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BACKGROUND: Immune checkpoint inhibitors (ICI) are widely used cancer treatments. There are limited data the risk for developing venous thromboembolism (VTE) among patients on an ICI. METHODS: This was a retrospective study of 2854 patients who received ICIs at a single academic center. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard imaging criteria. A self-controlled risk-interval design was applied with an “at-risk period” defined as the two-year period after, and the “control period”, defined as the two-year prior to treatment. The hazard ratio (HR) was calculated using a fixed-effect proportional hazards model. RESULTS: Of the 2854 patients, 1640 (57.5%) were men; mean age was 64±13 years. The risk for VTE was 7.4% at 6 months and 13.8% at 1 year after starting an ICI. The rate of VTE was >4-fold higher after starting an ICI (HR 4.98, 95% CI 3.65 – 8.59, p

Background Coronary vasospasm is a recognized side effect of 5-fluorouracil (5-FU). There are limited and conflicting data on the incidence, risk factors, and prognostic effect of 5-FU–associated vasospasm. Objectives This study sought to assess the incidence, risk factors, and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center. Methods The study conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram changes or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared with patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review. Results From approximately 4,019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (age 58 ± 13 years vs. 64 ± 13 years; p = 0.001) and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%; p = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. Conclusions In a large, single-center report of 5-FU–associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors, and had no significant difference in progression-free or overall survival compared with those who did not develop vasospasm.

This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP.In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment.Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p 0.001 for both).Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Background Type 2 myocardial infarction (T2MI) is common and associated with high cardiovascular event rates. However, the relationship between T2MI and heart failure (HF) is uncertain. Methods and Results We identified patients with T2MI at a large tertiary hospital between October 2017 and May 2018. Patient characteristics, causes of T2MI, and subsequent HF hospitalizations were determined by physician chart review. We identified 359 patients with T2MI over the study period; 184 patients had a history of HF. Among patients with ejection fraction (EF) assessment (N=180), the majority had preserved EF (N=107; 59.4%), followed by reduced EF (N=54; 30.0%), and mid‐range EF (N=19; 10.6%). Acute HF was the most common cause of T2MI (20.9%). Of those whose T2MI was precipitated by HF (N=75), the mean EF was 53.0±16.8% and 16 (21.3%) were de novo diagnoses of HF. Among patients with T2MI who were discharged alive with available follow‐up (N=289), 5.5% were hospitalized with acute HF within 30 days, 17.3% within 180 days, and 22.1% within 1 year. In subgroup analyses, among patients with T2MI with prevalent or new HF (N=161), the rate of HF hospitalization at 1 year was 34.2%, considerably higher than those with T2MI and no HF diagnosis at discharge (7.0%; N=9/128). Conclusions Index presentations of HF or worsening chronic HF represent the most common causes of T2MI. ≈1 in 5 patients with T2MI will be readmitted for HF within 1 year of their event. Strategies to prevent HF events after a T2MI are needed.

Background: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. Methods: In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. Results: Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m 2 , respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged −27.9% (95% CI, −35.1% to −20.7%; P P P Conclusions: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02887183.

Summary Objectives Skeletal myopathies are highly morbid, and in rare cases even fatal, immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI). Skeletal myopathies are also a recognized statin-associated side effect. It is unknown whether concurrent use of statins and ICIs increases the risk of skeletal myopathies. Methods This was a retrospective cohort study of all patients who were treated with an ICI at a single academic institution (Massachusetts General Hospital, Boston, MA, USA). The primary outcome of interest was the development of a skeletal myopathy. The secondary outcome of interest was an elevated creatine kinase level (above the upper limit of normal). Results Among 2757 patients, 861 (31.2%) were treated with a statin at the time of ICI start. Statin users were older, more likely to be male and had a higher prevalence of cardiovascular and non-cardiovascular co-morbidities. During a median follow-up of 194 days (inter quartile range 65–410), a skeletal myopathy occurred in 33 patients (1.2%) and was more common among statin users (2.7 vs. 0.9%, P < 0.001). Creatine kinase (CK) elevation was present in 16.3% (114/699) and was higher among statin users (20.0 vs. 14.3%, P = 0.067). In a multivariable Cox model, statin therapy was associated with a >2-fold higher risk for skeletal myopathy (HR, 2.19; 95% confidence interval, 1.07–4.50; P = 0.033). Conclusion In this large cohort of ICI-treated patients, a higher risk was observed for skeletal myopathies and elevation in CK levels in patients undergoing concurrent statin therapy. Prospective observational studies are warranted to further elucidate the potential association between statin use and ICI-associated myopathies., Graphical Abstract Graphical Abstract

