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African American Race Is Associated with Decreased Relapse-Free Survival in Immune Thrombotic Thrombocytopenic Purpura
Johnson, Andrew D. , Antun, Ana G., Farland, Andrew M., Metjian, Ara , Bagby, Kristin, Park, Yara, Ridder, Gustaaf de, Gibson, Briana, Eubanks, Susan, Akwaa, Frank, Kohli, Rahil, Upreti, Harsh Vardhan , Kocher, Nicole K. , Gangaraju, Radhika , Liu, Angela , Mazepa, Marshall , Davis, Elizabeth A. , Woods, Ryan R, Raval, Jay S. , Kasthuri, Raj S. , Liles, Darla , Kreuziger, Lisa Baumann , Sadler, J. Evan , Sridharan, Meera , Go, Ronald S. , McCrae, Keith R. , Lim, Ming Y , Zheng, X. Long , Cataland, Spero R. , Chaturvedi, Shruti

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 1066-1066

10.1182/blood-2019-131064 Get It

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal hematologic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ impairment. The incidence of iTTP is higher among African-Americans (AA), however, differences in presentation and outcomes have not been fully investigated. In a multi-center cohort of patients with iTTP from the United States Thrombotic Microangiopathy (USTMA) Consortium, we tested the hypothesis that AA race is an independent predictor of poor outcomes including iTTP related mortality and relapse. Methods: We queried data from the USTMA iTTP registry, which currently includes data from 785 individual patients from 15 institutions across the United States. Data from at least one iTTP episode are available for 734 patients. The cohort is 35.1% (N = 272) White, 58.7% (N = 455) African American, 0.4% (N=3) Asian, 1.8% (N=14) Hispanic, and 4.0 % (N=31) other/unknown race. We restricted our analyses to AA and White participants because of small numbers in the other groups. We compared presenting features and treatments using the chi-squared test and t-test for categorical and continuous variables, respectively. A relapse was defined as a recurrent iTTP episode occurring at least 30 days after last therapeutic plasma exchange. To evaluate relapse-free survival, we included only patients enrolled in the registry at their first TTP episode (144 White and 246 AA) since patients presenting with a relapse as their index episode are already confirmed to have relapsing iTTP. Kaplan Meier analysis was used to compare relapse-free survival in White and AA patients, and a Cox regression model was developed to evaluate the independent effect of race on relapse, adjusting for potential confounders including age, sex, and the use of rituximab. Results: Demographics and presenting features of 390 individuals (144 White and 246 AA) presenting with a first episode of iTTP are shown in Table 1. Presenting symptoms including fever, confusion, seizure, memory deficits, stupor, headache, stroke, chest pain, abdominal pain, fatigue, and dark urine were similar between Whites and AA except for petechiae, which were more frequently documented in Whites (28.8% vs 17.7%, p=0.011). Presenting laboratory studies were also comparable though AA had a higher rate of elevated serum troponin (50.6% vs 32.5%, p=0.003), lower hemoglobin level (8.27 ± 0.13 vs 8.81 ± 0.19, p=0.0176) and platelet count (20.3 ± 1.2 vs 26.2 ± 3.2, p=0.0432). In addition to therapeutic plasma exchange and corticosteroids, rituximab was administered to 23.7% of White patients and 22.7% of AA during their first iTTP episode (P=0.815). Median time to platelet count recovery (days of daily plasma exchange until normal platelet count for two consecutive days) was shorter in AA compared with White patients [5 (IQR 4, 10) vs. 8 (IQR 5, 14), log rank P = 0.004]. AA race remained a significant predictor of the shorter time to platelet count recovery [HR 1.44 (95% CI 1.12, 1.85), P=0.004] after adjusting for rituximab therapy [HR 0.60 (95% CI 0.0.46, 0.80), P<0.001], female sex [HR 0.95 (95% CI 0.73, 1.22), P=0.669], age [HR 0.99 (95% CI 0.99, 1.01), P=0.682], platelet count [HR 1.00 (95% CI 0.99, 1.04), P=0.820] and LDH at presentation [HR 1.00 (95% CI 1.00, 1.00), P=0.525]. Death during the first episode occurred in 8.9% of White patients and 5.5% of AA patients (P=0.206). Relapse-free survival after the first episode of iTTP was lower in AA than White patients (Figure 1). AA race was associated with the reduced relapse free survival [HR 1.79 (95% CI 1.08, 2.98), P=0.024] in a Cox regression model adjusted for age [HR 1.00 (95% CI 0.98, 1.01), P=0.683], sex [HR 0.96 (95% CI 0.60, 1.54), P=0.867], and rituximab therapy [HR 0.93 (95% CI 0.55, 1.59), P=0.806]. Conclusion: African Americans with iTTP have a higher relapse rate and shorter relapse free survival after the first episode of the disease compared with Caucasian patients, which is independent of age, sex and rituximab therapy. Contrary to our hypothesis, acute outcomes of iTTP (time to platelet count recovery and mortality) were not worse in AA patients. The factors contributing to the higher relapse rate in AA with iTTP need to be further investigated. Our findings suggest that AA patients may also benefit from closer follow up. Disclosures Farland: Sanofi: Membership on an entity's Board of Directors or advisory committees. Metjian:Sanofi: Membership on an entity's Board of Directors or advisory committees. Raval:Bayer, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Liles:Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell ; Novartis: Other: PI on clinical trial Sickle cell . Baumann Kreuziger:CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy. McCrae:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Zheng:Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Clotsolution: Other: Co-Founder; Shire/Takeda: Research Funding. Cataland:Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. Chaturvedi:Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy.
Cutaneous blastic plasmacytoid dendritic cell neoplasm arising in the context of TET2 and ZRSR2 mutated clonal cytopenias of unknown significance, secondary to somatic copy number losses involving CDK2NA/2NB and MTAP
Li, Marissa , Binder, Moritz , Carr, Ryan M. , Mangaonkar, Abhishek A. , Gangat, Naseema , Coltro, Giacomo , Tefferi, Ayalew , Dao, Linda N. , Peters, Margot S. , Chiu, April , Patnaik, Mrinal M. , Binder, Moritz , Carr, Ryan, Mangaonkar, Abhishek A. , Tefferi, Ayalew , Dao, Linda, Peters, Margot, Patnaik, Mrinal , Carr, Ryan M , Shah, Meera , Lasho, Terra L. , Li, Marissa M

