Estrogen Receptor Hormone Agonists Limit Trauma Hemorrhage Shock-Induced Gut and Lung Injury in Rats

Acute lung injury (ALI) and the development of the multiple organ dysfunction syndrome (MODS) is a major cause of death in trauma patients. Earlier studies in trauma hemorrhagic shock (T/HS) have documented that splanchnic ischemia leading to gut inflammation and loss of barrier function is an initial triggering event that leads to gut-induced ARDS and MODS. Since sex hormones have been shown to modulate the response to T/HS and proestrous (PE) females are more resistant to T/HS-induced gut and distant organ injury, the goal of our study was to determine the contribution of estrogen receptor (ER)alpha and ERbeta in modulating the protective response of female rats to T/HS-induced gut and lung injury.The incidence of gut and lung injury was assessed in PE and ovariectomized (OVX) female rats subjected to T/HS or trauma sham shock (T/SS) as well as OVX rats that were administered estradiol (E2) or agonists for ERalpha or ERbeta immediately prior to resuscitation. Marked gut and lung injury was observed in OVX rats subjected to T/HS as compared to PE rats or E2-treated OVX rats subjected to T/HS. Both ERalpha and ERbeta agonists were equally effective in limiting T/HS-induced morphologic villous injury and bacterial translocation, whereas the ERbeta agonist was more effective than the ERalpha agonist in limiting T/HS-induced lung injury as determined by histology, Evan's blue lung permeability, bronchoalevolar fluid/plasma protein ratio and myeloperoxidase levels. Similarly, treatment with either E2 or the ERbeta agonist attenuated the induction of the intestinal iNOS response in OVX rats subjected to T/HS whereas the ERalpha agonist was only partially protective.Our study demonstrates that estrogen attenuates T/HS-induced gut and lung injury and that its protective effects are mediated by the activation of ERalpha, ERbeta or both receptors

Trauma Hemorrhagic Shock-Induced Lung Injury Involves a Gut-Lymph-Induced TLR4 Pathway in Mice

Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury. Using C3H/HeJ mice that harbor a TLR4 mutation, we found that TLR4 activation was necessary for the development of T/HS porcine lymph-induced lung injury as determined by Evan's blue dye (EBD) lung permeability and myeloperoxidase (MPO) levels as well as the induction of the injurious pulmonary iNOS response. TRIF and Myd88 deficiency fully and partially attenuated T/HS lymph-induced increases in lung permeability respectively. Additional studies in TLR2 deficient mice showed that TLR2 activation was not involved in the pathology of T/HS lymph-induced lung injury. Lastly, the lymph samples were devoid of bacteria, endotoxin and bacterial DNA and passage of lymph through an endotoxin removal column did not abrogate the ability of T/HS lymph to cause lung injury in naïve mice.Our findings suggest that non-microbial factors in the intestinal mesenteric lymph after T/HS are capable of recreating T/HS-induced lung injury via TLR4 activation

A multidisciplinary approach to vascular surgery procedure coding improves coding accuracy, work relative value unit assignment, and reimbursement

BACKGROUND: Vascular surgery procedural reimbursement depends on accurate procedural coding and documentation. Despite the critical importance of correct coding, there has been a paucity of research focused on the effect of direct physician involvement. We hypothesize that direct physician involvement in procedural coding will lead to improved coding accuracy, increased work relative value unit (wRVU) assignment, and increased physician reimbursement. METHODS: This prospective observational cohort study evaluated procedural coding accuracy of fistulograms at an academic medical institution (January-June 2014). All fistulograms were coded by institutional coders (traditional coding) and by a single vascular surgeon whose codes were verified by two institution coders (multidisciplinary coding). The coding methods were compared, and differences were translated into revenue and wRVUs using the Medicare Physician Fee Schedule. Comparison between traditional and multidisciplinary coding was performed for three discrete study periods: baseline (period 1), after a coding education session for physicians and coders (period 2), and after a coding education session with implementation of an operative dictation template (period 3). The accuracy of surgeon operative dictations during each study period was also assessed. An external validation at a second academic institution was performed during period 1 to assess and compare coding accuracy. RESULTS: During period 1, traditional coding resulted in a 4.4% (P = .004) loss in reimbursement and a 5.4% (P = .01) loss in wRVUs compared with multidisciplinary coding. During period 2, no significant difference was found between traditional and multidisciplinary coding in reimbursement (1.3% loss; P = .24) or wRVUs (1.8% loss; P = .20). During period 3, traditional coding yielded a higher overall reimbursement (1.3% gain; P = .26) than multidisciplinary coding. This increase, however, was due to errors by institution coders, with six inappropriately used codes resulting in a higher overall reimbursement that was subsequently corrected. Assessment of physician documentation showed improvement, with decreased documentation errors at each period (11% vs 3.1% vs 0.6%; P = .02). Overall, between period 1 and period 3, multidisciplinary coding resulted in a significant increase in additional reimbursement ($17.63 per procedure; P = .004) and wRVUs (0.50 per procedure; P = .01). External validation at a second academic institution was performed to assess coding accuracy during period 1. Similar to institution 1, traditional coding revealed an 11$13,178 vs $14,630; P = .007) and a 12% loss in wRVU (293 vs 329; P = .01) compared with multidisciplinary coding. CONCLUSIONS: Physician involvement in the coding of endovascular procedures leads to improved procedural coding accuracy, increased wRVU assignments, and increased physician reimbursement

