Non-low Risk Research Articles

Prognostic impact of chronic lymphocytic leukemia comorbidity index in a young population: a real-world evidence study of a national gulf region cohort

In chronic lymphocytic leukaemia (CLL), comorbidities assessed by the CLL comorbidity index (CLL-CI) have been associated with outcomes in Western cohorts. We conducted a retrospective analysis of an unselected Middle Eastern cohort of newly diagnosed CLL patients seen at the Kuwait Cancer Control Center (n = 300). Compared to Western studies, these Middle Eastern patients were diagnosed at a younger age (median of 59) and had a higher comorbidity burden (69% non-low risk CLL-CI). A higher CLL-CI score was independently associated with significantly shorter event-free survival and greater risk of death. Our analysis demonstrates that CLL-CI is a valuable tool for comorbidity assessment and prognostic influence in (relatively young) Middle Eastern CLL patients.

Age-Related Differences in the Presentation, Management, and Clinical Outcomes of 100,000 Patients With Venous Thromboembolism in the RIETE Registry

IntroductionAlthough older adults represent a significant proportion of patients with venous thromboembolism (VTE), the data on the impact of age-related differences in the clinical presentation, management, and outcomes of VTE are scarce. MethodsWe analyzed data from the RIETE registry database, an ongoing global observational registry of patients with objectively confirmed VTE, to compare patient characteristics, clinical presentation, treatments, and outcomes between elderly (≥70 years) vs. non-elderly (<70 years) patients. ResultsFrom January 2001 to March 2021, 100,000 adult patients were enrolled in RIETE. Elderly patients (47.9%) were more frequently women (58.2% vs. 43.5%), more likely had unprovoked VTE (50.5% vs. 45.1%) and most often presented with severe renal failure (10.2% vs. 1.2%) and acute pulmonary embolism (PE) (vs. deep vein thrombosis) (54.3% vs. 44.5%) compared to non-elderly patients (p<0.001 for all comparisons). For the PE subgroup, elderly patients more frequently had non-low risk PE (78.9% vs. 50.7%; p<0.001), respiratory failure (33.9% vs. 21.8%; p<0.001) and myocardial injury (40.0% vs. 26.2%; p<0.001) compared to non-elderly patients. Thrombolysis (0.9% vs. 1.7%; p<0.001) and direct oral anticoagulants (8.8% vs. 11.8%; p<0.001) were less frequently administered to elderly patients. Elderly patients showed a significantly higher 30-day all-cause mortality (adjusted odds ratio [OR] 1.36, 95%CI: 1.22–1.52) and major bleeding (OR, 2.08; 95%CI, 1.85–2.33), but a lower risk of 30-day VTE recurrences (OR, 0.62, 95%CI, 0.54–0.71). ConclusionsCompared with non-elderly patients, elderly patients had a different VTE clinical profile. Advanced therapies were less frequently used in older patients. Age was an independent predictor of mortality.

Multicenter analysis to assess risk of major adverse cardiac events in patients undergoing high-sensitivity troponin testing in the emergency department.

Our objective was to evaluate 30-day major adverse cardiac events (MACE) in emergency department (ED) patients with normal high-sensitivity troponins (hs-trop). We hypothesized that MACE rates would be<1% in patients with (1) two normal troponins regardless of change in troponin (delta) and (2) index hs-trop below the limit of quantitation (LOQ) regardless of the institution modified HEART score. This was a multicenter, retrospective, cohort study of adult patients who presented to 1 of 18 EDs between July 2020 and April 2021 with acute coronary syndrome as defined by an institutional-modified HEART score completed by their treating physician or midlevel, no evidence of ST-elevation myocardial infarction, and an index or serial gender-adjusted hs-trop within normal limits. The primary outcome was MACE within 30 days of index ED encounter. A detailed case review was then performed for those patients experiencing a MACE. Of the 9084 patients who had single or serial normal troponins, 31 (0.34%; confidence interval [CI] 0.23%-0.48%) experienced MACE. Of the 6140 patients with 2 normal hs-trop and a delta (change in troponin)<4, 27 patients (0.44%; CI 0.29%-0.64%) experienced MACE. Only 1 of the 69 patients with 2 normal hs-trop results but delta (change in troponin) ≥ 4 (1.45%; CI 0.04%-7.81%) suffered MACE. This patient was classified as non-low risk by our institutional HEART score. Of 7498 patients with an index hs-trop<LOQ, 14 (0.19%; CI 0.10%-0.31%) experienced MACE, with 57% (N=8) deemed non-low risk by HEART score. Patients with 2 normal hs-trop values in the ED are unlikely to suffer 30-day MACE. Although it remains unclear whether patients with delta (change in troponin) ≥4 despite normal troponins will have a 30-day MACE, this situation is rare. Additionally, a single index hs-trop<6ng/L demonstrated a low risk for 30-day MACE independent of the institutional HEART score.

