Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVE: We tested the hypothesis that systemic administration of an A2AR agonist will reduce multiorgan IRI in a porcine model of ECPR. SUMMARY BACKGROUND DATA: Advances in ECPR have decreased mortality after cardiac arrest; however, subsequent IRI contributes to late multisystem organ failure. Attenuation of IRI has been reported with the use of an A2AR agonist. METHODS: Adult swine underwent 20 minutes of circulatory arrest, induced by ventricular fibrillation, followed by 6 hours of reperfusion with ECPR. Animals were randomized to vehicle control, low-dose A2AR agonist, or high-dose A2AR agonist. A perfusion specialist using a goal-directed resuscitation protocol managed all the animals during the reperfusion period. Hourly blood, urine, and tissue samples were collected. Biochemical and microarray analyses were performed to identify differential inflammatory markers and gene expression between groups. RESULTS: Both the treatment groups demonstrated significantly higher percent reduction from peak lactate after reperfusion compared with vehicle controls. Control animals required significantly more fluid, epinephrine, and higher final pump flow while having lower urine output than both the treatment groups. The treatment groups had lower urine NGAL, an early marker of kidney injury (P = 0.01), lower plasma aspartate aminotransferase, and reduced rate of troponin rise (P = 0.01). Pro-inflammatory cytokines were lower while anti-inflammatory cytokines were significantly higher in the treatment groups. CONCLUSIONS: Using a novel and clinically relevant porcine model of circulatory arrest and ECPR, we demonstrated that a selective A2AR agonist significantly attenuated systemic IRI and warrants clinical investigation.

Cost-Effectiveness of Negative Pressure Incision Management System in Cardiac Surgery.

BACKGROUND: Sternal wound infections (SWIs) can be a devastating long-term complication with significant morbidity and health care cost. The purpose of this analysis was to evaluate the cost-effectiveness of negative pressure incision management systems (NPIMS) in cardiac surgery. MATERIALS AND METHODS: All cardiac surgery cases at an academic hospital with risk scores available (2009-2017) were extracted from an institutional database (n = 4455). Patients were stratified by utilization of NPIMS, and high risk was defined as above the median. Costs included infection-related readmissions and were adjusted for inflation. Multivariable regression models assessed the risk-adjusted cost of SWI and efficacy of NPIMS use. Cost-effectiveness was modeled using TreeAge Pro using institutional results. RESULTS: The rate of deep SWI was 0.9% with an estimated cost of $111,175 (P < 0.0001). The rate of superficial SWI was 0.8% at a cost of $7981 (P = 0.08). Risk-adjusted NPIMS use was not significantly associated with reduced SWI (OR 1.2, P = 0.62) and thus not cost-effective. However, in the high-risk cohort with an OR 0.84 (P = 0.72) and SWI rate of 2.3%, NPIMS use cost $205 per patient with an incremental cost-effectiveness ratio of $179,092. Therefore, NPIMS is estimated to be cost-effective with a deep SWI rate over 1.3% or improved efficacy (OR < 0.83). CONCLUSIONS: SWIs are extremely expensive complications with estimates of $111,175 for deep yet only $7981 for superficial. Although NPIMS was not cost-effective for SWI prevention as currently utilized, a protocol for use on patients with a higher risk of sternal infection could be cost-effective.

Modifiable Factors Leading to Increased Length of Stay after Carotid Endarterectomy.

BACKGROUND: Carotid endarterectomy (CEA) is a commonly performed vascular operation. Yet, postoperative length of stay (LOS) varies greatly even within institutions. In this study, the morbidity and mortality, as well as financial impact of increased LOS were reviewed to establish modifiable factors associated with prolonged hospital stay. METHODS: The Society for Vascular Surgery Vascular Quality Initiative database was used to identify all patients undergoing primary CEA at a single institution between June 1, 2011 and November 28, 2014. Preoperative patient characteristics, intraoperative details, postoperative factors, long-term outcomes, and cost data were reviewed using an Institutional Review Board-approved prospectively collected database. Multivariate analysis was used to determine statistical difference between patients with LOS ≤1 day and >1 day. RESULTS: Complete 30-day variable and cost data were available for 219 patients with an average follow-up of 12 months. Seventy-nine (36%) patients had an LOS > 1 day. Variables determined to be statistically significant predictors of prolonged LOS included preoperative creatinine (P = 0.02) and severe congestive heart failure (P = 0.05) with self-pay status (P = 0.02) and preoperative beta-blocker therapy (P = 0.04) being protective. Shunt placement (P = 0.04), arterial re-exploration, and postoperative cardiac (P = 0.001) or neurological (P = 0.03) complications also resulted in prolonged hospitalization. Specific modifiable risk factors that contributed to increased LOS included operative start time after noon (P = 0.04), drain placement (P = 0.05), prolonged operative time (101 vs. 125 min, P = 0.01), return to the operating room (P = 0.01), and postoperative hypertension (P = 0.02) or hypotension (P = 0.04). Of note, there was no difference in LOS associated with technique (conventional versus eversion), patch use (P = 0.49), protamine administration (P = 0.60), electroencephalogram monitoring (P = 0.45), measurement of stump pressure (P = 0.63), Doppler (P = 0.36), or duplex (P = 0.92). Both hospital charges (P = 0.0001) and costs (P = 0.0001) were found to be significantly higher in patients with prolonged LOS, with no difference in physician charges (P = 0.10). Increased LOS after CEA was associated with an increase in 12-month mortality (P = 0.05). CONCLUSIONS: Increased LOS was associated with increased hospital charges, costs, as well as significant morbidity and midterm mortality following CEA. Furthermore, this study highlights several modifiable risk factors leading to increased LOS. Identified factors associated with increase LOS can serve as targets for improving care in vascular surgery.