BackgroundMyocarditis is a highly morbid complication of immune checkpoint inhibitor (ICI) use that remains inadequately characterized. The QRS duration and the QTc interval are standardized electrocardiographic measures that are prolonged in other cardiac conditions; however, there are no data on their utility in ICI myocarditis.MethodsFrom an international registry, ECG parameters were compared between 140 myocarditis cases and 179 controls across multiple time points (pre-ICI, on ICI prior to myocarditis, and at the time of myocarditis). The association between ECG values and major adverse cardiac events (MACE) was also tested.ResultsBoth the QRS duration and QTc interval were similar between cases and controls prior to myocarditis. When compared with controls on an ICI (93±19 ms) or to baseline prior to myocarditis (97±19 ms), the QRS duration prolonged with myocarditis (110±22 ms, pConclusionsThe QRS duration is increased in ICI myocarditis and is associated with increased MACE risk. Use of this widely available ECG parameter may aid in ICI myocarditis diagnosis and risk-stratification.

Background: Despite over one million cases of novel coronavirus disease 2019 (COVID-19) in the United States, limited data, including socioeconomic information and treatment strategies, exist regarding patients hospitalized with the viral infection. Methods: In this case series, we identified patients with COVID-19 admitted to 3 Partners Healthcare hospitals in Boston, Massachusetts between March 7th, 2020, and March 30th, 2020. Patient characteristics; treatment strategies; clinical outcomes including mortality, intensive care utilization, and cardiovascular events were determined. Findings: A total of 247 patients hospitalized with COVID-19 over the study period were identified; the median age was 61 (interquartile range [IQR]: 50-76 years), 58% were men, 30% of Hispanic ethnicity, 21% enrolled in Medicaid, and 12% dual-enrolled Medicare/Medicaid. The median estimated household income was $66,701 [IQR: $50,336- $86,601]. Among patients with employment data (204): 89 (36%) were retired, 23 (9.3%) worked in hospitality, 10 (4%) were healthcare workers, 5 (2%) worked in public transportation, and 21 (8.5%) were unemployed. The majority of patients were treated with hydroxychloroquine (72%), and statins (76%; newly initiated in 34%). Among those treated with hydroxychloroquine with available electrocardiogram data (172), 38% developed QTc prolongation. Discontinuation of statin therapy due to elevated creatinine kinase or elevated liver biochemical tests was also common (29%). New atrial fibrillation/flutter occurred in 8.9% of patients and ventricular tachycardia (non-sustained/sustained) in 7.3% of patients. Other cardiovascular events including myocardial infarction (4.9%) and venous thromboembolism (2.8%) were less common. Within the follow-up period, 103 (42%) required intensive care. At the end of the data collection period (April 19, 2020), 170 patients (68.8%) were discharged alive, 51 patients (20.7%) remain admitted, and 26 patients (10.5%) have died. Interpretation: Patients hospitalized with COVID-19 are frequently of vulnerable socioeconomic status and often require intensive care. Early in the pandemic, off-label drug prescriptions were common. Funding Statement: American Heart Association Declaration of Interests: Dr. Wasfy reports a grant from the American Heart Association (18 CDA 34110215). Dr. Natarajan is supported by a Hassenfeld Scholar Award from the Massachusetts General Hospital, a grant from Fondation Leducq (TNE-18CVD04), and National Heart, Lung, and Blood Institute grants (R01HL148565, R01HL148050, R01HL142711); has received grant support from Amgen, Apple, and Boston Scientific; and has served as a scientific advisor to Apple and Blackstone Life Sciences. Dr. Januzzi is supported by the Hutter Family Professorship, is a Trustee of the American College of Cardiology, has received grant support from Novartis Pharmaceuticals and Abbott Diagnostics, consulting income from Abbott, Janssen, Jana Care, Novartis, Prevencio, and Roche Diagnostics, and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, and Takeda. Dr. Hibbert receives grant support from the National Heart, Lung and Blood Institute (RO1-AI138999-01, UO1-HL123022-06). The remaining authors have no relevant conflicts of interest to disclose. Ethics Approval Statement: The study was approved by the Partners Healthcare Institutional Review Board and informed consent was waived based on secondary use of data from medical record review.

Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Left ventricular (LV) thrombus is a feared complication of LV dysfunction associated with high rates of systemic embolism, morbidity, and mortality. Traditionally, LV thrombus has been associated with acute myocardial infarction (MI). However, with improvements in percutaneous coronary intervention

Although the concept of myocardial infarction (MI) occurring in the absence of coronary thrombus was first identified in 1939, it was 2007 before the term type 2 MI , referring to infarctions related to supply–demand imbalance, was first introduced into clinical practice [(1)][1]. Since then, our

Background: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proB...

The Global Registry of Acute Coronary Events (GRACE) and Thrombolysis In Myocardial Infarction (TIMI) risk scores are validated to predict risk of adverse outcomes among patients with type 1 myocardial infarction (MI). Type 2 MI (T2MI) is common and is associated with significant mortality, yet the

Type 2 myocardial infarction (T2MI) is recognized as a frequent cause of myocardial injury and is associated with a grave prognosis; 20% of patients will not survive beyond 1 year [(1)][1]. However, little is known about treatment patterns and prognosis among subgroups of T2MI patients. Women with

Background Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. Methods Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. Results The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002). Conclusion The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV. Electronic supplementary material The online version of this article (10.1186/s40425-019-0535-y) contains supplementary material, which is available to authorized users.

Myocarditis is a rare but potentially fatal complication of immune checkpoint inhibitors (ICI). Among broad populations, late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is used for diagnosis and risk prediction in patients with myocarditis. There are no data on the use

Introduction Sacubitril/valsartan (S/V) promotes reverse cardiac remodeling in patients with HFrEF. Neprilysin inhibition results in increase of several vasoactive peptides that may mediate effects of S/V, however its effects on atrial natriuretic peptide (ANP) are largely unknown. Effects of ANP are mediated by cyclic guanosine monophosphate (cGMP). Hypothesis Longitudinal change in ANP concentration following initiation of S/V is associated with reverse cardiac remodeling. Methods Within a prospective open-label study of initiation and titration of S/V in patients with HFrEF, this pre-specified sub-study included patients in whom ANP was measured from samples collected in protease inhibitors to minimize its degradation. Concentrations of ANP and cGMP were measured at baseline and serially through 12 months of treatment. Echocardiographic assessment of LVEF and left atrial volume index (LAVi) was performed at baseline, 6 and 12 months. Results Among 144 participants (mean age 64.5 years; LVEF 30.8%), median ANP concentration at baseline was 102 pg/mL. Following initiation of S/V, ANP increased steeply and consistently during the first 2 months, with a significant increase in log-transformed ANP concentration at Day 14 (from 4.60 pg/mL to 5.05 pg/mL; Δ = 0.453; P Conclusions Concentrations of ANP increase substantially after initiation of S/V in patients with HFrEF. Larger early increases in ANP after S/V initiation were associated with greater magnitude of reverse cardiac remodeling (PROVE-HF; NCT02887183).

IMPORTANCE: Similar to other patients with acute myocardial infarction, patients with type 2 myocardial infarction (T2MI) are included in several value-based programs, including the Hospital Readmissions Reduction Program and the Hospital Value-Based Purchasing Program. To our knowledge, whether nonischemic myocardial injury is being misclassified as T2MI is unknown and may have implications for these programs. OBJECTIVE: To determine whether patients with nonischemic myocardial injury are being miscoded as having T2MI and if this has implications for 30-day readmission and mortality rates. DESIGN, SETTINGS, AND PARTICIPANTS: Using the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code, we identified patients who were coded as having T2MI between October 2017 and May 2018 at Massachusetts General Hospital. Strict adjudication using the fourth universal definition of MI was then applied. MAIN OUTCOME AND MEASURES: Clinical adjudication of T2MI and 30-day readmission and mortality rates as a function of T2MI or nonischemic myocardial injury. RESULTS: Of 633 patients, 369 (58.3%) were men and 514 (81.2%) were white. After strict adjudication, 359 (56.7%) had T2MI, 265 (41.9%) had myocardial injury, 6 (0.9%) had type 1 MI, and 3 (0.5%) had unstable angina. Patients with T2MI had a higher prevalence of cardiovascular comorbidities than those with myocardial injury. Patients with T2MI and myocardial injury had high in-hospital mortality rates (10.6% and 8.7%, respectively; P = .50). Of those discharged alive (563 [88.9%]), 30-day readmission rates (22.7% vs 21.1%; P = .68) and mortality rates (4.4% vs 7.4%; P = .14) were comparable among patients with T2MI and myocardial injury. CONCLUSIONS AND RELEVANCE: A substantial percentage of patients coded as having T2MI actually have myocardial injury. Both conditions have high 30-day readmission and mortality rates. Including patients with high-risk myocardial injury may have substantial implications for value-based programs.

