Effects of the COVID-19 Pandemic on Colectomy Outcomes for Inflammatory Bowel Disease.

OBJECTIVES: Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC). These two chronic inflammatory conditions can differ in severity, presentation, and anatomical localization, and can greatly affect quality of life if not managed properly. Given the many healthcare challenges during the coronavirus disease 2019 pandemic, we studied the effects of the pandemic and corresponding changes to medical resources on surgical outcomes for patients with IBD. METHODS: Deidentified data from patients who underwent a colectomy for CD or UC were collected from the National Surgical Quality Improvement Program database of the American College of Surgeons. We analyzed clinical factors and surgical outcomes between 2019 and 2020. RESULTS: Patients with IBD were more likely to have lost >10% of their body mass before the operation in 2020. Operations for patients with UC were significantly shorter in the first year of the pandemic. Patients with CD were less likely to have a urinary tract infection or sepsis postoperatively in 2020, whereas patients with UC were more likely to require a repeat operation. Interestingly, both patient populations were less likely to undergo an emergency operation in 2020 than in 2019. CONCLUSIONS: Colectomy outcomes for patients with CD in 2020 were similar or improved in comparison with those seen in 2019, whereas colectomies for UC saw a statistically but not clinically significant increase in the rate of repeat operations. Overall, these patients seem to have been well managed despite the coronavirus disease 2019 pandemic-induced strain on the healthcare system.

Effects of Preoperative COVID-19 Status on Emergent or Urgent Colectomy Outcomes.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 has been described as eliciting a powerful immune response. The association of coronavirus disease 2019 (COVID-19) infection with diseases requiring emergent or urgent colectomies may exacerbate the risk of surgical complications. We investigated the effect of preoperative COVID-19 infection on the clinical outcomes of patients who underwent a nonelective colectomy in 2021. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program Targeted Colectomy database for all of the patients who underwent a colectomy in 2021 and filtered for patients classified as "Urgent" or "Emergent." Two groups were created based on preoperative COVID-19 status: COVID+ (n = 242) and COVID- cohorts (n = 11,049). Several clinical variables were compared. RESULTS: Before filtering for urgent/emergent operations, a large percentage of COVID+ patients were found to have undergone an urgent or emergency colectomy (68.36% vs 25.05%). Preoperatively, these patients were more likely to be taking steroids (21.49% vs 12.41%) or have a bleeding issue requiring a transfusion (19.42% vs 11.00%). A larger percentage of infected patients returned to the operating room (14.05% vs 8.13%) and had a hospital stay >30 days (18.18% vs 5.35%). COVID-19 infection was associated with a higher rate of mortality (14.05% vs 8.08%) but did not independently predict it (odds ratio 1.25, P = 0.233), with all P ≤ 0.001. CONCLUSIONS: Urgent or emergent colectomy patients who were COVID-19+ preoperatively were more likely to present with comorbidities, which, along with the recent viral infection, contributed to markedly worse clinical outcomes, including an increased rate of mortality.

Effects of COVID-19 Status on Hip Fracture Surgical Outcomes: An ACS NSQIP Study.

BACKGROUND: Studies have indicated that patients infected with the SARS-CoV-2 virus fare worse clinically after a traumatic injury, especially those who are older and have other comorbidities. OBJECTIVE: This study aims to understand the effects of Corona Virus Disease 19 (COVID-19) diagnosis on patients undergoing surgery for hip fractures. METHODS: This is a retrospective review of the 2021 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Targeted Hip Fracture database for patients who underwent surgery. Two cohorts were formed based on patients' preoperative COVID-19 status, as tested within 14 days prior to the operation. Several clinical factors were compared. RESULTS: The COVID-positive cohort consisted of 184 patients, all of whom had a laboratory-confirmed or clinically suspected SARS-CoV-2 infection, while the COVID-negative cohort consisted of 12,211 patients with no infection. A lower proportion of COVID-positive patients had an emergent operation compared to the COVID-negative cohort (58.70% vs. 73.09%, p < .001). Preoperatively, the COVID-positive cohort showed higher rates of coagulopathy/bleeding disorders (22.83% vs. 14.12%), congestive heart failure (16.30% vs. 9.84%), diabetes mellitus (28.26% vs. 19.24%), and dementia (42.39% vs. 28.07%), with p ≤ .005 for all. Postoperatively, a higher proportion of COVID-positive patients died (9.78% vs. 5.40%) or had pneumonia (8.70% vs. 3.65%), hospital readmission within 30 days (10.87% vs. 6.76%), and pressure sores (8.15% vs. 4.55%), with p ≤ .033 for all. CONCLUSION: The diagnosis of COVID-19 in hip fracture patients was associated with higher rates of postoperative complications, including mortality, when compared to COVID-negative patients, indicating the severity of the viral infection.