Electronic Glycemic Management System and Endocrinology Service Improve Value in Cardiac Surgery.

BACKGROUND: Postoperative glycemic control improves cardiac surgery outcomes but insulin protocols are limited by complexity and inflexibility. We sought to evaluate the effect of implementing an electronic glycemic management system (eGMS) in conjunction with a cardiac surgery endocrinology consult service on glycemic control and outcomes after cardiac surgery. METHODS: All patients with a calculated preoperative risk of mortality who underwent cardiac surgery before and after implementation of an eGMS and an endocrinology consult service were identified. Glycemic control and surgical outcomes were compared using univariate analysis, and multivariate regression was used to model the risk-adjusted effects of the interventions on glycemic control, surgical outcomes, and resource utilization. The health care-related value added by the interventions was calculated by dividing risk-adjusted outcomes by total hospital costs. RESULTS: A total of 2612 patients were identified, with 1263 patients in the preimplementation cohort and 1349 in the postimplementation cohort. Multivariate regression demonstrated fewer postoperative hyperglycemic events (odds ratio [OR] 0.8, 95% CI, 0.65-0.99) after protocol implementation without an increase in hypoglycemic events (OR 0.96, 95% CI, 0.71-1.3). Average day-weighted mean glucose decreased from 144 to 138 mg/dL (P < .001). The improved glycemic control correlated with a risk-adjusted decrease in composite morbidity or mortality (OR 0.61, 95% CI, 0.47-0.79). Although hospital costs increased after implementation, the protocol increased health care-related value by 38%. CONCLUSION: Implementation of a protocol consisting of an eGMS paired with a cardiac surgery-specific endocrinology consult service was associated with improved glycemic control and reduced morbidity. Despite higher costs health care-related value increased as a result of eGMS implementation.

Reinforcement of the Staple Line during Gastric Sleeve: A Comparison of Buttressing or Oversewing, versus No Reinforcement- A Single-Institution Study.

Laparoscopic sleeve gastrectomy (LSG) is a well-established treatment for morbid obesity. Staple line leak (SLL) remains one of the most serious and life-threatening complications after LSG; however, no consensus exists for prevention. The purpose of this study is to review and compare the different methods of staple line management used at our institution. Retrospective review of preoperative, intraoperative, and postoperative factors was performed for all patients undergoing LSG at a single institution between September 2010 and August 2015. Primary outcome measure was SLL by reinforcement method (none/Seamguard/Oversewing). A total of 256 patients undergoing LSG were included, 197 (76.95%) were women and 233 (87.11%) were whites. The patients had a mean age of 44.64 years and body mass index of 49.24 kg/m-2. Among those patients, 145 (56.64%) had staple line reinforced with suture (28, 10.94%) or Gore Seamguard (115, 44.92%) and 111 (43.36%) had no reinforcement, with no difference in baseline factors between the groups (all P > 0.05). Gastric leaks were identified in nine patients (3.52%) with no difference between reinforcement (2.7 vs 2.1%, P = 0.54) or leak test method (air vs methylene blue). However, oversewing the staple line was associated with higher incidence of stenosis (P < 0.01). SLL after LSG is a serious complication with significant morbidity and mortality. This study demonstrated that staple line reinforcement does not provide significant leak reduction but does reduce intraoperative staple line bleeding. In addition, oversewing the staple line was associated with postoperative sleeve stenosis without added benefits.

Indoleamine-2,3-Dioxygenase in Non-Small Cell Lung Cancer: A Targetable Mechanism of Immune Resistance Frequently Coexpressed With PD-L1.

