24 results on '"Harr JN"'
Search Results
2. The effect of obesity on laparoscopic and robotic-assisted colorectal surgery outcomes: an ACS-NSQIP database analysis.
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Harr JN, Haskins IN, Amdur RL, Agarwal S, and Obias V
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- Aged, Colonic Diseases complications, Colonic Diseases epidemiology, Colonic Diseases surgery, Conversion to Open Surgery statistics & numerical data, Female, Humans, Male, Middle Aged, Postoperative Complications, Retrospective Studies, Treatment Outcome, Colorectal Surgery adverse effects, Colorectal Surgery methods, Colorectal Surgery statistics & numerical data, Laparoscopy adverse effects, Laparoscopy methods, Laparoscopy statistics & numerical data, Obesity complications, Obesity epidemiology, Robotic Surgical Procedures adverse effects, Robotic Surgical Procedures methods, Robotic Surgical Procedures statistics & numerical data
- Abstract
Advantages of robotic-assisted colorectal surgery have been reported, but the effect on outcomes between obese and non-obese patients undergoing laparoscopic and robotic-assisted colorectal surgery remains unclear. Patients who underwent elective laparoscopic and robotic colon or rectal resections between 2012 and 2014 were identified in the ACS-NSQIP database. Propensity score matching was performed to determine the effect of obesity on laparoscopic and robotic-assisted 30-day surgical outcomes. 29,172 patients met inclusion criteria; 27,693 (94.9%) underwent laparoscopic colorectal surgery while 1479 (5.1%) underwent robotic-assisted surgery. Mean BMI was 28.4 kg/m
2 and 35% of patients had a BMI ≥30 kg/m2 . A 10-to-1 propensity matching of laparoscopic to robotic approaches was performed, resulting in 14,770 (90.9%) laparoscopic patients and 1477 (9.1%) robotic-assisted patients available for analysis. Robotic-assisted surgery was associated with lower conversion to laparotomy (2.4 vs 3.4%; p = 0.04) and decreased length-of-stay (4.5±3.2 vs 5.1±4.5 days; p < 0.0001). After adjusting for BMI and surgical approach, obese patients undergoing robotic-assisted surgery had a reduced odds ratio for developing prolonged ileus (p = 0.03). Robotic-assisted colorectal surgery is associated with fewer conversions to laparotomy and shorter length-of-stays compared to laparoscopic surgery. Risk of prolonged ileus is significantly reduced in obese patients undergoing a robotic-assisted approach.- Published
- 2018
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3. Robotic-assisted colorectal surgery in obese patients: a case-matched series.
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Harr JN, Luka S, Kankaria A, Juo YY, Agarwal S, and Obias V
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- Adult, Aged, Case-Control Studies, Colonic Diseases complications, Conversion to Open Surgery statistics & numerical data, Female, Humans, Male, Middle Aged, Operative Time, Postoperative Complications epidemiology, Postoperative Complications etiology, Rectal Diseases complications, Retrospective Studies, Treatment Outcome, Colectomy methods, Colonic Diseases surgery, Laparoscopy methods, Obesity complications, Rectal Diseases surgery, Rectum surgery, Robotic Surgical Procedures
- Abstract
Background: Reports demonstrate laparoscopic colorectal surgery in obese patients is associated with higher conversion to laparotomy and complication rates. While several advantages of robotic-assisted surgery have been reported, outcomes in obese patients have not been adequately studied. Therefore, this study compares outcomes of robotic-assisted surgery in non-obese and obese patients., Methods: A retrospective review of 331 consecutive robotic procedures performed at a single institution between 2009 and 2015 was performed. Patients were divided into non-obese (BMI <30 kg/m
2 ) and obese (BMI ≥30 kg/m2 ) groups, and were clinically matched by gender, age, and procedure performed. Intraoperative and postoperative complications, operative time, estimated blood loss, and length of stay were examined., Results: Following matching, each group included 108 patients comprised of 50 men and 58 women. Mean BMI was 24.6 ± 3.15 and 36.2 ± 5.67 kg/m2 (p < 0.0001), and the mean age was 59.2 ± 11.28 years for non-obese patients and 57.1 ± 12.44 for obese patients (p = 0.18). Surgeries included low anterior resection, right colectomy, left colectomy, sigmoid colectomy, excision of rectal endometriosis, total proctocolectomy, APR, subtotal colectomy, ileocecectomy, proctectomy, rectopexy, transanal excision of rectal mass, and colostomy site hernia repair. The mean operative time was 272.69 ± 115.43 and 282.42 ± 120.51 min (p = 0.55), estimated blood loss 195.23 ± 230.37 and 289.19 ± 509.27 mL (p = 0.08), conversion to laparotomy 6.48 and 9.26 % (p = 0.45), and length of stay 5.38 ± 4.94 and 4.56 ± 4.04 days (p = 0.18) for the non-obese and obese groups, respectively. Twenty of the non-obese patients had postoperative complications as compared to 27 of the obese patients (p = 0.30). However, the prevalence of wound complications was higher in obese patients (1.9 vs 9.3 %; p = 0.03)., Conclusion: There is no difference in conversion to laparotomy and overall complication rates in non-obese and obese patients undergoing robotic-assisted colorectal surgery. However, obesity is associated with a higher prevalence of wound complications. Robotic-assisted surgery may minimize conversion to laparotomy and complications typically seen in obese patients due to improved visualization, instrumentation, and ergonomics.- Published
- 2017
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4. Sports hernia repair with adductor tenotomy.
