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Mesenchymal Stem Cell-Derived Exosomes Provide Neuroprotection and Improve Long-Term Neurologic Outcomes in a Swine Model of Traumatic Brain Injury and Hemorrhagic Shock
Williams, Aaron M; Dennahy, Isabel S; Bhatti, Umar F; Halaweish, Ihab; Xiong, Ye; Chang, Panpan; Nikolian, Vahagn C; Chtraklin, Kiril; Brown, Jordana; Zhang, Yanlu; Zhang, Zheng Gang; Chopp, Michael; Buller, Benjamin; Alam, Hasan B
Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remains a leading cause of preventable death worldwide. Mesenchymal stem cell-derived exosomes have demonstrated promise in small animal models of neurologic injury. To investigate the effects of exosome treatment in a clinically realistic large animal model, Yorkshire swine underwent TBI and HS. Animals were maintained in shock for 2 h before resuscitation with normal saline (NS). Animals were then resuscitated either with NS (3 × volume of shed blood) or with the same volume of NS with delayed exosome administration (1 × 1013 particles/4 mL) (n = 5/cohort). Exosomes were administered 9 h post-injury, and on post-injury days (PID) 1, 5, 9, and 13. Neurologic severity scores (NSS) were assessed for 30 days, and neurocognitive functions were objectively measured. Exosome-treated animals had significantly lower NSS (p < 0.05) during the first five days of recovery. Exosome-treated animals also had a significantly shorter time to complete neurologic recovery (NSS = 0) compared with animals given NS alone (days to recovery: NS = 16.8 ± 10.6; NS + exosomes = 5.6 ± 2.8; p = 0.03). Animals treated with exosomes initiated neurocognitive testing earlier (days to initiation: NS = 9.6 ± 0.5 vs. NS + exosomes = 4.2 ± 0.8; p = 0.008); however, no difference was seen in time to mastery of tasks. In conclusion, treatment with exosomes attenuates the severity of neurologic injury and allows for faster neurologic recovery in a clinically realistic large animal model of TBI and HS.
PMID: 29690826
ISSN: 1557-9042
CID: 5927292
Statewide Clinic Registries: The Michigan Surgical Quality Collaborative
Nikolian, Vahagn C; Regenbogen, Scott E
Regional clinical registries provide a unique opportunity for shared learning and population-based analyses of the quality of surgical care. Through the "Michigan Model" of pay for participation in strategic Value Partnerships, exemplified by the Michigan Surgical Quality Collaborative (MSQC), the state's dominant private insurer, Blue Cross Blue Shield of Michigan, has sponsored 20 statewide clinical quality improvement collaboratives. MSQC represents a partnership among 73 Michigan hospitals with a robust data infrastructure and flexible platform for the promulgation of best practices in surgical quality improvement. This article will describe the organizational structure of the MSQC, the contributions the registry has made to quality improvement in colorectal surgery, and how future work will align to improve the reliability of improvement-relevant registry data.
PMCID:6327739
PMID: 30647542
ISSN: 1531-0043
CID: 5927472
Patient-Reported Outcomes and Readmission after Ileostomy Creation in Older Adults
Kandagatla, Pridvi; Nikolian, Vahagn C; Matusko, Niki; Mason, Shayna; Regenbogen, Scott E; Hardiman, Karin M
Because of the concern about risk of poor outcome, ileostomy creation is sometimes avoided in older adults. We sought to evaluate the effect of a rigorous postoperative pathway and checklist on readmission and self-efficiacy in older surgical patients. After implementing a self-care checklist and standardized care pathway at our institution, we performed a retrospective review of patients between June 2013 and June 2016 and compared characteristics and outcomes for patients aged <65 and ≥65 years. Using logistic regression, we identified independent predictors of readmission. We also conducted a survey of patient self-efficacy after discharge to assess independence. There were 288 younger patients and 72 older patients. The older group had more patients with an American Society of Anesthesiologists >2 (53.0% vs 81.4%, P < 0.01) and were more likely to have had surgery for cancer (22.9% vs 48.5%, P < 0.01). In the multivariable analyses, age was not a predictor of readmission but American Society of Anesthesiologist and length of stay were. In the 57 patients surveyed after discharge, we found that older and younger patients reported similar self-efficacy scores. In our study, older and younger patients have similar rates of readmission and similar ability to independently care for their themselves after ileostomy creation.