Financial Implications of Evolving Breast Cancer Radiotherapy Treatment Protocols

Adjuvant radiotherapy for breast cancer represents a significant portion of radiotherapy (RT) treatments. The resource implications of evidence-based changes in treatment protocols must be defined to facilitate RT service planning. We designed a study to calculate the impact of past changes and create a model to allow prediction of costs implications for future changes. Changes in RT treatment (shown in table 1) in the past 3 years were identified in consultation with clinical staff and by reviewing institutional treatment guidelines. Resource and infrastructure costs were calculated for each protocol. Staff time was calculated using standard time slots where known (e.g., CT simulation appointment) and estimates based on discussion with staff (e.g., time to plan whole breast RT). Cost / Gy was calculated based on Linac cost of €2.5M, 10% annual service charge over 12-year lifetime, 2.7 patients treated / hour (verified institutional metric) and standard 2Gy fraction, giving €37.72 / Gy. We did not include facilities costs nor account for differing treatment outcomes. We collected relevant data on a consecutive 6-month sample (Jan - Jun 2019) of women receiving adjuvant RT for breast cancer (n = 224). Total costs were calculated by applying costs for each protocol change to the women in this cohort eligible for the changes. Protocol changes and costs are summarized in table 1. The use of DIBH for women <60 years receiving IMN RT (left and right sided) added a cost. The largest cost saving resulted from more selective tumor bed boost, a saving of €462,138. The potential impact of a 5-fraction boost for women with non-low risk DCIS was estimated. In the cohort analyzed, identified changes in adjuvant breast radiotherapy resulted in overall savings due to updated indications for boost and the implementation of ultra-hypofractionated radiotherapy. We are now analyzing the impact of introducing simultaneous integrated boost and partial breast radiotherapy.

Single-step Direct Drug Provocation Testing is Safe for Delabelling Selected Non−low-risk Penicillin Allergy Labels

To describe the outcome of an oral amoxicillin challenge in patients labeled allergic to penicillin.One hundred forty nine patients from 1 to 98 years of age labeled allergic to penicillin were included in the study.Patients were categorized as low risk (side effects, family history of penicillin allergy, remote [>5 years] history of penicillin allergy without IgE-mediated features, or unknown reaction not requiring hospitalization, n = 64) or nonlow risk (anaphylaxis, urticaria within 2 hours of penicillin administration, or angioedema with or without urticaria, n = 85). The low risk patients underwent challenge with a single dose of oral amoxicillin (125 mg for patients 1 to 11 months of age, 250 mg for 1 to 11 years, and 500 mg for all patients more than 12 years) followed by 2 hours of observation to evaluate for Gell and Coombs type 1/IgE-mediated/immediate-type hypersensitivity reactions. The nonlow risk patients underwent penicillin skin testing and if negative, oral amoxicillin challenge. Excluded patients were those with history of: (1) Gell and Coombs type 2 reactions, for example, hemolytic anemia or thrombocytopenia; (2) type 3 reactions, for example, serum sickness or vasculitis; or (3) severe type 4 or severe cutaneous adverse reactions, for example, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms.All (64 of 64, 100%) of the low risk patients tolerated the amoxicillin challenge without reaction during the observation period, although 3 developed a maculopapular rash subsequently. All (85 of 85, 100%) of the nonlow risk patients had negative penicillin skin testing, and 84 of 85 (99%) tolerated the amoxicillin challenge without reaction during the observation period, whereas 1 patient developed pruritus and rash that resolved with antihistamine treatment, and 2 subsequently developed a maculopapular rash.The authors conclude that a single step oral amoxicillin challenge is safe.Six percent of children are reported to be allergic to penicillin, although only about 5% of that 6% (0.3%) have positive penicillin skin tests. The remainder either never had IgE-mediated allergy or the allergy was lost over time. Being mislabeled as allergic to penicillin is not benign, but rather leads to suboptimal treatment, more side effects (eg, Clostridium difficile), higher costs, and more antibiotic resistance. Thus, there is currently a strong push to “delabel” the vast majority of children who are labeled as allergic to penicillin but are not. Children are typically referred to allergists to undergo oral amoxicillin challenges under observation with or without prior penicillin skin testing, depending on the history. However, this paper suggests that, given the safety of these challenges, consideration can be given to performing them in pediatricians’ offices. If a careful history excludes patients with histories of “nonlow risk” immediate allergic reactions and those with serious nonimmediate reactions, the remainder with low risk histories can undergo a single dose oral amoxicillin challenge, which the vast majority will tolerate and can be successfully “delabeled.”URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1016/j.anai. 2021.04.008

