An estimated 50% of patients scheduled to undergo surgical correction of their adult spinal deformity (ASD) are preoperatively managed with chronic opioid therapy. In recent years, preoperative opioid use has been correlated with increased morbidity and mortality following major abdominal, orthopaedic, and spine surgery. Despite high prevalence of chronic opioid consumption in ASD population, limited data is available to guide preoperative opoid tapering to improve postoperatve outcomes. First attempt to identify a morphine equianalgesic (MEA) dose threshold for patients undergoing spine procedures was described in Neurosurgery by Wick and co-workers. After calculating MEA values for 1020 cervical and lumbar spine surgical patients, the group reported MEA dose threshold beyond which patients are less likely to achieve the minimum clinically important difference (MCID). In patients undering a Complex Spine Surgical procedure, we hypothesize that an increased preoperative opioid dose may have a threshold beyond which patients are more likely to suffer from an adverse event. A trained data abstractor will collect data for the analysis during the retrospective chart review. In addition to data collection, abstractor will calculate morphine equivalent dose (MED) values for each patient meeting the inclusion criteria. Statistical analysis will be performed to evaluate association between MED values and postoperative outcomes. Parametic and non-parametic tests will be used as necessary, inclusing but not limited to t-tests for Equality of Means, Fishcer exact test, Chi-square, Independent Samples Mann-Whitney U Test, and logisitic regression. All data will be reported in aggregate. Reporting a defined opioid theshold for ASD patients may aid in developing a standardized tapering protocol aimed at improving postoperative outcomes. 

Midfacial hypoplasia (MFH) is a disorder of severe underdevelopment of the upper face. This problem is significant because MFH can lead to a deformity that impedes chewing, feeding, and breathing. Although it is known that MFH can occur due to gene mutations, teratogens, and trauma, it is unknown how these insults affect anterior growth of the face. Using a novel pig model, this project aims to isolate the location of structural changes to the skull caused by MFH. We first determined if MFH in pigs is isolated to the face, and then identified the specific bones of the face that are altered by MFH. To determine if MFH is isolated to the face, we measured and compared the length of the braincase, mandible, and upper face in pigs with MFH to that of normal pigs. We then measured and compared the dimensions of individual facial bones, including the maxilla, premaxilla, nasal bone, lacrimal bone, and zygoma. All measurements were done on dry skulls with calipers and compared using t-tests. Our initial qualitative comparison of 6 normal and 6 affected pigs has found that MFH is isolated to the face, with the premaxilla, maxilla, nasal bone, and lacrimal bone shortened. The zygoma and palatine bones were normal. We hypothesize that our qualitative comparison of approximately 35 MFH pigs and 115 normal pigs will show similar results. Identifying the bones affected by MFH will help us to hone in on the specific tissue changes and mechanisms that cause MFH, and to discover better treatments for this condition.

Spontaneous isolated abdominal aortic dissection (IAAD) is rare with poorly defined risk factors and the impact of risk factors on outcomes. We hypothesize that distinct phenotypes are associated with complicated and uncomplicated IAAD (cIAAD and uIAAD). Clinical and administrative records were reviewed for patients presenting to an academic medical system with IAAD between 1996 and 2018. Data abstraction included demographics, comorbidities, presentation, imaging findings, and outcomes. IAAD associated with rupture, malperfusion, and abdominal aortic aneurysm greater than 5 cm on presentation was designated as complicated IAAD (cIAAD) and compared to uncomplicated IAAD (uIAAD). A total of 36 patients presented with IAAD (mean age 55.7+14.9 years, 52.8% male). Of those, 11 (30.5%) had cIAAD. There were no differences in sex, history of hypertension, or smoking between cIAAD and uIAAD. Patients with cIAAD were significantly younger at presentation, had larger abdominal aortic aneurysms, more genetically triggered aortopathy, and died at a younger age. In contrast, patients with uIAAD had significantly more coronary artery disease and a trend of higher prevalence of concurrent malignancy and cirrhosis/hepatitis/ pancreatitis. Patients with cIAAD had more surgical repairs while most uIAAD patients were managed medically. IAAD has distinct phenotypes most likely related to the underlying etiology. Understanding these risk factors is essential to risk stratify individuals with IAAD and direct individualized management.