PMCID:6613972
PMID: 30747639
ISSN: 1555-9823
CID: 5927092
Pilot Study to Evaluate the Safety, Feasibility, and Financial Implications of a Postoperative Telemedicine Program
Nikolian, Vahagn C; Williams, Aaron M; Jacobs, Benjamin N; Kemp, Michael T; Wilson, Jesse K; Mulholland, Michael W; Alam, Hasan B
BACKGROUND:Telemedicine in surgery holds promise for improving access and decreasing costs, but its role remains ill-defined. This pilot study was performed to investigate the safety, feasibility, and financial implications of providing postoperative care using an electronic clinic (eClinic) at a university hospital. METHODS:An easy-to-use and secure eClinic platform was constructed in Epic (Epic Systems Corporation, Verona, WA). Patients undergoing laparoscopic cholecystectomy, appendectomy, and hernia repairs on an adult acute care surgery service were enrolled in this program over an 11-month period (March 2017 to January 2018). Patients with prolonged hospitalizations (greater than 4 nights), perioperative complications, drains, and open wounds were excluded. Demographics, clinical outcomes, encounter time, patient satisfaction survey results, and cost analysis were compared with the traditional clinic (tClinic) patient population. RESULTS:Two hundred thirty-three eligible patients (61% female; mean age 41 ± 16 years) were enrolled in this program. Their demographics were no different than the tClinic. Frequencies of readmission, reoperation, and emergency department visits (2.7%, 0%, and 4.2%, respectively) in the eClinic group were also similar to the tClinic group. However, total visit time was significantly shorter in the eClinic group (14 vs 145 minutes, P < 0.01). Anonymous surveys demonstrated a high degree of satisfaction, with 85% of patients expressing desire to utilize the eClinic again. This program enhanced the capacity for new visits to tClinic, with a resultant projected increase in additional operative cases and revenue for the health care system. CONCLUSIONS:A safe and efficient postoperative telemedicine program can be constructed utilizing a widely available electronic medical record system, which can improve patient satisfaction, optimize throughput, and increase gross charges for the healthcare system.
PMID: 30095477
ISSN: 1528-1140
CID: 5927012
Impact of a resident's sex on intraoperative entrustment of surgery trainees
Thompson-Burdine, Julie; Sutzko, Danielle C; Nikolian, Vahagn C; Boniakowski, Anna; Georgoff, Patrick E; Prabhu, Kaustubh A; Matusko, Niki; Minter, Rebecca M; Sandhu, Gurjit
BACKGROUND:Optimizing intraoperative education is critical for development of autonomous residents. Faculty decisions concerning intraoperative entrustment determine the degree to which a resident gains intraoperative responsibility. Accordingly, residents exhibit entrustable behaviors that further faculty entrustment in the operating room. Little empiric evidence exists evaluating how the sex of a resident influences faculty-resident decisions of entrustment. Studies involving perception-based measurements of autonomy report inequities for women residents. We sought to assess faculty behaviors in entrustment in relation to resident sex using OpTrust, a third-party objective measurement tool. METHODS:From September 2015 to June 2017 at the University of Michigan, surgical cases were observed and entrustment behaviors were rated using OpTrust. Critical case sampling was used to generate variation in operation type, case difficulty, faculty-resident pairings, faculty experience, and the level of the resident's training. Independent sample t-tests were conducted to compare faculty entrustment scores, as well as resident entrustability scores. RESULTS:A total of 56 faculty and 73 residents were observed across 223 surgical cases from 4 surgical specialties: general, plastic, thoracic, and vascular. There was no difference in faculty entrustment or entrustability scores between women and men (2.54 vs 2.35, P = .117 and 2.32 vs 2.22, P = .393, respectively). CONCLUSION:Using OpTrust scores, we found that a resident's sex does not appear to influence faculty entrustment in the OR. Faculty entrustment scores for women and men residents are similar across cases. This observation suggests that during the intraoperative interaction, faculty are not extending entrustment or opportunities for autonomy differently to women or men. Future research is needed to identify and measure perioperative elements that inform resident autonomy, which may contribute to inequities for women residents.
