Clinically applicable research
Lung Transplant Outcomes: Institutional Review
Principal Investigator: Scott B. Johnson, MD
Under this umbrella protocol, we are teasing out few of the factors that may affect the outcomes after a lung transplant through a retrospective chart review.
Outcomes after re-do lung transplants
Contributors: Scott B. Johnson, MD, Daniel T. DeArmond MD, Nitin A Das, Charles Huynh MS-3, JinWen Sui MS-4
The purpose of this retrospective chart review is to evaluate the outcomes after second lung transplants in terms of survival, complications and incidence of rejections. This is an important question as it impacts judicious utilization of valuable resources.
VATS vs. open lobectomy: comparison of outcomes in high adoption rate hospitals
Contributors: Daniel T. DeArmond, MD, Nitin A. Das, Stewart R. Miller PhD, Sajed Mohammed PhD
Summary: This study utilizes the Texas Discharge Database to evaluate factors that affect outcomes after VATS (minimally invasive) lobectomy as compared to Open (thoracotomy) in terms of major morbidity and in-hospital mortality.
Interleukin – 18 in Left Ventricular Hypertrophy, Aortic Aneurysms and Heart Transplants
Contributors: A. J. Carpenter, MD, PhD in collaboration with Bysani Chandrasekar, DVM. Ph.D (Columbia University, Missouri)
Dr. Carpenter is collaborating with Dr. Chandra to elucidate relationship between interleukin-18 and various cardiac morbidities. Past studies have shown increase in graft stenosis associated with high levels of IL-18 which was blocked by IL-18 binding proteins in rodents. Future studies are focusing on finding association between LVH, aortic aneurysms and cardiac remodeling.
TRAF3-IP2 in Chronic Hyperglycemia
Contributors: A. J. Carpenter, MD, PhD, Nitin A. Das, Bysani Chandrasekar, DVM. Ph.D (Columbia University, Missouri)
Summary: Chronic hyperglycemia increases TRAF3IP2 expression in all layers of the vessel wall, contributing to heightened inflammation, excessive accumulation of SMCs, and luminal occlusion. Our goal is to target increased TRAF3IP2 expression by either genetic or interventional approach to block chronic hyperglycemia-mediated injury-induced vascular inflammation, endothelial dysfunction, and intimal hyperplasia. If we are able to identify TRAF3IP2 as a master regulator of diabetes-induced neointima formation, we could develop inhibitors to target its expression and inhibit neointimal hyperplasia and extend the life of these CAB grafts.
Education related research
Longitudinal study of integrated CT Surgery residency applicants: future career choices
Contributors: Chirag Buch, Nitin A. Das, Edward Y. Sako, MD, PhD
With the availability of the 6 year integrated program for cardiothoracic surgery residency, the new medical graduates have a career choice to make early in their life. But it is a limited opportunity and not everyone manages to get into a program. So for those who do not secure a spot, do they continue to pursue this interest with the traditional pathway? As an educationist, Dr. Sako is curious about the effects of this new paradigm.
Familiarity as a factor in residency selection
Contributors: Merideth Geib, Nitin A. Das, Edward Y. Sako, MD, PhD
Multiple factors are involved in both choosing and being chosen by a residency program. In this study the prevalence of experiences beyond the application review and interview process are examined.
Biochemical changes in lung after reperfusion injury and its attenuation with tacrolimus – dose response
PI: Nitin A. Das
This project is funded by Morrison Trust.
Ischemia –reperfusion (I-R) injury is unavoidable event during a solid organ transplant and it increases the risk of rejection by upregulation of surface antigens in the donor organ. In a recently published study, our lab demonstrated attenuation of I-R injury in lung transplants using nanoparticle tacrolimus (nTac) when administered by inhalation to the donor lung prior to procurement(1). It was noted that this benefit was reduced when the tissue level of nTac was lower in the isograft and a possible dose-response effect was postulated which needs further evaluation.
Objective: To define the optimal dose of tacrolimus to the donor lung prior to harvest that would reduce I-R injury by evaluating the biochemical changes in the lung and blood with varying doses.