Cathepsin D interacts with adenosine A2A receptors in mouse macrophages to modulate cell surface localization and inflammatory signaling.

Adenosine A2A receptor (A2AR)-dependent signaling in macrophages plays a key role in the regulation of inflammation. However, the processes regulating A2AR targeting to the cell surface and degradation in macrophages are incompletely understood. For example, the C-terminal domain of the A2AR and proteins interacting with it are known to regulate receptor recycling, although it is unclear what role potential A2AR-interacting partners have in macrophages. Here, we aimed to identify A2AR-interacting partners in macrophages that may effect receptor trafficking and activity. To this end, we performed a yeast two-hybrid screen using the C-terminal tail of A2AR as the "bait" and a macrophage expression library as the "prey." We found that the lysosomal protease cathepsin D (CtsD) was a robust hit. The A2AR-CtsD interaction was validated in vitro and in cellular models, including RAW 264.7 and mouse peritoneal macrophage (IPMΦ) cells. We also demonstrated that the A2AR is a substrate of CtsD and that the blockade of CtsD activity increases the density and cell surface targeting of A2AR in macrophages. Conversely, we demonstrate that A2AR activation prompts the maturation and enzymatic activity of CtsD in macrophages. In summary, we conclude that CtsD is a novel A2AR-interacting partner and thus describe molecular and functional interplay that may be crucial for adenosine-mediated macrophage regulation in inflammatory processes.

Adenosine metabolized from extracellular ATP ameliorates organ injury by triggering A2BR signaling.

BACKGROUND: Trauma and a subsequent hemorrhagic shock (T/HS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5' triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A2BR. The aim of this study was to evaluate the role of CD39 and CD73 delivering adenosine to A2BRs in regulating the host's response to T/HS. METHODS: T/HS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A2BR) and conditional knockout (intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl) mice. At 3 three hours after resuscitation, blood and tissue samples were collected to analyze organ injury. RESULTS: T/HS upregulated the expression of CD39, CD73, and the A2BR in organs. ATP and adenosine levels increased after T/HS in bronchoalveolar lavage fluid. CD39, CD73, and A2BR mimics/agonists alleviated lung and liver injury. Antagonists or the CD39, CD73, and A2BR knockout (KO) exacerbated lung injury, inflammatory cytokines, and chemokines as well as macrophage and neutrophil infiltration and accumulation in the lung. Agonists reduced the levels of the liver enzymes aspartate transferase and alanine transaminase in the blood, whereas antagonist administration or CD39, CD73, and A2BR KO enhanced enzyme levels. In addition, intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl mice showed increased intestinal injury compared to their wild-type VillinCre controls. CONCLUSION: In conclusion, the CD39-CD73-A2BR axis protects against T/HS-induced multiple organ failure.

Racial Disparities in Clinical Outcomes of Emergency Colectomies for Diverticulitis.

OBJECTIVES: The literature suggests that there are ongoing racial disparities in healthcare outcomes between patients in White and non-White populations. As such, we examined the outcomes of patients who underwent an emergency colectomy for diverticulitis. METHODS: We identified 4841 White and 590 non-White patients, which include Black/African American and Asian patients, using the 2016-2019 American College of Surgeons National Surgical Quality Improvement Program databases. We compared Black/African American and Asian patients with White patients for differences in surgical outcomes. RESULTS: Non-White patients had more comorbidities than White patients (P < 0.05). These patients underwent longer operations, developed more postoperative complications, and were more likely to have lengths of stay >30 days. When controlling for all of the covariates in multivariate logistic regression models, White race was independently associated with a 22.14% lower odds of a hospital stay >30 days compared with non-White patients (P = 0.001). CONCLUSIONS: In this study, non-White patients developed more complications than did White patients and had longer hospitalizations. These disparities represent a more complex societal issue that cannot be managed perioperatively alone.