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Harr JN and Brody F
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- Adult, Athletic Injuries diagnostic imaging, Female, Groin diagnostic imaging, Groin surgery, Hernia diagnosis, Hernia diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Muscle, Skeletal diagnostic imaging, Muscle, Skeletal surgery, Pain etiology, Pain surgery, Pubic Bone injuries, Rectus Abdominis diagnostic imaging, Rectus Abdominis injuries, Rectus Abdominis surgery, Return to Sport, Suture Techniques, Tendinopathy diagnostic imaging, Tenotomy statistics & numerical data, Thigh, Young Adult, Athletic Injuries surgery, Herniorrhaphy methods, Tendinopathy surgery, Tenotomy methods
- Abstract
Purpose: Sports hernias, or athletic pubalgia, is common in athletes, and primarily involves injury to the fascia, muscles, and tendons of the inguinal region near their insertion onto the pubic bone. However, management varies widely, and rectus and adductor tenotomies have not been adequately described. The purpose of this manuscript is to demonstrate a suture repair and a rectus and adductor longus tenotomy technique for sports hernias., Methods: After magnetic-resonance-imaging confirmation of sports hernias with rectus and adductor tendonitis, 22 patients underwent a suture herniorrhaphy with adductor tenotomy. The procedure is performed through a 4-cm incision, and a fascial release of the rectus abdominis and adductor tenotomy is performed to relieve the opposing vector forces on the pubic bone., Results: All 22 patients returned to their respective sports and regained their ability to perform at a high level, including professional status. No further surgery was required., Conclusion: In athletes with MRI confirmation of rectus and adductor longus injuries, tenotomies along with a herniorraphy may improve outcomes. A suture repair to reinforce the inguinal floor prevents mesh-related complications, especially in young athletes.
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- 2017
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5. Median arcuate ligament syndrome in athletes.
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Harr JN, Haskins IN, and Brody F
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- Abdominal Pain etiology, Celiac Artery diagnostic imaging, Celiac Artery surgery, Constriction, Pathologic complications, Constriction, Pathologic diagnostic imaging, Humans, Laparoscopy methods, Magnetic Resonance Angiography, Median Arcuate Ligament Syndrome, Postprandial Period, Tomography, X-Ray Computed, Athletes, Celiac Artery abnormalities, Constriction, Pathologic surgery, Exercise, Ligaments surgery
- Abstract
Background: Exercise-related transient abdominal pain (ETAP) is a common entity in young athletes. Most occurrences are due to a "cramp" or "stitch," but an uncommon, and often overlooked, etiology of ETAP is median arcuate ligament syndrome (MALS). The initial presentation of MALS typically includes postprandial nausea, bloating, abdominal pain, and diarrhea, but in athletes, the initial presentation may be ETAP., Methods: We present a case series of three athletes who presented with exercise-related transient abdominal pain and were ultimately diagnosed and treated for MALS. Unlike other patients with median arcuate ligament syndrome, these athletes presented with exercise-induced pain, rather than the common postprandial symptoms. These symptoms persisted despite conservative measures. Work-up of patients with suspected MALS include a computed tomography or magnetic resonance angiography showing compression of the celiac artery with post-stenotic dilation, or a celiac artery ultrasound demonstrating increased velocities (>200 cm/s
2 ) with deep exhalation., Results: All patients underwent a laparoscopic median arcuate ligament release. Postoperatively, there were no complications, and all were discharged home on postoperative day #2. All patients have subsequently returned to athletics with resolution of their symptoms., Conclusion: ETAP is common in athletes and often resolves with preventative or conservative strategies. When ETAP persists despite these methods, alternative causes, including MALS, should be considered. A combination of a thorough history and physical exam, as well as radiographic data, is essential to make the appropriate diagnosis and treatment strategy.- Published
- 2017
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6. Laparoscopic Puestow: lateral pancreaticojejunostomy.
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Biteman BR, Harr JN, and Brody F
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- Humans, Male, Middle Aged, Calculi surgery, Laparoscopy methods, Pancreatic Diseases surgery, Pancreatic Ducts surgery, Pancreaticojejunostomy methods, Pancreatitis, Alcoholic surgery
- Abstract
Introduction: Chronic pancreatitis is a painful inflammatory disease that leads to progressive and irreversible destruction of pancreatic parenchyma [1]. A lateral pancreaticojejunostomy, also known as the Puestow procedure, is performed for symptomatic chronic pancreatitis associated with a dilated pancreatic duct secondary to calcifications or strictures [4]. An open approach is used traditionally due to the complexity of the case, and there have only been a handful of laparoscopic case reports [2]. This video depicts a laparoscopic lateral pancreaticojejunostomy for chronic pancreatitis., Methods: A 45-year-old gentleman with a 20-year history of chronic alcohol abuse presented with diffuse abdominal pain. His pain was worse postprandially and associated with loose stools. A computed tomography scan revealed multiple calcified deposits within the body and tail of the pancreas, and a dilated pancreatic duct measuring 1.4 cm with a proximal obstructing calcified stone. A 5-port foregut technique was used, and a 15-cm pancreatic ductotomy was performed with an ultrasonic scalpel. Calcified stones were cleared from the duct, and a roux-en-y pancreaticojejunostomy was performed using a hand-sewn technique., Results: The patient had a relatively uncomplicated hospital course with return of bowel function on postoperative day 4. His patient-controlled analgesic device was discontinued on post operative day 3. He was ambulating, tolerating a regular diet and discharged home on postoperative day 5. At 12- and 26-month follow-up, he remains off narcotics, but still requires 1-2 tabs of pancreatic enzyme replacement per meal. Most importantly, he has not had any alcohol for over 2 years., Conclusion: The two primary goals in treating chronic pancreatitis include long-term pain relief and improvements in quality of life [3]. For patients with chronic pancreatitis and a dilated pancreatic duct, a laparoscopic lateral pancreaticojejunostomy may be an effective approach to decrease pain and improve quality of life.
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- 2016
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7. Incisional and port-site hernias following robotic colorectal surgery.
