Impact of Medicaid Expansion on Abdominal Surgery Morbidity, Mortality, and Hospital Readmission.

INTRODUCTION: Medicaid expansion's (ME) impact on postoperative outcomes after abdominal surgery remains poorly defined. We aimed to evaluate ME's effect on surgical morbidity, mortality, and readmissions in a state that expanded Medicaid (Virginia) compared to a state that did not (Tennessee) over the same time period. METHODS: Virginia Surgical Quality Collaborative (VSQC) American College of Surgeons National Surgical Quality Improvement Program data for Medicaid, uninsured, and private insurance patients undergoing abdominal procedures before Virginia's ME (3/22/18-12/31/18) were compared with post-ME (1/1/19-12/31/19), as were corresponding non-ME state Tennessee Surgical Quality Collaborative (TSQC) data for the same 2018 and 2019 time periods. Postexpansion odds ratios for 30-d morbidity, 30-d mortality, and 30-d unplanned readmission were estimated using propensity score-adjusted logistic regression models. RESULTS: In Virginia, 4753 abdominal procedures, 2097 pre-ME were compared to 2656 post-ME. In Tennessee, 5956 procedures, 2484 in 2018 were compared to 3472 in 2019. VSQC's proportion of Medicaid population increased following ME (8.9% versus 18.8%, P < 0.001) while uninsured patients decreased (20.4% versus 6.4%, P < 0.001). Post-ME VSQC had fewer 30-d readmissions (12.2% versus 6.0%, P = 0.013). Post-ME VSQC Medicaid patients had significantly lower probability of morbidity (-8.18, 95% confidence interval: -15.52 ∼ -0.84, P = 0.029) and readmission (-6.92, 95% confidence interval: -12.56 ∼ -1.27, P = 0.016) compared to pre-ME. There were no differences in probability of morbidity or readmission in the TSQC Medicaid population between study periods (both P > 0.05); there were no differences in mortality between study periods in VSQC and TSQC patient populations (both P > 0.05). CONCLUSIONS: ME was associated with decreased 30-d morbidity and unplanned readmissions in the VSQC. Data-driven policies accounting for ME benefits should be considered.

Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery.

OBJECTIVE: To evaluate meaningful, patient-centered outcomes including alive-at-home status and patient-reported quality of life 1 year after cardiac surgery. BACKGROUND: Long-term patient-reported quality of life after cardiac surgery is not well understood. Current operative risk models and quality metrics focus on short-term outcomes. METHODS: In this combined retrospective/prospective study, cardiac surgery patients at an academic institution (2014-2015) were followed to obtain vital status, living location, and patient-reported outcomes (PROs) at 1 year using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS). We assessed the impact of cardiac surgery, discharge location, and Society of Thoracic Surgeons perioperative predicted risk of morbidity or mortality on 1-year outcomes. RESULTS: A total of 782 patients were enrolled; 84.1% (658/782) were alive-at-home at 1 year. One-year PROMIS scores were global physical health (GPH) = 48.8 ±â€Š10.2, global mental health (GMH) = 51.2 ±â€Š9.6, and physical functioning (PF) = 45.5 ±â€Š10.2 (general population reference = 50 ±â€Š10). All 3 PROMIS domains at 1 year were significantly higher compared with preoperative scores (GPH: 41.7 ±â€Š8.5, GMH: 46.9 ±â€Š7.9, PF: 39.6 ±â€Š9.0; all P < 0.001). Eighty-two percent of patients discharged to a facility were alive-at-home at 1 year. These patients, however, had significantly lower 1-year scores (difference: GPH = -5.1, GMH = -5.1, PF = -7.9; all P < 0.001). Higher Society of Thoracic Surgeons perioperative predicted risk was associated with significantly lower PRO at 1 year (P < 0.001). CONCLUSIONS: Cardiac surgery results in improved PROMIS scores at 1 year, whereas discharge to a facility and increasing perioperative risk correlate with worse long-term PRO. One-year alive-at-home status and 1-year PRO are meaningful, patient-centered metrics that help define long-term quality and the benefit of cardiac surgery.