COVID-19 Pandemic Effects on Clinical Outcomes of Hip Fractures Among Pediatric and Adult Patients.

BACKGROUND: Little is known about the distribution and outcomes of hip fractures in pediatric patients during the COVID-19 pandemic. OBJECTIVE: To study the clinical outcomes of both pediatric and adult patients who underwent hip fracture surgeries and determine the effects of changes surrounding the COVID-19 pandemic. METHODS: Both pediatric and adult surgical hip fracture cases were analyzed from the pandemic year (2020) and the control year (2019) using the American College of Surgeons National Surgical Quality Improvement Program database. RESULTS: Between the prepandemic (control) and pandemic years, a total of 2,438 pediatric and 28,180 adult cases were compared. Pediatric patients had similar perioperative characteristics and outcomes between the two years. Significantly fewer hip fractures were reported among adults during the pandemic (p < .001). Preoperatively, more adult patients had ventilator dependence (p = .020), transfusions (p = .029), and systemic inflammatory response syndrome (p < .001) in 2020. Adult operations were more likely to be emergent in 2020 (p < .001) and adults had more severe disease states. Length of stay (p < .001) and the time from operation to discharge (p < .001) were significantly longer for the adult cohort in 2020. Mortality was also higher for adults during the first year of the pandemic (p = .003), and superficial surgical site infections became more common (p = .036). CONCLUSION: Pediatric hip fracture patients had similar clinical outcomes between 2019 and 2020. Adults with hip fractures presented in more serious clinical conditions, which resulted in higher mortality in 2020. Further studies could better clarify the reasons as to why adult hip fracture patients had markedly worse clinical course during the COVID year than pediatric patients.

The impact of gender on clinical outcomes after sustaining a pelvic fracture.

INTRODUCTION: In trauma care, pelvic fractures contribute to morbidity and mortality. Since men and women have different pelvic structures and hormonal milieu, we studied if these gender differences affect clinical outcomes after pelvic fractures. METHODS: Using the 2016 American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) database, we stratified 24,425 patients with pelvic fractures by gender. Male and female patients were analyzed for differences in comorbidities,  mechanism of injury, complications, and other clinical parameters. RESULTS: Female patients were older (p < 0.001) and had more comorbidities (p < 0.001), such as bleeding disorder, congestive heart failure, chronic obstructive pulmonary disorder, dementia, chronic renal failure, diabetes mellitus, and hypertension. Although female patients were sicker before sustaining pelvic fractures, male patients had higher rates of post-trauma complications (p < 0.001), such as acute kidney injury, deep vein thrombosis, unplanned admission to the intensive care unit (ICU), and unplanned return to the operating room (OR). Multivariate logistic regression further supports this as male gender was independently associated with a 26.1% higher risk of developing at least one complication (p < 0.001), despite having a higher average Injury Severity Score (ISS) (21.91 ± 0.09 versus 20.71 ± 0.11, p < 0.001). Interestingly, male patients also had a longer hospital length of stay than female patients (13.36 ± 0.12 days versus 11.8 2± 0.14 days, p < 0.001). CONCLUSION: Even though female patients were older and had more pre-existing comorbidities, male patients developed more complications and had longer hospital stays. Trial registration number Not a clinical trial.

Inosine monophosphate and inosine differentially regulate endotoxemia and bacterial sepsis.

Inosine monophosphate (IMP) is the intracellular precursor for both adenosine monophosphate and guanosine monophosphate and thus plays a central role in intracellular purine metabolism. IMP can also serve as an extracellular signaling molecule, and can regulate diverse processes such as taste sensation, neutrophil function, and ischemia-reperfusion injury. How IMP regulates inflammation induced by bacterial products or bacteria is unknown. In this study, we demonstrate that IMP suppressed tumor necrosis factor (TNF)-α production and augmented IL-10 production in endotoxemic mice. IMP exerted its effects through metabolism to inosine, as IMP only suppressed TNF-α following its CD73-mediated degradation to inosine in lipopolysaccharide-activated macrophages. Studies with gene targeted mice and pharmacological antagonism indicated that A2A , A2B, and A3 adenosine receptors are not required for the inosine suppression of TNF-α production. The inosine suppression of TNF-α production did not require its metabolism to hypoxanthine through purine nucleoside phosphorylase or its uptake into cells through concentrative nucleoside transporters indicating a role for alternative metabolic/uptake pathways. Inosine augmented IL-ß production by macrophages in which inflammasome was activated by lipopolysaccharide and ATP. In contrast to its effects in endotoxemia, IMP failed to affect the inflammatory response to abdominal sepsis and pneumonia. We conclude that extracellular IMP and inosine differentially regulate the inflammatory response.