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Harr JN, Juo YY, Luka S, Agarwal S, Brody F, and Obias V
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- Body Mass Index, Colectomy adverse effects, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Colectomy methods, Incisional Hernia etiology, Laparoscopy adverse effects, Robotic Surgical Procedures
- Abstract
Background: The association between extraction site location, robotic trocar size, and the incidence of incisional hernias in robotic colorectal surgery remain unclear. Laparoscopic literature reports variable rates of incisional hernias versus open surgery, and variable rates of trocar site hernias. However, conclusions from these studies are confusing due to heterogeneity in closure techniques and may not be generalized to robotic cases. This study evaluates the effect of extraction site location on incisional hernia rates, as well as trocar hernia rates in robotic colorectal surgery., Materials and Methods: A retrospective review of multiport and single incision robotic colorectal surgeries from a single institution was performed. Patients underwent subtotal, segmental, or proctocolectomies, and were compared based on the extraction site through either a muscle-splitting (MS) or midline (ML) incision. Hernias were identified by imaging and/or physical exam. Demographics and risk factors for hernias were assessed. Groups were compared using a multivariate logistic regression analysis., Results: The study included 259 colorectal surgery patients comprising 146 with MS and 113 with ML extraction sites. Postoperative computed tomograms were performed on 155 patients (59.8 %) with a mean follow-up of 16.5 months. The overall incisional hernia rate was 5.8 %. A significantly higher hernia rate was found among the ML group compared to the MS group (12.4 vs. 0.68 %, p < 0.0001). Of the known risk factors assessed, only increased BMI was associated with incisional hernias (OR 1.18). No trocar site hernias were found., Conclusion: Midline extraction sites are associated with a significantly increased rate of incisional hernias compared to muscle-splitting extraction sites. There is little evidence to recommend fascia closure of 8-mm trocar sites.
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- 2016
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8. Robotic-assisted total proctocolectomy with ileal pouch-anal anastomosis and loop ileostomy--a video vignette.
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Harr JN and Obias V
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- Anal Canal surgery, Anastomosis, Surgical methods, Humans, Ileum surgery, Male, Middle Aged, Colitis, Ulcerative surgery, Colonic Pouches, Ileostomy methods, Proctocolectomy, Restorative methods, Robotic Surgical Procedures methods
- Published
- 2016
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9. Exercise-related transient abdominal pain secondary to median arcuate ligament syndrome: a case report.
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Haskins IN, Harr JN, and Brody F
- Subjects
- Adolescent, Female, Hockey, Humans, Laparoscopy, Ligaments surgery, Median Arcuate Ligament Syndrome, Abdominal Pain etiology, Celiac Artery abnormalities, Constriction, Pathologic diagnosis, Exercise
- Abstract
Exercise-related transient abdominal pain is a common entity in young athletes. An uncommon aetiology of this type of pain is median arcuate ligament syndrome. This article details an 18-year-old field hockey player who presented with a 1-year history of exercise-related transient abdominal pain. Despite a trial of preventative strategies, the patient's pain persisted, prompting surgical intervention. Following a laparoscopic median arcuate ligament release, the patient's symptoms resolved. Therefore, when exercise-related transient abdominal pain persists despite precautionary measures, median arcuate ligament syndrome should be considered.
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- 2016
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10. Robotic-assisted transanal excision of a large rectal mass--a video vignette.
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Harr JN and Obias V
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- Aged, Humans, Male, Patient Positioning, Adenoma, Villous surgery, Rectal Neoplasms surgery, Robotic Surgical Procedures methods, Transanal Endoscopic Surgery methods
- Published
- 2016
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11. Laparoscopic Repair of Paraesophageal Hernias with a Falciform Ligament Buttress.
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Laird R, Brody F, Harr JN, Richards NG, and Zeddun S
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- Aged, Female, Follow-Up Studies, Hernia, Hiatal complications, Hernia, Hiatal diagnostic imaging, Humans, Male, Middle Aged, Prospective Studies, Radiography, Recurrence, Hernia, Hiatal surgery, Herniorrhaphy methods, Laparoscopy, Ligaments surgery, Symptom Assessment
- Abstract
Background: Buttressing the crura in paraesophageal hernia (PEH) repairs with synthetic mesh may be associated with erosions and dysphagia, while biologic buttresses are expensive and do not decrease long-term recurrence rates. This study documents outcomes following laparoscopic PEH repairs using the falciform ligament as a buttress., Methods: This is a prospective study of laparoscopic PEH repairs with a falciform ligament buttress. Preoperatively and at 6 months follow-up, medications, radiologic studies and symptom scores were recorded. Patients included had a hiatal defect greater than 5 cm, while recurrent PEH or prior gastric surgery patients were excluded., Results: Thirty-four patients were included with a mean age of 61 years, and 33 patients completed postoperative evaluation with a mean follow-up of 7.1 months. The mean symptom severity decreased from 11.24 ± 1.71 to 3.24 ± 0.84, mean symptom frequency decreased from 11.62 ± 1.70 to 3.45 ± 0.85, and mean total symptom score decreased from 22.85 ± 3.40 to 6.69 ± 1.69 (p < 0.0001). Three patients had recurrences on the upper gastrointestinal (UGI) series. Only one required reoperation., Conclusions: Laparoscopic PEH repair with a falciform ligament buttress is a viable option. Ongoing follow-up will demonstrate the utility of this approach to decrease morbidity and recurrence rates for paraesophageal hernia repairs.
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- 2015
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12. Viscoelastic hemostatic fibrinogen assays detect fibrinolysis early.
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Harr JN, Moore EE, Chin TL, Chapman MP, Ghasabyan A, Stringham JR, Banerjee A, and Silliman CC
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- Blood Coagulation Disorders blood, Blood Coagulation Disorders physiopathology, Blood Pressure, Critical Care, Early Diagnosis, Fibrinolysis, Humans, Point-of-Care Systems, Sensitivity and Specificity, Shock, Hemorrhagic blood, Wounds and Injuries blood, Wounds and Injuries physiopathology, Blood Coagulation Disorders diagnosis, Shock, Hemorrhagic prevention & control, Thrombelastography instrumentation, Wounds and Injuries complications
- Abstract
Purpose: Viscoelastic hemostatic assays are emerging as the standard-of-care in the early detection of post-injury coagulopathy. TEG and ROTEM are most commonly used. Although similar in technique, each uses different reagents, which may affect their sensitivity to detect fibrinolysis. Therefore, the purpose of this study is to determine the ability of each device to detect fibrinolysis., Methods: TEG (Rapid, Kaolin, Functional Fibrinogen) and ROTEM (EXTEM, INTEM, FIBTEM) were run simultaneously on normal blood as well as blood containing tPA from healthy volunteers (n = 10). A two-tailed, paired t-test and ANOVA were used to determine the significance between parameters obtained from normal blood and blood with tPA, and individual TEG and ROTEM assays, respectively., Results: TEG detected significant changes in clot strength and 30-min lysis after the addition of tPA (p < 0.0001). All ROTEM assays detected changes in the 30-min lysis (p < 0.0001), but only INTEM detected changes in clot strength (p < 0.05). Kaolin and Rapid TEG assays detected greater changes in clot strength and lysis, but INTEM and EXTEM had decreased lysis onset times compared to TEG (p < 0.001). Functional Fibrinogen and FIBTEM assays detected lysis sooner than other TEG/ROTEM assays, and were comparable., Conclusions: TEG assays detect greater changes in clot strength compared to ROTEM. Despite this, Functional Fibrinogen and FIBTEM assays detect fibrinolysis sooner than their corresponding intrinsic and extrinsic assays. Therefore, fibrinogen assays should be employed in actively bleeding trauma patients in order to provide timely antifibrinolytic therapy.
