Schoen, Martin W.

University of Missouri: MOspace

October 11, 2016Missouri ACP 2015 Abstract Winnersmedicine2.missouri.edu/jahm/missouri-acp-2015-abstract-winners/The abstracts below represent the winners in the Residents and Medical Students categoriesat the 2015 Missouri ACP Chapter meeting.Winner, Resident Poster Contest Missouri ACP 2015Outcomes of Acute Myeloid Leukemia Induction with Addition of Cladribine. Martin W.Schoen, MD, MPH; James Braun Pharm.D; Susan Woelich Pharm.D. BCOP; Reshma RamlalMD; Carl E. Freter MD, Ph.D; FACP; Jack M. Lionberger MD, Ph.DIntroduction: A standard regimen for acute myeloid leukemia (AML) includes seven days ofcytarabine and three days of an anthracycline (7+3). At Saint Louis University (SLU), ourpreferred regimen is cytarabine 200mg/m  by continuous infusion, idarubicin 12mg/m  daily,and five days of cladribine 5mg/m  daily (IAC or ‘7+3+5’). This regimen was derived from aPolish Adult Leukemia Group (PALG) study that included patients ≤60 years old. The impact ofIAC on older patients is important to review considering cladribine adverse effects andoutcomes in this population have not been previously reported. Methods: Retrospectiveanalysis of patients who started IAC from July 2012 to August 2014 at SLU with follow-up untilSeptember 2015. Mortality, disease response, and adverse events were analyzed, withstratification by age and NCCN risk classification. Results: Of 44 patients identified, 27/44(61%) were ≥60 years old, 6/44 (14%) had abbreviated therapy (missing or reduced doses).Thirty-eight of 44 (86%) patients survived to hospital discharge, and 5 deaths occurred beforeday 28. Additionally, 5/6 of these early deaths occurred in patients aged 60 or older. NCCNstratification showed 7/44 (16%) favorable; 17/44 (39%) intermediate; and 20/44 (46%) poorrisk cases. Complete response (CR) occurred in 68% after first induction while 7% required asecond round, for a total CR rate of 75%. One-year overall survival was 26/44 (59%).Significantly more deaths (15/18 or 83%) occurred among patients ≥60 years old (OR 5.8, 95%CI 1.4-25), and among higher NCCN risk classes. No deaths occurred in favorable risk group,but 7/44 (41%) and 11/44 (55%) occurred in intermediate and high-risk strata, respectively(p=0.039 by Chi-Square test). Adverse events: Diarrhea occurred in 34/44 (77%) patients,26/44 (59%) developed rash, and 14/44 (32%) experienced mucositis/stomatitis. Intensive careunit admission occurred in 14/44 patients (32%). Fever was documented in 43/44 (98%)patients, of which 23/44 patients (52%) had a documented infection. For patients surviving todischarge (38/44), median hospitalization was 32 days, neutrophil recovery (ANC>500)occurred at a median of 28 days, and platelet recovery (>50,000) at 29 days. Conclusions:Addition of cladribine to cytarabine and idarubicin is an effective induction regimen for AMLwith similar rates of CR and treatment-related mortality compared to historical studies. Inpatients ≥60, this regimen deserves further study and could be an effective option in those withfavorable prognosis and limited co-morbidities. Continued survival analyses and investigation2 221/3of adverse events will help define the role of this regimen in induction chemotherapy for AML.Candida parapsilosis prosthetic valve endocarditis presenting as ST elevationmyocardial infarction. Ian Ross MD, Jaime Bolda MD, Gerome Escota MD. WashingtonUniversity in St. Louis. Introduction: Fungal prosthetic valve endocarditis is an uncommondisease, accounting for only 1.3-6% of all cases of infectious endocarditis1.  Candida albicansis the most common causative pathogen, and Candida parapsilosis is the most common non-albicans species2.  