@article{ludwig_abraham_mckinney_freund_stewart_garman_barbas_sudan_gonzalez_2023, title={45: Comparison of the Effects of Normothermic Machine Perfusion and Cold Storage Preservation on Porcine Intestinal Allograft Regenerative Potential and Viability}, volume={107}, ISSN={0041-1337}, url={http://dx.doi.org/10.1097/01.tp.0000945636.34372.db}, DOI={10.1097/01.tp.0000945636.34372.db}, abstractNote={Historically, intestinal transplantation (IT) has been reserved as the last treatment option for patients with irreversible intestinal failure who are unable to tolerate total parenteral nutrition. Successful IT is reliant upon graft health at the time of donation, minimizing graft injury that may occur during procurement, storage, and IT, and the ability of the graft to heal following insult. Unfortunately, the intestine is easily damaged by ischemia-reperfusion injury (IRI). IRI induces intestinal epithelial cell apoptosis and damages the mucosal barrier, which can result in bacterial translocation and activation of the local and systemic immune and inflammatory response, ultimately contributing to graft failure, rejection, and decreased recipient survival. The current, preferred method of intestinal preservation prior to IT is static cold storage (CS), however the prolonged hypothermic ischemia of CS causes cell injury and intensifies the IRI that occurs during transplantation. Furthermore, IRI to the epithelial crypt region diminishes the intestine’s ability to heal by inducing loss of the highly proliferative intestinal stem cells (ISCs) that are responsible for maintenance, regeneration, and repair of the epithelium, critical to graft health. Thus, the investigation of alternative organ preservation techniques that reduce IRI, cellular damage, and graft injury are warranted to overall improve IT success. Normothermic machine perfusion (NMP) is a preservation method that reduces inflammation and promotes graft regeneration in other organs by preventing CS-associated IRI. However, NMP has not been described for intestine. We hypothesized that, compared to CS, intestinal NMP will induce less epithelial injury and better protect ISC regenerative potential and viability. 15 porcine intestines were flushed with UW solution, stored at 4°C (CS), or perfused with 34°C perfusate (NMP) for 6hr, and transplanted (n=9). Recipient pigs were recovered from anesthesia. Jejunal and ileal segments were collected immediately after flushing, serving as control tissue (CO), after 6hr of CS or NMP, and after 1hr of reperfusion post-IT. Histologic injury was assessed. Crypts isolated after flushing (CO), 6hr CS or NMP, and 1hr of reperfusion post-IT were cultured. Spheroid number, size, and EdU staining quantified ISC viability and proliferation. Expression of ISC and cellular proliferation genes and proteins were measured. Histologically, NMP tissue had mild epithelial erosion and increased columnar cell attenuation and expression of ISC and proliferation genes/proteins was observed. NMP spheroid areas and proliferating cell numbers were significantly larger than control and CS. Apoptotic cells were increased following CS. Post-graft reperfusion, CS had increased injury compared to uninjured control and NMP tissue. Compared to CS, NMP may improve graft regenerative potential, resulting in transplantation of healthier bowel and superior recipient survival.}, number={7S}, journal={Transplantation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Ludwig, Elsa and Abraham, Nader and McKinney, Caroline and Freund, John and Stewart, Amy and Garman, Katherine and Barbas, Andrew and Sudan, Debra and Gonzalez, Liara}, year={2023}, month={Jun}, pages={25–25} }
 @inproceedings{poisson_mckinney-aguirre_freund_gonzalez_2023, title={A Novel Approach Using Side Population Analysis to Identify Intestinal Stem Cells in Wild-type Pigs}, booktitle={College of Veterinary Medicine Annual Research Forum, North Carolina State University}, author={Poisson, L. and McKinney-Aguirre, C. and Freund, J. and Gonzalez, L.M.}, year={2023} }