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- 2015
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13. Exploring ethical conflicts in emergency trauma research: the COMBAT (Control of Major Bleeding after Trauma) study experience.
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Chin TL, Moore EE, Coors ME, Chandler JG, Ghasabyan A, Harr JN, Stringham JR, Ramos CR, Ammons S, Banerjee A, and Sauaia A
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- Blood Coagulation Disorders etiology, Community-Based Participatory Research, Humans, Wounds and Injuries etiology, Blood Coagulation Disorders prevention & control, Emergency Medical Services ethics, Information Dissemination, Informed Consent, Wounds and Injuries therapy
- Abstract
Background: Up to 25% of severely injured patients develop trauma-induced coagulopathy. To study interventions for this vulnerable population for whom consent cannot be obtained easily, the Food and Drug Administration issued regulations for emergency research with an exception from informed consent (ER-EIC). We describe the community consultation and public disclosure (CC/PD) process in preparation for an ER-EIC study, namely the Control Of Major Bleeding After Trauma (COMBAT) study., Methods: The CC/PD was guided by the four bioethical principles. We used a multimedia approach, including one-way communications (newspaper ads, brochures, television, radio, and web) and two-way communications (interactive in-person presentations at community meetings, printed and online feedback forms) to reach the trials catchment area (Denver County's population: 643,000 and the Denver larger metro area where commuters reside: 2.9 million). Particular attention was given to special-interests groups (eg, Jehovah Witnesses, homeless) and to Spanish-speaking communities (brochures and presentations in Spanish). Opt-out materials were available during on-site presentations or via the COMBAT study website., Results: A total of 227 community organizations were contacted. Brochures were distributed to 11 medical clinics and 3 homeless shelters. The multimedia campaign had the potential to reach an estimated audience of 1.5 million individuals in large metro Denver area, the majority via one-way communication and 1900 in two-way communications. This resource intensive process cost more than $84,000., Conclusion: The CC/PD process is resource-intensive, costly, and complex. Although the multimedia CC/PD reached a large audience, the effectiveness of this process remains elusive. The templates can be helpful to similar ER-EIC studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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14. Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock.
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Stringham JR, Moore EE, Gamboni F, Harr JN, Fragoso M, Chin TL, Carr CE, Silliman CC, and Banerjee A
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- Acute Kidney Injury etiology, Acute Kidney Injury physiopathology, Acute Lung Injury etiology, Acute Lung Injury physiopathology, Animals, Arachidonate 5-Lipoxygenase urine, Biomarkers metabolism, Biomarkers urine, Disease Models, Animal, Enzyme Activation physiology, Injury Severity Score, Leukotrienes metabolism, Leukotrienes urine, Lymph Nodes enzymology, Lymph Nodes metabolism, Male, Mesentery enzymology, Mesentery metabolism, Multiple Organ Failure etiology, Multiple Organ Failure physiopathology, Random Allocation, Rats, Rats, Sprague-Dawley, Sensitivity and Specificity, Shock, Hemorrhagic diagnosis, Shock, Hemorrhagic etiology, Wounds and Injuries complications, Wounds and Injuries diagnosis, Acute Kidney Injury enzymology, Acute Lung Injury enzymology, Arachidonate 5-Lipoxygenase metabolism, Kidney enzymology, Multiple Organ Failure metabolism, Shock, Hemorrhagic enzymology, Wounds and Injuries enzymology
- Abstract
Background: Early acute kidney injury (AKI) following trauma is associated with multiorgan failure and mortality. Leukotrienes have been implicated both in AKI and in acute lung injury. Activated 5-lipoxygenase (5-LO) colocalizes with 5-LO-activating protein (FLAP) in the first step of leukotriene production following trauma and hemorrhagic shock (T/HS). Diversion of postshock mesenteric lymph, which is rich in the 5-LO substrate of arachidonate, attenuates lung injury and decreases 5-LO/FLAP associations in the lung after T/HS. We hypothesized that mesenteric lymph diversion (MLD) will also attenuate postshock 5-LO-mediated AKI., Methods: Rats underwent T/HS (laparotomy, hemorrhagic shock to a mean arterial pressure of 30 mm Hg for 45 minutes, and resuscitation), and MLD was accomplished via cannulation of the mesenteric duct. Extent of kidney injury was determined via histology score and verified by urinary neutrophil gelatinase-associated lipocalin assay. Kidney sections were immunostained for 5-LO and FLAP, and colocalization was determined by fluorescence resonance energy transfer signal intensity. The end leukotriene products of 5-LO were determined in urine., Results: AKI was evident in the T/HS group by derangement in kidney tubule architecture and confirmed by neutrophil gelatinase-associated lipocalin assay, whereas MLD during T/HS preserved renal tubule morphology at a sham level. MLD during T/HS decreased the associations between 5-LO and FLAP demonstrated by fluorescence resonance energy transfer microscopy and decreased leukotriene production in urine., Conclusion: 5-LO and FLAP colocalize in the interstitium of the renal medulla following T/HS. MLD attenuates this phenomenon, which coincides with pathologic changes seen in tubules during kidney injury and biochemical evidence of AKI. These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury.
