Search

As multigene panel testing for hereditary cancer syndromes becomes commonplace, germline mutations in genes other than BRCA1/2 are increasingly identified in breast cancer patients. While histopathologic features of BRCA-mutated breast cancers have been well-characterized, less is known about non-BRCA-related hereditary cancers. We herein investigate the clinicopathologic characteristics of breast cancers in women with non-BRCA germline mutations. Out of 612 women who underwent germline testing, 16 (2.6%) women with 18 cancers had mutations in non-BRCA genes: ATM, CHEK2, PALB2, TP53, BMPR1A, BRIP1, MUTYH, and RAD50. An additional 2 cancers were identified in a woman with a diagnosis of Bloom syndrome (BLM mutation) who was not germline tested. Average age at diagnosis was 50 (range: 27-77), and 65% had no personal cancer history. The majority (79%) of tumors were grade 1 to 2; 35% were either lobular or ductal with lobular features. Stromal responses varied from absent to desmoplastic to sclerotic; 69% of cases had an in situ component. With the exception of a brisk lymphocytic response in BLM- and TP53-mutated cancers, lymphocytic infiltration was mild or absent. In summary, the majority of non-BRCA-related hereditary breast cancers represent the patient's sentinel malignancy. Lobular features were seen in a subset, and high-grade, immunogenic carcinomas were uncommon except in the setting of BLM and TP53 mutations. Overall, these findings demonstrate a range of involved genes in non-BRCA mutation carriers with breast cancer and histopathologic heterogeneity in the associated cancers, arguing against use of histomorphology to inform panel testing algorithms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Targeted inhibition of programmed cell death-1 (PD-1) and its ligand (PD-L1) has emerged as first-line therapy for advanced non-small cell lung cancer. Although patients with high PD-L1 expression have improved outcomes with anti-PD-1/PD-L1-directed therapies, use as a predictive biomarker is complicated by robust responses in some patients with low-level expression. Furthermore, reported PD-L1 levels in lung cancers vary widely, and discrepancies exist with different antibodies. PD-L1 expression was thus compared by immunohistochemistry (IHC) versus RNA in situ hybridization (ISH) in 112 lung cancers by tissue microarray: 51 adenocarcinoma, 42 squamous cell carcinoma, 9 adenosquamous carcinoma, 5 carcinoid, 3 undifferentiated large cell carcinoma, 1 large cell neuroendocrine carcinoma, and 1 small cell carcinoma. At least 1% tumor cell staining was considered positive in each modality. A positive concordance of only 60% (67/112) was found between IHC and ISH. Fifty percent (56/112) were positive by IHC and 50% (56/112) by ISH; however, 20% (22/112) were ISH positive but IHC negative. Conversely, 21% (23/112) were IHC positive but ISH negative. There was no significant stratification of PD-L1 positivity by histologic subtype. A trend of more PD-L1-positive stage I cancers identified by ISH versus IHC was observed but was not statistically significant (50% [27/54] by IHC and 64% [35/55] by ISH, P = .18). No significant difference in survival was identified, with an average of 5.3 months in IHC versus 5.2 months in ISH-positive cases. The results demonstrate discordance between PD-L1 RNA levels and protein expression in non-small cell lung cancers, warranting comparison as predictive biomarkers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Determine effects of evidence-based clinical decision support (CDS) on the use and yield of computed tomographic pulmonary angiography for suspected pulmonary embolism (CTPE) in Emergency Department (ED) patients., Methods: This multi-site prospective quality improvement intervention conducted in three urban EDs used a pre/post design. For ED patients aged 18+years with suspected PE, CTPE use and yield were compared 19months pre- and 32months post-implementation of CDS intervention based on the Wells criteria, provided at the time of CTPE order, deployed in April 2012. Primary outcome was the yield (percentage of studies positive for acute PE). Secondary outcome was utilization (number of studies/100 ED visits) of CTPE. Chi-square and statistical process control chart assessed pre- and post-intervention differences. An interrupted time series analysis was also performed., Results: Of 558,795 patients presenting October 2010-December 2014, 7987 (1.4%) underwent CTPE (mean