 @article{ludwig_hobbs_mckinney-aguirre_gonzalez_2023, title={Biomarkers of Intestinal Injury in Colic}, volume={13}, ISSN={2076-2615}, url={http://dx.doi.org/10.3390/ani13020227}, DOI={10.3390/ani13020227}, abstractNote={Simple Summary Biomarkers are measurable substances within body tissues or fluids that allow for the identification of ongoing injury or disease. Colic secondary to gastrointestinal disease is one of the most frequent causes of morbidity and mortality in horses. Specifically, colic associated with intestinal ischemia is the most life-threatening variety of this disease. Optimization of biomarkers for the diagnosis of colic and identification of intestinal ischemia may expedite the diagnosis and management of this disease and thus help to alleviate this burden on the equid population. Lactate, and specifically the L isomer, is a commonly employed biomarker in colic evaluations. A variety of other biomarkers, however, have been preliminarily evaluated for equine colic. This paper reviews currently explored biomarkers in equine medicine for colic. Ultimately, based on this review, L-lactate continues to be the most reliable marker for intestinal ischemia during colic. However, further exploration of the biomarkers included here may eventually provide the key to accelerated identification, intervention, and thus better outcomes for horses suffering from intestinal ischemia. Abstract Biomarkers are typically proteins, enzymes, or other molecular changes that are elevated or decreased in body fluids during the course of inflammation or disease. Biomarkers pose an extremely attractive tool for establishing diagnoses and prognoses of equine gastrointestinal colic, one of the most prevalent causes of morbidity and mortality in horses. This topic has received increasing attention because early diagnosis of some forms of severe colic, such as intestinal ischemia, would create opportunities for rapid interventions that would likely improve case outcomes. This review explores biomarkers currently used in equine medicine for colic, including acute phase proteins, proinflammatory cytokines, markers of endotoxemia, and tissue injury metabolites. To date, no single biomarker has been identified that is perfectly sensitive and specific for intestinal ischemia; however, L-lactate has been proven to be a very functional and highly utilized diagnostic tool. However, further exploration of other biomarkers discussed in this review may provide the key to accelerated identification, intervention, and better outcomes for horses suffering from severe colic.}, number={2}, journal={Animals}, publisher={MDPI AG}, author={Ludwig, Elsa K. and Hobbs, Kallie J. and McKinney-Aguirre, Caroline A. and Gonzalez, Liara M.}, year={2023}, month={Jan}, pages={227} }
 @article{veerasammy_gonzalez_báez‐ramos_schaaf_stewart_ludwig_mckinney‐aguirre_freund_robertson_gonzalez_2023, title={Changes in equine intestinal stem/progenitor cell number at resection margins in cases of small intestinal strangulation}, volume={55}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/evj.13927}, DOI={10.1111/evj.13927}, abstractNote={BACKGROUND
Intestinal epithelial stem cells (ISC) are responsible for epithelial regeneration and are critical to the intestine's ability to regain barrier function following injury. Evaluating ISC biomarker expression in cases of small intestinal strangulation (SIS) may provide insight into clinical progression.


OBJECTIVES
Intestinal resection margins from cases of SIS were evaluated to determine if (1) evidence of injury could be identified using histomorphometry, (2) ISC biomarker expression was decreased in the proximal resection margin compared to control and distal resection margin, and (3) the ISC biomarker expression was associated with the number of preoperative risk factors negatively related to outcome, postoperative complications, or case outcome.


STUDY DESIGN
Retrospective cohort study.


METHODS
Intestinal samples were obtained intraoperatively from resection margins of adult horses with SIS and horses euthanised for reasons unrelated to colic. Preoperative risk factors negatively related to outcome, postoperative complications, and case outcome were obtained from medical records. Horses were grouped as euthanised intraoperatively, postoperatively, or survived to discharge. Histomorphometry and immunofluorescence were performed to evaluate tissue architecture and ISC and progenitor cell number. Groups were compared using one-way ANOVA. Associations between biomarker expression and the number of preoperative risk factors and postoperative complications negatively related to outcome were determined using linear regression modeling.


RESULTS
Thirty-six cases of SIS were evaluated. Ki67+ cell counts were decreased in the proximal (mean= 15.45 cells; 95% CI; 10.27-20.63, SD=4.17; p=0.02) and distal resection margins (mean=15.05; 95% CI= 8.46-21.64; SD=4.141; p=0.03) in horses euthanised postoperatively compared to control (mean=23.62 cells; 95% CI= 19.42-27.83; SD=5.883). In the distal resection margin, an increase in SOX9+ Ki67+ cells were associated with a decrease in the total number of preoperative risk factors negatively related to outcome (95% CI; 0.236-1.123; p=0.008, SE=0.1393).


MAIN LIMITATIONS
Small population size.