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- 2014
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15. Postinjury hyperfibrinogenemia compromises efficacy of heparin-based venous thromboembolism prophylaxis.
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Harr JN, Moore EE, Chin TL, Ghasabyan A, Gonzalez E, Wohlauer MV, Sauaia A, Banerjee A, and Silliman CC
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- Adolescent, Adult, Aged, Anticoagulants administration & dosage, Anticoagulants antagonists & inhibitors, Blood Coagulation drug effects, Dose-Response Relationship, Drug, Female, Fibrinogen pharmacology, Heparin, Low-Molecular-Weight administration & dosage, Heparin, Low-Molecular-Weight antagonists & inhibitors, Humans, Injury Severity Score, Male, Middle Aged, Thrombelastography methods, Treatment Outcome, Venous Thromboembolism blood, Wounds and Injuries blood, Young Adult, Anticoagulants therapeutic use, Fibrinogen metabolism, Heparin, Low-Molecular-Weight therapeutic use, Venous Thromboembolism etiology, Venous Thromboembolism prevention & control, Wounds and Injuries complications
- Abstract
Background: Venous thromboembolism (VTE) prophylaxis remains debated following trauma, and recommendations have not been established. Although hyperfibrinogenemia is a marker of proinflammatory states, it also contributes to thrombus formation. Postinjury hyperfibrinogenemia is common, but the effect of hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore, we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia., Methods: In vitro studies evaluated thromboelastography (TEG) parameters in 10 healthy volunteers after the addition of fibrinogen concentrate and heparin. Data from a recent randomized controlled trial, conducted at an academic level I trauma center surgical intensive care unit, were reviewed. Critically injured patients were randomized to standard VTE prophylaxis (5,000 U low-molecular-weight heparin daily) or TEG-guided prophylaxis (up to 10,000 U low-molecular-weight heparin daily) and were followed up for 5 days. Analysis was performed to evaluate the relationship between fibrinogen levels, measures of anticoagulation, and TEG parameters., Results: In vitro studies revealed increased fibrinogen reversed the effects of heparin as measured by TEG. Fifty patients were enrolled in the clinical study with 25 in each arm. Thromboelastography parameters, fibrinogen, platelet count, and anti-Xa levels did not differ between groups despite treatment provided. Fibrinogen levels increased over the 5-day study period (597 ± 24.0 to 689.3 ± 25.0), as well as clot strength (9.8 ± 0.4 to 14.5 ± 0.6), which had a significant correlation coefficient (P < 0.01). Moreover, there was a moderate inverse correlation between fibrinogen level and the effect of heparin (RF), which was significant on study days 1 and 3, implicating hyperfibrinogenemia in heparin resistance., Conclusions: Hypercoagulability and heparin resistance are common following trauma. The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor in heparin resistance.
- Published
- 2014
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16. Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy.
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Chapman MP, Moore EE, Ramos CR, Ghasabyan A, Harr JN, Chin TL, Stringham JR, Sauaia A, Silliman CC, and Banerjee A
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- Adult, Blood Coagulation Disorders etiology, Blood Coagulation Disorders therapy, Blood Transfusion, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Injury Severity Score, Male, Prognosis, Retrospective Studies, Thrombelastography, Time Factors, Treatment Outcome, Wounds and Injuries blood, Antifibrinolytic Agents administration & dosage, Blood Coagulation Disorders blood, Fibrinolysis drug effects, Wounds and Injuries complications
- Abstract
Background: The acute coagulopathy of trauma is present in up to one third of patients by the time of admission, and the recent CRASH-2 and MATTERs trials have focused worldwide attention on hyperfibrinolysis as a component of acute coagulopathy of trauma. Thromboelastography (TEG) is a powerful tool for analyzing fibrinolyis, but a clinically relevant threshold for defining hyperfibrinolysis has yet to be determined. Recent data suggest that the accepted normal upper bound of 7.5% for 30-minute fibrinolysis (LY30) by TEG is inappropriate in severe trauma, as the risk of death rises at much lower levels of clot lysis. We wished to determine the validity of this hypothesis and establish a threshold value to treat fibrinolysis, based on prediction of massive transfusion requirement and risk of mortality., Methods: Patients with uncontrolled hemorrhage, meeting the massive transfusion protocol (MTP) criteria at admission (n = 73), represent the most severely injured trauma population at our center (median Injury Severity Score [ISS], 30; interquartile range, 20-38). Citrated kaolin TEG was performed at admission blood samples from this population, stratified by LY30, and evaluated for transfusion requirement and 28-day mortality. The same analysis was conducted on available field blood samples from all non-MTP trauma patients (n = 216) in the same period. These represent the general trauma population., Results: Within the MTP-activating population, the cohort of patients with LY30 of 3% or greater was shown to be at much higher risk for requiring a massive transfusion (90.9% vs. 30.5%, p = 0.0008) and dying of hemorrhage (45.5% vs. 4.8%, p = 0.0014) than those with LY30 less than 3%. Similar trends were seen in the general trauma population., Conclusion: LY30 of 3% or greater defines clinically relevant hyperfibrinolysis and strongly predicts the requirement for massive transfusion and an increased risk of mortality in trauma patients presenting with uncontrolled hemorrhage. This threshold value for LY30 represents a critical indication for the treatment of fibrinolysis., Level of Evidence: Prognostic study, level III.
- Published
- 2013
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17. The authors reply.
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Harr JN, Moore EE, Johnson JL, Chin TL, Wohlauer MV, Banerjee A, Silliman CC, and Sauaia A
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- Female, Humans, Male, Acute Lung Injury epidemiology, Blood Transfusion statistics & numerical data, Multiple Organ Failure epidemiology, Platelet Aggregation Inhibitors therapeutic use, Wounds and Injuries mortality
- Published
- 2013
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18. Platelets are dominant contributors to hypercoagulability after injury.