Pulsed Ultrasound of the Spleen Prolongs Survival of Rats With Severe Intra-abdominal Sepsis.

BACKGROUND: The spleen is an important contributor to the uncontrolled, excessive release of proinflammatory signals during sepsis that leads to the development of tissue injury and diffuse end-organ dysfunction. Therapeutic pulsed ultrasound (pUS) has been shown to inhibit splenic leukocyte release and reduce cytokine production in other inflammatory disease processes. We hypothesized that pUS treatment inhibits spleen-derived inflammatory responses and increases survival duration in rats with severe intra-abdominal sepsis leading to septic shock. MATERIALS AND METHODS: Rats with intra-abdominal sepsis, induced by cecal ligation and incision, underwent abdominal washout, intra-peritoneal administration of cefazolin, and then either no further treatment (control), splenectomy, or pUS of the spleen. Animals were observed for the primary endpoint of survival duration. RESULTS: Survival curves were significantly different for all groups (P < 0.01). Median survival increased from 9.5 h in control rats to 19.8 h in pUS rats and 35.0 h in splenectomy rats (P < 0.01). At 4 h after cecal ligation and incision, the pUS group had decreased splenic contraction and leukocyte count (P = 0.03) compared with control, indicating reduced exodus of splenic leukocytes. In addition, elevation in plasma TNF-α and MCP-1 was significantly attenuated in the pUS group (P < 0.05 versus control). Splenic ß2 adrenergic receptor levels and phosphorylated Akt were significantly more elevated in the pUS group (P < 0.01 versus control). CONCLUSIONS: pUS significantly prolonged the survival duration of rats with severe intra-abdominal sepsis. This treatment may be an effective, noninvasive therapy that dampens detrimental immune responses during septic shock by activating ß2 adrenergic receptor-Akt phosphorylation in the cholinergic anti-inflammatory pathway.

Early Versus Delayed Pacemaker for Heart Block After Valve Surgery: A Cost-Effectiveness Analysis.

BACKGROUND: A significant percentage of patients who acutely develop high-grade atrioventricular block after valve surgery will ultimately recover, yet the ability to predict recovery is limited. The purpose of this analysis was to evaluate the cost-effectiveness of two different management strategies for the timing of permanent pacemaker implantation for new heart block after valve surgery. METHODS: A cost-effectiveness model was developed using costs and probabilities of short- and long-term complications of pacemaker placement, short-term atrioventricular node recovery, intensive care unit stays, and long-term follow-up. We aggregated the total expected cost and utility of each option over a 20-y period. Quality-adjusted survival with a pacemaker was estimated from the literature and institutional patient-reported outcomes. Primary decision analysis was based on an expected recovery rate of 36.7% at 12 d with timing of pacemaker implantation: early placement (5 d) versus watchful waiting for 12 d. RESULTS: A strategy of watchful waiting was more costly ($171,798 ± $45,695 versus $165,436 ± $52,923; P < 0.0001) but had a higher utility (9.05 ± 1.36 versus 8.55 ± 1.33 quality-adjusted life years; P < 0.0001) than an early pacemaker implantation strategy. The incremental cost-effectiveness ratio of watchful waiting was $12,724 per quality-adjusted life year. The results are sensitive to differences in quality-adjusted survival and rates of recovery of atrioventricular node function. CONCLUSIONS: Watchful waiting for pacemaker insertion is a cost-effective management strategy compared with early placement for acute atrioventricular block after valve surgery. Although this is cost-effective from a population perspective, clinical risk scores predicting recovery will aid in personalized decision-making.

Topical Neck Cooling Prolongs Survival of Rats with Intra-Abdominal Feculent Sepsis by Activation of the Vagus Nerve.