American Journal of Hematology | November 9, 2019 | Volume: 95 | Issue: 2 | Pages: No page available

10.1002/ajh.25675 | PMID 31705546 Get It

Falsely elevated vancomycin-concentration values from enzyme immunoassay leading to treatment failure
Singer, Bridger, Stevens, Ryan W. , Westley, Benjamin , Nicolau, David P. , Stevens, Ryan W

American Journal of Health-System Pharmacy | November 7, 2019 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1093/ajhp/zxz258 | PMID 31697345 Get It

Abstract Purpose A case of vancomycin enzyme immunoassay (EIA) interference confirmed by high-performance liquid chromatography (HPLC) is described. Summary Therapeutic drug monitoring is standard of practice in vancomycin dosing and monitoring in order to maximize the pharmacodynamic effects and minimize toxicity. After a 52-year-old woman received 5 doses of vancomycin, serum concentrations continued to rise for several days in the absence of ongoing vancomycin administration. Despite persistently elevated vancomycin concentrations, the patient clinically deteriorated and required treatment with an alternative agent. Subsequently, serum concentrations were processed via HPLC and analyzed for percent protein binding. Confirmatory analysis revealed substantially lower concentrations by HPLC than were obtained by EIA and an abnormal elevation in protein binding. After discharge from the index admission, the patient returned 11 months later and had a dectectable vancomycin concentration by EIA prior to receipt of vancomycin. HPLC analysis confirmed the true concentration was undetectable. Though the exact interfering substance was not identified, the above discrepancy in concentrations between the two assay methods indicates the presence of assay interference, and adds to the available literature suggesting similar occurrences. This case is particularly troubling given that the level of interference was not such that it would lead a clinician to immediately suspect interference, and the patient experienced treatment failure. Conclusion Falsely elevated values for serum vancomycin concentration, measured by EIA, contributed to treatment failure in a patient. The substance presumably responsible for EIA interferences was not identified.
The Effectiveness of a Non-Invasive Shot Blocking Device for Reducing Pain of In-office Injections in Hand Surgery
Rinker, Brian, Atashroo, David, Wermeling, F. Ryan, Rinker, Brian D , Stout, Megan A.