Observed versus expected morbidity and mortality in patients undergoing mitral valve repair.

OBJECTIVESMitral valve repair (MVP) is the gold standard treatment for degenerative mitral regurgitation. With the expansion of transcatheter technologies, this study compares the outcome of MVP in low-risk and non-low-risk patients to serve as a benchmark.METHODSThis retrospective, single-institution study examined all patients who underwent MVP for primary mitral regurgitation from 2005 to 2018. Patients were stratified into 2 risk categories: low-risk [Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (STS-PROM) ≤2%] and non-low risk (STS-PROM > 2% or age > 75), with a subgroup of very low risk (STS-PROM ≤1%, age <75).RESULTSA total of 1207 patients were included, and 1053 patients were classified as low risk and 154 as non-low risk. The non-low-risk group was significantly older, more likely to be female, and had a higher comorbidity burden than the low-risk group (all P < 0.01). For the low-risk group, the observed-to-expected (O:E) STS mortality ratio was 0.4 and the composite morbidity and mortality ratio was 0.6, whereas for the non-low risk, the O:E mortality was 1.5 and the composite morbidity and mortality was 0.9. When the subgroup of very low-risk group was assessed, the mortality O:E ratio was 0.CONCLUSIONSThe observed composite morbidity and mortality of patients undergoing MVP were persistently lower in low-risk patients, mainly driven by the very low-risk group. The excellent outcome of MVP in low-risk patients should be validated on a national level to determine how transcatheter technologies can be utilized in these patients.

Prognostic accuracy of syncope clinical prediction rules in older adults in the emergency department.

Study objectiveThe objective of this study is to evaluate the prognostic accuracy of existing rules (San Francisco Syncope Rule [SFSR], Canadian Syncope Risk Score [CSRS], and FAINT score) in older adults.MethodsThis is a cohort study of adults aged ≥60 years presenting to an academic emergency department (ED) with syncope or near syncope. We used original criteria for all rules except for the FAINT score, in which N‐terminal pro–brain natriuretic peptide was largely missing from the extracted data. Patients were deemed positive for each rule if classified as non‐low risk. The primary outcome was the presence of 30‐day serious outcome, as defined by syncope research guidelines. Sensitivity and negative likelihood ratio (NLR) were calculated with 95% confidence intervals (CIs).ResultsA total of 404 ED visits (mean age of patients, 75.5 years) were included. Of these, 44 (10.9%) had a 30‐day serious outcome, and 24 (5.9%) had incomplete 30‐day follow‐up. SFSR was positive for 280 of 380 visits with complete follow‐up. Its sensitivity and NLR for predicting 30‐day serious outcomes were 86.4% (95% CI, 72.0%–94.3%) and 0.53 (95% CI, 0.25–1.15), respectively. The CSRS was positive for 299 of 380 visits (sensitivity was 88.6% [95% CI, 76.4%–95.7%], and NLR was 0.50 [95% CI, 0.22–1.17]). The modified FAI(N)T score was positive for 318 of 380 visits (sensitivity was 90.9% [95% CI, 77.4%–97.0%], and NLR was 0.53 [95% CI, 0.20–1.38]).ConclusionExisting rules are suboptimal to predict 30‐day serious outcomes in older adults presenting with syncope or near syncope to the ED.