CONCLUSIONS
Proliferating cell and ISC numbers may be associated with case outcome. This article is protected by copyright. All rights reserved.}, number={6}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Veerasammy, Brittany and Gonzalez, Gabriel and Báez‐Ramos, Patricia and Schaaf, Cecilia R. and Stewart, Amy Stieler and Ludwig, Elsa K. and McKinney‐Aguirre, Caroline and Freund, John and Robertson, James and Gonzalez, Liara M.}, year={2023}, month={Feb}, pages={995–1002} }
 @inproceedings{antezana_mckinney-aguirre_ludwig_freund_gonzalez_2023, title={Comparison of Effects of Intestinal Normothermic Machine Perfusion and Cold Storage on Epithelial CD3+ Cell Populations}, booktitle={National Veterinary Scholars Symposium}, author={Antezana, A. and McKinney-Aguirre, C. and Ludwig, E. and Freund, J. and Gonzalez, L.}, year={2023} }
 @article{ludwig_abraham_schaaf_mckinney_freund_stewart_veerasammy_thomas_cardona_garman_et al._2023, title={Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability}, volume={10}, ISSN={1600-6135}, url={http://dx.doi.org/10.1016/j.ajt.2023.10.026}, DOI={10.1016/j.ajt.2023.10.026}, abstractNote={Intestinal transplantation (IT) is the final treatment option for intestinal failure. Static cold storage (CS) is the standard preservation method used for intestinal allografts. However, CS and subsequent transplantation induce ischemia-reperfusion injury (IRI). Severe IRI impairs epithelial barrier function, including loss of intestinal stem cells (ISC), critical to epithelial regeneration. Normothermic machine perfusion (NMP) preservation of kidney and liver allografts minimizes CS-associated IRI; however, it has not been used clinically for IT. We hypothesized that intestine NMP would induce less epithelial injury and better protect the intestine's regenerative ability when compared with CS. Full-length porcine jejunum and ileum were procured, stored at 4 °C, or perfused at 34 °C for 6 hours (T6), and transplanted. Histology was assessed following procurement (T0), T6, and 1 hour after reperfusion. Real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence, and crypt culture measured ISC viability and proliferative potential. A greater number of NMP-preserved intestine recipients survived posttransplant, which correlated with significantly decreased tissue injury following 1-hour reperfusion in NMP compared with CS samples. Additionally, ISC gene expression, spheroid area, and cellular proliferation were significantly increased in NMP-T6 compared with CS-T6 intestine. NMP appears to reduce IRI and improve graft regeneration with improved ISC viability and proliferation.}, journal={American Journal of Transplantation}, publisher={Elsevier BV}, author={Ludwig, Elsa K. and Abraham, Nader and Schaaf, Cecilia R. and McKinney, Caroline A. and Freund, John and Stewart, Amy S. and Veerasammy, Brittany A. and Thomas, Mallory and Cardona, Diana M. and Garman, Katherine and et al.}, year={2023}, month={Oct} }
 @inproceedings{ludwig_abraham_schaaf_mckinney-aguirre_freund_stewart_veerasammy_thomas_garman_barbas_et al._2023, title={Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability}, booktitle={MHSR Symposium}, author={Ludwig, E. and Abraham, N. and Schaaf, C.R. and McKinney-Aguirre, C.A. and Freund, J. and Stewart, A. and Veerasammy, B.M. and Thomas, M. and Garman, K. and Barbas, A. and et al.}, year={2023} }
 @inproceedings{cabrera_mckinney-aguirre_gonzalez_2023, title={Equine placental-derived extract enhances the regenerative capacity of equine intestinal epithelial cells}, booktitle={National Veterinary Scholars Symposium}, author={Cabrera, M. and McKinney-Aguirre, C. and Gonzalez, L.}, year={2023} }
 @inproceedings{cabrera_mckinney-aguirre_gonzalez_2023, title={Investigating the Impact of Novel Placental Extract on Equine Intestinal Repair}, booktitle={College of Veterinary Medicine Annual Research Forum, North Carolina State University}, author={Cabrera, M. and McKinney-Aguirre, C. and Gonzalez, L.}, year={2023} }
 @inproceedings{mckinney-aguirre_stewart_freund_tomblyn_hojnacki_berger_washburn_gonzalez_2023, title={Neonatal Porcine intestinal epithelial reparative capacity is fortified by acellular placental extract}, booktitle={Federation of American Societies of Experimental Biology}, author={McKinney-Aguirre, C. and Stewart, A. and Freund, J. and Tomblyn, S. and Hojnacki, J. and Berger, M. and Washburn, S. and Gonzalez, L.}, year={2023} }
 @inproceedings{ludwig_abraham_mckinney-aguirre_freund_stewart_garman_barbas_sudan_gonzalez_2023, title={Normothermic Machine Perfusion Reduces Ischemia Reperfusion Injury to Intestinal Allografts}, booktitle={College of Veterinary Medicine Annual Research Forum, North Carolina State University}, author={Ludwig, E. and Abraham, N. and McKinney-Aguirre, C. and Freund, J. and Stewart, A. and Garman, K. and Barbas, A. and Sudan, D. and Gonzalez, L.M.}, year={2023} }