Global hypothermia prolongs survival in rats with intraabdominal feculent sepsis by inhibiting inflammatory responses. We hypothesized that topical neck cooling (TNC) has similar benefits. Septic shock was induced by cecal ligation and incision (CLI) in Sprague Dawley rats. Rats were randomized to sham laparotomy, control with CLI, CLI with TNC, or vagotomy at the gastroesophageal junction before CLI and TNC. Two more groups underwent peritoneal washout with and without TNC two hours after CLI. TNC significantly lowered neck skin temperature (16.7 ± 1.4 vs. 30.5 ± 0.6 °C, p < 0.05) while maintaining core body normothermia. TNC rats recovered from anesthesia 70 min earlier than the control (p < 0.05). Three hours following CLI, the control and vagotomy with TNC groups had significantly more splenic contraction, fewer circulating leukocytes and higher plasma IL-1ß, IL-10 and TNF-α levels than TNC rats (p < 0.05). TNC prolonged survival duration after CLI by a median of four hours vs. control (p < 0.05), but no benefit was seen if vagotomy preceded TNC. Peritoneal washout alone increased survival by 3 h (9.2 (7.8-10.5) h). Survival duration increased dramatically with TNC preceding washout, to a 56% survival rate (>10 days). TNC significantly prolonged the survival of rats with severe intraabdominal sepsis by inhibiting systemic proinflammatory responses by activating vagal anti-inflammatory pathways.

SPECT imaging of lung ischemia-reperfusion injury using [99mTc]cFLFLF for molecular targeting of formyl peptide receptor 1.

Primary graft dysfunction after lung transplantation, a consequence of ischemia-reperfusion injury (IRI), is a major cause of morbidity and mortality. IRI involves acute inflammation and innate immune cell activation, leading to rapid infiltration of neutrophils. Formyl peptide receptor 1 (FPR1) expressed by phagocytic leukocytes plays an important role in neutrophil function. The cell surface expression of FPR1 is rapidly and robustly upregulated on neutrophils in response to inflammatory stimuli. Thus, we hypothesized that use of [99mTc]cFLFLF, a selective FPR1 peptide ligand, would permit in vivo neutrophil labeling and noninvasive imaging of IRI using single-photon emission computed tomography (SPECT). A murine model of left lung IRI was utilized. Lung function, neutrophil infiltration, and SPECT imaging were assessed after 1 h of ischemia and 2, 12, or 24 h of reperfusion. [99mTc]cFLFLF was injected 2 h before SPECT. Signal intensity by SPECT and total probe uptake by gamma counts were 3.9- and 2.3-fold higher, respectively, in left lungs after ischemia and 2 h of reperfusion versus sham. These values significantly decreased with longer reperfusion times, correlating with resolution of IRI as shown by improved lung function and decreased neutrophil infiltration. SPECT results were confirmed using Cy7-cFLFLF-based fluorescence imaging of lungs. Immunofluorescence microscopy confirmed cFLFLF binding primarily to activated neutrophils. These results demonstrate that [99mTc]cFLFLF SPECT enables noninvasive detection of lung IRI and permits monitoring of resolution of injury over time. Clinical application of [99mTc]cFLFLF SPECT may permit diagnosis of lung IRI for timely intervention to improve outcomes after transplantation.

Socioeconomic "Distressed Communities Index" Improves Surgical Risk-adjustment.

OBJECTIVE: We hypothesize the Distressed Communities Index (DCI), a composite socioeconomic ranking by ZIP code, will predict risk-adjusted outcomes after surgery. SUMMARY OF BACKGROUND DATA: Socioeconomic status affects surgical outcomes; however, the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) database does not account for these factors. METHODS: All ACS NSQIP patients (17,228) undergoing surgery (2005 to 2015) at a large academic institution were paired with the DCI, which accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. Developed by the Economic Innovation Group, DCI scores range from 0 (no distress) to 100 (severe distress). Multivariable regressions were used to evaluate ACS NSQIP predicted risk-adjusted effect of DCI on outcomes and inflation-adjusted hospital cost. RESULTS: A total of 4522 (26.2%) patients came from severely distressed communities (top quartile). These patients had higher rates of medical comorbidities, transfer from outside hospital, emergency status, and higher ACS NSQIP predicted risk scores (all P < 0.05). In addition, these patients had greater resource utilization, increased postoperative complications, and higher short- and long-term mortality (all P < 0.05). Risk-adjustment with multivariate regression demonstrated that DCI independently predicts postoperative complications (odds ratio 1.1, P = 0.01) even after accounting for ACS NSQIP predicted risk score. Furthermore, DCI independently predicted inflation-adjusted cost (+$978/quartile, P < 0.0001) after risk adjustment. CONCLUSIONS: The DCI, an established metric for socioeconomic distress, improves ACS NSQIP risk-adjustment to predict outcomes and hospital cost. These findings highlight the impact of socioeconomic status on surgical outcomes and should be integrated into ACS NSQIP risk models.