PMID: 30041964
ISSN: 1532-7361
CID: 5927002
Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine
Williams, Aaron M; Bhatti, Umar F; Dennahy, Isabel S; Chtraklin, Kiril; Chang, Panpan; Graham, Nathan J; Baccouche, Basil M; Roy, Shalini; Harajli, Mohammed; Zhou, Jing; Nikolian, Vahagn C; Deng, Qiufang; Tian, Yuzi; Liu, Baoling; Li, Yongqing; Hays, Gregory L; Hays, Julia L; Alam, Hasan B
Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the forefront of trauma care in recent years. Since complete aortic occlusion presents serious concerns, the concept of partial aortic occlusion has gained a growing attention. Here, we present a large animal model of hemorrhagic shock to investigate the effects of a novel partial aortic balloon occlusion catheter and compare it with a catheter that works on the principles of complete aortic occlusion. Swine are anesthetized and instrumented in order to conduct controlled fixed-volume hemorrhage, and hemodynamic and physiological parameters are monitored. Following hemorrhage, aortic balloon occlusion catheters are inserted and inflated in the supraceliac aorta for 60 min, during which the animals receive whole-blood resuscitation as 20% of the total blood volume (TBV). Following balloon deflation, the animals are monitored in a critical care setting for 4 h, during which they receive fluid resuscitation and vasopressors as needed. The partial aortic balloon occlusion demonstrated improved distal mean arterial pressures (MAPs) during the balloon inflation, decreased markers of ischemia, and decreased fluid resuscitation and vasopressor use. As swine physiology and homeostatic responses following hemorrhage have been well-documented and are like those in humans, a swine hemorrhagic shock model can be used to test various treatment strategies. In addition to treating hemorrhage, aortic balloon occlusion catheters have become popular for their role in cardiac arrest, cardiac and vascular surgery, and other high-risk elective surgical procedures.
PMCID:6231876
PMID: 30199035
ISSN: 1940-087x
CID: 5927032
Rapid valproic acid-induced modulation of the traumatic proteome in a porcine model of traumatic brain injury and hemorrhagic shock
Weykamp, Michael; Nikolian, Vahagn C; Dennahy, Isabel S; Higgins, Gerald A; Georgoff, Patrick E; Remmer, Henriette; Ghandour, Mohamed H; Alam, Hasan B
BACKGROUND:Histone deacetylase inhibitors such as valproic acid (VPA) improve survival in lethal models of hemorrhagic shock and polytrauma. Although VPA is known to modulate transcription, its ability to reduce mortality within minutes of administration suggests involvement of a rapid, posttranslational mechanism. We hypothesized that VPA treatment would cause proteomic changes within minutes of treatment including quantitative and/or posttranslational differences in structural and/or effector proteins. MATERIALS AND METHODS:We used a porcine model of traumatic brain injury (computer-controlled cortical impact, 12 mm depth) and hemorrhagic shock (40% hemorrhage). Animals were kept in shock for 2 h and randomized to two groups (n = 3): normal saline (volume = 3:1 hemorrhage volume) or normal saline + VPA (150 mg/kg, single dose). Peripheral blood mononuclear cells were collected at baseline, postshock, and postresuscitation. Intracellular protein profiles were assessed using 1 dimensional gel electrophoresis, liquid chromatography, mass spectrometry, and analyzed with Ingenuity Pathway Analysis software. RESULTS:Animals treated with VPA demonstrated significant proteomic changes. Quantitative differences were found in over 200 proteins including effector, regulatory, and structural proteins in critical cell signaling pathways. Posttranslational modification analysis demonstrated differential VPA-induced acetylation of lysine residues in histone and nonhistone proteins. Pathway analysis correlated these changes with significant increases in numerous prosurvival and cytoskeletal intracellular pathways, including Rho GTPase signaling (P = 1.66E-11), integrin signaling (P = 4.19E-21), and a decrease in Rho guanosine nucleotide dissociation inhibitor signaling (P = 4.83E-12). CONCLUSIONS:In a porcine model of severe injuries, a single dose of VPA is associated with protective changes in the proteome that are measurable within minutes of treatment.