 @inproceedings{singh_deck_ludwig_blakeley ruiz_rose_mckinney-aguirre_blikslager_gonzalez_2023, title={Post-injury probiotic treatment may impact intestinal microbiota and epithelial recovery in a pig surgical model}, booktitle={World Congress on Undergraduate Research}, author={Singh, A. and Deck, C. and Ludwig, E. and Blakeley Ruiz, J.A. and Rose, E. and McKinney-Aguirre, C. and Blikslager, A. and Gonzalez, L.M.}, year={2023} }
 @inproceedings{mckinney-aguirre_schaaf_ludwig_antezana_freund_rose_gonzalez_2023, title={Pre-transplantation storage method impacts immune cell populations in intestinal grafts following transplantation}, booktitle={College of Veterinary Medicine Annual Research Forum, North Carolina State University}, author={McKinney-Aguirre, C. and Schaaf, C. and Ludwig, E. and Antezana, A. and Freund, J. and Rose, D. and Gonzalez, L.}, year={2023} }
 @inproceedings{mckinney-aguirre_stewart_freund_tomblyn_hojnacki_berger_washburn_gonzalez_2023, title={Preserving reparative capacity in neonatal porcine intestinal epithelium with acellular placental extract}, booktitle={Comparative Gastrointestinal Biology and Disease Research Competition}, author={McKinney-Aguirre, C. and Stewart, A. and Freund, J. and Tomblyn, S. and Hojnacki, J. and Berger, M. and Washburn, S. and Gonzalez, L.}, year={2023} }
 @article{abraham_ludwig_schaaf_veerasammy_stewart_mckinney_freund_samy_gao_kahan_et al._2022, title={212.1: Normothermic Machine Perfusion and Orthotopic Allotransplantation of the Full Length Porcine Intestine}, volume={106}, ISSN={0041-1337}, url={http://dx.doi.org/10.1097/01.tp.0000885324.41684.49}, DOI={10.1097/01.tp.0000885324.41684.49}, abstractNote={Background: A limitation of intestinal transplantation is severe graft injury during cold storage, leadng to sepsis and rejection. Improved graft preservation will improve post-transplant outcomes. Recently, trials of oxygenated machine perfusion (MP) in liver transplantation show superior outcomes compared to cold storage. We hypothesized oxygenated MP of intestinal grafts would be feasible and improve outcomes after intestine transplantation, similar to other transplanted organs. The aim of this study was to develop a translational normothermic machine perfusion (NMP) protocol of full-length intestine allograft and validate feasibility of MP by orthotopic transplantation in a porcine model. Methods: The NMP protocol underwent 3 iterative stages of development, generation 1, 2, and 3 (GEN1, GEN2, GEN3). GEN1 (n=8 grafts) protocol was adapted from published liver NMP protocols. Changes were made after review of 6-8 graft perfusions with a standardized approach. The perfusion circuit consisted of a graft chamber with open venous return into a reservoir below. A roller pump circulated perfusate from the reservoir into the oxygenator into the craniomesenteric artery at a mean arterial pressure of 50 ± 5 mmHg for 6 hours. Vasodilators were administered into the arterial line by constant infusion. Perfusion pressure, temperature, and arterial flow were monitored continuously using in-line sensors. A dialysis circuit was used to maintain the normal chemistries in GEN2 & 3. We compared gross and histologic appearance of paired samples from the time of organ procurement and after six hours of oxygenated MP. After optimization, transplantation of porcine intestine allografts after 6 hr NMP were then undertaken and postoperative recovery of gut function, physical activity, lab parameters and vital signs were monitored for 2 days before sacrifice. Results: During protocol development, we identified several factors that appear unique to the intestine allograft and posed challenges during MP, including metabolic, electrolyte, acid-base disturbances, as well as differential perfusion of the jejunum and Ileum. These factors coincided with graft and mesenteric edema, luminal hemorrhage, and ileal ischemia with the initial protocol. Addition of dialysis and introduction of vasodilating medications corrected the metabolic derangements in perfusate chemistries, and gross and histologic appearance suggested excellent preservation in GEN3. We report successful transplantation of 3 porcine intestinal allografts after MP with excellent post-operative recovery of gut function, physical activity, oral intake and maintenance of normal vital signs and lab values. At 48 hours inspection of the bowel graft demonstrated viable pink serosa without evidence of mucosal injury. Conclusions: This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of the intestinal allograft in a porcine model. U.S Department of Defense (DOD).}, number={9S}, journal={Transplantation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Abraham, Nader and Ludwig, Elsa K. and Schaaf, Cecilia R. and Veerasammy, Brittany and Stewart, Amy S. and McKinney, Caroline and Freund, John and Samy, Kannan P. and Gao, Qimeng and Kahan, Riley and et al.}, year={2022}, month={Sep}, pages={S21–S21} }