A2A adenosine receptor activation prevents neutrophil aging and promotes polarization from N1 towards N2 phenotype.

Extracellular adenosine is a biologically active signaling molecule that accumulates at sites of metabolic stress in sepsis. Extracellular adenosine has potent immunosuppressive effects by binding to and activating G protein-coupled A2A adenosine receptors (A2AARs) on the surface of neutrophils. A2AAR signaling reproduces many of the phenotypic changes in neutrophils that are characteristic of sepsis, including decreased degranulation, impaired chemotaxis, and diminished ability to ingest and kill bacteria. We hypothesized that A2AARs also suppress neutrophil aging, which precedes cell death, and N1 to N2 polarization. Using human neutrophils isolated from healthy subjects, we demonstrate that A2AAR stimulation slows neutrophil aging, suppresses cell death, and promotes the polarization of neutrophils from an N1 to N2 phenotype. Using genetic knockout and pharmacological blockade, we confirmed that A2AARs decrease neutrophil aging in murine sepsis induced by cecal ligation and puncture. A2AARs expression is increased in neutrophils from septic patients compared to healthy subject but A2AAR expression fails to correlate with aging or N1/N2 polarization. Our data reveals that A2AARs regulate neutrophil aging in healthy but not septic neutrophils.

Vessel Sealant Devices in Thyroidectomies: An ACS-NSQIP Study.

OBJECTIVES: Thyroidectomies involve meticulous dissection of a highly vascularized organ and complications may develop, such as hematoma, hypocalcemia, and even hypoparathyroidism. Because some of these complications may be fatal, we sought to identify the differences in postthyroidectomy outcomes when the use of a vessel sealant device (VSD) such, as LigaSure or Harmonic scalpel, is compared with more traditional techniques, such as ligatures and clips. METHODS: Using the 2016 American College of Surgeons National Surgical Quality Improvement Program Targeted Thyroidectomy database, we compared patients who underwent a thyroidectomy using a VSD with patients without a VSD for differences in postoperative complications. RESULTS: A total of 5146 cases were identified and 3452 of those cases used a VSD, whose use was associated with significantly lower rates of hematoma, deep vein thrombosis, and hypocalcemia before discharge, as well as a shorter length of stay and longer operation time. Multivariate logistic regression showed that VSD was associated with 32.27% and 39.15% lower odds of hypocalcemia and hematoma, respectively. VSDs also were used more frequently in cases that had multinodular, severe, or substernal goiter or Graves disease as the primary indication for surgery and in patients with a higher body mass index. There was no significant difference in the incidence of recurrent laryngeal nerve injury between the two groups. CONCLUSIONS: Analysis of the American College of Surgeons National Surgical Quality Improvement Program data indicates that VSDs are associated with a lower risk of complications, such as hypocalcemia, hematoma, and deep vein thrombosis, suggesting that VSDs may be a more effective method of hemostasis than traditional techniques.

Comparison of Robotic and Laparoscopic Colectomies Using the 2019 ACS NSQIP Database.

OBJECTIVES: Robot-assisted laparoscopic surgeries (RLSs) have become increasingly common in the past decade alongside conventional laparoscopic surgeries (CLSs). In general, RLSs have been reported to be superior to CLSs; therefore, we compared both methods among patients undergoing an elective colectomy for differences in perioperative factors and postoperative complications. METHODS: A retrospective analysis was conducted using the 2019 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. We stratified 5879 patients into two cohorts according to their preoperative diagnosis of either colon cancer or chronic diverticulitis. Patients within each group were further stratified by operative approach. RESULTS: Of the 5879 patients, 3210 colon cancer and 2669 chronic diverticulitis patients underwent an elective colectomy. There were no differences in length of stay and time from operation to discharge between RLSs and CLSs. RLSs, however, had significantly longer operation times (minutes; colon cancer: RLS 242.9 ± 91.0 vs CLS 177.4 ± 78.2, P < 0.001; chronic diverticulitis: RLS 226.2 ± 87.4 vs CLS 181.7 ± 74.4, P < 0.001). Among all of the colon cancer patients, RLS had higher rates of unplanned return to the operating room (P = 0.028) and organ space surgical site infection (P = 0.035). Among chronic diverticulitis patients, RLS was associated with higher rates of postoperative sepsis, anastomotic leak, organ space surgical site infection, and unplanned readmission (all P < 0.05). CONCLUSIONS: CLS may be the more efficient operative technique because it was associated with a shorter average operation time and fewer postoperative complications. This paradigm, however, may change as the robotic technology develops and surgeons become more experienced with RLS.