age 52±17.5years, 66% female, 60.1% black); 34.7% of patients presented pre- and 65.3% post-CDS implementation. Overall CTPE diagnostic yield was 9.8% (779/7987 studies positive for PE). Yield increased a relative 30.8% after CDS implementation (8.1% vs. 10.6%; p=0.0003). There was no statistically significant change in CTPE utilization (1.4% pre- vs. 1.4% post-implementation; p=0.25). A statistical process control chart demonstrated immediate and sustained improvement in CTPE yield post-implementation. Interrupted time series analysis demonstrated the slope of PE findings versus time to be unchanged before and after the intervention (p=0.9). However, there was a trend that the intervention was associated with a 50% increased probability of PE finding (p=0.08), suggesting an immediate rather than gradual change after the intervention., Conclusions: Implementing evidence-based CDS in the ED was associated with an immediate, significant and sustained increase in CTPE yield without a measurable decrease in CTPE utilization. Further studies will be needed to assess whether stronger interventions could further improve appropriate use of CTPE., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The objective was to determine whether sex was independently associated with door to ST-elevation myocardial infarction (STEMI) activation time. We hypothesized that women are more likely to experience longer delays to STEMI activation than men., Methods: We conducted a retrospective cohort study of adults ≥18 years who underwent STEMI activation at 3 urban emergency departments between 2010 and 2014. The Wilcoxon rank sum test and logistic regression were used to compare men and women regarding time to activation and proportion with times <15 minutes, respectively., Results: Of 400 eligible patients, we excluded 61 (15%) with prehospital activations, 44 (11%) arrests, and 3 (1%) transfers. Of the remaining 292 patients, mean age was 61±13 years, 64% were men, 57% were black, and 37% arrived by ambulance. Median door to STEMI activation time was 7.0 minutes longer for women than for men (25.5 vs 18.5 minutes, P=.028). In addition, men were more likely than women to have a door to STEMI activation time <15 minutes (45% vs 28%, P=.006). After adjusting for race, hospital site, Emergency Severity Index triage level, arrival mode, and chief concern of chest pain, the odds of men having STEMI activation times <15 minutes were 1.9 times more likely than women., Conclusions: Women have longer median door to STEMI activation times than men. A significantly lower proportion of women (28% vs 45%) are treated per American Heart Association guidelines of door to STEMI activation <15 minutes when compared with men, adjusting for confounders. Further investigation may identify possible etiology of bias and potential areas for intervention., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Research on how race affects access to analgesia in the emergency department (ED) has yielded conflicting results. We assessed whether patient race affects analgesia administration for patients presenting with back or abdominal pain., Methods: This is a retrospective cohort study of adults who presented to 2 urban EDs with back or abdominal pain for a 4-year period. To assess differences in analgesia administration and time to analgesia between races, Fisher exact and Wilcoxon rank sum test were used, respectively. Relative risk regression was used to adjust for potential confounders., Results: Of 20,125 patients included (mean age, 42 years; 64% female; 75% black; mean pain score, 7.5), 6218 (31%) had back pain and 13,907 (69%) abdominal pain. Overall, 12,109 patients (60%) received any analgesia and 8475 (42%) received opiates. Comparing nonwhite (77 %) to white patients (23%), nonwhites were more likely to report severe pain (pain score, 9-10) (42% vs 36%; P < .0001) yet less likely to receive any analgesia (59% vs 66%; P < .0001) and less likely to receive an opiate (39% vs 51%; P < .0001). After controlling for age, sex, presenting complaint, triage class, admission, and severe pain, white patients were still 10% more likely to receive opiates (relative risk, 1.10; 95% confidence interval, 1.06-1.13). Of patients who received analgesia, nonwhites waited longer for opiate analgesia (median time, 98 vs 90 minutes; P = .004)., Conclusions: After controlling for potential confounders, nonwhite patients who presented to the ED for abdominal or back pain were