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Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation
An, Dong Ai , Tønnesen, Hanne , Raveendran, Raviraj, Abdullah, Hairil Rizal , Pfeifer, Kurt , Maa, John, Finegan, Barry A. , Li, Emily, Webb, Ashley , Edwards, Angela F., Preston, Paul, Bentov, Nathalie , Richman, Deborah C. , Wong, Jean , Urman, Richard D , Warner, David O. , Chung, Frances

Anesthesia & Analgesia | November 25, 2019 | Volume: 131 | Issue: 3 | Pages: 955-968

10.1213/ane.0000000000004508 | PMID 31764157 Get It

Smokers are at increased risk for surgical complications. Despite the known benefits of smoking cessation, many perioperative health care providers do not routinely provide smoking cessation interventions. The variation in delivery of perioperative smoking cessation interventions may be due to limited high-level evidence for whether smoking cessation interventions used in the general population are effective and feasible in the surgical population, as well as the challenges and barriers to implementation of interventions. Yet smoking is a potentially modifiable risk factor for improving short- and long-term patient outcomes. The purpose of the Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation is to present recommendations based on current scientific evidence in surgical patients. These statements address questions regarding the timing and intensity of interventions, roles of perioperative health care providers, and behavioral and pharmacological interventions. Barriers and strategies to overcome challenges surrounding implementation of interventions and future areas of research are identified. These statements are based on the current state of knowledge and its interpretation by a multidisciplinary group of experts at the time of publication.
Focused Cardiac Ultrasonography for Left Ventricular Systolic Function
Prada, Gabriel , Fritz, Ashley Virginia , Restrepo-Holguín, Mariana , Díaz‐Gómez, José L. , Fritz, Ashley V, Díaz-Gómez, José L , Guru, Pramod

New England Journal of Medicine | November 20, 2019 | Volume: 381 | Issue: 21 | Pages: e36

10.1056/nejmvcm1802841 | PMID 31747728 Get It

Infections Are Associated with Higher Risk of Venous Thromboembolism in Hospitalized Children with Nephrotic Syndrome
Carpenter, Shannon L. , Sherman, Ashley , Selewski, David T. , Kallash, Mahmoud , Tran, Cheryl L. , Seamon, Meredith, Katsoufis, Chryso , Ashoor, Isa , Supe‐Markovina, Katarina , Hernandez, Joel D., Silva, Cynthia, Gonzalez, Nilka De Jesus, Formeck, Cassandra L. , Woll, Christopher , Geier, Pavel, Smoyer, William E. , Goldman, Jennifer L. , Vasylyeva, Tetyana L. , Gbadegesin, Rasheed , Devarajan, Prasad , Kerlin, Bryce A. , Rheault, Michelle N.