HAND | November 6, 2019 | Volume: 16 | Issue: 6 | Pages: 770-775

10.1177/1558944719884655 | PMID 31690117 Get It

Background: The gate control theory asserts that non-painful stimuli can block pain perception. The ShotBlocker™ device is a plastic disk with blunt projections that rests on the skin, and we hypothesize that it will reduce pain during hand injections. Methods: This is a prospective randomized trial of 117 patients undergoing injections for common hand conditions. Patients were randomized into 3 groups: device, placebo (device with projections removed), and control. Patients recorded on an analog pain scale the pain severity of the injection, as well as their most recent tetanus shot. A normalized pain score was obtained from the difference between the injection and tetanus shot pain scores. The mean non-normalized and normalized scores for each treatment group were compared to the control group using the Wilcoxon signed rank test. Results: There were 91 women and 26 men. Common diagnoses included trigger finger (n = 53), DeQuervain’s tendonitis (n = 33), and basal joint arthritis (n = 22). The groups did not differ significantly in age, gender, or diagnosis. Mean pain score in the device group was 5.2 out of 10, and it was 5.7 for the control group. The normalized pain score in the device group was significantly lower than the control group. Normalized and non-normalized pain scores for the placebo group were not significantly lower than the control group. Conclusions: The shot blocking device effectively reduced pain of injection versus controls when pain scores were normalized for pain tolerance. The modified device did not reduce the pain of injection, suggesting that gate control is the mechanism of action.
Multicenter Study of the Treatment of Appendicitis in America
Eid, Ahmed , Young, Katelyn , Wild, Jeffrey, Kaafarani, Haytham M.A. , Ray-Zack, Mohamed D. , Kanaan, Tala , Lawless, Ryan A. , Cralley, Alexis , Crandall, Marie , Gök, Ali , Kasotakis, George , Ray-Zack, Mohamed, Kana'an, Tala, Yeh, D. Dante

Annals of Surgery | November 4, 2019 | Volume: 273 | Issue: 3 | Pages: 548-556

10.1097/sla.0000000000003661 | PMID 31663966 Get It

Objective: We sought to describe contemporary presentation, treatment, and outcomes of patients presenting with acute (A), perforated (P), and gangrenous (G) appendicitis in the United States. Summary Background Data: Recent European trials have reported that medical (antibiotics only) treatment of acute appendicitis is an acceptable alternative to surgical appendectomy. However, the type of operation (open appendectomy) and average duration of stay are not consistent with current American practice and therefore their conclusions do not apply to modern American surgeons. Methods: This multicenter prospective observational study enrolled adults with appendicitis from January 2017 to June 2018. Descriptive statistics were performed. P and G were combined into a “complicated” outcome variable and risk factors were assessed using multivariable logistic regression. Results: A total 3597 subjects were enrolled across 28 sites: median age was 37 (27–52) years, 1918 (53%) were male, 90% underwent computed tomography (CT) imaging, 91% were initially treated by appendectomy (98% laparoscopic), and median hospital stay was 1 (1–2) day. The 30-day rates of Emergency Department (ED) visit and readmission were 10% and 6%. Of 219 initially treated with antibiotics, 35 (16%) required appendectomy during index hospitalization and 12 (5%) underwent appendectomy within 30 days, for a cumulative failure rate of 21%. Overall, 2403 (77%) patients had A, whereas 487 (16%) and 218 (7%) patients had P and G, respectively. On regression analysis, age, symptoms >48 hours, temperature, WBC, Alvarado score, and appendicolith were predictive of “complicated” appendicitis, whereas co-morbidities, smoking, and ED triage to appendectomy >6 hours or >12 hours were not. Conclusion: In the United States, the majority of patients presenting with appendicitis receive CT imaging, undergo laparoscopic appendectomy, and stay in the hospital for 1 day. One in five patients selected for initial non-operative management required appendectomy within 30 days. In-hospital delay to appendectomy is not a risk factor for “complicated” appendicitis.
Recent Preoperative Concussion and Postoperative Complications: A Retrospective Matched-cohort Study
D’Souza, Ryan S. , Sexton, Matthew A. , Schulte, Phillip J. , Pasternak, Jeffrey J., Abcejo, Arnoley S., D'Souza, Ryan S

Journal of Neurosurgical Anesthesiology | October 25, 2019 | Volume: 33 | Issue: 3 | Pages: 221-229

10.1097/ana.0000000000000654 | PMID 31651548 Get It

Background: Physiological alterations during the perianesthetic period may contribute to secondary neurocognitive injury after a concussion. Methods: Patients exposed to concussion and who received an anesthetic within 90 days were matched to unexposed patients without concussion. Intraoperative and postoperative events were compared. Subgroup analyses assessed relationships among patients with a concussion in the prior 30, 31 to 60, and 61 to 90 days and their respective unexposed matches. To facilitate identification of potential targets for further investigation, statistical comparisons are reported before, as well as after, correction for multiple comparisons. Results: Sixty concussion patients were matched to 176 unexposed patients. Before correction, 28.3% postconcussion versus 14.8% unexposed patients reported postanesthesia care unit pain score≥7 (P=0.02); 16.7% concussion versus 6.5% unexposed patients reported headache within 90 days of anesthesia (P=0.02) and 23.5% of patients who received surgery and anesthesia within 30 days of concussion experienced headache within 90 days of anesthesia compared with 7.1% in the unexposed group (P=0.01). Patients who experienced concussion and had anesthesia between 31 and 60 days after injury had a postanesthesia care unit Richmond Agitation and Sedation Scale score of −1.61±1.29 versus a score of −0.2±0.45 in unexposed patients (P=0.002). After adjusting the P-value threshold for multiple comparisons, the P-value for significance was instead 0.0016 for the overall cohort. Our study revealed no significant associations with application of adjusted significance thresholds. Conclusions: There were no differences in intraoperative and postoperative outcomes in patients with recent concussion compared with unexposed patients. Before correction for multiple comparisons, several potential targets for further investigation are identified. Well-powered studies are warranted.
2432. Durability Against Antibiotics After Response to Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection
Pardi, Ryan, Pardi, Darrell S. , Khanna, Sahil , Saha, Srishti , Tariq, Raseen