Impacts of opium addiction on patterns of angiographic findings in patients with acute coronary syndrome

Opium is one of the most abused substances in the Middle East. The effects of opium use on coronary artery disease (CAD) are a matter of debate. This study aimed to assess the association between opium use and angiographic findings as well as the complexity of CAD in patients with acute coronary syndrome (ACS) diagnosis. In this case–control study, all patients admitted for coronary angiography from 2019 to 2020 were evaluated. After applying the eligibility criteria, they were categorized into two groups opium and non-opium based on their history of opium use. Both groups were matched regarding the demographic features. The prevalence, location, and severity of obstruction of the vessels were compared between the non-opium and opium groups. The SYNTAX score was also calculated and compared between the two groups. The scores ≤ 22 are considered low risk and the higher scores are a non-low risk. P value < 0.05 is considered significant. A total of 170 patients with a mean age of 61.59 ± 9.07 years were finally enrolled in our study. Regarding the severity of vascular involvement, there was a significant difference between the non-opium and opium groups in LAD (P = 0.025), and PLV (P = 0.018) vessels. From the location points of view of obstructive coronary artery involved segments, only in the PDA (P = 0.006), and LCX (P = 0.004) vessels, a significant difference was observed. Moreover, 47.1% of opium and 30.6% of non-opium use group were in the non-low risk SYNTAX score classification which is a statistically significant difference between these two groups (P value = 0.048). Opium, as an independent risk factor for cardiovascular diseases, can have specific effects on angiographic findings in patients with acute coronary syndrome. Likewise, the complexity of CAD in opium users who undergo percutaneous coronary intervention is significantly higher.

Clinical utility and prognostic implications of the 4S-AF scheme: Report from Asia Pacific Heart Rhythm Society Atrial Fibrillation Registry.

The 4S-AF classification scheme comprises of four domains (stroke risk [St], symptoms [Sy], severity of atrial fibrillation (AF) burden [Sb] and substrate [Su]), which has been recommended in the 2020 ESC guidelines to characterize and evaluate patients with AF. We aimed to determine whether the 4S-AF scheme would be useful for AF characterization and provides prognostic information in a large contemporary prospective Asian registry conducted by the Asia Pacific Heart Rhythm Society (APHRS). Among 4666 patients enrolled in APHRS registry, 3586 of them whose data about left atrial (LA) dimension and European Heart Rhythm Association (EHRA) symptom score were available have constituted as the study population. The 4S-AF score was calculated as the sum of each domain with a maximum score of 9. The clinical endpoint was defined as the 1-year composite risk of any thromboembolic event, ischaemic stroke, heart failure, acute coronary syndrome, significant coronary artery disease requiring coronary intervention and all-cause mortality. Based on the 4S-AF domains, 86.7% were 'non-low risk' for stroke; 94.3% had EHRA Class I-II, 48.5% were newly diagnosed or paroxysmal AF; and only 8.4% had no cardiovascular risk factors or LA enlargement. The risk of clinical events was higher in patients who were 'non-low risk' for stroke (aOR 2.175, 95% CI 1.060-4.461), with permanent AF (aOR 1.579, 95% CI 1.106-2.225) and increasing points for substrate (aORs 2.376-4.968 from score 2 to 4). When compared to the first tertile of 4S-AF score (0-3 points), patients in the second tertile (4-5 points) had approximately 2.5-fold increase in adverse events (OR 2.478, 95% CI 1.678-3.661, p < .001), while those in the third tertile (6-9 points), had a 3.5-fold increase (OR 3.484, 95% CI 2.322-5.226, p < .001), both without significant differences between the 5 participating countries (p for interaction > .05). If all 4S-AF domains were appropriately treated, this was associated with a lower risk of composite clinical outcomes (aOR 0.384, p < .001; p for interaction for different countries=.234). Categorization according to the 4S-AF scheme can be related to the risk of the composite adverse event rate in Asian AF patients, and appropriate treatments based on the 4S-AF scheme resulted in better clinical outcomes. These observations support the characterization and management according to the 4S-AF scheme in Asian patients.

Monoclonal gammopathy of (un)known significance

Monoclonal gammopathies are a frequently diagnosed entity. However, the diagnosis is not always clinically relevant. The diagnosis of a monoclonal gammopathy requires serum electrophoresis, immunofixation and free light chain measurement. Sometimes, monoclonal gammopathies occur in the course of transient or autoimmune inflammation. Further diagnostics should only be performed after risk assessment according to Mayo criteria. In non-low risk patients, a symptomatic myeloma has to be ruled out via SLiM-CRAB criteria. The diagnostic work-up should include whole-body MRI and a bone marrow puncture as well as a 24 h urine sample. If it does not imply myeloma, the diagnosis of MGUS is confirmed and a follow-up after 6 months is recommended. After that, low-risk patients only need SLiM-CRAB screening at clinical signs of progression. All other patients should receive serologic follow-ups once a year. Importantly, MGUS patients show higher morbidity. Amongst a higher prevalence of osteoporosis and immunodeficiency, a wide array of MGUS-associated diseases such as AL amyloidosis, deposition diseases and Fc binding-dependent effects can occur. This article gives an overview over the work-up, observation and caveats of monoclonal gammopathy of (un)known significance.