Midfacial Hypoplasia (MFH) is an underdevelopment of the upper jaw, cheekbones and eye sockets. MFH sometimes results in difficulty in breathing in children. Severe cases are treated with serious surgeries that often have unsuccessful outcomes. Understanding the consequences of MFH is a critical step in treating this disorder. The goal of my project is to use Yucatan pigs as a model for MFH. MFH is common in Yucatan pigs and resembles MFH in humans which makes it useful for a model. In addition, pigs resemble humans in physiology, anatomy and growth. Humans with MFH have reduced nasal airway capacity, and this is likely true for Yucatan pigs as well. The nature of airway deficiency is not fully understood, but it may be due to reduction of the nasal airway surface area. Reduction in the surface area would hamper the ability of the nasal passage to regulate air temperature and humidity. I hypothesize shortening of the nasal cavity in MFH reduces the surface area inside the cavity. Using CT scans from pigs, I measured the dimensions of the nasal passages via Metamorph and Photoshop software. Based on my hypothesis, I expect to observe lower surface area in pigs with MFH. If a correlation between MFH and surface area is found, this research will provide new insights about the consequences of MFH that will be relevant for better treatment of this disorder.

Osteoporosis is the leading cause of decreased bone density in elderly patients, putting them at increased risk of insufficiency fractures. Surgical fixation of these fractures faces high rates of failure in part due to the difficulties in achieving secure fixation of hardware in weakened bones. This has become an increasingly prominent issue in recent years due to the notable increase in sacral insufficiency fractures. This project studies the distribution of bone density across the cortical and trabecular bone of the sacrum in order to highlight areas of variable bone density for better surgical planning of screw placement. We hypothesized that there would be significant differences in local cortical and trabecular bone density associated with age and sex. CT scans of the abdomen/pelvis were obtained for 50 patients without fractures. The sacral bones were segmented and manually edited to produce a 3D model of the sacrum. Bone density values were then determined for the full bone from calibrated CT data. This allowed us to create a linear model including age and sex as a predictor of bone density at each of the surface and internal points. A heat map of the bone models was created using a color scale in order to visualize the cortical and trabecular bone mineral density. A trajectory following the typical path of fixation screws in the S1 and S2 segments were manually identified on these bone models and density values across this were estimated. We were able to locate regions of the sacrum where bone mineral density was significantly associated with age as well as sex. This data can be used to identify areas to avoid or target during the surgical planning of screw fixation to improve screw purchase. Further cadaveric biomechanical investigations are suggested to explore this concept. 

Breathing rhythms are initiated in the ventrolateral medulla, in a region known as the preBötzinger complex (preBötC). The preBötC generates normal inspiratory activity and breaths of greater volume called sighs. Sighs prevent the spontaneous collapse of alveoli in the lungs, termed atelectasis, and mice that lack the ability to sigh die of atelectasis after birth. For many years, respiratory physiologists have tried to understand how one network, the preBötC, is able to generate two rhythms with distinct timing mechanisms. In order to test this hypothesis that glia drive the sigh rhythm through purinergic signaling, I will make recordings of neuronal population activity from the preBötC in the horizontal brainstem slice preparation, and apply caged ATP. Brief light pulses will uncage the ATP. We predict that ATP and its conversion to ADP will bind to purinergic receptors to facilitate calcium spread and recruit neurons along the inspiratory column to generate these large breaths. Then, I will apply the purinergic receptor antagonist that we have established is effective in blocking sighs. We observed this result in a preliminary experiment, but more data needs to be collected to confirm this relationship. Next, we will confirm that glial increases in intracellular calcium coincide with sigh generation. We will perform calcium imaging using two photon microscopy in the horizontal slice preparation isolated from transgenic cre mice that express GcAMP6f driven by the astrocyte-specific promoter, Aldh1l1. We predict that calcium activity in astrocytes will correspond with the sigh rhythm, and that we can inhibit sighs by applying purinergic antagonists.