Surgeon leadership in the coding, billing, and contractual negotiations for fenestrated endovascular aortic aneurysm repair increases medical center contribution margin and physician reimbursement

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) allows endovascular treatment of thoracoabdominal and juxtarenal aneurysms previously outside the indications of use for standard devices. However, because of considerable device costs and increased procedure time, FEVAR is thought to result in financial losses for medical centers and physicians. We hypothesized that surgeon leadership in the coding, billing, and contractual negotiations for FEVAR procedures will increase medical center contribution margin (CM) and physician reimbursement. METHODS: At the UMass Memorial Center for Complex Aortic Disease, a vascular surgeon with experience in medical finances is supported to manage the billing and coding of FEVAR procedures for medical center and physician reimbursement. A comprehensive financial analysis was performed for all FEVAR procedures (2011-2015), independent of insurance status, patient presentation, or type of device used. Medical center CM (actual reimbursement minus direct costs) was determined for each index FEVAR procedure and for all related subsequent procedures, inpatient or outpatient, 3 months before and 1 year subsequent to the index FEVAR procedure. Medical center CM for outpatient clinic visits, radiology examinations, vascular laboratory studies, and cardiology and pulmonary evaluations related to FEVAR were also determined. Surgeon reimbursement for index FEVAR procedure, related adjunct procedures, and assistant surgeon reimbursement were also calculated. All financial analyses were performed and adjudicated by the UMass Department of Finance. RESULTS: The index hospitalization for 63 FEVAR procedures incurred $2,776,726 of direct costs and generated$3,027,887 in reimbursement, resulting in a positive CM of $251,160. Subsequent related hospital procedures (n = 26) generated a CM of$144,473. Outpatient clinic visits, radiologic examinations, and vascular laboratory studies generated an additional CM of $96,888. Direct cost analysis revealed that grafts accounted for the largest proportion of costs (55$492,521. Average surgeon reimbursements per FEVAR from 2011 to 2015 increased from $1601 to$2480 while the surgeon payment denial rate declined from 50% to 0%. Surgeon-led negotiations with the Centers for Medicare and Medicaid Services during 2015 resulted in a 27% increase in physician reimbursement for the remainder of 2015 ($2480 vs$3068/case) and a 91% increase in reimbursement from 2011 ($1601 vs$3068). Assistant surgeon reimbursement also increased ($266 vs$764). Concomitant FEVAR-related procedures generated an additional $27,347 in surgeon reimbursement. CONCLUSIONS: Physician leadership in the coding, billing, and contractual negotiations for FEVAR results in a positive medical center CM and increased physician reimbursement

Outcomes of fenestrated and branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms

BACKGROUND: More than 80% of infrarenal aortic aneurysms are treated by endovascular repair. However, adoption of fenestrated and branched endovascular repair for complex aortic aneurysms has been limited, despite high morbidity and mortality associated with open repair. There are few published reports of consecutive outcomes, inclusive of all fenestrated and branched endovascular repairs, starting from the inception of a complex aortic aneurysm program. Therefore, we examined a single center\u27s consecutive experience of fenestrated and branched endovascular repair of complex aortic aneurysms. METHODS: This is a single-center, prospective, observational cohort study evaluating 30-day and 1-year outcomes in all consecutive patients who underwent fenestrated and branched endovascular repair of complex aortic aneurysms (definition: requiring one or more fenestrations or branches). Data were collected prospectively through an Institutional Review Board-approved registry and a physician-sponsored investigational device exemption clinical trial (G130210). RESULTS: We performed 100 consecutive complex endovascular aortic aneurysm repairs (November 2010 to March 2016) using 58 (58%) commercially manufactured custom-made devices and 42 (42%) physician-modified devices to treat 4 (4%) common iliac, 42 (42%) juxtarenal, 18 (18%) pararenal, and 36 (36%) thoracoabdominal aneurysms (type I, n = 1; type II, n = 4; type III, n = 12; type IV, n = 18; arch, n = 1). The repairs included 309 fenestrations, branches, and scallops (average of 3.1 branch arteries/case). All patients had 30-day follow-up for 30-day event rates: three (3%) deaths; six (6%) target artery occlusions; five (5%) progressions to dialysis; eight (8%) access complications; one (1%) paraparesis; one (1%) bowel ischemia; and no instances of myocardial infarction, paralysis, or stroke. Of 10 type I or type III endoleaks, 8 resolved (7 with secondary intervention, 1 without intervention). Mean follow-up time was 563 days (interquartile range, 156-862), with three (3%) patients lost to follow-up. On 1-year Kaplan-Meier analysis, survival was 87%, freedom from type I or type III endoleak was 97%, target vessel patency was 92%, and freedom from aortic rupture was 100%. Average lengths of intensive care unit stay and inpatient stay were 1.4 days (standard deviation, 3.3) and 3.6 days (standard deviation, 3.6), respectively. CONCLUSIONS: These results show that complex aortic aneurysms can now be treated with minimally invasive fenestrated and branched endovascular repair. Endovascular technologies will likely continue to play an increasingly important role in the management of patients with complex aortic aneurysm disease