Blood | November 17, 2019 | Volume: 128 | Issue: 22 | Pages: 3811-3811

10.1182/blood.v128.22.3811.3811 Get It

Abstract Introduction: Although it is known that children with nephrotic syndrome (NS) are at greater risk for certain complications, the frequency of these complications and predisposing risk factors are poorly defined. In particular, nephrotic syndrome has long been considered a hypercoagulable state. Risk for development of venous thromboembolism (VTE) is known to be increased in the setting of an active infection. The objective of this study was to determine the prevalence of infection and VTE among a cohort of hospitalized children with NS, and the association of these complications on outcomes. Methods: Records of hospitalized children with NS admitted to any of 17 participating pediatric hospitals across North America from 2010-2012 were included. Data including demographics, clinical pattern of NS, renal biopsy results, number of hospitalizations, nephrotoxic medication usage, infection and VTE history were recorded. Descriptive statistics were used to determine prevalence of infection and VTE. Wilcoxon rank sum was used to perform comparisons between groups. Logistic regression analysis was utilized to determine predictors of VTE development. Results: Seven-hundred thirty hospitalizations occurred among 370 children. One-hundred forty-eight children (40%) had at least 1 infection with a total of 211 infectious episodes; 11 (3%) had VTE. Those with infection were more likely to have VTE (p = 0.0457). Infections associated with VTE were C. difficile (1 subject), methicillin sensitive S. Aureus (2), Streptococcus pneumoniae (1), and unknown (3). There were no differences between those with and without infection regarding gender or ethnicity. Those with infection were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008), and steroid resistant NS was more highly associated with infection than all other clinical diagnoses (steroid-sensitive NS, steroid-dependent NS, other) (p = 0.003). The most common types of infections encountered included peritonitis (23%), pneumonia (22%), and bacteremia (16%). Bacterial pathogens (Streptococcus pneumoniae 41%, Escherichia coli 16%, Clostridium difficile 10%) were most commonly identified. Children with VTE, infection, or both, also required significantly more days in hospital. The median hospital stay for those without infection was 5 days vs. 10 in those with infection (p< 0.0001). Similarly, median hospital days for those without VTE were 6 days as compared to 22 in those with VTE (p < 0.0001). Of those with infection, 13% had an ICU stay compared with 3.3% of those without. Those with VTE also had a median of 4 days in the intensive care unit as compared to 0 days in those without VTE (p < 0.0001). In a logistic regression analysis, only the number of ICU days was predictive of the presence of VTE (OR 1.074, 95% CI 1.013 - 1.138). Conclusions: Children with NS who are hospitalized have high rates of infection. While the rate of VTE was not high in this cohort, presence of VTE was associated with infection. Both infection and VTE were associated with longer hospitalizations and intensive care unit stays. Streptococcus pneumoniae remains the most commonly identified bacterial pathogen in children with nephrotic syndrome, though methicillin sensitive S. Aureus was identified in 2 of 11 patients with VTE. Further studies are needed to identify potentially modifiable risk factors that could minimize these complications in this already high risk population. Disclosures No relevant conflicts of interest to declare.
Convulsive Syncope Masquerading as Seizure After an Epidural Blood Patch
D’Souza, Ryan S. , Dahl, Ashley R, Watson, James C. , Watson, James, D'Souza, Ryan S , Warner, Nafisseh S.

Pain Medicine | November 14, 2019 | Volume: 21 | Issue: 3 | Pages: 646-651

10.1093/pm/pnz333 | PMID 31910260 Get It

Incidence and Outcomes of Pneumocystis pneumonia When Utilizing PCR-Based Diagnosis in Patients with Hodgkin Lymphoma Receiving Intensive Chemotherapy
Barreto, Jason N. , Thompson, Carrie A. , Sierzchulski, Amanda G. , Potter, Ashley , Tosh, Pritish K. , Mara, Kristin C. , Limper, Andrew H.