Fungal endocarditis embolizes more frequently than bacterial endocarditisand can rarely present as an ST elevation myocardial infarction. Case Description: A 57-year-old male with a history of aortic bileaflet mechanical prosthetic valve and intravenous drug usepresented to the ER with complaints of chest pain, syncope, and abdominal pain. An ECGshowed 2 mm ST elevations in the inferior leads. Immediate cardiac catheterization wasaborted due to coagulopathy. The patient’s myocardial infarction was managed medically.Echocardiography showed a 1.4×0.8 cm echogenic mass on the anterior leaflet of themechanical aortic valve. Subsequent imaging showed hemoperitoneum, superior mesentericartery and splenic mycotic aneurysms, as well as renal infarcts. Blood cultures grew Candidaparapsilosis. The patient was treated with micafungin and fluconazole and underwent valvereplacement. His aneurysms and hemoperitoneum were treated surgically. Discussion:Candida parapsilosis is an important pathogen in fungal endocarditis, and is especiallyprevalent in intravenous drug users3. Coronary septic embolism is a rare cause of STelevation myocardial infarction and was first described by Virchow4. It is estimated to occur inonly 0.5-10% of cases of infective endocarditis, and the left anterior descending artery is mostcommonly affected. Fungal endocarditis is associated with a higher incidence of embolicevents than bacterial endocarditis. Elements in the history and presentation that can aid indiagnosis include a history of intravenous drug use, valve replacement, or concurrentlyobserved embolic/hemorrhagic phenomena. Combined medical and surgical therapy is themainstay of treatment, with isolates usually susceptible to amphotericin and azole antifungals.Winner: 2015 ACP-Missouri Chapter Medical Student CompetitionAcid-sensing ion channels are required for amphetamine sensitization. ComronHassanzadeh, Qian Jiang, Xiangping Chu. Department of Basic Medical Science, School ofMedicine, University of Missouri-Kansas City, Kansas City, MO 64108Drug addiction is a persistent mental illness and there is no effective therapy for patients. Theprecise mechanisms underlying addictive responses have not been completely deciphered.Increasing evidence has been shown that ion channels in the brain reward circuits are believedto play a vital role in drug addiction. Recently, protons are identified as neurotransmitter andone of the candidate for sensing proton is acid-sensing ion channels (ASICs). ASICs arehighly expressed in brain reward circuits with ASIC1a and ASIC2 channels being thepredominant subtypes. These channels are enriched at synaptic sites and are critical for theregulation of normal synaptic transmission. Moreover, increasing evidence has indicated thatASICs contribute to the neuropsychiatric disorders. We and others have shown that ASICs areinvolved in cocaine addiction. Here, we hypothesized that amphetamine (AMPH), apsychostimulant similar to cocaine, may also impact the function of ASICs. Following IACUC2/3approval, adult wild-type (WT) C57BL/6J, ASIC1a and ASIC2 knock-out (KO) mice wereplaced in individual test chambers to allow accommodation to novel environment for 60minutes. They then received a single intraperitoneal (i.p) injection of AMPH and their locomotoractivities were recorded for 150 minutes. The experiment was repeated daily for a total of 5days. After a 2-week withdrawal period, the mice were brought back to the behavioral chamberfollowed by a final challenge i.p injection of AMPH at half dosage of pretreatment. Locomotoractivity to this challenge dose was measured for 150 min. Acute AMPH injection (1.0, 1.5, 2.0,and 3.0 mg/kg) induced a typical dose-dependent increase in locomotor activities in WT,ASIC1a and ASIC2 KO mice. However, the increase in locomotor activities were attenuated inASIC1a, but not ASIC2 KO mice as compared to WT mice. Repeated exposure of AMPHresulted in a progressive and persistent enhancement of locomotor response in all genotypes.All WT, ASIC1a and ASIC2 KO mice showed sensitization to AMPH. However, either ASIC1aor ASIC2 KO mice showed higher behavioral sensitization to AMPH than WT mice. Our dataprovides new understanding of the complex genetic and molecular mechanisms of ASICs inresponse to AMPH exposure. Thus, targeting ASICs might represent a novel therapeuticstrategy for drug addiction. Acknowledgement: This work was supported by NIH grantDA031259 to XPC.3/3

Missouri ACP 2015 Abstract Winners

https://mospace.umsystem.edu/xmlui/bitstream/10355/65858/1/AmericanJournalOfHospitalMedicine2016V8Iss4Schoen.pdf

Missouri ACP 2015 Abstract Winners

Abstract

Similar works

Full text

Available Versions

University of Missouri: MOspace