Citations

Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children’s Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children’s hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.

Background: Left atrial appendage occlusion with the Watchman device is an alternative strategy for stroke risk reduction in patients with non-valvular atrial fibrillation. There are rare case reports of Watchman associated infection. Currently, there is no formal study that evaluated the incidence and outcomes of Watchman-related infections. Methods: All patients who underwent Watchman implantation over a 14 year study period (July 2004 through December 2018) comprised our cohort. Baseline characteristics, procedural data, and post-implantation events were identified. Primary study outcomes included Watchman related infection, other cardiovascular device related infection, bacteremia, and mortality. Results: A total of 181 patients with an average age of 75, and a median CHA2DS2-VASc Score of 4 (interquartile range 2) and a median HAS-BLED Score of 3 (interquartile range 1), were included for analysis. A total of 534.7 patient years of follow up was accrued with an average of 2.9 years per patient. The most common indications for implantation included gastrointestinal bleeding (56 patients; 30.9%) and intracerebral bleeding (51 patients; 28.2%). During follow up, 38 patients (21%) died. Six developed evidence of bacteremia. Only one developed an implantable cardioverter defibrillator (ICD) infection that required complete system extraction. None of the cohort developed Watchman-related device infection during the study period. Conclusion: In a single center study spanning a 14 year period, we report no Watchman-related devices infections. This is despite the presence of patients with bacteremia, as well as an ICD infection requiring extraction. These data suggest that Watchman devices are extremely unlikely to become infected.

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA , PDGFRB or FGFR1 or with PCM1-JAK2 . In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

BACKGROUND Baseline expression of FCRL5 , a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS A previously validated quantitative PCR–based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6, 12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression ≥ 0.01 expression units (termed FCRL5 hi ) exhibited significantly higher CR rates at 6, 12, and 18 months as compared with FCRL5 lo subjects (84% versus 57% [ P = 0.016], 68% versus 40% [ P = 0.02], and 68% versus 29% [ P = 0.0009], respectively). CONCLUSION Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner. FUNDING The analysis for this study was funded by Genentech Inc.

Abstract Background: Racial disparities in breast cancer outcomes persist in the US, in which black women are more likely to die from breast cancer than white women. Despite levels of mammographic screening comparable to the US, Atlanta has a disproportionate burden of late-stage breast tumors and higher mortality rates, especially among black women. To better understand this disparity, we sought to identify tumor, treatment, and patient characteristics that may contribute to the observed differences in breast cancer mortality between black and white women in the metropolitan Atlanta area. Methods: In this study, patients were identified from the Georgia Cancer Registry. We included 4943 non-Hispanic white and 3580 non-Hispanic black women with an initial diagnosis of stage I-IV primary breast cancer between January 2010 and December 2014 in Atlanta. Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to compare black vs. white breast cancer mortality by tumor (stage, grade, ER status, and molecular subtype), treatment (surgery type, receipt of chemotherapy, radiation, hormone therapy, and trastuzumab), and patient (insurance, marital status, SES, and location of service) characteristics. We performed a mediation analysis to evaluate the contribution of subtype, stage, and socioeconomic status (SES) as mediators on the path between race and breast cancer mortality. Results: Compared with white breast cancer patients, black women were younger with tumors that were higher stage, higher grade, and more likely to be larger, node positive and triple negative. In fully adjusted models, black women diagnosed with Luminal A subtype were 58% more likely to die of breast cancer compared to their white counterparts (HR=1.58, 95%CI 1.31-2.00). Similarly, black women with private insurance were 60% more likely to die of breast cancer (HR=1.61, 95%CI 1.25-1.98), and black women in the highest SES group were more than twice as likely to die from breast cancer (HR=2.26, 95%CI 1.26-4.06) than white women with comparable SES. The smallest disparities in breast cancer mortality by race were observed among women without insurance, in the lowest SES index, or those diagnosed with triple-negative breast cancer. The mediation analysis showed 84.8% of the effect between race and breast cancer mortality was through stage, subtype, and SES. Conclusion: Our results indicate variation in racial disparities in breast cancer mortality by tumor and patient characteristics. Consistent with previous reports, our mediation results suggest that later stage and triple-negative subtype among black women are major contributors of the observed disparity. However, our results also shed new light on the disparity, suggesting that the largest disparities are observed among women with ER+ tumors amenable to adjuvant therapies and are most pronounced among women of high SES. More research is needed to understand the drivers of disparities in these treatable tumors. Citation Format: Lindsay J. Collin, Renjian Jiang, Kevin C. Ward, Keerthi Gogineni, Preeti D. Subhedar, Mark Sherman, Mia M. Gaudet, Carmen Radecki Breitkopf, Olivia D'Angelo, Sheryl Gabram-Mendola, Jolie Siegel, Rana Aneja, Anne Gaglioti, Lauren E. McCullough. Identification of factors contributing to breast cancer mortality disparities in the metropolitan Atlanta area [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C053.