An intensive vascular surgical skills and simulation course for vascular trainees improves procedural knowledge and self-rated procedural competence

BACKGROUND: Surgical skills and simulation courses are emerging to meet the demand for vascular simulation training for vascular surgical skills, but their educational effect has not yet been described. We sought to determine the effect of an intensive vascular surgical skills and simulation course on the procedural knowledge and self-rated procedural competence of vascular trainees and to assess participant feedback regarding the course. METHODS: Participants underwent a 1.5-day course covering open and endovascular procedures on high-fidelity simulators and cadavers. Before and after the course, participants completed a written test that assessed procedural knowledge concerning index open vascular and endovascular procedures. Participants also assessed their own procedural competence in open and endovascular procedures on a 5-point Likert scale (1: no ability to perform, 5: performs independently). Scores before and after the course were compared among postgraduate year (PGY) 1-2 and PGY 3-7 trainees. Participants completed a survey to rate the relevance and realism of open and endovascular simulations. RESULTS: Fifty-eight vascular integrated residents and vascular fellows (PGY 1-7) completed the course and all assessments. After course participation, procedural knowledge scores were significantly improved among PGY 1-2 residents (50% correct before vs 59% after; P \u3c .0001) and PGY 3-7 residents (52% correct before vs 63% after; P = .003). Self-rated procedural competence was significantly improved among PGY 1-2 (2.2 +/- 0.1 before vs 3.1 +/- 0.1 after; P \u3c .0001) and PGY 3-7 (3.0 +/- 0.1 before vs 3.7 +/- 0.1 after; P \u3c /= .0001). Self-rated procedural competence significantly improved for both endovascular (2.4 +/- 0.1 before vs 3.3 +/- 0.1 after; P \u3c .0001) and open procedures (2.7 +/- 0.1 before vs 3.5 +/- 0.1 after; P \u3c .0001). More than 93% of participants reported they were satisfied or very satisfied with the relevance and realism of the open and endovascular simulations. All participants reported they would recommend the course to other trainees. CONCLUSIONS: This intensive vascular surgical skills and simulation course improved procedural knowledge concerning index open vascular and endovascular procedures among PGY 1-2 and PGY 3-7 trainees. The course also improved self-rated procedural competence across all levels of training for open and endovascular procedures. Trainees rated the value of a surgical skills and simulation course highly. These results support strong consideration for the implementation of similar intensive simulation and surgical skills courses with ongoing objective assessment of their educational effect

Endovascular repair of ruptured abdominal aortic aneurysms does not reduce later mortality compared with open repair