Association Between Body Mass Index and Morbidity and Mortality During Hospitalization After Trauma.

BACKGROUND: Literature suggests that unhealthy body mass index is a risk factor for adverse clinical outcomes. OBJECTIVES: To study the association between unhealthy body mass index and morbidity and mortality after trauma using the 2016 American College of Surgeons Trauma Quality Improvement Program database. METHODS: A retrospective review was conducted comparing the normal weight control group to the underweight, overweight, obese, severely obese, and morbidly obese groups for differences in demographic factors, injury severity score, comorbidities, length of stay, and complications. RESULTS: Underweight, overweight, obese, severely obese, and morbidly obese body mass indexes, in comparison to normal weight body mass index, were associated with a higher probability of developing at least one complication after trauma. Additionally, we observed a J-shaped curve when analyzing body mass index and mortality, suggesting that both high and low body mass indexes are positively associated with mortality. In fact, morbidly obese patients had the highest mortality rate, followed by underweight patients (p < .001). Interestingly, however, multivariate logistic regression demonstrated that, compared with normal weight body mass index, overweight and obese body mass indexes were independently associated with 9.6% and 10.5% lower odds of mortality, respectively (p < .001 and p = .001). CONCLUSION: Irrespective of preexisting comorbidities, injury severity score, and mechanism of injury, underweight, overweight, obese, severely obese, and morbidly obese body mass indexes were independently associated with higher risks of morbidity, whereas overweight and obese body mass indexes were associated with lower mortality risks. These findings emphasize the complex relationship between body mass index and clinical outcomes for trauma patients.

Colonic dysmotility associated with high-fat diet-induced obesity: Role of enteric glia.

The present study was designed to examine the role of enteric glial cells (EGCs) in colonic neuromuscular dysfunctions in a mouse model of high-fat diet (HFD)-induced obesity. C57BL/6J mice were fed with HFD or standard diet (SD) for 1, 2, or 8 weeks. Colonic interleukin (IL)-1ß, IL-6, and malondialdehyde (MDA) levels were measured. Expression of occludin in colonic tissues was examined by western blot. Substance P (SP), S100ß, GFAP, and phosphorylated mitogen-activated protein kinase 1 (pERK) were assessed in whole mount specimens of colonic plexus by immunohistochemistry. Colonic tachykininergic contractions, elicited by electrical stimulation or exogenous SP, were recorded in the presence or absence of fluorocitrate (FC). To mimic exposure to HFD, cultured EGCs were incubated with palmitate (PA) and/or lipopolysaccharide (LPS). SP and IL-1ß levels were assayed in the culture medium by ELISA. HFD mice displayed an increase in colonic IL-1ß and MDA, and a reduction of occludin at week 2. These changes occurred to a greater extent at week 8. In vitro electrically evoked tachykininergic contractions were enhanced in HFD mice after 2 or 8 weeks, and they were blunted by FC. Colonic IL-6 levels as well as substance P and S100ß density in myenteric ganglia of HFD mice were increased at week 8, but not at week 1 or 2. In cultured EGCs, co-incubation with palmitate plus LPS led to a significant increase in both SP and IL-1ß release. HFD-induced obesity is characterized by a hyperactivation of EGCs and is involved in the development of enteric motor disorders through an increase in tachykininergic activity and release of pro-inflammatory mediators.

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation.

Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.

Interplay between colonic inflammation and tachykininergic pathways in the onset of colonic dysmotility in a mouse model of diet-induced obesity.