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.

Socioeconomically Distressed Communities Index independently predicts major adverse limb events after infrainguinal bypass in a national cohort.

BACKGROUND: Socioeconomic status is a major determinant of not only quality of life, but also mortality and health care-related outcomes. We hypothesized that patients coming from distressed communities would have worse short- and long-term limb related outcomes after infrainguinal bypass. METHODS: The infrainguinal bypass national Vascular Quality Initiative datasets for 2003 to 2018 were used. Clinical data were paired with the Distressed Communities Index (DCI) score before extraction. The DCI accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies at the zip code level, with a range of 0 (no distress) to 100 (severe distress). Severely distressed communities were defined as DCI greater than 75 for univariate analysis. Hierarchical multivariable modeling adjusted for baseline and operative risk factors, and clustering at the hospital level. RESULTS: The 9711 patients who underwent infrainguinal bypass from severely distressed communities (out of 40,109 total) were younger, more likely to smoke, disproportionately African American, with more comorbid disease (all P < .05). Patients from less distressed communities had lower rates of critical limb ischemia (56% DCI ≤ 75 vs 60% DCI > 75; P < .0001) and prior amputation (4.7 vs 6.3%; P < .0001). There was no difference in in-hospital mortality (1.3% vs 1.3%; P = .906) or major adverse cardiovascular events (4.1% vs 3.7%; P = .097). However, patients from distressed communities had higher rates of major adverse limb events (MALE; 11.7% vs 14.4%; P < .0001), and the components amputation, thrombectomy, and revision. After risk adjustment, DCI remained an independent predictor of in-hospital MALE (odds ratio, 1.05 per 25 DCI points; 95% confidence interval [CI], 1.02-1.08; P = .001) and long-term MALE (hazard ration [HR] 1.02; 95% CI, 1.00-1.04; P = .045). DCI is predictive of long-term graft occlusion (HR, 1.04; 95% CI, 1.00-1.07; P = .028) and amputation (HR, 1.09; 95% CI, 1.06-1.12; P < .0001). CONCLUSIONS: The DCI is an independent predictor of MALE after infrainguinal bypass. Patients from distressed communities are at an increased risk of long-term graft occlusion, which is disproportionately treated with amputation instead of surgical limb-saving alternatives. Socioeconomic factors impact vascular disease and surgical outcomes with disparities that warrant further investigation.

Socioeconomic Distressed Communities Index associated with worse limb-related outcomes after infrainguinal bypass.

