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Association of Thoraco-Abdominal Pressure Gradient and Esophageal Acid Exposure in Patients with End-Stage Lung Disease
TRANSPLANTATION AND TISSUE ENGINEERING pre-transplant esophageal high-resolution manometry (HRM) and 24-hr pH study. TAPG was calculated by: Intra-abdominal pressure (pressure at 1 cm bellow lower border of cruz) minus intrathoracic pressure (pressure at 5 cm above upper border of lower esophageal sphincter (LES). Adjusted TAPG was calculated by: TAPG minus resting LES pressure.
Silencing p53 Pathway of Apoptosis Alleviates Ischemia-Reperfusion Injury (IRI) in the Liver Maximiliaan F Thijssen, Carolina G Moore, PhD, E Xiaofei, PhD, Xiaofei Wang, MD, Pranoti Mandrekar, PhD, Adel Bozorgzadeh, MD, Robert J Porte, MD, PhD, Timothy F Kowalik, PhD, Paulo Martins, MD, PhD University of Massachusetts Medical School, Worcester, MA; University of Groningen Groningen, Netherlands INTRODUCTION: Ischemia-reperfusion injury (IRI) is an unavoidable relevant consequence of organ transplantation and influences transplant outcome. Exposure to cellular stress can trigger the p53 tumor suppressor, a transcription factor which can induce cell apoptosis. By temporarily silencing p53 using RNA interference, our study aims to protect the liver against the detrimental effects of IRI, combining RNA interference and machine perfusion preservation. METHODS: In this preliminary study, rats were injected with cy3-labeled p53 siRNA before inducing liver damage using CCL4. After 3 days the rats were euthanized and samples were collected for further analysis. RESULTS: Liver sections of the treated animals showed positive fluorescence for cy-3 by confocal microscopy. Light microscopy of liver sections showed less hepatocyte vacuolization and less cell infiltration in the treated animals. Immunostaining for caspase-3 showed less positive cells in treated animals. Flow cytometry analysis showed that p53 siRNA has no effect on the relative distribution of immune cell populations such as total lymphocytes, CD4, CD8, NK cells, neutrophils, monocytes and B cells, in the blood nor the spleen.
RESULTS: A total of 204 patients underwent lung transplant between Jan-2015 to Dec-2016 of which both pre-operative HRM and pH-study were available for 109 patients. Mean age was 61.210.3 years with 60 males and BMI of 26.05.1. Forty-one patients (37.6%) had abnormal DeMeester score. There was no difference in absolute TAPG, prevalence of hiatal-hernia, hypotensive LES and esophageal dysmotility between patients with normal and abnormal % total time pH<4 (normal<4.2%). Adjusted TAPG was significantly higher in patients who had abnormal total time pH<4 than normal score cohort (median -5.5 vs -10.5 mmHg, p¼0.048). CONCLUSIONS: High adjusted TAPG is associated with distal esophageal acid exposure in patients with severe lung disease.
Cannabis and Other Substance Use in Solid Organ Transplant Patients Jason B Brill, MD, Ryan J Schutt, DO, James D Wallace, MD, Jamie Case, PhD, Nicole Moore, MD, Christopher L Marsh, MD, FACS, Randolph L Schaffer III, MD, FACS, Jonathan S Fisher, MD, FACS Scripps Green Hospital, San Diego, CA
CONCLUSIONS: In this preliminary study we conclude that silencing the p53 gene has beneficial effects in alleviating IRI, with no secondary effects on immune cell population. The addition of siRNA treatment to machine perfusion therapy is currently being tested.
INTRODUCTION: Recent legislation in 7 states prohibits denial of transplantation solely on the basis of cannabis use. Evidence is lacking regarding the impact of cannabis use on transplant recipients, with case reports comprising the majority of available literature. To address this need, we investigated cannabis use, known risk factors for poor outcomes, and self-reported outcomes in our center’s recipients.
Association of Thoraco-Abdominal Pressure Gradient and Esophageal Acid Exposure in Patients with End-Stage Lung Disease Takahiro Masuda, MD, Saurabh Singhal, MBBS, Sreeja Biswas Roy, MBBS, Michael Smith, Jasmine L Huang, MD, FACS, Sumeet K Mittal, MD, FACS, Ross M Bremner, MD, PhD Norton Thoracic Institute, St Joseph’s, Phoenix, AZ
METHODS: Paper surveys were mailed to all adult solid organ recipients in the last 12 years from a single transplant center. Self-reported survey results were analyzed for associations among cannabis use, other substance use, medication noncompliance, frequency of respiratory illnesses, episodes of diagnosed rejection, and socioeconomic factors. Chi square analysis tested for univariate associations, while multiple logistic regression evaluated associations among cannabis use and outcomes.
INTRODUCTION: Advanced lung disease has been reported to be associated with gastroesophageal reflux (GER). Thoracoabdominal pressure gradient (TAPG) is suggested as a predictive factor of GER. The aim of this study is to explore the relationship between TAPG and GER in patients with end-stage lung disease.
RESULTS: Of 900 mailed surveys, 370 (41.1 %) were returned completed and 84 (9.3%) were undeliverable, for a response rate of 45.3%. Most patients received kidney (n¼200) or liver transplants (n¼144). Seventeen (4.6 %) were active cannabis users post-transplant. Pre- and post-transplant cannabis use was significantly associated (p<0.0001). Pre- or post-transplant cannabis use was associated with alcohol (p¼0.0003) and tobacco (p<0.0001) use. Lack of social support and cannabis use trended towards significance (p¼0.06).