OBJECTIVE: Endovascular aneurysm repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs) reduces in-hospital mortality compared with open repair (OR), but it is unknown whether EVAR reduces long-term mortality. We hypothesized that EVAR of RAAA would independently reduce long-term mortality compared with OR. METHODS: The Vascular Quality Initiative database (2003-2013) was used to determine Kaplan-Meier 1-year and 5-year mortality after EVAR and OR of RAAA. Multivariate analysis was performed to identify patient and operative characteristics associated with mortality at 1 year and 5 years after RAAA repair. RESULTS: Among 590 patients who underwent EVAR and 692 patients who underwent OR of RAAA, the lower mortality seen in the hospital after EVAR (EVAR 23% vs OR 35%; P \u3c .001) persisted at 1 year (EVAR 34% vs OR 42%; P = .001) and 5 years (EVAR 50% vs OR 58%; P = .003) after repair. After adjusting for patient and operative characteristics, EVAR did not independently reduce mortality at 1 year (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.7-1.1) or 5 years (HR, 0.95; 95% CI, 0.77-1.2) compared with OR. Dialysis dependence (HR, 3.9; 95% CI, 1.8-8.6), home oxygen use (HR, 1.9; 95% CI, 1.3-2.7), cardiac ejection fraction \u3c 50% (HR, 1.5; 95% CI, 1.03-2.1), female gender (HR, 1.3; 95% CI, 1.04-1.6), and age (HR, 1.06; 95% CI, 1.05-1.08 per 5 years) as well as cardiac arrest (HR, 3.4; 95% CI, 2.5-4.5), loss of consciousness (HR, 1.7; 95% CI, 1.3-2.2), and preoperative systolic blood pressure \u3c 90 mm Hg (HR, 1.4; 95% CI, 1.1-1.8) on admission predicted mortality at 1 year and 5 years after RAAA repair. Type I endoleak (HR, 2.2; 95% CI, 1.2-3.8) also predicted mortality at 1 year. CONCLUSIONS: EVAR does not independently reduce long-term mortality compared with OR. Patient comorbidities and indices of shock on admission are the primary independent determinants of long-term mortality. However, the lower early mortality observed in the Vascular Quality Initiative for patients selected to undergo EVAR of RAAA compared with patients selected for OR is sustained over time, suggesting that EVAR for RAAA is beneficial in appropriate candidates. Better elucidation of the key selection factors, including aneurysm anatomy, is needed to best select patients for EVAR and OR to reduce long-term mortality

In patients stratified by preoperative risk, endovascular repair of ruptured abdominal aortic aneurysms has a lower in-hospital mortality and morbidity than open repair

OBJECTIVE: Previous studies have reported that endovascular repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs) has lower postoperative mortality than open repair (OR). However, comparisons involved heterogeneous populations that lacked adjustment for preoperative risk. We hypothesize that for RAAA patients stratified by a validated measure of preoperative mortality risk, EVAR has a lower in-hospital mortality and morbidity than does OR. METHODS: In-hospital mortality and morbidity after EVAR and OR of RAAA were compared in patients from the Vascular Quality Initiative (2003-2013) stratified by the validated Vascular Study Group of New England RAAA risk score into low-risk (score 0-1), medium-risk (score 2-3), and high-risk (score 4-6) groups. RESULTS: Among 514 patients who underwent EVAR and 651 patients who underwent OR of RAAA, EVAR had lower in-hospital mortality (25% vs 33%, P = .001). In risk-stratified patients, EVAR trended toward a lower mortality in the low-risk group (n = 626; EVAR, 10% vs OR, 15%; P = .07), had a significantly lower mortality in the medium-risk group (n = 457; EVAR, 37% vs OR, 48%; P = .02), and no advantage in the high-risk group (n = 82; EVAR, 95% vs OR, 79%; P = .17). Across all risk groups, cardiac complications (EVAR, 29% vs OR, 38%; P = .001), respiratory complications (EVAR, 28% vs OR, 46%; P \u3c .0001), renal insufficiency (EVAR, 24% vs OR, 38%; P \u3c .0001), lower extremity ischemia (EVAR, 2.7% vs OR, 8.1%; P \u3c .0001), and bowel ischemia (EVAR, 3.9% vs OR, 10%; P \u3c .0001) were significantly lower after EVAR than after OR. Across all risk groups, median (interquartile range) intensive care unit length of stay (EVAR, 2 [1-5] days vs OR, 6 [3-13] days; P \u3c .0001) and hospital length of stay (EVAR, 6 [4-12] days vs OR, 13 [8-22] days; P \u3c .0001) were lower after EVAR. CONCLUSIONS: This novel risk-stratified comparison using a national clinical database showed that EVAR of RAAA has a lower mortality and morbidity compared with OR in low-risk and medium-risk patients and that EVAR should be used to treat these patients when anatomically feasible. For RAAA patients at the highest preoperative risk, there is no benefit to using EVAR compared with OR

Estradiol and ERβ are more effective than ERα in conferring protection against T/HS induced lung injury.

<p>A) T/HS-induced lung injury, as represented by the percentage of EBD leak within the BALF or B) by the BALF/plasma protein ratio, was increased in the ovariectomized rats and reduced by the administration of estradiol of the estrogen receptor agonists. Data expressed as mean ± SD with 6–8 rats per group. *p<0.01 vs all other groups except the ERα T/HS group. #p<0.01 vs ERα T/SS group. C) T/HS increased the degree of lung neutrophil sequestration, as reflected in MPO levels, in the OVX rats and this was abrogated by the administration of E2 and the ERβ but not the ERα agonist. *p<0.05 vs all other groups.</p