OBJECTIVE: Several studies have demonstrated that socioeconomic factors may affect surgical outcomes. Analyses in vascular surgery have been limited by the availability of individual or community-level socioeconomic data. We sought to determine whether the Distressed Communities Index (DCI), a composite socioeconomic ranking by ZIP code, could predict short- and long-term outcomes for patients with peripheral artery disease. METHODS: All Virginia Quality Initiative patients (n = 2578) undergoing infrainguinal bypass (2011-2017) within a region of 17 centers were assigned a composite DCI score. The score was developed by the Economic Innovation Group and is normally distributed from 0 (no distress) to 100 (severe distress) based on measures of community unemployment, education level, poverty rate, median income, business growth, and housing vacancies. Severely distressed communities were defined as the top quartile DCI (>75). Hierarchical regression assessed short-term outcomes, and time-to-event analyses assessed long-term results. RESULTS: Infrainguinal bypass patients in this study came from disproportionately distressed communities, with 29% of patients living within the highest distress DCI quartile (P < .0001), with high variability by hospital (DCI range, 12-67). These patients from severely distressed areas were younger, more likely to smoke, and disproportionately African American and had higher rates of medical comorbidities (all P < .05). Whereas patients from severely distressed communities had an equivalent rate of 30-day major adverse cardiac and cerebrovascular events (5% vs 4%; P = .86), they had increased rates of major adverse limb events (MALEs) at 13% vs 10% (P = .03). This trend persisted in the long term, with higher 1-year estimates of MALEs (21% vs 17%; P = .01) as well as the components of amputation (17% vs 12%; P = .006) and thrombectomy (11% vs 6%; P = .002). Patients with high socioeconomic distress also had higher rates of occlusion (17% vs 11%; P = .003). CONCLUSIONS: In this study, patients from severely distressed communities were found to have increased rates of MALEs, an association that persisted long term. Mitigating risk associated with socioeconomic determinants of health has the potential to improve outcomes for patients with peripheral artery disease.

Socioeconomically Distressed Communities Associated With Long-term Mortality After Bariatric Surgery.

BACKGROUND: Surgical outcomes are affected by socioeconomic status, yet these factors are poorly accounted for in clinical databases. We sought to determine if the Distressed Communities Index (DCI), a composite ranking by zip code that quantifies socioeconomic risk, was associated with long-term survival after bariatric surgery. METHODS: All patients undergoing Roux-en-Y gastric bypass (1985-2004) at a single institution were paired with DCI. Scores range from 0 (no distress) to 100 (severe distress) and account for unemployment, education, poverty, median income, housing vacancies, job growth, and business establishment growth. Distressed communities, defined as DCI ≥75, were compared with all other patients. Regression modeling was used to evaluate the effect of DCI on 10-year bariatric outcomes, whereas Cox Proportional Hazards and Kaplan-Meier analysis examined long-term survival. RESULTS: Gastric bypass patients (n = 681) come from more distressed communities compared with the general public (DCI 60.5 ± 23.8 versus 50 ± 10; P < 0.0001). A total of 221 (32.3%) patients came from distressed communities (DCI ≥75). These patients had similar preoperative characteristics, including BMI (51.5 versus 51.7 kg/m2; P = 0.63). Socioeconomic status did not affect 10-year bariatric outcomes, including percent reduction in excess body mass index (57% versus 58%; P = 0.93). However, patients from distressed communities had decreased risk-adjusted long-term survival (hazard ratio, 1.38; P = 0.043). CONCLUSIONS: Patients with low socioeconomic status, as determined by the DCI, have equivalent outcomes after bariatric surgery despite worse long-term survival. Future quality improvement efforts should focus on these persistent disparities in health care.

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.

Determining Which Prosthetic to Use During Aortic Valve Replacement in Patients Aged Younger than 70 Years: A Systematic Review of the Literature.

BACKGROUND: The choice of bioprosthesis versus mechanical prosthesis in patients aged less than 70 years undergoing aortic valve replacement (AVR) remains controversial, with guidelines disparate in their recommendations. The objective of this study was to explore outcomes after AVR for various age ranges based on type of prosthesis. METHODS: A systematic review was undertaken according to the Preferred Reporting Instructions for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using Medline (PubMed), Cochrane, Web of Science, Embase, and Scopus databases. Rates of long-term survival (primary outcome), reoperation, major bleeding, thromboembolism, stroke, structural valve deterioration, and endocarditis were compared between subjects receiving biologic and mechanical prostheses. Findings were grouped into patients aged <60 years, aged ≤65 years, and finally aged <70 years. RESULTS: A total of 19 studies met inclusion criteria. Seven evaluated patients aged <60 years, 4 of which found mechanical prosthesis patients to have higher long-term survival, whereas the remaining studies found no difference. Eight additional studies included patients aged 65 years or younger, and 9 studies included patients aged <70 years. The former found no difference in survival between prosthesis groups, whereas the latter favored mechanical prostheses in 3 studies. Bleeding, thromboembolism, and stroke were more prevalent in patients with a mechanical prosthesis, whereas reoperation was more common in those receiving a bioprosthesis. CONCLUSIONS: Published literature does not preclude the use of bioprostheses for AVR in younger patients. As new valves are developed, the use of bioprosthetic aortic valves in younger patients will likely continue to expand. Clinical trials are needed to provide surgeons with more accurate guidelines.