Association of ‘Low Risk’ Fractures With Abuse in Young Children

Association of ‘Low Risk’ Fractures With Abuse in Young Children

Potential impact of a novel pathway for suspected myocardial infarction utilising a new high-sensitivity cardiac troponin I assay

BackgroundHigh-sensitivity cardiac troponin I (hs-cTnI) assays promise high diagnostic accuracy for myocardial infarction (MI). In an ED where conventional cTnI was in use, we evaluated an assessment pathway using the...

Risk Stratification of Ductal Carcinoma In Situ and Texture Analysis of Contrast-Enhanced Breast Magnetic Resonance Imaging.

The aim of this study was to investigate whether texture analysis of contrast-enhanced T1 weighted images could predict risk of ductal carcinoma in situ (DCIS). The study included 185 DCIS lesions that were classified as either low risk or non-low risk using surgical pathology records. All magnetic resonance imaging texture analyses were performed using postprocessing software, and texture-derived parameters were extracted. The sphericity, compactness, and spherical disproportion were significantly different in the low-risk and non-low risk groups using the Van Nuys Prognostic Index (mean ± SD, 0.479 ± 0.189 vs 0.414 ± 0.176, 0.161 ± 0.159 vs 0.112 ± 0.134, and 2.569 ± 1.434 vs 2.934 ± 1.374, respectively; P < 0.05). In the univariate analyses, sphericity (odds ratio, 7.091; 95% confidence interval, 1.236-40.666; P = 0.028) and compactness (odds ratio, 9.267; 95% confidence interval, 1.125-76.360; P = 0.039) were significantly associated with a high probability of being low risk according to the Van Nuys Prognostic Index. Whole-lesion texture analysis may be helpful in identifying patients classified as having low-risk DCIS before surgery.

LGG-02. PEDIATRIC LOW-GRADE GLIOMA RISK STRATIFICATION IN THE MOLECULAR ERA

BackgroundPediatric low-grade gliomas (LGG), in particular those not amenable to surgical resection, are a therapeutic challenge owing to their heterogeneity in clinical behavior. Identification of the RAS/MAPK pathway as a universal feature of these tumors has led to an improved understanding and the development of targeted therapeutics. We examined the impact of known biological and novel molecular risk factors on patient outcomes at our institution. MethodsWe retrospectively reviewed risk factors and clinical outcomes in 38 LGG cases diagnosed by histopathology at Norton Children’s Hospital in Louisville, KY, USA from March 2015 to Jan 2019. Progression free survival (PFS) rates were generated using the Kaplan-Meier method. Log-rank tests and hazard ratios were used to identify prognostic factors by univariable analysis. ResultsAmong previously described biological risk factors, subtotal resection/biopsy only (HR 3.67, p=0.0257), non-WHO Grade I histology (HR 3.34, p=0.0101), and infant age (< 3 years) (HR 4.19, p=0.0031) were associated with shorter PFS. Brainstem location had no significant impact on PFS. (HR 0.86, p=0.8071). H3K27M mutant status was predictably associated with worse PFS (HR 5.86, p=0.0012). BRAF v600e mutant status, however, was not associated with inferior outcomes. On the contrary, in our study population, BRAF v600e mutant status had a suggested protective effect (HR 0.14, p=0.0247). Patients with 2 or more oncogenic driver mutations demonstrated worsened PFS (HR 4.78, p=0.0059). We utilized the following scoring system for risk stratification: 1 point was allocated for each of the above biological and molecular risk factors except for H3K27M, which was allocated 3 points. A score of < 3 was designated low risk. Non-low risk classification was associated with significantly inferior PFS (median PFS 13 vs. 62 mos, HR 4.26, p=0.0012). ConclusionWe herein demonstrate the utility of a combined biological and molecular risk classification for pediatric LGG.

Neoadjuvant Androgen Deprivation Therapy Effects on Perioperative Outcomes Prior to Radical Prostatectomy: Eleven Years of Experiences at Ramathibodi Hospital.