METHODS: The prospectively maintained database of lung transplant patients was queried to identify patients who underwent
e167
http://dx.doi.org/10.1016/j.jamcollsurg.2017.07.979 ISSN 1072-7515/17
Silencing p53 Pathway of Apoptosis Alleviates Ischemia-Reperfusion Injury (IRI) in the Liver Maximiliaan F Thijssen, Carolina G Moore, PhD, E Xiaofei, PhD, Xiaofei Wang, MD, Pranoti Mandrekar, PhD, Adel Bozorgzadeh, MD, Robert J Porte, MD, PhD, Timothy F Kowalik, PhD, Paulo Martins, MD, PhD University of Massachusetts Medical School, Worcester, MA; University of Groningen Groningen, Netherlands INTRODUCTION: Ischemia-reperfusion injury (IRI) is an unavoidable relevant consequence of organ transplantation and influences transplant outcome. Exposure to cellular stress can trigger the p53 tumor suppressor, a transcription factor which can induce cell apoptosis. By temporarily silencing p53 using RNA interference, our study aims to protect the liver against the detrimental effects of IRI, combining RNA interference and machine perfusion preservation. METHODS: In this preliminary study, rats were injected with cy3-labeled p53 siRNA before inducing liver damage using CCL4. After 3 days the rats were euthanized and samples were collected for further analysis. RESULTS: Liver sections of the treated animals showed positive fluorescence for cy-3 by confocal microscopy. Light microscopy of liver sections showed less hepatocyte vacuolization and less cell infiltration in the treated animals. Immunostaining for caspase-3 showed less positive cells in treated animals. Flow cytometry analysis showed that p53 siRNA has no effect on the relative distribution of immune cell populations such as total lymphocytes, CD4, CD8, NK cells, neutrophils, monocytes and B cells, in the blood nor the spleen.
RESULTS: A total of 204 patients underwent lung transplant between Jan-2015 to Dec-2016 of which both pre-operative HRM and pH-study were available for 109 patients. Mean age was 61.210.3 years with 60 males and BMI of 26.05.1. Forty-one patients (37.6%) had abnormal DeMeester score. There was no difference in absolute TAPG, prevalence of hiatal-hernia, hypotensive LES and esophageal dysmotility between patients with normal and abnormal % total time pH<4 (normal<4.2%). Adjusted TAPG was significantly higher in patients who had abnormal total time pH<4 than normal score cohort (median -5.5 vs -10.5 mmHg, p¼0.048). CONCLUSIONS: High adjusted TAPG is associated with distal esophageal acid exposure in patients with severe lung disease.
Cannabis and Other Substance Use in Solid Organ Transplant Patients Jason B Brill, MD, Ryan J Schutt, DO, James D Wallace, MD, Jamie Case, PhD, Nicole Moore, MD, Christopher L Marsh, MD, FACS, Randolph L Schaffer III, MD, FACS, Jonathan S Fisher, MD, FACS Scripps Green Hospital, San Diego, CA
CONCLUSIONS: In this preliminary study we conclude that silencing the p53 gene has beneficial effects in alleviating IRI, with no secondary effects on immune cell population. The addition of siRNA treatment to machine perfusion therapy is currently being tested.
INTRODUCTION: Recent legislation in 7 states prohibits denial of transplantation solely on the basis of cannabis use. Evidence is lacking regarding the impact of cannabis use on transplant recipients, with case reports comprising the majority of available literature. To address this need, we investigated cannabis use, known risk factors for poor outcomes, and self-reported outcomes in our center’s recipients.
Association of Thoraco-Abdominal Pressure Gradient and Esophageal Acid Exposure in Patients with End-Stage Lung Disease Takahiro Masuda, MD, Saurabh Singhal, MBBS, Sreeja Biswas Roy, MBBS, Michael Smith, Jasmine L Huang, MD, FACS, Sumeet K Mittal, MD, FACS, Ross M Bremner, MD, PhD Norton Thoracic Institute, St Joseph’s, Phoenix, AZ
METHODS: Paper surveys were mailed to all adult solid organ recipients in the last 12 years from a single transplant center. Self-reported survey results were analyzed for associations among cannabis use, other substance use, medication noncompliance, frequency of respiratory illnesses, episodes of diagnosed rejection, and socioeconomic factors. Chi square analysis tested for univariate associations, while multiple logistic regression evaluated associations among cannabis use and outcomes.
INTRODUCTION: Advanced lung disease has been reported to be associated with gastroesophageal reflux (GER). Thoracoabdominal pressure gradient (TAPG) is suggested as a predictive factor of GER. The aim of this study is to explore the relationship between TAPG and GER in patients with end-stage lung disease.
RESULTS: Of 900 mailed surveys, 370 (41.1 %) were returned completed and 84 (9.3%) were undeliverable, for a response rate of 45.3%. Most patients received kidney (n¼200) or liver transplants (n¼144). Seventeen (4.6 %) were active cannabis users post-transplant. Pre- and post-transplant cannabis use was significantly associated (p<0.0001). Pre- or post-transplant cannabis use was associated with alcohol (p¼0.0003) and tobacco (p<0.0001) use. Lack of social support and cannabis use trended towards significance (p¼0.06).
METHODS: The prospectively maintained database of lung transplant patients was queried to identify patients who underwent
e167
http://dx.doi.org/10.1016/j.jamcollsurg.2017.07.979 ISSN 1072-7515/17