Can Lung Transplant Surgeons Still Be Scientists? High Productivity Despite Competitive Funding.

BACKGROUND: Today's declining federal budget for scientific research is making it consistently more difficult to become federally funded. We hypothesized that even in this difficult era, surgeon-scientists have remained among the most productive and impactful researchers in lung transplantation. METHODS: Grants awarded by the NIH for the study of lung transplantation between 1985 and 2015 were identified by searching NIH RePORTER for 5 lung transplantation research areas. A grant impact metric was calculated for each grant by dividing the sum of impact factors for all associated manuscripts by the total funding for that grant. We used nonparametric univariate analysis to compare grant impact metrics by department. RESULTS: We identified 109 lung transplantation grants, totaling approximately $300 million, resulting in 2304 papers published in 421 different journals. Surgery has the third highest median grant impact metric (4.2 per $100,000). The department of surgery had a higher median grant impact metric compared to private companies (P <.0001). There was no statistical difference in the grant impact metric compared to all other medical specialties, individual departments with multiple grants, or all basic science departments (all P >.05). CONCLUSIONS: Surgeon-scientists in the field of lung transplantation have received fewer grants and less total funding compared to other researchers but have maintained an equally high level of productivity and impact. The dual-threat academic surgeon-scientist is an important asset to the research community and should continue to be supported by the NIH.

Pannexin-1 channels on endothelial cells mediate vascular inflammation during lung ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury (IRI), which involves inflammation, vascular permeability, and edema, remains a major challenge after lung transplantation. Pannexin-1 (Panx1) channels modulate cellular ATP release during inflammation. This study tests the hypothesis that endothelial Panx1 is a key mediator of vascular inflammation and edema after I/R and that IRI can be blocked by Panx1 antagonism. A murine hilar ligation model of IRI was used whereby left lungs underwent 1 h of ischemia and 2 h of reperfusion. Treatment of wild-type mice with Panx1 inhibitors (carbenoxolone or probenecid) significantly attenuated I/R-induced pulmonary dysfunction, edema, cytokine production, and neutrophil infiltration versus vehicle-treated mice. In addition, VE-Cad-CreERT2+/Panx1fl/fl mice (tamoxifen-inducible deletion of Panx1 in vascular endothelium) treated with tamoxifen were significantly protected from IRI (reduced dysfunction, endothelial permeability, edema, proinflammatory cytokines, and neutrophil infiltration) versus vehicle-treated mice. Furthermore, extracellular ATP levels in bronchoalveolar lavage fluid is Panx1-mediated after I/R as it was markedly attenuated by Panx1 antagonism in wild-type mice and by endothelial-specific Panx1 deficiency. Panx1 gene expression in lungs after I/R was also significantly elevated compared with sham. In vitro experiments demonstrated that TNF-α and/or hypoxia-reoxygenation induced ATP release from lung microvascular endothelial cells, which was attenuated by Panx1 inhibitors. This study is the first, to our knowledge, to demonstrate that endothelial Panx1 plays a key role in mediating vascular permeability, inflammation, edema, leukocyte infiltration, and lung dysfunction after I/R. Pharmacological antagonism of Panx1 activity may be a novel therapeutic strategy to prevent IRI and primary graft dysfunction after lung transplantation.

Molecular imaging of pulmonary diseases.