 @inproceedings{mckinney-aguirre_stewart_veerasammy_hojnacki_tomblyn_washburn_gonzalez_2022, title={Acellular placental extract accelerates in vitro neonatal porcine intestinal epithelial wound healing}, booktitle={Comparative Gastrointestinal Biology and Disease Research Competition}, author={McKinney-Aguirre, C. and Stewart, A. and Veerasammy, B. and Hojnacki, J. and Tomblyn, S. and Washburn, S. and Gonzalez, L.}, year={2022} }
 @inproceedings{mckinney-aguirre_stewart_veerasammy_hojnacki_tomblyn_washburn_gonzalez_2022, title={Acellular placental extract improves neonatal porcine intestinal epithelial recovery following traumatic injury}, booktitle={Digestive Disease Week}, author={McKinney-Aguirre, C. and Stewart, A. and Veerasammy, B. and Hojnacki, J. and Tomblyn, S. and Washburn, S. and Gonzalez, L.}, year={2022} }
 @inproceedings{ludwig_abraham_sudan_barbas_schaaf_freund_thomas_stewart_veerasammy_mckinney-aguirre_et al._2022, title={Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability}, booktitle={Digestive Disease Week}, author={Ludwig, E. and Abraham, N. and Sudan, D. and Barbas, B. and Schaaf, C.R. and Freund, J. and Thomas, M. and Stewart, A.S. and Veerasammy, B. and McKinney-Aguirre, C. and et al.}, year={2022} }
 @inproceedings{abraham_ludwig_kucera_veerasammy_stewart_mckinney_freund_samy_gao_kahan_et al._2022, title={Differential vascular resistance of the jejunum and ileum during machine perfusion}, booktitle={American Society of Transplant Surgeons}, author={Abraham, N. and Ludwig, E. and Kucera, C. and Veerasammy, B. and Stewart, A. and McKinney, C. and Freund, J. and Samy, K. and Gao, Q. and Kahan, R. and et al.}, year={2022} }
 @inproceedings{o’donnell_mckinney-aguirre_bayless_sheats_gonzalez_2022, title={Investigating the impact of novel placental extract on equine intestinal epithelial repair}, booktitle={National Veterinary Scholars Symposium}, author={O’Donnell, K. and McKinney-Aguirre, C. and Bayless, R. and Sheats, K. and Gonzalez, L.}, year={2022} }
 @article{abraham_ludwig_schaaf_veerasammy_stewart_mckinney_freund_brassil_samy_gao_et al._2022, title={Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion}, volume={8}, ISSN={2373-8731}, url={http://dx.doi.org/10.1097/TXD.0000000000001390}, DOI={10.1097/TXD.0000000000001390}, abstractNote={Background. Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model. Methods. Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice. Results. In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function. Conclusions. This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.}, number={11}, journal={Transplantation Direct}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Abraham, Nader and Ludwig, Elsa K. and Schaaf, Cecilia R. and Veerasammy, Brittany and Stewart, Amy S. and McKinney, Caroline and Freund, John and Brassil, John and Samy, Kannan P. and Gao, Qimeng and et al.}, year={2022}, month={Oct}, pages={e1390} }
 @inproceedings{singh_deck_ludwig_blakeley-ruiz_rose_mckinney-aguirre_blikslager_gonzalez_2022, title={Post-injury probiotic treatment may impact intestinal microbiota and epithelial recovery in a pig surgical model}, booktitle={Comparative Medicine Institute Summer Symposium}, author={Singh, A. and Deck, C. and Ludwig, E. and Blakeley-Ruiz, J.A. and Rose, E. and McKinney-Aguirre, C. and Blikslager, A. and Gonzalez, L.M.}, year={2022} }
 @inproceedings{mckinney_stewart_veerasammy_gonzalez_2021, title={Acellular placental extract improves neonatal porcine intestinal epithelial recovery following traumatic injury}, booktitle={College of Veterinary Medicine Annual Research Forum, North Carolina State University}, author={McKinney, C. and Stewart, A. and Veerasammy, B. and Gonzalez, L.}, year={2021} }
 @inproceedings{mckinney_stewart_veerasammy_hojnacki_tomblyn_washburn_gonzalez_2021, title={Acellular placental extract improves neonatal porcine intestinal epithelial recovery following traumatic injury}, booktitle={Comparative Gastrointestinal Biology and Disease Poster Competition}, author={McKinney, C. and Stewart, A. and Veerasammy, B. and Hojnacki, J. and Tomblyn, S. and Washburn, S. and Gonzalez, L.}, year={2021} }