ObjectiveThe aim of this study was to demonstrate the efficacy of neoadjuvant androgen deprivation therapy (NADT) on perioperative outcomes in patients who underwent radical prostatectomy (RP).Materials and MethodsFrom January 2008 to July 2018, we collected retrospective data of patients with clinically localized prostate cancer who underwent RP to assess their perioperative and pathological outcomes. The data included age, body mass index (BMI), serum prostate specific antigen (PSA) level, clinical stage, neoadjuvant ADT usage, operative time, estimated blood loss (EBL), perioperative complications, blood transfusion rate, adjacent organ injury rate, length of hospital stay, pathological stage, Gleason score (GS) of the biopsy and pathological specimen, specimen weight (g), and margin status.ResultsOf the 718 RPs performed, 138 (19.22%) were NADT and 580 (80.78%) were non-NADT. Patients who underwent NADT had a significant benefit in operative time (185 vs 195 mins), EBL (300 vs 500 mL) and specimen weight. These benefits were more obvious in non-low risk prostate cancer with less operative time, EBL, blood transfusion rate, length of hospital stay and specimen weight. However, the margin status and adjacent organ injury rate were similar in the NADT and non-NADT groups.ConclusionNADT provides significantly better perioperative outcomes, especially in non-low risk prostate cancer, and has comparable pathological outcomes.

Estimating the real-world performance of the PROMISE minimal-risk tool

Stable chest pain is a common indication for cardiac catheterization. We assessed the prognostic value of the Prospective Multicenter Imaging Study for Evaluation (PROMISE) Minimal-Risk Tool in identifying patients who are at very low risk of obstructive coronary artery disease (CAD) or downstream cardiovascular adverse outcomes. We applied the PROMISE Minimal-Risk Tool to consecutive patients without known CAD who underwent elective cardiac catheterization for stable angina from January 1, 2000 to December 31, 2014 in the Duke Databank for Cardiovascular Disease (DDCD). Patients with scores >0.46 (top decile of lowest-risk from the PROMISE cohort) were classified as low-risk. Logistic regression modeling compared likelihood of freedom from obstructive coronary artery disease on index angiography, 2-year survival, and 2-year survival free of myocardial infarction (MI) and MI/revascularization between low- and non low-risk patients. Alternative cut points to define low- risk patients were also explored. Among 6251 patients undergoing cardiac catheterization for stable chest pain, 1082 (17.3%) were low-risk per the PROMISE minimal-risk tool. Among low risk patients, obstructive coronary artery disease was observed in 14.9% and left main disease (≥ 50% Stenosis) was rare (0.9%). Compared with other patients, low risk patients had a higher likelihood of freedom from obstructive coronary disease on index catheterization (85.1% vs. 44.2%, OR 4.84, 95% CI 4.06-5.77). Low risk patients had significantly higher survival (98.2% vs. 94.4%, OR 3.18, 95% CI 1.99-5.08), MI-free survival (97.2% vs. 91.9%, OR 3.03, 95% CI 2.07-4.45), and MI/revascularization-free survival (86.2 vs. 59.9%, OR 4.19, 95% CI 3.48-5.05) at 2 years than non-low risk patients. Operating characteristics for predicting the outcomes of interest varied modestly depending on the low-risk cut-point used but the positive predictive value for 2 year freedom from death was >98% regardless. The PROMISE minimal-risk tool identifies 17% of stable chest pain patients referred to cardiac catheterization as low risk. These patients have a low prevalence of obstructive CAD and better survival than non-low risk patients. While this suggests that these patients are unlikely to benefit from catheterization, further research is needed to confirm a favorable downstream prognosis with medical management alone.

Abstract GS2-04: A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01)