Introduction: CBD is a major phytocannabinoid in hemp ( Cannabis sativa containing less than 0.3% THC). Hemp cigarettes are a combustible form of hemp consisting of dried and smokable flowers, which represent 2% of the overall CBD market, and the market is expected to grow. Combustion and pyrolysis of organic material are associated with the production of carbonyl compounds, which are known toxicants and are associated with adverse health outcomes. Concentrations of carbonyl compounds in mainstream hemp cigarette smoke are unknown. Materials and Methods: We analyzed and compared carbonyl concentrations in the mainstream smoke produced by a hemp cigarette (Brand B), a premium hemp cigarette (Brand A), Marlboro Red tobacco cigarette, and a research reference tobacco cigarette using high-performance liquid chromatography. We measured carbonyl concentrations in μg per puff and mg per cigarette. Carbonyls investigated were formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde, crotonaldehyde, 2-butanone, and butyraldehyde. Significance was determined using Tukey's test. Results: We observed that Brand B had significantly higher butyraldehyde than any cigarette. No significant differences were observed in crotonaldehyde concentration in the cigarettes. For the remaining carbonyls, Brand A had consistently lower concentrations in mainstream smoke than tobacco cigarettes. Hemp cigarettes emit carbonyls in a lower concentration in μg/puff than tobacco cigarettes, but the magnitude of significance generally decreases when normalized to mg/cigarette. Conclusions: Smoke from hemp cigarettes contains carbonyls at biologically significant concentrations. Opportunities may exist to reduce carbonyl production in these products, and identified potential risks must be considered when balancing the harms and benefits of hemp cigarettes when used for therapeutic purposes.

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non‐traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016. Seventy‐four patients in this cohort presented with non‐traumatic ICH. Medical records including imaging data were reviewed to identify those with CAA and record baseline variables and outcomes of interest; 38 of our 74 patients (51.4%) (mean age 81.5 years) met Modified Boston Criteria for possible or probable CAA. Twenty‐six of 74 patients (35%) died during the first 30 days while 56 of the 74 (76%) patients died by 10 years follow‐up after index ICH. Overall mortality was not significantly different between the CAA and non‐CAA groups at any point of time during follow‐up ( P =0.89) even amongst patients restarted on anticoagulation +/− antiplatelet (n=19) ( P =0.46) or those patients restarted only on antiplatelet therapy (n=22) ( P =0.66). Three of the 41 patients who restarted on antithrombotic therapy had a recurrent ICH; these 3 patients met criteria for possible or probable CAA. Conclusions Although more than half of our patients with atrial fibrillation on antithrombotic therapy and non‐traumatic ICH met Modified Boston Criteria for CAA, CAA did not significantly influence the high mortality seen in this cohort.

Abstract Trial Information Click here to access other published clinical trials. Lessons Learned The results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist. Background Regorafenib is a multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients. Methods Patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1. Results Forty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI], 0.92–3.67) months for regorafenib versus 2.07 (95% CI, 1.64–3.44) months for placebo; stratified hazard ratio [HR], 0.85 (95% CI, 0.46, 1.58), p = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI, 4.16–23.48) months for regorafenib and 4.89 (95% CI, 3.02–9.77) months for placebo, stratified HR, 0.66 (95% CI, 0.31–1.40), p = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib. Conclusion Regorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.

In this article, we describe the long-term outcomes of children who were previously reported to have developed hypophosphatemic bone disease in association with elemental formula use. An extended chart review allowed for an updated report of 34 children with regard to severity/duration of bone disease, extent of recovery, and time to correction using radiology reports and biochemical data. After implementation of formula change and/or phosphate supplementation, we found that serum phosphorus concentration increased and serum alkaline phosphatase activity decreased in all patients, normalizing by 6.6 ± 4.0 (mean ± SD) months following diagnosis. The decrease in serum alkaline phosphatase from diagnosis to the time of correction was moderately correlated with the concurrent increase in serum phosphorus ( R = 0.48, P < .05). Age at diagnosis significantly correlated with time to resolution ( R = 0.51, P = .01). This study supports the earlier report that bone disease associated with hypophosphatemia during elemental formula use responds to formula change and/or phosphate supplementation.

11006 Background: Interest in pursuing a career in oncology has decreased among internal medicine residents completing an inpatient oncology rotation. Over several years, our institutional data at Indiana University School of Medicine reflected lower resident satisfaction with the oncology inpatient ward rotation compared to other rotations. Methods: A hybrid model of inpatient consultations and outpatient clinics replaced the traditional inpatient oncology rotation at our institution. Over a six-month period preceding and following the change in format, residents completed anonymous rotation assessments and rated their experiences on a 5-point Likert scale (low 1 to high 5). Areas assessed included: patient load, educational value of patient mix, quality of didactics and teaching, quality of patient care delivery, adequacy of time for reading, and overall educational quality of the rotation. Results: The hybrid oncology rotation (8 respondents out of 10 residents approached) was rated as significantly superior to the traditional ward format (15 respondents out of 16 residents approached) in six out of eight areas. Improvements in the perceived quality of patient care delivery (p=0.139) and quality of didactics (p=0.058) were also observed without reaching statistical significance. The balance of inpatient and outpatient experiences with the hybrid rotation was highly rated (4.5 ± 0.5). Conclusions: The implementation of a hybrid oncology rotation was associated with perceived improvement in educational value, patient mix, and time for reflection and study without apparent compromise in the quality of patient care delivery. [Table: see text]