Imaging holds an important role in the diagnosis of lung diseases. Along with clinical tests, noninvasive imaging techniques provide complementary and valuable information that enables a complete differential diagnosis. Various novel molecular imaging tools are currently under investigation aimed toward achieving a better understanding of lung disease physiopathology as well as early detection and accurate diagnosis leading to targeted treatment. Recent research on molecular imaging methods that may permit differentiation of the cellular and molecular components of pulmonary disease and monitoring of immune activation are detailed in this review. The application of molecular imaging to lung disease is currently in its early stage, especially compared to other organs or tissues, but future studies will undoubtedly reveal useful pulmonary imaging probes and imaging modalities.

Expanding the donor lung pool: how many donations after circulatory death organs are we missing?

BACKGROUND: The number of patients with end-stage pulmonary disease awaiting lung transplantation is at an all-time high, while the supply of available organs remains stagnant. Utilizing donation after circulatory death (DCD) donors may help to address the supply-demand mismatch. The objective of this study is to determine the potential donor pool expansion with increased procurement of DCD organs from patients who die at hospitals. MATERIAL AND METHODS: The charts of all patients who died at a single, rural, quaternary-care institution between August 2014 and June 2015 were reviewed for lung transplant candidacy. Inclusion criteria were age <65 y, absence of cancer and lung pathology, and cause of death other than respiratory or sepsis. RESULTS: A total of 857 patients died within a 1-year period and were stratified by age: pediatric <15 y (n = 32, 4%), young 15-64 y (n = 328, 38%), and old >65 y (n = 497, 58%). Those without cancer totaled 778 (90.8%) and 512 (59%) did not have lung pathology. This leaves 85 patients qualifying for DCD lung donation (pediatric n = 10, young n = 75, and old n = 0). Potential donors were significantly more likely to have clear chest X-rays (24.3% versus 10.0%, P < 0.0001) and higher mean PaO2/FiO2 (342.1 versus 197.9, P < 0.0001) compared with ineligible patients. CONCLUSIONS: A significant number of DCD lungs are available every year from patients who die within hospitals. We estimate the use of suitable DCD lungs could potentially result in a significant increase in the number of lungs available for transplantation.

Stimulation of the Beta2 Adrenergic Receptor at Reperfusion Limits Myocardial Reperfusion Injury via an Interleukin-10-Dependent Anti-Inflammatory Pathway in the Spleen.

BACKGROUND: In addition to the airway-relaxing effects, ß2 adrenergic receptor (ß2AR) agonists are also found to have broad anti-inflammatory effects. The current study was conducted to define the role of ß2AR agonists in limiting myocardial ischemia/reperfusion injury (IRI). Methods and Results: Adult male wild-type (WT) and interleukin (IL)-10 knockout (KO) mice underwent a 40-min left coronary artery ligation and 60-min reperfusion. A selective ß2AR agonist, Clenbuterol, at doses of 0.1 µg or 1 µg/g weight i.v. 5 min before reperfusion, significantly reduced myocardial infarct size (IS) by 28% and 39% (vs. control, P<0.05) in WT mice respectively, but had no protective effect in IL-10 KO mice. Inhalational therapy with nebulized Clenbuterol, Albuterol, Salmeterol or Arformoterol immediately before ischemia significantly reduced IS (P<0.05) in WT mice. Splenectomy similarly reduced IS as Clenbuterol-treated mice, but intravenous Clenbuterol did not further reduce IS in splenectomized mice. In splenectomized WT mice, acute transfer of isolated splenocytes, not the Clenbuterol-pretreated splenocytes, restored the myocardial IS to the level of intact mice. Intravenous Clenbuterol significantly increased splenic protein levels of ß2AR, phosphorylated Akt and IL-10 and plasma IL-10, and inhibited the expression of pro-inflammatory mRNAs. CONCLUSIONS: Both intravenous and inhalational ß2AR agonists exert a cardioprotective effect against IRI by activating the anti-inflammatory ß2AR-IL-10 pathway.