PMID: 29907235
ISSN: 1095-8673
CID: 5926992
Improving the feasibility and utility of OpTrust-A tool assessing intraoperative entrustment
Nikolian, Vahagn C; Sutzko, Danielle C; Georgoff, Patrick E; Matusko, Niki; Boniakowski, Anna; Prabhu, Kaustubh; Church, Joseph T; Thompson-Burdine, Julie; Minter, Rebecca M; Sandhu, Gurjit
BACKGROUND:Changes in the surgical training landscape have sparked an interest in developing new educational models anchored on entrustment assessment. We sought to optimize the validated OpTrust entrustment assessment tool by comparing ratings from short-course video reviews to previously validated intraoperative assessments. METHODS:Entrustment assessment scores for video-based and 1-h (short-course) observations were compared to previously validated intraoperative assessment scores. Faculty and residents were surveyed for their perceptions related to operative observation. RESULTS: = 0.65-0.76, p < 0.01). The majority of faculty and residents (>97%) felt observation did not negatively impact operative experience. CONCLUSIONS:Assessment of entrustment behaviors using short-course video review provides a feasible approach to intraoperative assessment. This latest application of OpTrust allows for the tool to be incorporated into surgical training programs across a variety of environments.
PMID: 29128100
ISSN: 1879-1883
CID: 5927212
Association of Faculty Entrustment With Resident Autonomy in the Operating Room
Sandhu, Gurjit; Thompson-Burdine, Julie; Nikolian, Vahagn C; Sutzko, Danielle C; Prabhu, Kaustubh A; Matusko, Niki; Minter, Rebecca M
IMPORTANCE:A critical balance is sought between faculty supervision, appropriate resident autonomy, and patient safety in the operating room. Variability in the release of supervision during surgery represents a potential safety hazard to patients. A better understanding of intraoperative faculty-resident interactions is needed to determine what factors influence entrustment. OBJECTIVE:To assess faculty and resident intraoperative entrustment behaviors and to determine whether faculty behaviors drive resident entrustability in the operating room. DESIGN, SETTING, AND PARTICIPANTS:This observational study was conducted from September 1, 2015, to August 31, 2016, at Michigan Medicine, the University of Michigan's health care system. Two surgical residents, 1 medical student, 2 behavioral research scientists, and 1 surgical faculty member observed surgical intraoperative interactions between faculty and residents in 117 cases involving 28 faculty and 35 residents and rated entrustment behaviors. Without intervening in the interaction, 1 or 2 researchers observed each case and noted behaviors, verbal and nonverbal communication, and interaction processes. Immediately after the case, observers completed an assessment using OpTrust, a validated tool designed to assess progressive entrustment in the operating room. Purposeful sampling was used to generate variation in type of operation, case difficulty, faculty-resident pairings, faculty experience, and resident training level. MAIN OUTCOMES AND MEASURES:Observer results in the form of entrustability scores (range, 1-4, with 4 indicating full entrustability) were compared with resident- and faculty-reported measures. Difficulty of operation was rated on a scale of 1 to 3 (higher scores indicate greater difficulty). Path analysis was used to explore direct and indirect effects of the predictors. Associations between resident entrustability and observation