 @article{mckinney_bedenice_pacheco_oliveira_paradis_mazan_widmer_2021, title={Assessment of clinical and microbiota responses to fecal microbial transplantation in adult horses with diarrhea}, volume={16}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0244381}, DOI={10.1371/journal.pone.0244381}, abstractNote={Background and aims Fecal microbial transplantation (FMT) is empirically implemented in horses with colitis to facilitate resolution of diarrhea. The purpose of this study was to assess FMT as a clinical treatment and modulator of fecal microbiota in hospitalized horses with colitis. Methods A total of 22 horses with moderate to severe diarrhea, consistent with a diagnosis of colitis, were enrolled at two referral hospitals (L1: n = 12; L2: n = 10). FMT was performed in all 12 patients on 3 consecutive days at L1, while treatment at L2 consisted of standard care without FMT. Manure was collected once daily for 4 days from the rectum in all colitis horses, prior to FMT for horses at L1, and from each manure sample used for FMT. Fecal samples from 10 clinically healthy control horses housed at L2, and 30 healthy horses located at 5 barns in regional proximity to L1 were also obtained to characterize the regional healthy equine microbiome. All fecal microbiota were analyzed using 16S amplicon sequencing. Results and conclusions As expected, healthy horses at both locations showed a greater α-diversity and lower β-diversity compared to horses with colitis. The fecal microbiome of healthy horses clustered by location, with L1 horses showing a higher prevalence of Kiritimatiellaeota. Improved manure consistency (lower diarrhea score) was associated with a greater α-diversity in horses with colitis at both locations (L1: r = -0.385, P = 0.006; L2: r = -0.479, P = 0.002). Fecal transplant recipients demonstrated a greater overall reduction in diarrhea score (median: 4±3 grades), compared to untreated horses (median: 1.5±3 grades, P = 0.021), with a higher incidence in day-over-day improvement in diarrhea (22/36 (61%) vs. 10/28 (36%) instances, P = 0.011). When comparing microbiota of diseased horses at study conclusion to that of healthy controls, FMT-treated horses showed a lower mean UniFrac distance (0.53±0.27) than untreated horses (0.62±0.26, P<0.001), indicating greater normalization of the microbiome in FMT-treated patients.}, number={1}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={McKinney, Caroline A. and Bedenice, Daniela and Pacheco, Ana P. and Oliveira, Bruno C. M. and Paradis, Mary-Rose and Mazan, Melissa and Widmer, Giovanni}, editor={Thangamani, ShankarEditor}, year={2021}, month={Jan}, pages={e0244381} }
 @article{sage_bedenice_mckinney_long_pacheco_wagner_mazan_paradis_2021, title={Assessment of the impact of age and of blood‐derived inflammatory markers in horses with colitis}, volume={31}, ISSN={1479-3261 1476-4431}, url={http://dx.doi.org/10.1111/vec.13099}, DOI={10.1111/vec.13099}, abstractNote={OBJECTIVES
To determine the impact of age on survival in horses with colitis and to elucidate whether a lower type-1/type-2 cytokine ratio or an exaggerated inflammatory state contribute to reduced survival in aged horses.


DESIGN
Part 1: Retrospective cohort analysis. Part 2: Analytic observational study.


ANIMALS
Part 1: One hundred twenty-four adult horses with colitis. Part 2: Twenty-nine adult horses with new diarrhea onset while hospitalized.


MEASUREMENTS AND MAIN RESULTS
Part 1: Patient signalment, select clinicopathological data, diagnoses, treatment, hospitalization length, and invoice were compared between survivors (n = 101) and nonsurvivors (n = 23). Only age and plasma transfusion retained statistical significance in the final multivariate outcome model, with 8.5 times lower odds of survival in transfused horses (95% confidence interval [CI], 2.6-27.2%). Additionally, the likelihood of nonsurvival increased by 11.8% (95% CI, 4-20.2%) for every year the horse aged (P = 0.002). Similarly, geriatric horses (≥20 years) were 15.2 times more likely to die than young-adults (2-12 years, P = 0.03), independent of financial investment, documented comorbidities, and duration of hospitalization. Part 2: Select cytokine analyses were performed on serum collected from hospitalized horses within 1 hour of diarrhea onset (T0) and 6 hours later. At T0, all recorded clinicopathological variables were comparable between geriatric and young-adult horses, suggesting a similar degree of systemic illness. The median concentration of type-2 cytokines interleukin-4 and interleukin-10, and type-1 cytokine interferon-γ did not differ between age groups. Inflammatory cytokines interleukin-6 and tumor necrosis factor-α were significantly higher in geriatric compared to young-adult horses at both sampling time points.