Patients with type 2 myocardial infarction (MI) related to supply-demand inequity are frequently encountered in clinical practice but, in the absence of evidence-based therapies, their prognosis remains poor; 5-year survival is less than 40%. Cardiac rehabilitation is associated with reduced all

Background When evaluating new reperfusion regimens for ST elevation MI, it is important to adjust for factors that influence the likelihood of achieving normal epicardial flow and complete ST resolution. Methods and Results A total of 610 patients from TIMI 14 contributed to the angiographic analyses. The electrocardiographic analyses were based on 544 patients from TIMI 14 and 763 patients from InTIME-II. For each hour from onset of symptoms to initiation of pharmacological reperfusion, the odds of achieving TIMI3 flow at 90min or complete ST resolution at 60–90min decreased significantly ( P =0·03). Anterior location of infarction was associated with a reduction in the odds of achieving TIMI3 flow or complete ST resolution. The use of abciximab as part of the reperfusion regimen significantly increased the odds of TIMI3 flow ( P =0·01) and ST resolution ( P

Background: Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related fatalities, but its incidence and associated patient and transfusion characteristics are poorly understood. To inform surgical transfusion practice and to begin mitigating perioperative TACO, the authors aimed to define its epidemiology. Methods: In this retrospective cohort study, the medical records of adult patients undergoing noncardiac surgery with general anesthesia during 2004 or 2011 and receiving intraoperative transfusions were screened using an electronic algorithm for identification of TACO. Those patients who were screened as high probability for TACO underwent rigorous manual review. Univariate and multivariate analyses evaluated associations between patient and transfusion characteristics with TACO rates in a before-and-after study design. Results: A total of 2,162 and 1,908 patients met study criteria for 2004 and 2011, respectively. The incidence of TACO was 5.5% (119 of 2,162) in 2004 versus 3.0% (57 of 1,908) in 2011 (P < 0.001), with comparable rates for men (4.8% [98 of 2,023]) and women (3.8% [78 of 2,047]) (P = 0.09). Overall, vascular (12.1% [60 of 497]), transplant (8.8% [17 of 193]), and thoracic surgeries (7.2% [10 of 138]) carried the highest TACO rates. Obstetric and gynecologic patients had the lowest rate (1.4% [4 of 295]). The incidence of TACO increased with volume transfused, advancing age, and total intraoperative fluid balance (all P < 0.001). Conclusions: The incidence of perioperative TACO is similar to previous estimates in nonsurgical populations. There was a reduction in TACO rate between 2004 and 2011, with incidence patterns remaining comparable in subgroup analyses. Future efforts exploring risk factors for TACO may guide preventive or therapeutic interventions, helping to further mitigate this transfusion complication.

Objective To develop an algorithm for the discovery of drug treatment patterns for endocrine breast cancer therapy within an electronic medical record and to test the hypothesis that information extracted using it is comparable to the information found by traditional methods. Materials The electronic medical charts of 1507 patients diagnosed with histologically confirmed primary invasive breast cancer. Methods The automatic drug treatment classification tool consisted of components for: (1) extraction of drug treatment-relevant information from clinical narratives using natural language processing (clinical Text Analysis and Knowledge Extraction System); (2) extraction of drug treatment data from an electronic prescribing system; (3) merging information to create a patient treatment timeline; and (4) final classification logic. Results Agreement between results from the algorithm and from a nurse abstractor is measured for categories: (0) no tamoxifen or aromatase inhibitor (AI) treatment; (1) tamoxifen only; (2) AI only; (3) tamoxifen before AI; (4) AI before tamoxifen; (5) multiple AIs and tamoxifen cycles in no specific order; and (6) no specific treatment dates. Specificity (all categories): 96.14%–100%; sensitivity (categories (0)–(4)): 90.27%–99.83%; sensitivity (categories (5)–(6)): 0–23.53%; positive predictive values: 80%–97.38%; negative predictive values: 96.91%–99.93%. Discussion Our approach illustrates a secondary use of the electronic medical record. The main challenge is event temporality. Conclusion We present an algorithm for automated treatment classification within an electronic medical record to combine information extracted through natural language processing with that extracted from structured databases. The algorithm has high specificity for all categories, high sensitivity for five categories, and low sensitivity for two categories.