Abstract Background: Wholebreast irradiation (WBI) after breast conserving surgery for DCIS reduces therisk of local recurrence including invasive recurrence. The objective of BIG3-07/TROG 07.01 is to test radiation dose escalation to the tumor bed (tumorbed boost) and fractionation sensitivity of whole breast irradiation (WBI) inpatients with non-low risk DCIS treated with breast conserving therapy. Methods: BIG3-07/TROG 07.01 is an international, multicenter, randomized, controlled, phase 3 trial. Eligible women were ≥18 years ofage with completely resected non-low risk DCIS defined as age &amp;lt;50 years orage ≥50 years plus at least one of the risk factors for local recurrence (palpable tumor,multifocal disease, tumor size ≥ 1.5cm, intermediate or high nuclear grade, central necrosis, comedo histologyand/or surgical margin &amp;lt;10 mm). Patients were randomized to have tumor bedboost (16 Gy in 8 daily fractions) or no boost following conventional WBI (50Gy in 25 daily fractions) or hypofractionated WBI (42.5 Gy in 16 dailyfractions) in one of three randomization categories selected by centers priorto study activation. Randomization A was a 4-arm randomization of no boost vs. boostfollowing conventional WBI vs. hypofractionated WBI. Patients in RandomizationB and Randomization C were assigned no boost or boost following conventional WBIand hypofractionated WBI, respectively. The primary endpoint was time to localrecurrence, analyzed by intention to treat. The trial was designed to detect a3% difference in 5-year free-from- local recurrence rates between the no boostand boost groups (93% vs 96%; hazard ratio, 0.56) with 90% power and 2-sidedalpha level of 5%. The primary effect of boost was assessed on all randomizedpatients. The secondary effect of WBI dose-fractionation and the interactionbetween boost and WBI dose-fractionation were assessed on patients in RandomizationA and additionally on all patients. Results: BetweenJune 2007 and June 2014, 1608 patients were randomized to have no boost (805patients) or boost (803 patients) after WBI. Conventional WBI was given in 831 patients(no boost in 416 patients; boost in 415 patients). Hypofractionated WBI wasgiven in 777 patients (no boost in 389 patients; boost in 388 patients). Adjuvantendocrine therapy was planned in 106 patients (13%) in the no boost group and105 patients (13%) in the boost group. Median follow-up was 6.6 years. The 5-yearfree-from- local recurrence rates were 93% in the no boost group and 97% in theboost group (hazard ratio, 0.47; 95% confidence interval [CI], 0.31 to 0.72;P&amp;lt;0.001). Forty-four percent and 45% of LRs were invasive in the no boostgroup and boost group, respectively. The effect of boost did not vary significantlyby age, tumor size, nuclear grade, surgical margin or endocrine therapy. Therewere no significant differences in the 5-year free-from- local recurrence ratesbetween the conventional WBI group and hypofractionated WBI group inRandomization A (94% vs. 94%, P=0.84) and in all randomized patients (95% vs.95%, P=0.89). The test for interaction between boost and dose-fractionation wasnot significant in Randomization A or in all randomized patients (both P=0.89).The rates of grade ≥2 breastpain (12% vs. 16%, P=0.84) and skin and subcutaneous tissue fibrosis (6% vs.15%, P=0.14) did not differ significantly between the groups. Conclusions: Inwomen with non-low risk DCIS treatedwith breast conserving surgery, the addition of tumor bed boost followingconventional or hypofractionated WBI reduced local recurrence rates. There wasno difference in local recurrence rates between conventional WBI andhypofractionated WBI. (Registered with ClinicalTrials.gov, NCT00470236.) Citation Format: Boon Hui Chua, Emma Link, Ian Kunkler, Ivo Olivotto, Antonia Helen Westenberg, Timothy Whelan, Guenther Gruber, Breast International Group (BIG)-aisbl, Trans Tasman Radiation Oncology Group, Scottish Cancer Trials Breast Group, Canadian Cancer Trials Group, European Organization for Research and Treatment of Cancer, International Breast Cancer Study Group, Cancer Trials Ireland. A randomized phase III study of radiation doses and fractionation schedules in non-low risk ductal carcinoma in situ (DCIS) of the breast (BIG 3-07/TROG 07.01) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS2-04.

HEART Pathway Implementation Safely Reduces Hospitalizations at One Year in Patients With Acute Chest Pain

We determine whether implementation of the HEART (History, ECG, Age, Risk Factors, Troponin) Pathway is safe and effective in emergency department (ED) patients with possible acute coronary syndrome through 1 year of follow-up. A preplanned analysis of 1-year follow-up data from a prospective pre-post study of 8,474 adult ED patients with possible acute coronary syndrome from 3 US sites was conducted. Patients included were aged 21 years or older, evaluated for possible acute coronary syndrome, and without ST-segment elevation myocardial infarction. Accrual occurred for 12 months before and after HEART Pathway implementation, from November 2013 to January 2016. The HEART Pathway was integrated into the electronic health record at each site as an interactive clinical decision support tool. After integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or nonlow risk (appropriate for further inhospital evaluation). Safety (all-cause death and myocardial infarction) and effectiveness (hospitalization) at 1 year were determined from health records, insurance claims, and death index data. Preimplementation and postimplementation cohorts included 3,713 and 4,761 patients, respectively. The HEART Pathway identified 30.7% of patients as low risk; 97.5% of them were free of death and myocardial infarction within 1 year. Hospitalization at 1 year was reduced by 7.0% in the postimplementation versus preimplementation cohort (62.1% versus 69.1%; adjusted odds ratio 0.70; 95% confidence interval 0.63 to 0.78). Rates of death or myocardial infarction at 1 year were similar (11.6% versus 12.4%; adjusted odds ratio 1.00; 95% confidence interval 0.87 to 1.16). HEART Pathway implementation was associated with decreased hospitalizations and low adverse event rates among low-risk patients at 1-year follow-up.