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Harr JN, Moore EE, Chin TL, Ghasabyan A, Gonzalez E, Wohlauer MV, Banerjee A, Silliman CC, and Sauaia A
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- Adult, Anticoagulants administration & dosage, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Injury Severity Score, Male, Platelet Count, Prognosis, Prospective Studies, Thrombelastography, Thrombophilia complications, Thrombophilia drug therapy, Thrombosis blood, Thrombosis prevention & control, Wounds and Injuries blood, Wounds and Injuries diagnosis, Blood Coagulation, Blood Platelets physiology, Heparin, Low-Molecular-Weight administration & dosage, Platelet Aggregation Inhibitors administration & dosage, Thrombophilia blood, Thrombosis etiology, Wounds and Injuries complications
- Abstract
Background: Venous thromboembolic (VTE) disease has a high incidence following trauma, but debate remains regarding optimal prophylaxis. Thrombelastography (TEG) has been suggested to be optimal in guiding prophylaxis. Thus, we designed a phase II randomized controlled trial to test the hypothesis that TEG-guided prophylaxis with escalating low-molecular weight heparin (LMWH), followed by antiplatelet therapy would reduce VTE incidence., Methods: Surgical intensive care unit trauma patients (n = 50) were randomized to receive 5,000 IU of LMWH daily (control) or to TEG-guided prophylaxis, up to 5,000 IU twice daily with the addition of aspirin, and were followed up for 5 days. In vitro studies were also conducted in which apheresis platelets were added to blood from healthy volunteers (n = 10)., Results: Control (n = 25) and TEG-guided prophylaxis (n = 25) groups were similar in age, body mass index, Injury Severity Score, and male sex. Fibrinogen levels and platelet counts did not differ, and increased LMWH did not affect clot strength between the control and study groups. The correlation of clot strength (G value) with fibrinogen was stronger on Days 1 and 2 but was superseded by platelet count on Days 3, 4, and 5. There was also a trend in increased platelet contribution to clot strength in patients receiving increased LMWH. In vitro studies demonstrated apheresis platelets significantly increased clot strength (7.19 ± 0.35 to 10.34 ± 0.29), as well as thrombus generation (713.86 ± 12.19 to 814.42 ± 7.97) and fibrin production (274.03 ± 15.82 to 427.95 ± 16.58)., Conclusion: Increased LMWH seemed to increase platelet contribution to clot strength early in the study but failed to affect the overall rise clot strength. Over time, platelet count had the strongest correlation with clot strength, and in vitro studies demonstrated that increased platelet counts increase fibrin production and thrombus generation. In sum, these data suggest an important role for antiplatelet therapy in VTE prophylaxis following trauma, particularly after 48 hours., Level of Evidence: Therapeutic study, level III.
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- 2013
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19. Antiplatelet therapy is associated with decreased transfusion-associated risk of lung dysfunction, multiple organ failure, and mortality in trauma patients.
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Harr JN, Moore EE, Johnson J, Chin TL, Wohlauer MV, Maier R, Cuschieri J, Sperry J, Banerjee A, Silliman CC, and Sauaia A
- Subjects
- Acute Lung Injury classification, Cohort Studies, Female, Humans, Injury Severity Score, Male, Middle Aged, Multiple Organ Failure classification, Multivariate Analysis, Risk Assessment, United States epidemiology, Acute Lung Injury epidemiology, Blood Transfusion statistics & numerical data, Multiple Organ Failure epidemiology, Platelet Aggregation Inhibitors therapeutic use, Wounds and Injuries mortality
- Abstract
Objective: To determine whether prehospital antiplatelet therapy was associated with reduced incidence of acute lung dysfunction, multiple organ failure, and mortality in blunt trauma patients., Design: Secondary analysis of a cohort enrolled in the National Institute of General Medical Sciences Trauma Glue Grant database., Setting: Multicenter study including nine U.S. level-1 trauma centers., Patients: A total of 839 severely injured blunt trauma patients at risk for multiple organ failure (age > 45 yr, base deficit > 6 mEq/L or systolic blood pressure < 90 mm Hg, who received a blood transfusion). Severe/isolated head injuries were excluded., Measurements and Main Results: Primary outcomes were lung dysfunction (defined as grades 2-3 by the Denver multiple organ failure score), multiple organ failure (Denver multiple organ failure score >3), and mortality. Patients were documented as on antiplatelet therapy if taking acetylsalicylic acid, clopidogrel, and/or ticlopidine. Fifteen percent were taking antiplatelet therapy prior to injury. Median injury severity score was 30 (interquartile range 22-51), mean age 61 + 0.4 yr and median RBCs volume transfused was 1700 mL (interquartile range 800-3150 mL). Overall, 63% developed lung dysfunction, 19% had multiple organ failure, and 21% died. After adjustment for age, gender, comorbidities, blood products, crystalloid/12 hrs, presence of any head injury, injury severity score, and 12 hrs base deficit > 8 mEq/L, 12 hrs RBC transfusion was associated with a significantly smaller risk of lung dysfunction and multiple organ failure among the group receiving antiplatelet therapy compared with those not receiving it (lung dysfunction p = 0.0116, multiple organ failure p = 0.0291). In addition, antiplatelet therapy had a smaller risk (albeit not significant, p = 0.06) of death for patients receiving RBC compared to those not on antiplatelet therapy after adjustment for confounders,, Conclusions: Pre-injury antiplatelet therapy is associated with a decreased risk of lung dysfunction, multiple organ failure, and possibly mortality in high-risk blunt trauma patients who received blood transfusions. These findings suggest platelets have a role in organ dysfunction development and have potential therapeutic implications.
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- 2013
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20. Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma.
