Surgeon\u27s guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation.

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two part review, agents commonly encountered by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part one, we review warfarin and the new direct oral anticoagulants. In part two, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulation and antiplatelet therapy

Getting the invite list right : a discussion of sepsis severity scoring systems in severe complicated intra-abdominal sepsis and randomized trial inclusion criteria

Background: Severe complicated intra-abdominal sepsis (SCIAS) is a worldwide challenge with increasing incidence. Open abdomen management with enhanced clearance of fluid and biomediators from the peritoneum is a potential therapy requiring prospective evaluation. Given the complexity of powering multi-center trials, it is essential to recruit an inception cohort sick enough to benefit from the intervention; otherwise, no effect of a potentially beneficial therapy may be apparent An evaluation of abilities of recognized predictive systems to recognize SCIAS patients was conducted using an existing intra-abdominal sepsis (IAS) database. Methods: All consecutive adult patients with a diffuse secondary peritonitis between 2012 and 2013 were collected from a quaternary care hospital in Finland, excluding appendicitis/cholecystitis. From this retrospectively collected database, a target population (93) of those with either ICU admission or mortality were selected. The performance metrics of the Third Consensus Definitions for Sepsis and Septic Shock based on both SOFA and quick SOFA, the World Society of Emergency Surgery Sepsis Severity Score (WSESSSS), the APACHE II score, Manheim Peritonitis Index (MPI), and the Calgary Predisposition, Infection, Response, and Organ dysfunction (CPIRO) score were all tested for their discriminant ability to identify this subgroup with SCIAS and to predict mortality. Results: Predictive systems with an area under-the-receiving-operating characteristic (AUQ curve >= 0.8 included SOFA, Sepsis-3 definitions, APACHE II, WSESSSS, and CPIRO scores with the overall best for CPIRO. The highest identification rates were SOFA score >= 2 (78.4%), followed by the WSESSSS score >= 8 (73.1%), SOFA >= 3 (752%), and APACHE II >= 14 (68.8%) identification. Combining the Sepsis-3 septic-shock definition and WSESSS >= 8 increased detection to 80%. Including CPIRO score >= 3 increased this to 82.8% (Sensitivity-SN; 83% Specificity-SP; 74%. Comparatively, SOFA >= 4 and WSESSSS >= 8 with or without septic-shock had 83.9% detection (SN; 84%, SP; 75%, 25% mortality). Conclusions: No one scoring system behaves perfectly, and all are largely dominated by organ dysfunction. Utilizing combinations of SOFA, CPIRO, and WSESSSS scores in addition to the Sepsis-3 septic shock definition appears to offer the widest "inclusion-criteria" to recognize patients with a high chance of mortality and ICU admission.Peer reviewe

Closed Or Open after Source Control Laparotomy for Severe Complicated Intra-Abdominal Sepsis (the COOL trial) : study protocol for a randomized controlled trial

Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. Principles of treatment include early antibiotic administration and operative source control. A further therapeutic option may be open abdomen (OA) management with active negative peritoneal pressure therapy (ANPPT) to remove inflammatory ascites and ameliorate the systemic damage from SCIAS. Although there is now a biologic rationale for such an intervention as well as non-standardized and erratic clinical utilization, this remains a novel therapy with potential side effects and clinical equipoise. Methods The Closed Or Open after Laparotomy (COOL) study will constitute a prospective randomized controlled trial that will randomly allocate eligible surgical patients intra-operatively to either formal closure of the fascia or use of the OA with application of an ANPTT dressing. Patients will be eligible if they have free uncontained intra-peritoneal contamination and physiologic derangements exemplified by septic shock OR a Predisposition-Infection-Response-Organ Dysfunction Score ≥ 3 or a World-Society-of-Emergency-Surgery-Sepsis-Severity-Score ≥ 8. The primary outcome will be 90-day survival. Secondary outcomes will be logistical, physiologic, safety, bio-mediators, microbiological, quality of life, and health-care costs. Secondary outcomes will include days free of ICU, ventilation, renal replacement therapy, and hospital at 30 days from the index laparotomy. Physiologic secondary outcomes will include changes in intensive care unit illness severity scores after laparotomy. Bio-mediator outcomes for participating centers will involve measurement of interleukin (IL)-6 and IL-10, procalcitonin, activated protein C (APC), high-mobility group box protein-1, complement factors, and mitochondrial DNA. Economic outcomes will comprise standard costing for utilization of health-care resources. Discussion Although facial closure after SCIAS is considered the current standard of care, many reports are suggesting that OA management may improve outcomes in these patients. This trial will be powered to demonstrate a mortality difference in this highly lethal and morbid condition to ensure critically ill patients are receiving the best care possible and not being harmed by inappropriate therapies based on opinion only. Trial registration ClinicalTrials.gov , NCT03163095