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 4052-4052

10.1182/blood-2019-122060 Get It

Background: The overall incidence of Pneumocystis Pneumonia (PJP) in lymphoma varies according to diagnosis, host factors and treatment rendered.(Carmona, et al. 2011) A meta-analysis suggested that prophylaxis is appropriate when the chance of incurring PJP is 3.5% or greater.(Green, et al. 2007) Accurately characterizing the incidence of PJP is further complicated by a transition in diagnostic methods from direct immunofluorescence assay (DFA) to a DNA-based polymerase chain reaction (PCR) technique.(Caliendo et al., 1998, Wilson JW, et al., 2011) The incidence of PCR-based diagnosis of PJP and the need for anti-Pneumocystis prophylaxis in patients diagnosed with Hodgkin lymphoma receiving chemotherapy requires further investigation. Methods: This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. Consecutive adult patients with a diagnosis of Hodgkin lymphoma receiving chemotherapy between January 2006 and August 2018 were evaluated. Patients with history of bone marrow transplant were excluded. Kaplan-Meier estimation was used to calculate the cumulative incidence of PJP with a 95% confidence interval. Cox proportional hazard models were used to demonstrate the strength of association between the independent variables and PJP rate. Results: The 506 included patients had a median (IQR) age of 40.3 (28.6, 59.7) years, 287 (56.7%) were male, and 470 (92.9%) were Caucasian. Further baseline demographics and clinical characteristics are described in table 1 with no significant differences between those diagnosed and those free from PJP. Chemotherapy combined with radiation therapy was prescribed for 163 (32.3%) patients while 342 (67.7%) patients received chemotherapy alone. Chemotherapy regimen distribution included 356 patients (70.4%) receiving bleomycin-containing chemotherapy. Median (IQR) total Bleomycin dose was 122 (IQR: 78, 178) Units. Bleomycin-containing combination chemotherapy regimen was not significantly associated with a higher risk for PJP when compared to other combination regimens (HR=1.59, 95% CI 0.55-4.62 p=0.40). Bleomycin-related lung compromise was suspected in 130 (25.7%) patients. Anti-pneumocystis prophylaxis was provided for 97 patients (n=39 a priori, 58 after chemotherapy initiation) and this was not significantly associated with a decreased incidence of PJP (HR=0.51, 95% CI 0.15-1.71, p=0.28). The cumulative incidence of PJP 1 year after start of chemotherapy was 6.2% (95% CI 3.8%-8.5%) and is shown in figure 1. Diagnosis of PJP occurred most commonly during the 2nd (n=8, 30.7%), 3rd (n=8, 30.7%), and 4th (n=7, 26.9%) cycles of chemotherapy. Trimethoprim-sulfamethoxazole was the only agent prescribed as PJP management. There were 10 (38%) patients with PCP that required ICU admission with 9 needing mechanical ventilation, 4 necessitating vasopressor support, and none requiring dialysis. Mortality 30-days from PJP diagnosis was 8% (n=2) with one death attributable to PJP infection. Conclusion: Cumulative incidence of PJP was 6.2% in patients receiving intensive chemotherapy for Hodgkin lymphoma. As the incidence is above the 3.5% threshold previously described, the clinician should consider the potential value of prophylaxis. Defining the overall utility of universal vs. targeted anti-pneumocystis prophylaxis requires further prospective, randomized investigation. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Trimethoprim/Sulfamethoxazole, Pentamidine isethionate, and dapsone will be discussed as prevention of Pneumocystis Pneumonia in the HIV-negative population
Prevalence and the Impact of Hypogammaglobulinemia in Newly Diagnosed, Untreated Diffuse Large B Cell Lymphoma
McCarthy, Ashley, Nowakowski, Grzegorz S. , Singh, Namrata , Mott, Sarah L. , Syrbu, Sergei , Habermann, Thomas M. , Feldman, Andrew L. , Slager, Susan L. , Witzig, Thomas E. , Farooq, Umar , Cerhan, James R. , Ballas, Zuhair K. , Link, Brian K.

