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Objectives: Although surgical site infection (SSI) is a commonly used quality metric after lower-limb revascularization surgery, outcomes associated with development of this complication are poorly characterized. We conducted a systematic review and meta-analysis of studies reporting associations between development of an SSI after these procedures and clinical outcomes and healthcare resource use., Methods: We searched MEDLINE, Embase, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 4th, 2023) for studies examining adjusted associations between development of an SSI after lower-limb revascularization surgery and clinical outcomes and healthcare resource use. Two investigators independently screened abstracts and full-text citations, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Heterogeneity was assessed using I 2 statistics. GRADE was used to assess estimate certainty., Results: Among 6671 citations identified, we included 11 studies (n = 61,628 total patients) that reported adjusted-associations between development of an SSI and 13 different outcomes. Developing an SSI was associated with an increased adjusted-risk of hospital readmission (pooled adjusted-risk ratio (aRR) = 3.55; 95% CI (confidence interval) = 1.40-8.97; n = 4 studies; n = 13,532 patients; I 2 = 99.0%; moderate certainty), bypass graft thrombosis within 30-days (pooled aRR = 2.09; 95% CI = 1.41-3.09; n = 2 studies; n = 23,240 patients; I 2 = 51.1%; low certainty), reoperation (pooled aRR = 2.69; 95% CI = 2.67-2.72; n = 2 studies; n = 23,240 patients; I 2 = 0.0%; moderate certainty), bleeding requiring a transfusion or secondary procedure (aRR = 1.40; 95% CI = 1.26-1.55; n = 1 study; n = 10,910 patients; low certainty), myocardial infarction or stroke (aRR = 1.21; 95% CI = 1.02-1.43; n = 1 study; n = 10,910 patients; low certainty), and major (i.e., above-ankle) amputation (pooled aRR = 1.93; 95% CI = 1.26-2.95; n = 4 studies; n = 32,859 patients; I 2 = 83.0; low certainty). Development of an SSI >30-days after the index operation (aRR = 2.20; 95% CI = 1.16-4.17; n = 3 studies; n = 21,949 patients; low certainty) and prosthetic graft infection (aRR = 6.72; 95% CI = 3.21-12.70; n = 1 study; n = 272 patients; low certainty) were both associated with an increased adjusted-risk of major amputation. Prosthetic graft infection was also associated with an increased adjusted-risk of mortality >30-days after the index procedure (aRR = 6.40; 95% CI = 3.32-12.36; n = 1 study; n = 272 patients; low certainty)., Conclusions: This systematic review and meta-analysis suggests that development of an SSI after lower-limb revascularization surgery significantly increases patient morbidity and healthcare resource use. SSI is therefore a valuable quality metric after these surgeries. However, current estimates are based on heterogenous, low-to-moderate certainty evidence and should be confirmed by large, multicenter, cohort studies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Objectives: Blunt cerebrovascular injury (BCVI) includes carotid and/or vertebral artery injury following trauma, and conveys an increased stroke risk. We conducted a systematic review and meta-analysis to provide a comprehensive summary of prognostic factors associated with risk of stroke following BCVI., Methods: We searched the EMBASE and MEDLINE databases from January 1946 to June 2023. We identified studies reporting associations between patient or injury factors and risk of stroke following BCVI. We performed meta-analyses of odds ratios (ORs) using the random effects method and assessed individual study risk of bias using the QUIPS tool. We separately pooled adjusted and unadjusted analyses, highlighting the estimate with the higher certainty., Results: We included 26 cohort studies, involving 20,458 patients with blunt trauma. The overall incidence of stroke following BCVI was 7.7 %. Studies were predominantly retrospective cohorts from North America and included both carotid and vertebral artery injuries. Diagnosis of BCVI was most commonly confirmed with CT angiography. We demonstrated with moderate to high certainty that factors associated with increased risk of stroke included carotid artery injury (as compared to vertebral artery injury, unadjusted odds ratio [uOR] 1.94, 95 % CI 1.62 to 2.32), Grade III Injury (as compared to grade I or II) (uOR 2.45, 95 % CI 1.88 to 3.20), Grade IV injury (uOR 3.09, 95 % CI 2.20 to 4.35), polyarterial injury (uOR 3.11 (95 % CI 2.05 to 4.72), occurrence of hypotension at the time of hospital admission (adjusted odds ratio [aOR] 1.32, 95 % CI 0.87 to 2.03) and higher total body injury severity (aOR 5.91, 95 % CI 1.90 to 18.39)., Conclusion: Local anatomical injury pattern, overall burden of injury and flow dynamics contribute to BCVI-related stroke risk. These findings provide the foundational evidence base for risk stratification to support clinical decision making and further research., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Competing Interests: Intérêts concurrents: Hans Rosenberg déclare avoir reçu une rémunération de l’Association canadienne de protection médicale pour son rôle en tant qu’expert médicolégal et du soutien pour ses déplacements de l’Association canadienne des médecins d’urgence. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Hans Rosenberg reports payment from the Canadian Medical Protective Association as a medicolegal expert and travel support from the Canadian Association of Emergency Physicians. No other competing interests were declared.