less likely than whites to receive analgesia and waited longer for their opiate medication., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: We sought to determine the impact of 3 validated scales of physician risk behavior on imaging use in emergency department (ED) patients with abdominal pain., Methods: We performed a prospective cohort study of nonpregnant ED patients with acute, nontraumatic abdominal pain and then administered 3 instruments (a risk-taking subscale of the Jackson Personality Index, the stress from uncertainty scale, and a malpractice fear scale) to attending physicians who had evaluated these patients and made decisions regarding abdominal imaging. Outcomes were the use of abdominal pelvic computed tomography (CT) and any imaging use (CT, ultrasound, or abdominal plain film). Hierarchical logistic regression was used to determine the effect of risk scales on abdominal imaging use., Results: Of 838 patients with acute abdominal pain, 487 (58%) received imaging studies; 395 (47%) received an CT, 111 (13%) ultrasound, and 122 (15%) an abdominal plain film. Both CT and any imaging use were lower among the physicians who were least risk-averse as measured by the risk-taking subscale (highest quartiles vs 3 lower quartiles). In adjusted analysis, probability of CT in the least risk-averse group was 35% (95% confidence interval [CI], 28%-44%) compared to 50% (95% CI, 45%-54%) among more risk-averse physicians, and the probability of any imaging was 53% (95% CI, 44%-61%) compared to 64% (95% CI, 61%-68%). Malpractice fear and stress due to uncertainty were not predictive of imaging use., Conclusion: Self-reported physician risk-taking behavior predicts the use of imaging in ED patients with abdominal pain, whereas malpractice fear and stress due to uncertainty do not.

Objective: We hypothesized adult parenting smokers in the emergency department (ED) have a higher interest in quitting and may be more amenable to tobacco cessation counseling than smokers without children., Study Design: Cross-sectional survey study of adult smokers in 8 US academic EDs., Results: One thousand one hundred sixty-eight smokers enrolled, 441 (37.8%) with household children (total of 973 exposed children). Compared to smokers without household children, smokers with children were younger (mean age, 37.4 vs 42.8 years), more female (60.3% vs 40.3%), and nonwhite (57.5% vs 44.5%) (all P < .006). Groups did not differ in nicotine addiction (median Fagerstrom score, 4 vs 4; P = .31). Parenting smokers were more interested in quitting (mean Ladder of Contemplation score, 4.8 vs 5.1 [P = .02]), felt it more important to quit (median score, 9 vs 8 [P = .01]), and more confident to quit (7 vs 6 [P = .004]) than nonparenting smokers. Smoking inside the home was banned by 45% of smokers with children vs 30% without household children (P < .001)., Conclusions: Adult ED parenting smokers are interested in quitting and taking steps to limit their children's secondhand smoke exposure. Asking adult ED smokers about household children may enhance motivation to quit.

Objective: The objective of the study was to develop a simple prediction rule to reliably identify abdominal pain patients with diarrhea who may require surgical intervention., Methods: We performed a secondary analysis of a prospective cohort study of adults with acute nontraumatic abdominal pain and diarrhea in an urban emergency department (ED). Structured data collection included 109 historical and 28 physical examination items, laboratory and radiographic results, and final diagnosis. The main outcome was operative intervention., Results: One thousand patients were enrolled; 174 patients with diarrhea were included in this analysis. Patients had a mean age of 39 +/- 16 years and were likely to be female (64%) and black (60%). Fifteen (9%) patients received a surgical intervention from the ED. Clinical variables associated with the need for surgical intervention using univariate analysis were age older than 40 years, constant pain, and peritonitis on examination. Using recursive partitioning multivariate analysis, the derived prediction rule included 2 variables: age older than 40 years and constant pain. This rule had a sensitivity of 1.0 (95% confidence interval, 0.78-1.0) and specificity of 0.23 (95% confidence interval, 0.16-0.30)., Conclusion: Patients older than 40 years with constant abdominal pain and diarrhea are likely to have a surgical cause of their symptoms.