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 1604-1604

10.1182/blood-2019-122737 Get It

Background: While there is evidence in the literature of increased prevalence of hypogammaglobulinemia in chronic lymphocytic leukemia (CLL), there are no studies evaluating the prevalence of hypogammaglobulinemia in newly diagnosed diffuse large B cell lymphoma (DLBCL) or the relationship between hypogammaglobulinemia and presentation or outcomes. The objective of this study was to examine the prevalence of hypogammaglobulinemia in newly diagnosed DLBCL patients and to test the hypothesis that DLBCL patients with baseline hypogammaglobulinemia have a distinct clinical profile and outcome. Methods: We obtained banked frozen sera from 200 newly diagnosed, treatment-naïve, DLBCL patients from the Lymphoma SPORE Molecular Epidemiology Resource (MER), a prospective cohort study conducted at the Mayo Clinic and the University of Iowa. IgG/A/M levels were measured using immunoturbidimetric assay whereas IgE level was measured using electrochemiluminescence immunoassay; deficiency was defined using standard reference ranges. IgE levels were considered deficient if &lt;2 UI/ml. The associations between Ig deficiencies and clinical factors were evaluated with Wilcoxon rank sum and chi-squared (Fisher's exact, where appropriate) tests. Event-free survival (EFS) was defined as time from diagnosis to progression, relapse, retreatment, or death, and EFS24 was defined as EFS at 24 months after diagnosis (achieve or failure to achieve EFS24). The association of Ig levels with EFS24 was estimated using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression, and with EFS, overall survival (OS), and lymphoma-specific survival (LSS) was estimated using Kaplan-Meier curves and hazard ratios (HR) and 95% CI from Cox regression. Results: The mean age (SD) of the cohort was 65.6 (13.4) years, 54% were males and 98% of the patients were white. Over a median follow-up of five years, there were 59 (29.5%) deaths. The prevalence of hypogammaglobulinemia, defined as any deficiency, in newly diagnosed, treatment-naïve DLBCL was 22.1% (44/199) in our cohort, and the most common Ig deficiency was for IgG (&lt;700 mg/dL, 13.5%), followed by IgM (&lt;40 mg/dL, 9.0%), IgE (&lt;2 UI/ml, 7.5%) and IgA (&lt;70 mg/dL, 4.0%) (Table1). There were no statistically significant differences between Ig deficient and non-deficient patients in terms of age at diagnosis, gender, stage, cell of origin, or MYC double hit status. However, median LDH levels were higher in Ig deficient patients (228 vs 194, p&lt;0.01). Any immunoglobulin deficiency was associated with inferior EFS (HR 1.94, 95% CI 1.16-3.24) (Figure 1) and OS (HR 2.02, 95% CI 1.17-3.49), and these associations were not attenuated after adjustment for the international prognostic index (IPI). Any Ig deficiency was also associated with failure to achieve EFS24 (OR=2.13, 95% CI 1.00-4.60) after adjusting for IPI. Conclusions: To the best of our knowledge, this is the first study to report the prevalence of hypogammaglobulinemia in treatment naïve DLBCL. We found that any Ig deficiency was not uncommon in our cohort and it was associated with an inferior EFS and OS in DLBCL patients. The prevalence of hypogammaglobulinemia in DLBCL patients seems to be lower than has been described in CLL patients. While the underlying relationship between these two immunologic disorders deserves further study, our findings highlight the interaction between global immune dysfunction and emergence of a clonal B cell process. Disclosures Nowakowski: Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding. Farooq:Celgene: Honoraria; Kite Pharma: Research Funding. Cerhan:NanoString: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees.
Newly Diagnosed AML Patient Samples Demonstrate High Degree of Concordance in Identification of Pathogenic Mutations By Next Generation Sequencing (NGS) Performed at Enrolling Institutions Compared to Central Laboratory Results in the Beat AML Master Trial
Borate, Uma , Ruppert, Amy S. , Yang, Fei , Caruthers, Sean, Zhao, Weiqiang , Vergilio, Jo‐Anne, Burd, Amy , Pavlick, Dean, Juckett, Luke, Stein, Eytan M. , Patel, Prapti A. , Baer, Maria R. , Schiller, Gary J. , Blum, William , Kovacsovics, Tibor , Litzow, Mark R. , Foran, James M. , Heerema, Nyla A. , Rosenberg, Leonard, Marcus, Sonja, Yocum, Ashley O. , Stefanos, Mona , Byrd, John C. , Byrd, John C. , Jones, Dan M. , Stock, Wendy , Druker, Brian J , Levine, Ross L. , Mims, Alice S , Byrd, John C