Background: The Consultation and Relational Empathy (CARE) Measure, a validated questionnaire designed to assess patients' perceptions of their physician's communication skills and empathy, has been used to assess empathy in medical specialties but has seldom been applied to surgery. We assessed empathy and communication skills among a group of surgeons within a single academic institution., Methods: All surgeons within our department of surgery were invited to participate. Patients seen in clinics of participating surgeons were recruited prospectively from July 2018 to February 2019. At the end of each clinical encounter, they were asked to complete a CARE survey. Surveys were analyzed according to previously validated inclusion and exclusion criteria. We calculated mean scores for each surgeon and surgical division. About 6 months after study completion, surgeons were provided with their individual score and de-identified division scores, and were asked to complete a follow-up survey assessing their attitudes toward the CARE Measure., Results: Of the 82 surgeons invited, 51 (62%) agreed to participate; 7 had fewer than 25 completed surveys and were excluded from analysis. A total of 1801 surveys for 44 surgeons (33 male and 11 female) were included in the final analysis. The average CARE score across the department was 46.9 (95% confidence interval [CI] 46.6-47.1). Female surgeons received significantly higher scores than male surgeons (mean 47.6 [95% CI 47.1-48.0] v. 46.7 [95% CI 46.4-48.0]). Of the 35 surgeons who responded to the follow-up survey, 31 (89%) felt that the questions in the CARE Measure applied to their practice, and half of these reported that they intended to make changes in response to the feedback., Conclusion: We found high communication and empathy scores among surgeons in the outpatient setting, with enough variability to encourage continued improvement. The CARE Measure appears to have face validity among surgeons, and the vast majority found it relevant to their practice. Further study is needed to formally assess the relevance, performance, reliability and construct validity of this measure., Competing Interests: Competing interests: Nadia Khan is cochair of the Canadian Association of General Surgeons Resident Committee. Neal Rowe reports funding from AMT Surgical for travel to an educational course. He is a board member of the Canadian Urological Association and the Urologic Society for Transplantation and Renal Surgery. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Purpose: Acute pancreatitis is a potentially life-threatening condition with a wide spectrum of clinical presentation and illness severity. An infection of pancreatic necrosis (IPN) results in a more than twofold increase in mortality risk as compared with patients with sterile necrosis. We sought to identify prognostic factors for the development of IPN among adult patients with severe or necrotizing pancreatitis., Methods: We conducted this prognostic review in accordance with systematic review methodology guidelines. We searched six databases from inception through March 21, 2021. We included English language studies describing prognostic factors associated with the development of IPN. We pooled unadjusted odds ratio (uOR) and adjusted odds ratios (aOR) for prognostic factors using a random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the GRADE approach., Results: We included 31 observational studies involving 5,210 patients. Factors with moderate or higher certainty of association with increased IPN risk include older age (uOR, 2.19; 95% confidence interval [CI], 1.39-3.45, moderate certainty), gallstone etiology (aOR, 2.35; 95% CI, 1.36-4.04, high certainty), greater than 50% necrosis of the pancreas (aOR, 3.61; 95% CI, 2.15-6.04, high certainty), delayed enteral nutrition (aOR, 2.09; 95% CI, 1.26-3.47, moderate certainty), multiple or persistent organ failure (aOR, 11.71; 95% CI, 4.97-27.56, high certainty), and invasive mechanical ventilation (uOR, 12.24; 95% CI, 2.28-65.67, high certainty)., Conclusion: This meta-analysis confirms the association between several clinical early prognostic factors and the risk of IPN development among patients with severe or necrotizing pancreatitis. These findings provide the foundation for the development of an IPN risk stratification tool to guide more targeted clinical trials for prevention or early intervention strategies., Level of Evidence: Systematic review and meta-analysis, Level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Ruptured abdominal aortic aneurysm (rAAA) is a life-threatening condition, and rapid diagnosis is necessary to facilitate early surgical intervention. We sought to evaluate the accuracy of presenting symptoms, physical examination signs, computed tomography with angiography (CTA), and point-of-care ultrasound (PoCUS) for diagnosis of rAAA., Methods: We searched six databases from inception through April 2021. We included studies investigating the accuracy of any of the above tests for diagnosis of rAAA. The primary reference standard used in all studies was intraoperative diagnosis or death from rAAA. Because PoCUS cannot detect rupture, we secondarily assessed its accuracy for the diagnosis of AAA, using the reference standard of intraoperative or CTA diagnosis. We used GRADE to assess certainty in estimates., Results: We included 20 studies (2,077 patients), with 11 of these evaluating signs and symptoms, seven evaluating CTA, and five evaluating PoCUS. Pooled sensitivities of abdominal pain, back pain, and syncope for rAAA were 61.7%, 53.6%, and 27.8%, respectively (low certainty). Pooled sensitivity of hypotension and pulsatile abdominal mass were 30.9% and 47.1%, respectively (low certainty). CTA had a sensitivity of 91.4% and specificity of 93.6% for diagnosis of rAAA (moderate certainty). In our secondary analysis, PoCUS had a sensitivity of 97.8% and specificity of 97.0% for diagnosing AAA in patients suspected of having rAAA (moderate certainty)., Conclusions: Classic clinical symptoms associated with rAAA have poor sensitivity, and their absence does not rule out the condition. CTA has reasonable accuracy, but misses some cases of rAAA. PoCUS is a valuable tool that can help guide the need for urgent transfer to a vascular center in patients suspected of having rAAA., (© 2022 Society for Academic Emergency Medicine.)