BACKGROUND: The murine model of high fat diet (HFD)-induced obesity is characterized by an increment of intestinal permeability, secondary to an impairment of mucosal epithelial barrier and enteric inflammation, followed by morphofunctional rearrangement of the enteric nervous system. The present study investigated the involvement of abdominal macrophages in the mechanisms underlying the development of enteric dysmotility associated with obesity. METHODS: Wild type C57BL/6J mice were fed with HFD (60% kcal from fat) or normocaloric diet (NCD, 18% kcal from fat) for 8 weeks. Groups of mice fed with NCD or HFD were treated with clodronate encapsulated into liposomes to deplete abdominal macrophages. Tachykininergic contractions, elicited by electrical stimulation or exogenous substance P (SP), were recorded in vitro from longitudinal muscle colonic preparations. Substance P distribution was examined by confocal immunohistochemistry. The density of macrophages in the colonic wall was examined by immunohistochemical analysis. Malondialdehyde (MDA, colorimetric assay) and IL-1ß (ELISA assay) levels were also evaluated. RESULTS: MDA and IL-1ß levels were increased in colonic tissues from HFD-treated animals. In colonic preparations, electrically evoked tachykininergic contractions were enhanced in HFD mice. Immunohistochemistry displayed an increase in substance P immunoreactivity in myenteric ganglia, as well as in the muscular layers of colonic cryosections from obese mice. Macrophage depletion in HFD mice was associated with a significant reduction of colonic inflammation. In addition, the decrease in macrophage density attenuated the morphofunctional alterations of tachykininergic pathways observed in obese mice. CONCLUSION: Obesity elicited by HFD determines a condition of colonic inflammation, followed by a marked rearrangement of motor excitatory tachykininergic enteric nerves. Macrophage depletion counteracted the morphofunctional changes of colonic neuromuscular compartment, suggesting a critical role for these immune cells in the onset of enteric dysmotility associated with obesity.

Adenosine receptors differentially regulate type 2 cytokine production by IL-33-activated bone marrow cells, ILC2s, and macrophages.

Group 2 innate lymphoid cells (ILC2s) represent a rapid source of type 2 cytokines, such as IL-5 and IL-13, and play an important role in orchestrating type 2 immune response. Adenosine is an endogenous purine nucleoside, a catabolite of ATP that binds and activates ≥1 of 4 transmembrane G protein-coupled cell-surface adenosine receptors (ARs)-A1, A2A, A2B, and A3. Here, we studied the role of ARs in the regulation of cytokine production by ILC2s. We found that A2BARs suppress the production of both IL-5 and IL-13 by ILC2s, whereas A2AARs augment IL-5 production and fail to affect IL-13 release. Combined stimulation of all ARs led to the suppression of both IL-5 and IL-13 production, which indicated that A2BARs dominate A2AARs. Both pre- and post-transcriptional processes may be involved in the AR modulation of ILC2 IL-5 and IL-13 production. Thus, we identify adenosine as a novel negative regulator of ILC2 activation.-Csóka, B., Németh, Z. H., Duerr, C. U., Fritz, J. H., Pacher, P., Haskó, G. Adenosine receptors differentially regulate type 2 cytokine production by IL-33-activated bone marrow cells, ILC2s, and macrophages.

Analysis of Transport to an American College of Surgeons Level I Trauma Center.

INTRODUCTION: Efficient patient transportation by ground emergency medical services (GEMS) or helicopter emergency medical services (HEMS) to a trauma center is vital for optimal care. We investigated differences between the modes of transport in terms of demographics, injury, scene location, and outcome. SETTING: Morristown Medical Center (MMC), Morristown, NJ METHODS: All 903 trauma admissions in 2016 by advanced life support (ALS) to MMC, a Level I Trauma Center, were retrospectively analyzed. RESULTS: 22% of admissions were HEMS and 78% were GEMS. HEMS patients had higher Injury Severity Scores (ISS) (p<0.001); however, mortality and length of stay were not statistically different. The percentage of pediatric patients transported by HEMS that were discharged home after emergency department evaluation was greater than the older populations (p<0.001). Older age and higher ISS had the largest impact on mortality (p<0.001). CONCLUSION: We believe our current use of HEMS is adequate since patient outcomes between HEMS and GEMS was similar, even though HEMS patients have higher ISS. However, helicopter use in the pediatric population was over-utilized, possibly due to the scarcity of hospitals capable of managing pediatric traumas. Implementation of the Air Medical Prehospital Triage scoring system may also help correct for these unnecessary HEMS transports.