Preliminary data: Bayer, Das, et al. demonstrated attenuation of I-R injury, with functional improvement (better oxygenation) and lower pro-inflammatory cytokine and cellular infiltrate in the isograft when pre-treated with nTac by inhalation prior to procurement(1).
Study Design: This study will evaluate the release of cytokines and chemokines in the transplanted lungs and systemic circulation after period of ischemia and reperfusion. We will correlate these levels with the level of tacrolimus and reduction of I-R injury in the lungs.
Lung expansion and aeration monitor in a pig model
Contributors: Daniel T. DeArmond, MD, Nitin A. Das, Joel E. Michalek PhD
Brief Description: Surgery of the lung, for example removing a tumor in the lung, and trauma to the lung, for example a gunshot wound to the lung, have the potential to lead to partial or complete collapse of the lung; this condition can develop rapidly or in a delayed manner and may be fatal or lead to significant patient complications. Collapse of the lung in these situations is most often caused by air or fluid/blood accumulating in the space between the lung and the rib cage. Because the rib cage is a rigid structure and the lung is relatively compressible, the build-up of air or fluid/blood in the space between the rib cage and the lung pushes on the lung and causes the lung to collapse. This type of lung collapse is treated by placing a large tube into the space between the rib cage and the lung to suction out the air and/or fluid/blood and re-expand the lung; importantly, this treatment is not always successful. Early detection of lung collapse in these scenarios can save lives, minimize complications, and potentially lower the costs of patient care but currently there is no direct, real-time way to monitor the space between the rib cage and lung. There is a missed opportunity in this clinical realm in that the tubes that are placed into the space between the lung and the rib cage to suction air and/or fluid/blood could easily be connected to a pressure sensor which could give care-givers real-time, continuous information about the status of lung-expansion. Such a pressure sensor could monitor the success of treatment of lung collapse by detecting a pressure change when the lung was re-expanded and could monitor the ongoing maintenance of lung expansion in patients who had recently undergone lung surgery or lung trauma in real time. In a similar manner, it could also be used in the setting of heart surgery to make sure that blood was not accumulating around the heart, a common problem after heart surgery which can decrease the pumping strength of the heart and lead to complications or death after heart surgery. In our lab, we have developed a pressure sensor based on the electrical properties of the lung and the heart. We have used this device to prove that we can detect lung collapse and confirm the restoration of lung re-expansion in experimental rats. We have shown that our pressure sensor is more sensitive than chest x-ray (the current gold standard) at detecting lung collapse in rats. We hope in the future to be able to translate the use of this device into humans but the next step is to test in a large mammalian animal model as this is the next closest model to humans.
Collaborator(s): Bhattacharya,Shamik PhD
Summary: Tricuspid valve (TV) disease is gaining increasing clinical significance, particularly the role of treatment for TV regurgitation. Annulus dilation is a major feature in functional tricuspid regurgitation but its mechanism is not understood. After tricuspid annuloplasty, a form of surgical therapy for TV regurgitation, up to 30% recurrence and ring dehiscence has been reported. The incomplete efficacy of current tricuspid surgical repair procedures demands a deeper understanding of the TV biomechanics and function. It is hypothesized detailed understanding of normal and suboptimal TV biomechanics will help to improve existing surgical techniques or develop new repair techniques. The objective of the proposed research is to initiate the study of TV biomechanics in order to improve treatment of TV regurgitation. The specific aims proposed are: 1) To quantify the tension required to cinch the normal and dilated tricuspid valve annulus, 2) To analyze the microstructure of normal and dilated annulus segment after cinching. TV annulus mechanics between TV annulus cinching force and right ventricle myocardial force will be helpful to understand the myocardial expansion force and mechanism of annulus dilation. A novel experimental method will be used to quantify the tension required to cinch the dilated TV annulus followed by the microstructure analysis of the TV annulus segment. Statistical analysis will be based on the assumption that the observations are normally distributed. For the comparison between control and other conditions and to draw an inference from the data, both paired and unpaired t-test for means, analysis of variance (ANOVA) and other relevant statistical tests will be used. Project milestones are to 1) increase collaboration between St. Mary’s Mechanical Engineering faculty with experience in mitral valve tissue mechanics and clinical expertise of the UTHCSA group to ensure clinical relevance, 2) offer engineering rationale for a better TV annuloplasty design 3) train first generation undergraduate students in the field of biomechanics and biomedical engineering and 3) at the conclusion, have sufficient data to warrant a NIH R-15 study to elucidate the biomechanical roles of tricuspid valve apparatus in tricuspid regurgitation.