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 2145-2145

10.1182/blood-2019-131253 Get It

Background: NGS of myeloid mutations is an integral part of AML clinical decision-making. There is currently no information regarding concordance between NGS panels in AML using samples from the same patient across various platforms in different diagnostic laboratories. To study this important question, we analyzed NGS of myeloid mutations in diagnostic samples from The Beat AML Master Trial (BAMT) for newly diagnosed older AML patients, and compared variant calls made between institutional laboratories enrolling the study subject with those made by Foundation Medicine (FM), the central laboratory used for treatment assignment in this precision medicine trial. Methods: We identified newly diagnosed AML patient samples (peripheral blood (PB) and/or bone marrow (BM)) from 2 lead institutions in the BAMT(Ohio State, OSU and Oregon Health and Sciences University, OHSU) that were analyzed by both the institutional and by FM from Nov 15, 2016 to Apr 15, 2019. Samples sent to both laboratories >3 days apart were excluded. Samples were analyzed at the institutional laboratories using their respective NGS mutational panels and by FM using the FoundationOne®Heme(FMH) NGS panel which utilizes capture based sequencing. The OSU NGS assay utilizes sequencing on Illumina MiSeq. The OHSU NGS assay employs semiconductor-based sequencing (Ion Torrent PGM platform). The variant allele frequency (VAF) sensitivity for detection for all 3 laboratories range from 1-2%. We evaluated the ability to identify mutations in 8 genes : FLT3, IDH1/ 2, NPM1, TET2, DNMT3A, WT1 and TP53 used in treatment assignment in theBAMT. A detection cutoff of 2% was used to define the presence or absence of a mutation. Overall, agreement was defined as the number of times the local and central laboratories made the same call divided by the total number of patients. Sensitivity was defined as the number of present calls made locally divided by the number of present calls made centrally, and specificity as the number of absent calls made locally divided by the number of absent calls made centrally. The overall kappa statistic, controlling for institution, provided another measure of agreement between local and central calls, where a value of 1 indicates perfect agreement. Results: 194 patient samples were identified using methods above and analyzed locally at the screening institution (125 at OSU, 69 at OHSU) and centrally at FM. Type of tissue analyzed for variants between local site and FM were 59 PB, 129 BM, and 6 with BM/PB mismatch. Overall agreement in presence/absence calls between local and central results for each of the 8 genes was over 95% (Table 1). There was perfect agreement for NPM1. The sensitivity was above 94% for all genes except TP53 (88.6%) and WT1 (63.6%). Failure to detect a mutation locally was primarily due to reporting of all TP53 variants, including variants of unknown significance (VUS) (5) by FM as agreed upon in the study protocol, detection at low levels below local site sensitivity cutoff (1), detection of variants in a portion of gene not covered at the local site(1)and possible artifact (1). For the WT1 gene, discordance in 5 samples included VUS (3) reported by FM ,a variant detected in a portion of the gene not covered at the local site(1).and difference in leukemic tissue analyzed with mutation not detected by the central laboratory on a PB sample, and present at the institutional lab on a BM sample; affecting the overall agreement and specificity but not sensitivity. Specificity was at least 98% for each of the 8 genes. Finally, most discrepancies in reported mutations in FLT3 (n=2), IDH1 (n=1), IDH2 (n=2), DNMT3A (n=4) and TET2 (n=5) were due to reporting of VUS in one laboratory and not by another. Conclusion: Detection of pathogenic myeloid mutations using orthogonal assays showed a high degree of concordance for genes used in therapeutic assignment on the BAMT.The small number of discordant results, in TP53 and WT1, were attributed to the reporting of VUS. This study illustrates the importance of quality control and standardization as NGS continues to be widely utilized in AML for clinical decision making, with a variety of platforms across multiple laboratories. Our next steps involve evaluating the differences in VAFs reported between local and central laboratories when a given mutation is identified, as well as the potential reasons for observed differences and clinical implications of known pathogenic mutations vs putative VUS. Disclosures Borate: Daiichi Sankyo: Consultancy; AbbVie: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Pfizer: Consultancy. Vergilio:Foundation Medicine: Employment; Roche Holding AG: Equity Ownership. Stein:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo, Inc.: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma US, Inc: Membership on an entity's Board of Directors or advisory committees; Bioline: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees. Patel:France Foundation: Honoraria; Dava Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Baer:Astellas: Research Funding; Abbvie: Research Funding; AI Therapeutics: Research Funding; Forma: Research Funding; Incyte: Research Funding; Kite: Research Funding; Takeda: Research Funding. Stock:Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; UpToDate: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Schiller:Amgen: Other, Research Funding; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding; Bristol Myer Squibb: Research Funding; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; Agios: Research Funding, Speakers Bureau. Blum:AmerisourceBergen: Consultancy; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas,: Research Funding; Xencor: Research Funding; Forma: Research Funding. Kovacsovics:Pfizer: Research Funding; Jazz: Consultancy; Novartis: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding. Foran:Agios: Honoraria, Research Funding. Druker:Pfizer: Research Funding; OHSU (licensing fees): Patents & Royalties: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees ; Cepheid: Consultancy, Honoraria; Aileron Therapeutics: #2573, Constructs and cell lines harboring various mutations in TNK2 and PTPN11, licensing fees , Membership on an entity's Board of Directors or advisory committees; ALLCRON: Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Aptose Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Beta Cat: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; GRAIL: Equity Ownership, Other: former member of Scientific Advisory Board; Patient True Talk: Consultancy; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees, Other: Stock options; Beat AML LLC: Other: Service on joint steering committee; CureOne: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Gilead Sciences: Other: former member of Scientific Advisory Board; ICON: Other: Scientific Founder of Molecular MD, which was acquired by ICON in Feb. 2019; Monojul: Other: former consultant; Novartis: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Patents & Royalties: Patent 6958335, Treatment of Gastrointestinal Stromal Tumors, exclusively licensed to Novartis, Research Funding; Bristol-Myers Squibb: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Pfizer: Other: PI or co-investigator on clinical trial(s) funded via contract with OHSU., Research Funding; Merck & Co: Patents & Royalties: Dana-Farber Cancer Institute license #2063, Monoclonal antiphosphotyrosine antibody 4G10, exclusive commercial license to Merck & Co; Dana-Farber Cancer Institute (antibody royalty): Patents & Royalties: #2524, antibody royalty; Burroughs Wellcome Fund: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Patents & Royalties, Research Funding. Byrd:Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Acerta: Research Funding; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; Ohio State University: Patents & Royalties: OSU-2S. Levine:C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Isoplexis: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees; Qiagen: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Prelude Therapeutics: Research Funding; Novartis: Consultancy; Gilead: Consultancy; Lilly: Honoraria; Imago Biosciences: Membership on an entity's Board of Directors or advisory committees. Mims:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; PTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.
Management of Supraventricular Tachycardia in Pregnancy
Peterson, Ashley , Sharpe, Emily E. , Peterson, Ashley A, Arendt, Katherine W. , Sharpe, Emily E

