-Meier estimator. The primary objective of part 1 was to estimate adherence to ribociclib treatment in the adjuvant setting. Results: In total, 81 patients were enrolled between February 2018 and September 2019, and 25 (31%) discontinued ribociclib treatment early, with no significant difference between study arms. The most common grade 3 or greater adverse events (AEs) leading to study discontinuation were neutropenia (44%), alanine aminotransferase increase (28%), and aspartate aminotransferase increase (16%). Among patients who discontinued early, neutropenia was more frequent in the 600 mg arm, 9 of 12 patients (75%), versus 2 of 13 patients (15%) in the 400 mg arm. No patients discontinued early due to prolonged QTc. Ribociclib was dose reduced for 22 patients (27%), with no significant difference between study arms (p = 0.12). After a median follow-up of 20 months, two patients have experienced disease recurrence with recurrence-free survival of 100% at 1 year and 97% (95% CI 88-99%) at 2 years. Biomarker (ctDNA) results will be reported at the meeting. Conclusions: Results demonstrate that while serious AEs with one year of adjuvant ribociclib are low, a substantial number of patients discontinued adjuvant CDK 4/6 inhibitor within 1 year. Overall, with limited follow-up, only two patients had recurrent disease since completion of ribociclib treatment. Tolerability and identifying patient subsets who will most benefit need to be carefully considered with CDK 4/6 inhibitors in the adjuvant setting. Citation Format: Laura M Spring, Lauren Scarpetti, Andrzej Niemierko, Steven J Isakoff, Beverly Moy, Seth A Wander, Elisabeth Smith, Elizabeth Abraham, Jennifer Shin, Jaymin M Patel, Amy Comander, Therese Mulvey, Aditya Bardia. Phase II study of adjuvant endocrine therapy with CDK 4/6 inhibitor, ribociclib, for localized ER+/HER2- breast cancer (LEADER, part 1) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-14-02.

Higher Adherence to ERAS Society® Recommendations is Associated with Shorter Hospital Stay Without an Increase in Postoperative Complications or Readmissions in Bariatric Surgery: the Association Between Use of Enhanced Recovery After Surgery Protocols and Postoperative Complications after Bariatric Surgery (POWER 3) Multicenter Observational Study.

The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery. Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions. ClinicalTrials.gov Identifier: NCT03864861.