duration, observation month, and faculty entrustment scores were assessed by pairwise Pearson correlation coefficients. RESULTS:Twenty-eight faculty and 35 residents were observed across 117 surgical cases from 4 surgical specialties. Cases observed by postgraduate year (PGY) of residents were distributed as follows: PGY-1, 21 (18%); 2, 15 (13%); 3, 17 (15%); 4, 27 (23%); 5, 28 (24%); and 6, 9 (8%). Case difficulty was evenly distributed: 36 (33%) were rated easy/straightforward; 43 (40%), moderately difficult; and 29 (27%), very difficult by attending physicians. Path analysis showed that the association of PGY with resident entrustability was mediated by faculty entrustment (0.23 [.03]; P < .001). At the univariate level, case difficulty (mean [SD] resident entrustability score range, 1.97 [0.75] for easy/straightforward cases to 2.59 [0.82] for very difficult cases; F = 6.69; P = .01), PGY (range, 1.31 [0.28] for PGY-1 to 3.16 [0.54] for PGY-6; F = 22.85; P < .001), and faculty entrustment (2.27 [0.79]; R2 = 0.91; P < .001) were significantly associated with resident entrustability. Mean (SD) resident entrustability scores were highest for very difficult cases (2.59 [0.82]) and PGY-6 (3.16 [0.54]). CONCLUSIONS AND RELEVANCE:Faculty entrustment behaviors may be the primary drivers of resident entrustability. Faculty entrustment is a feature of faculty surgeons' teaching style and could be amenable to faculty development efforts.
PMID: 29466559
ISSN: 2168-6262
CID: 5927282
Valproic Acid Treatment Decreases Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels in Swine Subjected to Traumatic Brain Injury
Korley, Frederick K; Nikolian, Vahagn C; Williams, Aaron M; Dennahy, Isabel S; Weykamp, Michael; Alam, Hasan B
The primary aim of this study was to examine the effects of valproic acid (VPA) treatment on serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NF-L) levels. To achieve this aim, we obtained serum samples from: 1) 10 Yorkshire swine subjected to controlled cortical impact traumatic brain injury (CCI TBI) + polytrauma and randomized to receive either normal saline (NS) + VPA (n = 5) or NS alone (n = 5) and 2) five additional swine subjected to CCI TBI without polytrauma and treated with VPA. GFAP and NF-L levels were measured in samples obtained from baseline until 10 days post-injury using a digital immunoassay from Quanterix Corporation. We found that elevated GFAP and NF-L levels were first detected at 2 h post-injury; and peaked at 24 h and 72 h respectively. GFAP levels returned to baseline levels by Day 10, while NF-L remained elevated at Day 10. In TBI + polytrauma swine, the magnitude and duration of biomarker elevation, quantified by the area under the biomarker-concentration-versus-time curve during the first 10 days (AUC0-10days), was higher in the NS group, compared with the VPA group. For GFAP, the AUC0-10days was 45,535 (IQR: 35,741-105,711) and 22,837 (IQR: 8,082-46,627) for the NS and NS+VPA groups, respectively. For NF-L, the AUC0-10days was 43,073 (IQR: 18,739-120,794) and 4,475 (2,868-11,157) for the NS and NS+VPA groups, respectively. Twenty-four hour GFAP and NF-L levels had the strongest correlation with lesion size and time to normalization of behavior. Accordingly, we conclude that treatment with VPA results in significantly lower serum GFAP and NF-L levels. The time-point at which GFAP and NF-L levels have the strongest correlation with outcome is 24 h post-injury.
PMID: 29415612
ISSN: 1557-9042
CID: 5927272