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Harr JN, Moore EE, Ghasabyan A, Chin TL, Sauaia A, Banerjee A, and Silliman CC
- Subjects
- Adult, Blood Coagulation physiology, Blood Coagulation Disorders blood, Blood Coagulation Disorders diagnosis, Female, Fibrinogen physiology, Humans, Male, Middle Aged, Platelet Count, Prospective Studies, Thrombelastography methods, Wounds and Injuries blood, Blood Coagulation Disorders etiology, Fibrinogen analysis, Wounds and Injuries complications
- Abstract
Thromboelastography (TEG) is emerging as the standard in the management of acute coagulopathies in injured patients. Although TEG is sensitive in detecting abnormalities in clot strength, one shortcoming is differentiating between fibrinogen and platelet contributions to clot integrity. Current American algorithms suggest platelet transfusion, whereas European guidelines suggest fibrinogen concentrates for correcting low clot strength. Therefore, we hypothesized that a TEG-based functional fibrinogen (FF) assay would assess the contribution of fibrinogen and platelets to clot strength and provide insight to transfusion priorities. Blood samples were obtained from trauma patients on arrival to the emergency department or who were admitted to the surgical intensive care unit (n = 68). Citrated kaolin TEG, FF, and von Clauss fibrinogen levels (plasma-based clinical standard) were measured. Correlations were assessed using linear regression models. In vitro studies were also performed with adding fibrinogen concentrates to blood collected from healthy volunteers (n = 10). Functional fibrinogen and citrated kaolin TEG parameters were measured. Functional fibrinogen strongly correlated with von Clauss fibrinogen levels (R = 0.87) and clot strength (R = 0.80). The mean fibrinogen contribution to clot strength was 30%; however, there was a direct linear relationship with fibrinogen level and percent fibrinogen contribution to clot strength (R = 0.83). Traditional TEG parameters associated with fibrinogen activity (α angle and kinetic time) had significantly lower correlations with FF (R = 0.70 and 0.35). Furthermore, platelet count had only a moderate correlation to clot strength (R = 0.51). The addition of fibrinogen concentrate in in vitro studies increased clot strength (MA) (60.44 ± 1.48 to 68.12 ± 1.39) and percent fibrinogen contribution to clot strength (23.8% ± 1.8% to 37.7% ± 2.5%). Functional fibrinogen can be performed rapidly with TEG and correlates well with the standard von Clauss fibrinogen assay. Both fibrinogen and platelet contribution of clot strength can be derived from FF. Moreover, FF had a stronger correlation to clot strength, and increased levels were directly associated with increased percent contribution to clot strength. In vitro studies also demonstrated an increase in FF, clot strength, and percent fibrinogen contribution to clot strength with the addition of fibrinogen concentrate. These data suggest that fibrinogen should be addressed early in trauma patients manifesting acute coagulopathy of trauma.
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- 2013
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21. Elderly patients may benefit from tight glucose control.
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Chin TL, Sauaia A, Moore EE, Chandler JG, Harr JN, Johnson JL, and Banerjee A
- Subjects
- Adult, Age Factors, Comorbidity, Diabetes Mellitus epidemiology, Female, Humans, Hyperglycemia epidemiology, Hyperglycemia metabolism, Infusions, Intravenous, Injections, Intravenous, Injury Severity Score, Logistic Models, Male, Multiple Organ Failure epidemiology, Obesity epidemiology, Survival Rate, Trauma Centers, Blood Glucose metabolism, Critical Care methods, Diabetes Mellitus drug therapy, Hyperglycemia prevention & control, Insulin administration & dosage, Wounds and Injuries epidemiology
- Abstract
Background: While minimizing hyperglycemia in critically injured patients improves outcomes, it is debatable whether postinjury glucose control should aim for conventional glucose control levels (≤180 mg/dL) or tight glucose control levels (81-108 mg/dL). We queried our 17-year prospective database of patients at risk for postinjury multiple organ failure to examine the association between glucose levels and adverse outcomes., Methods: Acutely injured patients admitted to a Level I trauma center intensive care unit from 1992 to 2008 who were more than 15 years of age, had Injury Severity Scores >15, and who survived >48 hours were eligible for the study. Multiple logistic regression was used to determine the independent association of glucose control with adverse outcomes (death, ventilator-free days, intensive care unit-free days, and major infections), adjusted for Injury Severity Score, age, and red blood cell transfusion in the first 12 hours., Results: Overall, 2,231 patients were eligible, of whom 153 (6.9%) died. The mean age was 37.8 ± 0.4 years, and the median Injury Severity Score was 27 (interquartile range, 21-35). The majority (77%) of these patients maintained mean glucose within conventional glucose control levels and only 10% achieved mean glucose levels within tight glucose control levels. Nonsurvivors required greater doses of insulin to control glucose levels and had greater mean insulin to glucose ratios (t test; P = .025). After adjusting for confounders, mean glucose remained significantly associated with the studied adverse outcomes. Age significantly modified all these associations with older patients seeming to benefit more from tight glucose control levels than their younger counterparts., Conclusion: Age is an effect modifier of the association between glucose levels and adverse outcomes. Future studies including larger samples of elderly trauma patients are needed to determine the ideal levels for glucose control in this growing population., (Copyright © 2012 Mosby, Inc. All rights reserved.)
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- 2012
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22. Isoflurane prevents acute lung injury through ADP-mediated platelet inhibition.
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Harr JN, Moore EE, Stringham J, Wohlauer MV, Fragoso M, Jones WL, Gamboni F, Silliman CC, and Banerjee A
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- Acute Lung Injury etiology, Anesthetics, Inhalation therapeutic use, Animals, Clopidogrel, Fluorescent Antibody Technique, Isoflurane therapeutic use, Lung pathology, Male, Platelet Aggregation Inhibitors therapeutic use, Purinergic P2Y Receptor Antagonists administration & dosage, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2, Receptors, Purinergic P2Y12, Resuscitation, Shock, Hemorrhagic complications, Ticlopidine administration & dosage, Ticlopidine analogs & derivatives, Acute Lung Injury prevention & control, Anesthetics, Inhalation pharmacology, Blood Platelets drug effects, Isoflurane pharmacology
- Abstract
Background: Growing evidence suggests platelets are essential in posttraumatic, acute lung injury (ALI). Halogenated ethers interfere with the formation of platelet-granulocyte aggregates. The potential benefit of halogenated ethers has not been investigated in models of trauma/hemorrhagic shock (T/HS). Therefore, we hypothesized that isoflurane decreases T/HS-mediated ALI through platelet inhibition., Methods: Sprague-Dawley rats (n = 47) were anesthetized by either pentobarbital or inhaled isoflurane and placed into (1) control, (2) trauma (laparotomy) sham shock, (3) T/HS (mean arterial pressure, 30 mmHg × 45 min), (4) pretreatment with an ADP receptor antagonist, or (5) T/HS with isoflurane initiated during resuscitation groups. ALI was determined by protein and pulmonary immunofluorescence bronchoalveolar lavage (BAL) fluid. Platelet Mapping specifically evaluated thrombin-independent inhibition of the ADP and AA pathways of platelet activation., Results: Pretreatment with isoflurane abrogated ALI as measured by both BAL fluid protein and pulmonary immunofluorescence (P < .001). Platelet Mapping revealed specific inhibition of the platelet ADP-pathway with isoflurane (P < .001). Pretreatment with an ADP receptor antagonist decreased ALI to sham levels, confirming that specific platelet ADP inhibition decreases ALI. Isoflurane initiated during resuscitation also decreased ALI (P < .001)., Conclusion: Isoflurane attenuates ALI through an antiplatelet mechanism, in part, through inhibition of the platelet ADP pathway. Isoflurane given postinjury also protects against ALI, and highlights the potential applications of this therapy in various clinical scenarios of ischemia/reperfusion., (Copyright © 2012 Mosby, Inc. All rights reserved.)