Predictive Accuracy of Electrocardiographic Monitoring of Patients With Syncope in the Emergency Department: The SyMoNE Multicenter Study.

Arrhythmia is one of the most worrisome causes of syncope. Electrocardiographic (ECG) monitoring is crucial for the management of non-low-risk patients in the emergency department (ED). However, its diagnostic accuracy and optimal duration are unknown. We aimed to assess the diagnostic accuracy of ECG monitoring in non-low-risk patients with syncope in the ED. This prospective multicenter observational study included adult patients presenting to the ED after syncope. Patients without an obvious etiology after ED evaluation who were classified by ED physicians as being at non-low risk of adverse events underwent ECG monitoring. We assessed sensitivity, specificity, and diagnostic yield (defined as the proportion of patients with true-positive ECG monitoring findings) of ECG monitoring in the identification of 7- and 30-day adverse and arrhythmic events according to monitoring duration. Of 242 patients included in the study, 29 patients had 7-day serious outcomes. Ten additional patients had serious outcomes at 30 days. The overall sensitivity, specificity, and diagnostic yield of ECG monitoring in the identification of 7-day adverse events were 0.55 (95% confidence interval [CI]= 0.36 to 0.74], 0.93 (95% CI= 0.89 to 0.96), and 0.07 (95% CI= 0.04 to 0.10), respectively. The sensitivity, specificity, and diagnostic yield of >12-hour ECG monitoring in the identification of 7-day adverse events were 0.89 (95% CI= 0.65 to 0.99), 0.78 (95% CI= 0.67 to 0.87), and 0.18 (95% CI= 0.12 to 0.28), respectively. Similar results were observed for 30-day adverse events. The median (interquartile range) ECG monitoring time was 6.5 (6 to 15) hours. ECG monitoring findings were positive in 31 patients. Although the overall diagnostic accuracy of ECG monitoring is fair, its sensitivity at>12 hours' duration is substantially higher. These results suggest that prolonged (>12 hours) monitoring is a safe alternative to hospital admission in the management of non-low-risk patients with syncope in the ED.

Performance of cardiac troponins within the HEART score in predicting major adverse cardiac events at the emergency department

BackgroundThis study compared the performance of a single blood draw of high-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI) and conventional troponin I (cTnI) within a modified HEART score for predicting 30-day MACE at Emergency Department (ED) presentation, and established local reference norms for all three assays by determining the cut-off point which yielded the highest sensitivity and negative predictive value for acute myocardial infarction and 30-day MACE. MethodsThis single-center prospective cohort study recruited chest pain patients at the ED, whose hsTnT, hsTnI and cTnI were taken on admission. Subjects were classified into low and non-low risk group according to their modified HEART score, with MACE as the primary endpoint. Receiver-operating characteristic (ROC) curves were generated, area under the curves (AUCs) were calculated; the performance characteristics were determined. ResultsThe performance of modified HEART scores was comparable among the three assays for 30-day MACE (84.9–87.0% sensitivity, 95.6–96.0% NPV, 95%CI) and none of these had very high AUC and specificity (AUC 0.70–0.71, 53.7–56.7% specificity, 95% CI). The modified HEART score using a single blood draw of either hsTnT (3.9ng/L), hsTnI (0.9ng/L) or cTnI (0.0ng/L) at presentation yielded a sensitivity of 100% for 30-day MACE. ConclusionThe modified HEART score using a single blood draw of either hsTnT, hsTnI or cTnI was equally effective in risk-stratifying chest pain patients for safe discharge. The theoretical cut-off points yielding 100% sensitivity are potentially useful (when achieved) for safely discharging low risk patients with undifferentiated chest pain in the ED.