CONCLUSIONS
Outcome of colitis was less favorable in aging horses and patients receiving a plasma transfusion. Although an exaggerated inflammatory state, based on increased interleukin-6 and tumor necrosis factor-α concentrations, in geriatric horses may contribute to reduced survival, a lower type-1/type-2 cytokines ratio was not identified in our geriatric population.}, number={6}, journal={Journal of Veterinary Emergency and Critical Care}, publisher={Wiley}, author={Sage, Sophie E. and Bedenice, Daniela and McKinney, Caroline A. and Long, Alicia E. and Pacheco, Ana and Wagner, Bettina and Mazan, Melissa R. and Paradis, Mary Rose}, year={2021}, month={Aug}, pages={779–787} }
 @inproceedings{thomas_ludwig_mckinney_schaaf_freund_gonzalez_2021, title={Comparison of the effects of normothermic perfusion and cold storage preservation on intestinal stem cell growth}, booktitle={Undergraduate Research and Creativity Symposium}, author={Thomas, M. and Ludwig, E.K. and McKinney, C. and Schaaf, C. and Freund, J.M. and Gonzalez, L.M.}, year={2021} }
 @inproceedings{brodsky_cortes_pridgen_schaaf_mckinney_hazzard_odle_blikslager_gonzalez_dawson_et al._2021, title={Domestic pigs represent a novel translational model for eosinophilic esophagitis}, booktitle={Conference of Research Workers in Animal Diseases}, author={Brodsky, D and Cortes, L.M. and Pridgen, T and Schaaf, C and McKinney, C and Hazzard, A and Odle, J and Blikslager, A and Gonzalez, Lm and Dawson, H and et al.}, year={2021} }
 @inproceedings{hazzard_mckinney_schaaf_kaeser_gonzalez_2021, title={Modeling Eosinophilic Gastrointestinal Disease in a Novel Porcine Model}, booktitle={Undergraduate Research Symposium}, author={Hazzard, A. and McKinney, C and Schaaf, C and Kaeser, T and Gonzalez, L}, year={2021} }
 @article{butty_mckinney_prisk_2021, title={Treatment of a flunixin meglumine overdose with intravenous administration of lipid emulsion and therapeutic plasma exchange in a Nigerian dwarf buck kid (<i><scp>Capra aegagrus</scp> hircus</i>)}, volume={35}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.16124}, DOI={10.1111/jvim.16124}, abstractNote={Abstract A 12 week‐old Nigerian dwarf (Capra aegagrus hircus) buck kid was hospitalized for management of obstructive urolithiasis. Postoperatively, he was inadvertently administered 16‐times greater than his calculated dose of a nonsteroidal anti‐inflammatory drug (NSAID; 17.5 mg/kg flunixin meglumine, IV). The goat was treated with intravenous administration of lipid emulsion (ILE) prior to membrane‐based therapeutic plasma exchange (mTPE) under general anesthesia. The increased coagulability inherent to small ruminants in comparison with dogs and cats warranted specific adjustments in the prescription of anticoagulation, blood flow, and filtration fraction to avoid circuit clotting during mTPE. Serum flunixin meglumine concentration measured before, during, and after mTPE revealed marked reduction in drug concentration. After the combined treatments, no clinical evidence of NSAID gastrointestinal or renal toxicosis was detected. This case report describes successful management of flunixin meglumine overdose in a small ruminant using combined ILE and mTPE.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Butty, Emmanuelle Marie and McKinney, Caroline Ann and Prisk, Amanda Jane}, year={2021}, month={May}, pages={1626–1630} }
 @article{conrado_iapoce_batista‐linhares_lopez_matthews_mckinney_rothacker_2020, title={Circulating melanin‐containing cells and neutrophils with phagocytized melanin granules in a horse with disseminated melanoma}, volume={49}, ISSN={0275-6382 1939-165X}, url={http://dx.doi.org/10.1111/vcp.12914}, DOI={10.1111/vcp.12914}, abstractNote={An 18-year-old, grey, Thoroughbred Cross gelding was referred to the Cummings School of Veterinary Medicine at Tufts University following a 3-week history of low-grade fever of unknown origin, distal limb swelling, and weight loss. Clinical examination identified a few black, round, smooth nodules along the ventral aspect of the proximal tail. Transabdominal ultrasound showed a markedly enlarged heterogenous spleen, hyperechoic liver nodules, and evidence of peritonitis with fibrin deposition. A mature neutrophilia was noted on complete blood count with variable numbers of phagocytized granules within neutrophils. The granules did not stain with Perl's Prussian blue, and were intensely positive when stained with Fontana-Mason, consistent with melanin. On necropsy, the spleen occupied approximately one-third of the abdominal cavity and was diffusely firm with abundant black pigment on cut section. The medullary space of the 18th thoracic vertebra was also diffusely blackened. The splenic, mediastinal, and tracheobronchial lymph nodes were five times the normal size and diffusely pigmented. The final anatomic diagnosis was disseminated malignant melanoma with extensive splenic involvement and hemolymphatic and vascular neoplastic dissemination. To the authors' knowledge, this is the first full report to identify circulating neutrophils containing phagocytized melanin granules, which confirmed an antemortem diagnosis of disseminated melanoma.}, number={4}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Conrado, Francisco O. and Iapoce, Nicholas and Batista‐Linhares, Mainity and Lopez, Sharleen and Matthews, Morgan H. and McKinney, Caroline A. and Rothacker, Caitlin}, year={2020}, month={Nov}, pages={624–631} }