Loss of Medicaid insurance after successful bariatric surgery: an unintended outcome.

BACKGROUND: Bariatric surgery leads to dramatic weight loss and improved overall health, which may affect insurance status for certain patients. Traditional Medicaid provides coverage for children, pregnant women, and disabled adults, while expanded Medicaid provides insurance coverage to all adults with incomes up to 138% of the federal poverty level. We hypothesized that successful bariatric surgery would lead to improved health status but an unintended loss of Medicaid coverage. METHODS: All patients who underwent bariatric surgery at a single institution in a non-expansion state from 1985 through 2015 were identified using a prospectively collected database. Univariate and multivariate analyses were used to identify differences in patients who lost Medicaid coverage after bariatric surgery. RESULTS: Over the 30-year study period, 3487 patients underwent bariatric surgery, with 373 (10.7%) having Medicaid coverage at the time of surgery. This cohort of patients had a median age of 37 years and a preoperative Body Mass Index (BMI) of 54 kg/m2. At one-year follow-up, 155 (41.6%) patients lost Medicaid coverage, of which 76 (49.0%) had no coverage. The preoperative prevalence of diabetes (32.3 vs. 44.0%, p = 0.02), age (36 vs. 38 years, p = 0.01), and BMI (53 vs. 55 kg/m2, p = 0.04) were significantly lower in patients who no longer qualified for Medicaid after bariatric surgery. Multivariate regression demonstrated that for every 10 point increase in BMI (OR 0.755, p = 0.01), a patient was 25% less likely to lose their coverage at one year. CONCLUSIONS: Successful surgery in a state not expanding Medicaid resulted in over 40% of patients losing Medicaid coverage postoperatively, with half of those patients returning for follow-up with no insurance coverage at all. This barrier to care has major implications in patients undergoing bariatric surgery, which requires life-long follow-up and nutrition screening.

Inguinal hernia repair: is there a benefit to using the robot?

BACKGROUND: The number of robotic surgical procedures performed yearly is constantly rising, due to improved dexterity and visualization capabilities compared with conventional methods. We hypothesized that outcomes after robotic-assisted inguinal hernia repair would not be significantly different from outcomes after laparoscopic or open repair. METHODS: All patients undergoing inguinal hernia repair between 2012 and 2016 were identified using institutional American College of Surgeons National Surgical Quality Improvement Program data. Demographics; preoperative, intraoperative, and postoperative characteristics; and outcomes were evaluated based on method of repair (Robot, Lap, or Open). Categorical variables were analyzed by Chi-square test and continuous variables using Mann-Whitney U. RESULTS: A total of 510 patients were identified who underwent unilateral inguinal hernia repair (Robot: 13.8% [n = 69], Lap: 48.1% [n = 241], Open: 38.1% [n = 191]). There were no demographic differences between groups other than age (Robot: 52 [39-62], Lap: 57 [45-67], and Open: 56 [48-67] years, p = 0.03). Operative duration was also different (Robot: 105 [76-146] vs. Lap: 81 [61-103] vs. Open: 71 [56-88] min, p < 0.001). There were no operative mortalities and all patients except one were discharged home the same day. Postoperative occurrences (adverse events, readmissions, and death) were similar between groups (Robot: 2.9% [2], Lap: 3.3% [8], Open: 5.2% [10], p = 0.53). Although rare, there was a significant difference in rate of postoperative skin and soft tissue infection (Robot: 2.9% [2] vs. Lap: 0% [0] vs. Open: 0.5% [1], p = 0.02). Cost was significantly different between groups (Robot: $7162 [$5942-8375] vs. Lap: $4527 [$2310-6003] vs. Open: $4264 [$3277-5143], p < 0.001). CONCLUSIONS: Outcomes after robotic-assisted inguinal hernia repair were similar to outcomes after laparoscopic or open repair. Longer operative duration during robotic repair may contribute to higher rates of skin and soft tissue infection. Higher cost should be considered, along with surgeon comfort level and patient preference when deciding whether inguinal hernia repair is approached robotically.