Recently concluded Projects
Understanding Pulmonary Valve Architecture and Variation: Implications for the Ross Procedure
Contributors: Hayden Joseph*, Conner Ryan*, Will Fancher, Nitin A. Das, Lauren C. Kane, S Adil Husain, John H. Calhoon (*authors share equal credit)
Anatomical variation in pulmonary valve architecture has not been well defined. An understanding of such variances may impact surgical techniques employed for operations such as the Ross Procedure.
Central Venous Catheters: A Qualitative Analysis Of Patient And Nursing Preference
Contributors: Hayden Joseph*, Conner Ryan*, Nitin A. Das, John H. Calhoon, MD
There appears to be no consensus about complication rates of infection, thrombotic event and arterial injury when comparing central venous catheter (CVC) insertion sites. The aim in this study is to gain an understanding of patient and nursing preference for central line location, internal jugular vein (IJ) versus subclavian vein (SC), based on qualitative measures of comfort, ease of use, function, and satisfaction.
An In-vitro Model for Evaluation of Extubation
Contributors: William N. Fancher*, Nitin A. Das, Lauren C. Kane, John H. Calhoon
*Funded by the American Association for Thoracic Surgery Graham Foundation
In clinical practice a common method of extubation involves complete deflation of the cuff prior to ETT removal. This technique may result in retention of subglottic secretions as the ETT passes through the vocal cords, with subsequent aspiration. We hypothesize that passive deflation of the cuff by cutting the pilot tube will result in less retained secretions compared to active, complete deflation using a syringe.
Total Anomalous Pulmonary Venous Connection: Factors affecting outcomes
Contributors: Elizabeth Tapley, Elaine Campbell MD, Nitin A. Das, Adil S. Husain MD, Lauren C. Kane MD, John H. Calhoon, MD
Aprotinin Use In Bilateral Lung Transplantation Requiring Cardiopulmonary Bypass: Data Refutes Clinical Impression
Contributors: Eilers AE, Albahra S, Das NA, Prihoda TJ, Baisden CE, DeArmond DT, and Johnson SB
Objective: Aprotinin was used extensively in cardiothoracic as an agent to reduce blood loss and transfusion requirements until taken off the market in 2008 secondary to mounting litigation and concerns that it may cause neurologic and/or renal impairment. It was our clinical impression however that aprotinin was very effective at minimizing blood loss in patients undergoing bilateral lung transplantation utilizing cardiopulmonary bypass (CPB), and that it did so without causing significant neurologic or renal impairment. The purpose of this study was to review our own experience using aprotinin in this specific patient population.
Esophageal Stenting: Indications, Outcomes and Expectations
Contributors: Scott B. Johnson, MD , Nitin A. Das and HelenMari L. Merritt, DO
Purpose: The use of esophageal stents is evolving as a useful adjunct in the treatment of complex esophageal disorders. We reviewed our own stenting experience to examine patient outcomes, complications and rates of re-intervention as they relate to indications and underlying patient diagnoses.
Topics of Interest / Future Studies
Incidence of sternal wound infection and correlation with timing of pre-op antibiotic ( John H. Calhoon, MD)
Length of antibiotic treatment necessary after surgical treatment of endocarditis (John H. Calhoon, MD.)
Mapping the cardiac conduction system (Chirag Buch, John H. Calhoon, MD.)
Cervical anastomotic complications with and without Penrose drain after esophagectomy ( Scott B. Johnson, MD)
Evaluation of mechanotransduction in attenuation of ischemic injury to rat lung (Nitin A. Das)
Development of Ex-Vivo Lung Perfusion at UTHSCSA ( Nitin A. Das)
Heart I-R injury in mice with tacrolimus (Nitin A. Das)
Stem cells in rat lung transplantation (rejection and I-R injury) (Nitin A. Das)
Stem cells in rat lung transplantation (rejection and I-R injury) (Nitin A. Das)