 @article{mckinney_oliveira_bedenice_paradis_mazan_sage_sanchez_widmer_2020, title={The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea}, volume={15}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0230148}, DOI={10.1371/journal.pone.0230148}, abstractNote={Background and aims Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity. Methods To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2–12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing. Results and conclusions In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.}, number={3}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={McKinney, Caroline A. and Oliveira, Bruno C. M. and Bedenice, Daniela and Paradis, Mary-Rose and Mazan, Melissa and Sage, Sophie and Sanchez, Alfredo and Widmer, Giovanni}, editor={Carbonero, FranckEditor}, year={2020}, month={Mar}, pages={e0230148} }
 @article{kumar_chaudhary_lu_duff_heffel_mckinney_bedenice_marthaler_2019, title={Metagenomic Next-Generation Sequencing Reveal Presence of a Novel Ungulate Bocaparvovirus in Alpacas}, volume={11}, ISSN={1999-4915}, url={http://dx.doi.org/10.3390/v11080701}, DOI={10.3390/v11080701}, abstractNote={Viruses belonging to the genus Bocaparvovirus (BoV) are a genetically diverse group of DNA viruses known to cause respiratory, enteric, and neurological diseases in animals, including humans. An intestinal sample from an alpaca (Vicugna pacos) herd with reoccurring diarrhea and respiratory disease was submitted for next-generation sequencing, revealing the presence of a BoV strain. The alpaca BoV strain (AlBoV) had a 58.58% whole genome nucleotide percent identity to a camel BoV from Dubai, belonging to a tentative ungulate BoV 8 species (UBoV8). Recombination events were lacking with other UBoV strains. The AlBoV genome was comprised of the NS1, NP1, and VP1 proteins. The NS1 protein had the highest amino acid percent identity range (57.89–67.85%) to the members of UBoV8, which was below the 85% cut-off set by the International Committee on Taxonomy of Viruses. The low NS1 amino acid identity suggests that AlBoV is a tentative new species. The whole genome, NS1, NP1, and VP1 phylogenetic trees illustrated distinct branching of AlBoV, sharing a common ancestor with UBoV8. Walker loop and Phospholipase A2 (PLA2) motifs that are vital for virus infectivity were identified in NS1 and VP1 proteins, respectively. Our study reports a novel BoV strain in an alpaca intestinal sample and highlights the need for additional BoV research.}, number={8}, journal={Viruses}, publisher={MDPI AG}, author={Kumar and Chaudhary and Lu and Duff and Heffel and McKinney and Bedenice and Marthaler}, year={2019}, month={Jul}, pages={701} }
 @article{mckinney_mueller_frank_2015, title={Effects of Therapeutic Riding on Measures of Stress in Horses}, volume={35}, ISSN={0737-0806}, url={http://dx.doi.org/10.1016/j.jevs.2015.08.015}, DOI={10.1016/j.jevs.2015.08.015}, abstractNote={The popularity of therapeutic riding is growing rapidly. With greater numbers of horses used in this field, it is becoming increasingly important to understand how this work impacts horse quality of life. Salivary cortisol concentrations and behavior scores are two measures of stress in horses, and the goal of this study was to test the hypothesis that horses used in therapeutic riding exercises have greater increases in cortisol concentrations during therapeutic riding, when compared to a traditional hunt seat lesson program or at rest. Salivary cortisol concentrations were measured in six adult horses on 3 days per week for a total of 6 weeks. Horses served as their own controls, and salivary cortisol concentrations were measured during therapeutic riding, traditional riding, and at rest, with samples collected at 0, 30, and 60 minutes. Delta cortisol concentrations were calculated by subtracting baseline cortisol concentrations from values obtained at 30 or 60 minutes. Delta salivary cortisol values were compared among different types of activity by the nonparametric Wilcoxon matched-pairs signed-rank test. No significant differences in delta cortisol values were detected between riding conditions. Delta salivary cortisol values at 30 minutes were 0.147, 0.0762, and −0.032 μg/dL for rest, traditional riding, and therapeutic riding conditions, respectively, and delta values at 60 minutes were −0.0177, −0.002, and −0.031 μg/dL, respectively. Behavior scores did not differ significantly between different riding conditions. Our hypothesis was not supported, and we conclude that therapeutic riding was not associated with increased stress in horses in this sample.}, number={11-12}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={McKinney, Caroline and Mueller, Megan K. and Frank, Nicholas}, year={2015}, month={Nov}, pages={922–928} }