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- 2012
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23. Activated platelets in heparinized shed blood: the "second hit" of acute lung injury in trauma/hemorrhagic shock models.
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Harr JN, Moore EE, Wohlauer MV, Fragoso M, Gamboni F, Liang X, Banerjee A, and Silliman CC
- Subjects
- Animals, Blood Platelets physiology, Male, Platelet Activation, Rats, Rats, Sprague-Dawley, Shock, Hemorrhagic pathology, Wounds and Injuries pathology, Acute Lung Injury pathology, Acute Lung Injury therapy, Blood Platelets immunology, Blood Transfusion, Autologous adverse effects, Shock, Hemorrhagic therapy, Wounds and Injuries therapy
- Abstract
The return of heparinized shed blood (SB) in trauma/hemorrhagic shock (T/HS) models remains controversial because of potential anti-inflammatory properties. Although ubiquitous as an anticoagulant, heparin is ineffective on cellular coagulation as an antithrombotic agent. Therefore, we hypothesized that returning heparinized SB would paradoxically enhance acute lung injury (ALI) after T/HS because of the infusion of activated platelets. Sprague-Dawley rats, anesthetized with pentobarbital, underwent laparotomy and hemorrhage-induced shock (MAP of 30 mmHg × 45 min). Animals were resuscitated with a combination of normal saline and returned SB. Shed blood was collected in either 80 U/kg of heparin, 800 U/kg of heparin, or citrate or diluted 1:8 with normal saline. An additional group of animals were pretreated with a platelet P2Y12 receptor antagonist (clopidogrel) before T/HS. Bronchoalveolar lavage, lung myeloperoxidase assays, pulmonary immunofluorescence, and blood smears were conducted. Bronchoalveolar lavage protein increased in animals resuscitated with heparinized SB (T/HS + 80 U/kg Hep 1.62 ± 0.29, T/HS + 800 U/kg Hep 1.30 ± 0.15 vs. T/SS 0.51 ± 0.16 and T/HS Citrate 0.7 ± 0.09) (P < 0.0001). Blood smears and platelet function assays revealed platelet aggregates and increased platelet activation. Animals pretreated with a platelet P2Y12 receptor antagonist were protected from postinjury ALI (P < 0.0001). Animals with return of SB had increased pulmonary polymorphonuclear leukocyte sequestration (P < 0.0001). Pulmonary immunofluorescence demonstrated microthrombi only in the T/HS group receiving heparinized SB (P < 0.0001). The return of heparinized SB functions as a "second hit" to enhance ALI, with activated platelets propagating microthrombi and pulmonary polymorphonuclear leukocyte recruitment.
- Published
- 2011
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24. The acute coagulopathy of trauma is due to impaired initial thrombin generation but not clot formation or clot strength.
- Author
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Harr JN, Moore EE, Wohlauer MV, Droz N, Fragoso M, Banerjee A, and Silliman CC
- Subjects
- Acute Disease, Animals, Disease Models, Animal, Fibrinolysis physiology, Male, Rats, Rats, Sprague-Dawley, Shock, Hemorrhagic blood, Shock, Hemorrhagic complications, Thrombelastography, Thrombin metabolism, Blood Coagulation physiology, Disseminated Intravascular Coagulation blood, Disseminated Intravascular Coagulation etiology, Thrombin biosynthesis, Wounds and Injuries blood, Wounds and Injuries complications
- Abstract
Background: Acute coagulopathy of trauma (ACOT) has been described as a very early hypocoagulable state, but the mechanism remains controversial. One proposed mechanism is tissue hypoperfusion leading to protein C activation, with subsequent inhibition of Factors V and VIII. Variability in trauma has impeded the use of clinical data towards the elucidation of the mechanisms of ACOT, but thrombelastography (TEG) may provide insight by assessing hemostatic function from initial thrombin activation to fibrinolysis. We hypothesized that in a controlled animal model of trauma/hemorrhagic shock, clotting factor dysfunction is the predominant mechanism in early ACOT., Methods: Rats anesthetized by inhaled isoflurane (n = 6) underwent laparotomy, and hemorrhage was induced to maintain a MAP of 35 mm Hg for 30 min. Rats were then resuscitated with twice their shed blood volume in normal saline. TEG was performed at baseline, shock, and post-resuscitation periods. No heparin was given. Statistical analysis was performed by ANOVA with post-hoc Fisher's test., Results: Coagulation factor function was significantly impaired in the early stages of trauma/hemorrhagic shock. TEG R and SP-values were significantly increased from baseline to shock (P < 0.001) and from shock to post-resuscitation periods (P < 0.05). Delta (R-SP), a measure of thrombin generation, showed a significant increase (P < 0.05) from baseline to shock. No significant changes were found in K, Angle, MA, and LY30 values., Conclusion: Clotting factor derangement leading to impaired thrombin generation is the principle etiology of ACOT in this model and not the dynamics of clot formation, fibrin cross-linking, clot strength/platelet function, or fibrinolysis., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
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