BACKGROUND Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies. OBJECTIVES This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States. METHODS In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates. RESULTS In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers. CONCLUSIONS In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891 )

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IMPORTANCE Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown. OBJECTIVE To determine whether stress CMR is associated with patient mortality. DESIGN, SETTING, AND PARTICIPANTS Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index. MAIN OUTCOMES AND MEASURES All-cause patient mortality. RESULTS Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P < .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P < .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P < .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (

A B S T R A C T PurposeCigarette smoking induces CYP1A1/1A2 and is hypothesized to alter erlotinib pharmacokinetics. This study aimed to determine the maximum tolerated dose (MTD) of erlotinib in advanced non-small-cell lung cancer (NSCLC) patients who smoke and compare the pharmacokinetics of erlotinib at the MTD in current smokers with 150 mg. Patients and MethodsCohorts of NSCLC patients currently smoking Ն 10 cigarettes per day for Ն 1 year received escalating doses of erlotinib for 14 days until dose-limiting toxicity (DLT). A separate cohort of patients was then randomly assigned to erlotinib at either MTD or 150 mg daily with pharmacokinetics assessed at day 14. Erlotinib was continued until progression or intolerable toxicity. ResultsFour dose levels were evaluated in 22 patients: 200, 250, 300, and 350 mg. DLT was observed in one of six patients at 300 mg (rash) and two of five patients at 350 mg (acneiform dermatitis and fatigue/decreased Eastern Cooperative Oncology Group performance status). Thirty-five patients were randomly assigned to 150 mg or 300 mg. Common adverse events (all grades) were: skin toxicity (150 mg, 29%; 300 mg, 67%), diarrhea (150 mg, 18%; 300 mg, 50%), and fatigue (150 mg, 12%; 300 mg, 17%). Erlotinib exposure was dose-proportional within dose range tested. Median steady-state trough erlotinib plasma concentrations were 0.375 and 1.22 g/mL for 150 mg and 300 mg, respectively. ConclusionThe MTD of erlotinib in NSCLC patients who smoke was 300 mg. Steady-state trough plasma concentrations and incidence of rash and diarrhea in smokers at 300 mg were similar to those in former or never smokers receiving 150 mg in previous studies. The potential benefit of higher erlotinib doses in current smokers warrants further evaluation.

The objective of this study was to examine the relationship between descriptors of breathlessness and its underlying cause in patients with lung cancer and cardiopulmonary diseases to see whether descriptors might be used to help determine the cause of breathlessness, particularly in patients with lung cancer. We studied 131 patients with primary or secondary lung cancer, whose breathlessness was attributed to tumor mass, pleural effusion, lung collapse, metastases, pleural thickening or lymphangitis carcinomatosis, and 130 patients with breathlessness attributed to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease or cardiac failure. Patients selected statements (descriptors) that described the quality of their breathlessness from a 15-item questionnaire and the relationship between the descriptors and the attributed cause of breathlessness was evaluated by cluster analysis. All patient groups were characterized by more than one cluster and several clusters were shared between groups. Specific sets of clusters were associated with breathlessness due to asthma, COPD and cardiac failure, and to cancer causing collapse, metastases or pleural thickening. The association of different sets of clusters with the different diagnostic groups suggests that patients are describing qualitatively different experiences of breathlessness, but the relationship does not appear to be sufficiently robust for the questionnaire to aid differential diagnosis.

AG337 administration was associated with increased tumor tracer retention that was consistent with tumor cell uptake of exogenous 2-[11C]thymidine as a result of TS inhibition. 2-[11C]Thymidine PET can be used to measure thymidine salvage kinetics directly in the tissue of interest.

Background Colorectal cancer surgery is complex and can result in severe post-operative complications. Optimisation of surgical outcomes requires a thorough understanding of the background complexity and comorbid status of patients. Aim The aim of this study is to determine whether certain pre-existing comorbidities are associated with high grade post-operative complications following colorectal cancer surgery. The study also aims to define the prevalence of demographic, comorbid and surgical features in a population undergoing colorectal cancer resection. Method A colorectal cancer database at The Prince Charles Hospital was established to capture detailed information on patient background, comorbidities and clinicopathological features. A single-centre retrospective study was undertaken to assess the effect of comorbidities on post-operative outcomes following colorectal cancer resection. Five hundred and thirty-three patients were reviewed between 2010–2018 to assess if specific comorbidities were associated with higher grade post-operative complications. A Clavien-Dindo grade of three or higher was defined as a high grade complication. Results Fifty-eight percent of all patients had an ASA grade of ASA III or above. The average BMI of patients undergoing resection was 28 ± 6.0. Sixteen percent of all patients experienced a high grade complications. Patients with high grade complications had a higher mean average age compared to patients with low grade or no post-operative complications (74 years vs 70 years, p = 0.01). Univariate analysis revealed patients with atrial fibrillation, COPD, ischaemic heart disease and heart failure had an increased risk of high grade complications. Multivariate analysis revealed pre-existing atrial fibrillation (OR 2.70, 95% CI 1.53–4.89, p <0.01) and COPD (OR 2.02 1.07–3.80, p = 0.029) were independently associated with an increased risk of high grade complications. Conclusion Pre-existing atrial fibrillation and COPD are independent risk factors for high grade complications. Targeted perioperative management is necessary to optimise outcomes.

BackgroundThere is a critical need for non-invasive methods to detect coronary allograft vasculopathy and to risk stratify heart transplant recipients. Vasodilator stress testing using cardiovascular magnetic resonance imaging (CMR) is a promising technique for this purpose. We aimed to evaluate the safety and the prognostic value of regadenoson stress CMR in heart transplant recipients.MethodsTo evaluate the safety, we assessed adverse effects in a retrospective matched cohort study of consecutive heart transplant recipients who underwent regadenoson stress CMR matched in a 2:1 ratio to age- and gender-matched non-heart transplant patients. To evaluate the prognostic value, we compared the outcomes of patients with abnormal vs. normal regadenoson stress CMRs using a composite endpoint of myocardial infarction, percutaneous intervention, cardiac hospitalization, retransplantation or death.ResultsFor the safety analysis, 234 regadenoson stress CMR studies were included - 78 performed in 57 heart transplant recipients and 156 performed in non-heart transplant patients. Those in heart transplant recipients were performed at a median of 2.74 years after transplantation. Thirty-four (44%) CMR studies were performed in the first two years after heart transplantation. There were no differences in the rates of adverse effects between heart transplant recipients and non-heart transplant patients. To study the prognostic value of regadenoson stress CMRs, 20 heart transplant recipients with abnormal regadenoson stress CMRs were compared to 37 with normal regadenoson stress CMRs. An abnormal regadenoson stress CMR was associated with a significantly higher incidence of the composite endpoint compared with a normal regadenoson stress CMR (3-year cumulative incidence estimates of 32.1% vs. 12.7%, p = 0.034).ConclusionsRegadenoson stress CMR is safe and well tolerated in heart transplant recipients, with no incidence of sinus node dysfunction or high-degree atrioventricular block, including in the first two years after heart transplantation. An abnormal regadenoson stress CMR identifies heart transplant recipients at a higher risk for major adverse cardiovascular events.