The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown. One hundred two cases of NSCLC (51 adenocarcinomas, 9 adenosquamous carcinomas, and 42 squamous cell carcinomas) were evaluated for IDO-1 and PD-L1 expression by immunohistochemistry. IDO-1 expression was identified in 43% of NSCLC (42% of adenocarcinomas, 44% of adenosquamous carcinomas, and 43% of squamous cell carcinomas). Coexpression with PD-L1 (≥1%) was common (27% overall; 27% of adenocarcinomas, 33% of adenosquamous carcinomas, and 26% of squamous cell carcinomas). A smaller population of tumors showed isolated PD-L1 (25% overall; 16% of adenocarcinomas, 44% of adenosquamous carcinomas, and 33% of squamous cell carcinomas) or IDO-1 expression (15% overall; 14% of adenocarcinomas, 11% of adenosquamous carcinomas, and 17% of squamous cell carcinomas). In summary, IDO-1 is commonly expressed by NSCLC, and its frequent coexpression with PD-L1 may account for the increased efficacy seen with dual blockade of PD-1/PD-L1 and IDO in clinical studies. IDO-1 immunohistochemistry may be a useful biomarker for selection of patients who could benefit from dual-agent therapy and should be evaluated in prospective clinical trials using PD-1/PD-L1 and IDO inhibitors.

Mitral Valve Repair: The French Correction Versus the American Correction.

Degenerative mitral valve disease causing mitral regurgitation is the most common organic valve pathology and is classified based on leaflet motion. The "French correction" mitral valve repair method restores normal valvular anatomy with extensive leaflet resection, chordal manipulation, and rigid annuloplasty. The American correction attempts to restore normal valve function through minimal leaflet resection, flexible annuloplasty, and use of artificial chordae. These differing methods of mitral valve repair reflect an evolution in principles, but both require understanding of the valve pathology and correction of leaflet prolapse and annular dilatation. Adhering to those unifying principles and ensuring that no patient leaves the operating room with significant persistent mitral regurgitation produces durable results and satisfactory patient outcomes.

Patient Reported Outcomes 10 years After Roux-en-Y Gastric Bypass.

BACKGROUND: Following weight-loss surgery, patients who failed to achieve or sustain weight loss have nevertheless reported high satisfaction with their long-term bariatric experience. Understanding this phenomenon better will likely improve patients' experiences. OBJECTIVE: The purpose of this study was to explore patients' long-term experiences following bariatric surgery. SETTING: A 604-bed academic health system in the USA. METHODS: Participants rated satisfaction and shared spontaneous comments regarding their gastric bypass experience. A phenomenological mode of inquiry explored participants' experiences. Transcribed phrases were categorized and themes identified. RESULTS: In a 2004 surgical cohort, with 55% (155/281) participation, 99% of participants rated bariatric experience satisfaction (mean score 8.4) and 74% (115/155) shared comments regarding experiences. Responses were categorized as positive (63% 72/115), neutral (25% 29/115), or negative (12% 14/115). Satisfaction, Appreciation, and Gratefulness emerged as themes from positive comments, with 8% (6/72) explicitly acknowledging amount of weight loss achieved. Twenty-five percent (18/72) spontaneously mentioned undergoing surgery again or recommending the procedure to others. Neutral comments contained the themes of Reflection, Acknowledgment, and Wistfulness. Themes of Dissatisfaction, Disappointment, and Regret emerged from negative comments. Forty-three percent (6/14) of negative comments remarked on regaining weight or not reaching goal weight. Twenty-one percent (3/14) of negative comments explicitly stated regret at having undergone surgery. CONCLUSIONS: Participants readily shared comments regarding their gastric bypass experience. Exploring themes provided insight into patients' satisfaction with bariatric surgery even when weight-loss goals were not met and conversely substantial dissatisfaction even when weight loss occurred. This study underscores the importance of understanding the patients' long-term experience following bariatric surgery.

The surgical treatment of type two diabetes mellitus.

Since the discovery that gastric bypass surgery leads to the rapid reversal of type 2 diabetes mellitus in morbidly obese patients, researchers have been searching for possible mechanisms to explain the result. The significance of bariatric surgery is twofold. It offers hope and successful therapy to the severely obese; those with T2DM, sleep apnea, or polycystic ovary disease; and others plagued by the comorbidities of the metabolic syndrome. This article examines four surgical procedures and their outcomes.

Impact of pancreatic cancer and subsequent resection on glycemic control in diabetic and nondiabetic patients.

The incidence of new onset or worsening diabetes is surprisingly low in patients after partial pancreatectomy for cancer, leading us to question what factors predict diminished glycemic control in those undergoing resection. All patients undergoing pancreatectomy for cancer at a large, rural university teaching hospital between 1996 and 2010 were identified. The incidence of new onset, or worsening, existing diabetes was determined based on pre and postoperative medication requirement. Univariate analysis was undertaken to identify factors that predict worsened glycemic control. One hundred and one (1 total, 79 Whipple, 21 distal) patients were identified, 41 per cent of which had preexisting diabetes. Nearly half of existing diabetics manifested an increased medication requirement prior to their cancer diagnosis. New onset diabetes occurred in 20 per cent of postoperative patients. Of established diabetics, 34 per cent had either improved glycemic control (9/41) or were cured (5/41) despite the reduction of islet cell mass that occurred with surgery. On univariate analysis, only prolonged hospitalization was associated with worsened glycemic control. Diminished glycemic control is a frequent presenting symptom of pancreatic cancer. Worsened or new onset diabetes is associated with length of stay, which can be influenced by a number of factors including complications and comorbidities.