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Novel Therapies for Myocardial Irritability following Extreme Hydroxychloroquine Toxicity

Introduction. Hydroxychloroquine (HCQ) overdose is rare and potentially deadly when consumed in large doses. Management of severe HCQ toxicity is limited and infrequently reported. This report presents the case of a massive ingestion of HCQ. Case Report. A 23-year-old female presents following an intentional ingestion of approximately 40 g of HCQ. Within six hours after ingestion, she developed severe hemodynamic instability resulting from myocardial irritability with frequent ventricular ectopic activity leading to runs of polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) requiring multiple defibrillations. Additional treatments included intravenous diazepam, epinephrine, norepinephrine, sodium bicarbonate, and magnesium sulfate. Despite the ongoing hemodynamic instability, the patient was also treated with Intralipid (ILE) and received hemodialysis. Improvements in her hemodynamics were observed after 18 hours. She survived her massive overdose of HCQ. Conclusion. HCQ poisoning is rare but serious because of its rapid progression to life-threatening symptoms. Hemodynamic support, gastric decontamination, electrolyte monitoring and replacement, and management of arrhythmias are the mainstays of treatment. The combined role of dialysis and ILE in the setting of massive HCQ overdose may improve outcomes

Correct the Coagulopathy and Scoop It Out: Complete Reversal of Anuric Renal Failure through the Operative Decompression of Extraperitoneal Hematoma-Induced Abdominal Compartment Syndrome

We report two cases of extraperitoneal compression of the intra-abdominal space resulting in abdominal compartment syndrome (ACS) with overt renal failure, which responded to operative decompression of the extra-peritoneal spaces. This discussion includes patient presentation, clinical course, diagnosis, interventions, and outcomes. Data was collected from the patient’s electronic medical record and a radiology database. ACS appears to be a rare but completely reversible complication of both retroperitoneal hematoma (RH) and rectus sheath hematoma (RSH). In patients with large RH or RSH consideration of intra-abdominal pressure (IAP) monitoring combined with aggressive operative drainage after correction of the coagulopathy should be considered. These two cases illustrate how a relatively benign pathology can result in increased IAP, organ failure, and ultimately ACS. Intervention with decompressive laparotomy and evacuation of clot resulted in return to normal physiologic function

Correct the Coagulopathy and Scoop It Out: Complete Reversal of Anuric Renal Failure through the Operative Decompression of Extraperitoneal Hematoma-Induced Abdominal Compartment Syndrome

We report two cases of extraperitoneal compression of the intra-abdominal space resulting in abdominal compartment syndrome (ACS) with overt renal failure, which responded to operative decompression of the extra-peritoneal spaces. This discussion includes patient presentation, clinical course, diagnosis, interventions, and outcomes. Data was collected from the patient’s electronic medical record and a radiology database. ACS appears to be a rare but completely reversible complication of both retroperitoneal hematoma (RH) and rectus sheath hematoma (RSH). In patients with large RH or RSH consideration of intra-abdominal pressure (IAP) monitoring combined with aggressive operative drainage after correction of the coagulopathy should be considered. These two cases illustrate how a relatively benign pathology can result in increased IAP, organ failure, and ultimately ACS. Intervention with decompressive laparotomy and evacuation of clot resulted in return to normal physiologic function.Peer Reviewe