Research Spotlight

Posted December 15th 2016

HLA compatibility assessment and management of highly sensitized patients under the new kidney allocation system (KAS): A 2016 status report from twelve HLA laboratories across the U.S.

Lynne Klingman M.T.

Lynne Klingman M.T.

Kamoun, M., D. Phelan, H. Noreen, N. Marcus, L. Klingman and H. M. Gebel (2016). “Hla compatibility assessment and management of highly sensitized patients under the new kidney allocation system (kas): A 2016 status report from twelve hla laboratories across the u.S.” Hum Immunol: 2016 Nov [Epub ahead of print].

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Twelve HLA laboratories were surveyed to assess the methods and operational issues involved to define highly sensitized patients and to assess HLA compatibility under the new kidney allocation system (KAS) in the U.S. All laboratories used single antigen bead assays both pre- and post-KAS to define both broad and allele-specific HLA antibodies. The methods and threshold used to list HLA unacceptable antigens in UNet for virtual crossmatch (vXM) and the criteria used for determining HLA compatibility varied among laboratories. Laboratories reported several limitations of the current assays including the accuracy of quantifiable antibody fluorescence values, inadequate coverage of common alleles on the bead panels, and challenges in calibrating the vXM. The new KAS has resulted in a significant surge of deceased donor organ offers requiring vXM evaluation under tight time constraints. In the post-KAS period, eight of twelve laboratories (67%) indicated that their center did not proceed to transplant based on vXM without a prospective lymphocyte crossmatch. In conclusion, HLA laboratories play a critical role in deceased donor allocation for highly sensitized patients under the new KAS. Significant opportunities exist to improve the methods used in the assessment of HLA compatibility to safely transplant highly sensitized patients.


Posted December 15th 2016

Mesenchymal stromal cell secretomes are modulated by suspension time, delivery vehicle, passage through catheter, and exposure to adjuvants.

Osman Mir M.D.

Osman Mir M.D.

Parsha, K., O. Mir, N. Satani, B. Yang, W. Guerrero, Z. Mei, C. Cai, P. R. Chen, A. Gee, P. J. Hanley, J. Aronowski and S. I. Savitz (2016). “Mesenchymal stromal cell secretomes are modulated by suspension time, delivery vehicle, passage through catheter, and exposure to adjuvants.” Cytotherapy: 2016 Nov [Epub ahead of print].

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BACKGROUND AIMS: Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections. METHODS: MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed. RESULTS: Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed. DISCUSSION: Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration.


Posted December 15th 2016

The Utilization of Robotic Pets in Dementia Care.

Jill L. Studley M.D.

Jill L. Studley M.D.

Petersen, S., S. Houston, H. Qin, C. Tague and J. Studley (2016). “The utilization of robotic pets in dementia care.” J Alzheimers Dis 55(2): 569-574.

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BACKGROUND: Behavioral problems may affect individuals with dementia, increasing the cost and burden of care. Pet therapy has been known to be emotionally beneficial for many years. Robotic pets have been shown to have similar positive effects without the negative aspects of traditional pets. Robotic pet therapy offers an alternative to traditional pet therapy. OBJECTIVE: The study rigorously assesses the effectiveness of the PARO robotic pet, an FDA approved biofeedback device, in treating dementia-related symptoms. METHODS: A randomized block design with repeated measurements guided the study. Before and after measures included reliable, valid tools such as: RAID, CSDD, GDS, pulse rate, pulse oximetry, and GSR. Participants interacted with the PARO robotic pet, and the control group received standard activity programs. Five urban secure dementia units comprised the setting. RESULTS: 61 patients, with 77% females, average 83.4 years in age, were randomized into control and treatment groups. Compared to the control group, RAID, CSDD, GSR, and pulse oximetry were increased in the treatment group, while pulse rate, pain medication, and psychoactive medication use were decreased. The changes in GSR, pulse oximetry, and pulse rate over time were plotted for both groups. The difference between groups was consistent throughout the 12-week study for pulse oximetry and pulse rate, while GSR had several weeks when changes were similar between groups. CONCLUSIONS: Treatment with the PARO robot decreased stress and anxiety in the treatment group and resulted in reductions in the use of psychoactive medications and pain medications in elderly clients with dementia.


Posted December 15th 2016

Effect of ceftriaxone and cefepime on high-dose methotrexate clearance.

Jon D. Herrington Pharm.D.

Jon D. Herrington Pharm.D.

Tran, H. X. and J. D. Herrington (2016). “Effect of ceftriaxone and cefepime on high-dose methotrexate clearance.” J Oncol Pharm Pract 22(6): 801-805.

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Numerous drug interactions with methotrexate have been identified, which can lead to serious life-threatening effects. Up to 90% of methotrexate is excreted unchanged in the urine with primary excretion dependent on organic anion transport in the renal proximal tubule. The two pathways responsible for methotrexate secretion are organic anion transport 1 and primarily organic anion transport 3. Penicillins undergo tubular secretion via organic anion transport, and cephalosporins are believed to also possess a similar risk when administered with methotrexate; however, there are no human studies observing this interaction with cephalosporins and methotrexate. Ceftriaxone undergoes biliary clearance and has low affinity for the same organic anion transports as methotrexate; therefore, ceftriaxone has a low potential to interact with methotrexate. Cefepime is primarily secreted by organic cation transport N2, and also has a low potential to interact with methotrexate. This case report describes the pharmacokinetic effect of concomitant beta-lactam therapy in a patient receiving high-dose methotrexate.


Posted December 15th 2016

Changing antiepileptic drug use for seizures in US neonatal intensive care units from 2005 to 2014.

Veeral N. Tolia M.D.

Veeral N. Tolia M.D.

Ahmad, K. A., S. J. Desai, M. M. Bennett, S. F. Ahmad, Y. T. Ng, R. H. Clark and V. N. Tolia (2016). “Changing antiepileptic drug use for seizures in us neonatal intensive care units from 2005 to 2014.” J Perinatol: 2016 Nov [Epub ahead of print].

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OBJECTIVE: Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period. STUDY DESIGN: Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014. RESULTS: Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate. CONCLUSIONS: Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.