Objective: We hypothesized that emergency physicians would use more resources to evaluate acute abdominal pain in obese patients as compared with that in nonobese patients., Methods: We conducted a secondary analysis of a prospective cohort of adults with acute abdominal pain. Collected data included self-reported height and weight, demographics, medical history, laboratory and x-ray results, and final diagnosis. We followed the patients until they obtained their final diagnosis or for up to 21 days. Patients were grouped according to their body mass index (BMI): nonobese (BMI < 30 kg/m2), obese (BMI = 30-40 kg/m2), and morbidly obese (BMI > 40 mg/m2). The main outcome measure was laboratory and radiographic testing. chi2 Tests and analysis of variance were used as appropriate., Results: Of the 971 patients (mean age, 41 years; 62% black; 65% female), 665 (68%) were nonobese, 246 (25%) were obese, and 60 (6%) were morbidly obese. In comparing nonobese patients with obese patients, we found no difference in laboratory or radiographic testing (3.20 vs 3.21 tests; mean difference, 0.004; 95% confidence interval [CI], -0.26 to 0.27), physicians' pre-computed tomographic scan confidence level in their diagnosis (6.17 vs 6.04, mean difference, -0.13; 95% CI, -0.76 to 0.49), and emergency department (ED) length of stay (LOS; 7.40 vs 7.57 hours; mean difference, -0.17; 95% CI, -0.49 to 0.83). In comparing all 3 groups, we found no difference in diagnostic testing, ED LOS, surgical intervention (10% vs 5% vs 9%, P = .2), disposition, and final diagnosis (P > .05)., Conclusions: Physicians do not use more resources to identify the etiology of acute abdominal pain in obese patients as compared with that in nonobese patients. Furthermore, ED LOS, likelihood of surgical intervention, physicians' confidence level in their preimaging diagnosis, and final diagnosis do not appear to be influenced by BMI.

Study Objective: Despite creatinine clearance (CrCl) being a better estimate of renal function, serum creatinine (Cr) is more commonly used to screen for renal insufficiency in patients scheduled for an enhanced abdominal computed tomography (CT) in an attempt to reduce the likelihood of contrast-induced nephropathy (CIN). Our objective was to determine the incidence of renal insufficiency (a CrCl <60 mL/min) among patients who have serum Cr below 1.5 mg/dL (the most commonly accepted Cr cutoff for the administration of intravenous contrast). This study was conducted in a population of emergency department patients with acute abdominal pain being considered for CT scan., Methods: We performed post hoc analysis of a prospective cross-sectional study that enrolled nongravid adults with acute nontraumatic abdominal pain. Patients on dialysis were excluded. The data that we collected included demographics, history, duration/description of pain, patient reported weight, laboratory data, imaging studies, and final diagnosis. Creatinine clearance values (< or >60 mL/min) were compared to Cr values of 1.0, 1.2, 1.5, and 1.8 mg/dL to determine the percentage of patients at risk for nephropathy after contrast injection at each Cr cutoff. Descriptive statistics were used with 95% confidence intervals (CIs)., Results: Seven hundred sixty-five patients were enrolled; 59% (451/765) had an abdominal CT scan. Of 108 patients with CrCl less than 60 mL/min, 59 patients had a Cr less than 1.8 mg/dL (55%; 95% CI, 45%-64%); 43 had a Cr less than 1.5 mg/dL, the most commonly accepted Cr cutoff for contrast administration (40%; 95% CI, 31%-50%); 21 patients had a Cr less than 1.2 mg/dL (19%; 95% CI, 12%-28%); and 10 had a Cr less than 1.0 mg/dL (9%; 95% CI, 5%-16%)., Conclusion: The most commonly used Cr cutoff (1.5 mg/dL) for contrast administration fails to identify 40% of the patients at risk for CIN. Future studies should address whether using CrCl rather than serum Cr decreases the incidence of contrast-induced nephropathy.