Pain Medicine | November 13, 2019 | Volume: 21 | Issue: 2 | Pages: 426-428

10.1093/pm/pnz330 | PMID 31845980 Get It

Abstract Supraventricular tachycardia is a common arrhythmia in pregnancy. During labor and delivery, neuraxial analgesia is important to prevent arrhythmia recurrence. We present the case of a 27-year-old gravida 2 para 1 woman at 35 weeks’ gestation presenting with supraventricular tachycardia that converted to normal sinus rhythm with adenosine. To prevent recurrence of the arrhythmia, an early epidural was provided during labor to minimize catecholamine release.
ANGI-11. SEX DIFFERENCES IN IMAGING-BASED ASSESSMENT OF GLIOBLASTOMA INVASION
Grove, Rebecca, He, Lihong , Stokes, Ashley M. , Gonzalez, Ashlyn, Nespodzany, Ashley , Eschbacher, Jenny, Smith, Kris A. , McGee, Samuel C., Burns, Terence, Hu, Leland , Swanson, Kristin R. , Swanson, Kristin R , Massey, Susan Christine , Hawkins‐Daarud, Andrea , Jackson, Pamela , Grove, Rebecca, Bakken, Katrina K. , Mladek, Ann C. , Baxter, Leslie C. , Nakaji, Peter , Bendok, Bernard R. , Sarkaria, Jann N.

Neuro-Oncology | November 11, 2019 | Volume: 21 | Issue: Supplement_6 | Pages: vi32-vi32