Open Forum Infectious Diseases | October 23, 2019 | Volume: 6 | Issue: Supplement_2 | Pages: S841-S841

10.1093/ofid/ofz360.2110 Get It

Abstract Background Fecal microbiota transplantation (FMT) cures ~90% of patients with recurrent Clostridioides difficile infection (rCDI). Ongoing or repeated exposure to risk factors, especially antibiotics (a modifiable risk factor but often necessary), may lead to future CDI. However, it is not known if FMT provides durable protection against future CDI despite subsequent antibiotic exposure. We studied the long-term durability of FMT against antibiotic exposure post-FMT. Methods A retrospective cohort study of patients undergoing FMT via colonoscopy for rCDI from Sep 2012 - Jun 2018 was performed. Patients were followed up for 1 year after FMT; data regarding future CDI episodes (watery diarrhea with positive stool test after interim symptom resolution), healthcare exposure, systemic non-CDI antibiotics and acid blocker therapy were collected. Primary outcome was ‘durability’ of response to FMT (defined as no CDI within 1 year post-FMT). Descriptive statistics, Chi square test, Wilcoxon test and multivariate logistic regression were used as appropriate. Results The study included 460 patients; median age 57 years (range 18–94 years), 65.2% (300) female. Overall 31.6% (144) received antibiotics; median number of courses of antibiotics, 2 (range 1–7). Of those who received antibiotics, the incidence of future CDI was 24.3% (n = 34), compared with 9% (n = 28) of those who did not receive antibiotics (P < .001). Median time to first CDI episode post-FMT was 103 (range 5–338) days. Incremental antibiotic courses did not lead to increased risk of future CDI (comparing 1, 2 or ≥3 courses, p = .68). In patients with antibiotic exposure, age and risk factors were similar in patients with and without future CDI (Table 1). Amongst those without antibiotic exposure, inflammatory bowel disease (IBD) predicted future CDI (p = .02). After controlling for risk factors and comorbidities, antibiotic use (p = .004) and IBD (p = .02) independently increased risk of future CDI. Conclusion The majority of patients with rCDI have a durable response to FMT despite ongoing risk factors. These data suggest that three-fourth of patients who receive antibiotics after FMT do not develop future CDI. IBD and antibiotic exposure independently increase the risk of future CDI. Disclosures All authors: No reported disclosures.
Analysis of Temporal Trends and Variation in the Use of Defibrillation Testing in Contemporary Practice
Borne, Ryan T. , Randolph, Tiffany C., Wang, Yongfei , Curtis, Jeptha P. , Peterson, Pamela N., Masoudi, Frederick A. , Sandhu, Amneet , Zipse, Matthew M. , Thomas, Kevin L. , Kutyifa, V., Cha, Yong‐Mei , Hsu, Jonathan C. , Russo, Andrea M. , Hsu, Jonathan C , Peterson, Pamela N. , Desai, Nihar R.

JAMA Network Open | October 18, 2019 | Volume: 2 | Issue: 10 | Pages: e1913553

10.1001/jamanetworkopen.2019.13553 | PMID 31626314 Get It

IC‐P‐099: SUBJECT FACTORS RELATED TO CSF DYNAMICS CONFOUND MEASUREMENT OF CSF BIOMARKERS IN ADNI
Townley, Ryan , Gunter, Jeffrey L. , Wiste, Heather J. , Graff‐Radford, Jonathan , Senjem, Matthew L. , Jack, Clifford R. , Jones, David T.

Alzheimer's & Dementia | October 18, 2019 | Volume: 15 | Issue: 7S_Part_2 | Pages: No page available

10.1016/j.jalz.2019.06.4942 Get It

IC‐P‐078: ALTERED CSF DYNAMICS INFLUENCE DISCREPANCIES BETWEEN CSF AND PET BIOMARKERS OF AMYLOID
Gunter, Jeffrey L. , Townley, Ryan , Wiste, Heather J. , Graff‐Radford, Neill R. , Graff‐Radford, Jonathan , Senjem, Matthew L. , Jack, Clifford R. , Jones, David T.

Alzheimer's & Dementia | October 18, 2019 | Volume: 15 | Issue: 7S_Part_1 | Pages: No page available

10.1016/j.jalz.2019.06.4921 Get It