10.1093/neuonc/noz175.121 Get It

Abstract INTRODUCTION Neuroimaging dogma for glioblastoma asserts that hyperintensity on T1Gd MRI reveals the bulk of the tumor, while T2/FLAIR signal indicates edema. However, it is unclear whether this edema results from immune response or increased tumor cells. Further, one significant driver of the known sex differences in glioblastoma may be differences in immune response, due to the X-linkage of many immune genes. Based on this, we hypothesized that assumptions regarding tumor cellularity in T2/FLAIR images should be tailored to the biological sex of the patient. METHODS Using a retrospective cohort of 18 primary glioblastoma patients receiving multiple image-localized biopsies (82 total) and standard MRI, we assessed: distance of biopsy from T1Gd and T2 areas; a pathologist’s score of percent tumor cell density; and an imaging-based invasion metric, D/ρ. This metric is derived from the biomathematical Proliferation-Invasion model of glioma growth, which features two parameters, net growth rate (ρ) and net invasion rate (D). Their ratio D/ρ is related to degree of invasion, and is estimated from volumetric measurements of MRI abnormalities. Additionally, 25 patient-derived xenograft models implanted in females were grown until moribund, at which point brains were excised and stained for DAPI (to show all cells) and Lamin (to highlight tumor cells). Image processing of lamin-stained sections defines contours of intensity correlating with cell density. RESULTS Outside both the T1Gd and T2 region, male patient biopsies had higher tumor cell densities than females. Males also tended to have higher invasion metrics. Although each set derived from different patients, preclinical metrics of invasion were positively correlated with clinical invasion in females but negatively correlated in males. CONCLUSION Our preliminary finding that cell distribution patterns correlate with imaging metrics differently between the sexes supports the hypothesis that the degree of tumor cell density represented on certain MRI sequences may be sex-specific.
NIMG-28. VALIDATION OF SINGLE-DOSE DSC-MRI PROTOCOLS FOR ROBUST PERFUSION ASSESSMENT IN BRAIN TUMORS
Quarles, C. Chad , Semmineh, Natenael , Fuentes, Alberto, Nespodzany, Ashley , Alhilai, Lea, Karis, John P. , Rand, Scott D. , Dardis, Chris, Braun, Kelly, Connelly, Jennifer , Hu, Leland , Boxerman, J. L., Stokes, Ashley M. , Bell, Laura C. , Prah, Melissa A. , Connelly, Jennifer , Zhou, Yuxiang , Schmainda, Kathleen M

Neuro-Oncology | November 11, 2019 | Volume: 21 | Issue: Supplement_6 | Pages: vi167-vi167

10.1093/neuonc/noz175.699 Get It

Abstract Dynamic susceptibility contrast (DSC) MRI measures of brain tumor cerebral blood volume (CBV) are able to predict grade, overall survival and response to treatment. Wide-spread acceptance of DSC-MRI has been challenged by the need to balance contrast agent dose and CBV accuracy. The goal of this study was to identify and validate single-dose, BTIP compliant, DSC-MRI protocols. Using a validated, patient-based DRO, we evaluated CBV accuracy across a range of acquisition parameters (field strength, TR, TE, flip angle, multi-echo acquisitions, dosing protocols) and post-processing steps. To validate the optimal protocols, we next collected DSC-MRI data following ASFNR’s recommended “double – dose” approach, where a single-dose preload (to minimize T1 effects) is given prior to a second bolus injection (for DSC-MRI data acquisition). The single-dose DSC-MRI data was collected during the preload bolus injection. Consistency of the derived CBV data, visual agreement and data characteristics (e.g. CNR) was statistically evaluated. When using a single-dose and routine single-echo pulse sequence, the DRO analysis found that a low flip angle (LFA = 30o) and 30ms TE provided the highest CBV accuracy (concordance correlation coefficient (CCC) = 0.92) and precision (coefficient of variation (CV) = 8.2%)). For comparison, the maximum accuracy found with the DRO utilizes a double-dose injection protocol and yielded a CCC of 0.98 and CV of 6.8%. Single-dose, multi-echo acquisitions provided higher accuracy than the LFA data and matched that found with the double-dose approach. In patients (data collection ongoing), the agreement between single-dose LFA (n > 40) or multi-echo (n > 40) based CBV values and the reference double-dose approach was very high (CCC > 0.94) and were statistically equivalent. Optimized single-dose DSC-MRI protocols provide highly accurate CBV data, use lower doses of contrast agent, and simplify scan procedures, indicating their potential for robust use in clinical practice and trials.