Background: Prior studies of rapid response team (RRT) implementation for surgical patients have demonstrated mixed results with respect to reductions in poor outcomes. The aim of this study was to identify predictors of in-hospital mortality and hospital costs among surgical inpatients requiring RRT activation., Methods: We analyzed data prospectively collected from May 2012 to May 2016 at The Ottawa Hospital. We included patients who were at least 18 years of age, who were admitted to hospital, who received either preoperative or postoperative care, and and who required RRT activation. We created a multivariable logistic regression model to describe mortality predictors and a multivariable generalized linear model to describe cost predictors., Results: We included 1507 patients. The in-hospital mortality rate was 15.9%. The patient-related factors most strongly associated with mortality included an Elixhauser Comorbidity Index score of 20 or higher (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.96-6.60) and care designations excluding admission to the intensive care unit and cardiopulmonary resuscitation (OR 3.52, 95% CI 2.25-5.52). The strongest surgical predictors included neurosurgical admission (OR 2.09, 95% CI 1.17-3.75), emergent surgery (OR 2.04, 95% CI 1.37-3.03) and occurrence of 2 or more operations (OR 1.73, 95% CI 1.21-2.46). Among RRT factors, occurrence of 2 or more RRT assessments (OR 2.01, 95% CI 1.44-2.80) conferred the highest mortality. Increased cost was strongly associated with admitting service, multiple surgeries, multiple RRT assessments and medical comorbidity., Conclusion: RRT activation among surgical inpatients identifies a population at high risk of death. We identified several predictors of mortality and cost, which represent opportunities for future quality improvement and patient safety initiatives., Competing Interests: Andrew Seely holds patents related to multiorgan variability analysis and is the founder and CEO of Therapeutic Monitoring Systems Inc. No other competing interests were declared., (© 2020 Joule Inc. or its licensors.)

Background: Abdominal aortic aneurysm (AAA) repair is associated with significant morbidity and mortality. As a result, many of these patients are monitored postoperatively in the intensive care unit (ICU). However, little is known about resource utilization and costs associated with ICU admission in this population. We sought to evaluate predictors of total costs among patients admitted to the ICU after repair of nonruptured or ruptured AAA., Methods: We retrospectively analyzed prospectively collected data (2011-2016) of ICU patients admitted after AAA repair. The primary outcome was total hospital costs. We used elastic net regression to identify pre-ICU admission predictors of hospitalization costs separately for nonruptured and ruptured AAA patients., Results: We included 552 patients in the analysis. Of these, 440 (79.7%) were admitted after repair of nonruptured AAA, and 112 (20.3%) were admitted after repair of ruptured AAA. The mean age of patients with nonruptured AAA was 74 (standard deviation, 9) years, and the mean age of patients with ruptured AAA was 70 (standard deviation, 8) years. Median total hospital cost (in Canadian dollars) was $21,555 (interquartile range, $17,798-$27,294) for patients with nonruptured AAA and $33,709 (interquartile range, $23,173-$53,913) for patients with ruptured AAA. Among both nonruptured and ruptured AAA patients, increasing age, illness severity, use of endovascular repair, history of chronic obstructive pulmonary disease, and excessive blood loss (≥4000 mL) were associated with increased costs, whereas having an anesthesiologist with vascular subspecialty training was associated with lower costs., Conclusions: Patient-, procedure-, and clinician-specific variables are associated with costs in patients admitted to the ICU after repair of AAA. These factors may be considered future targets in initiatives to improve cost-effectiveness in this population., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Static indices, such as the central venous pressure, have proven to be inaccurate predictors of fluid responsiveness. An emerging approach uses dynamic assessment of fluid responsiveness (FT-DYN), such as stroke volume variation (SVV) or surrogate dynamic variables, as more accurate measures of volume status. Recent work has demonstrated that goal-directed therapy guided by FT-DYN was associated with reduced intensive care unit (ICU) mortality; however, no study has specifically assessed this in surgical ICU patients. This study aimed to conduct a systematic review and meta-analysis on the impact of employing FT-DYN in the perioperative care of surgical ICU patients on length of stay in the ICU. As secondary objectives, we performed a cost analysis of FT-DYN and assessed the impact of FT-DYN versus standard care on hospital length of stay and mortality. We identified all randomized controlled trials (RCTs) through MEDLINE, EMBASE, and CENTRAL that examined adult patients in the ICU who were randomized to standard care or to FT-DYN from inception to September 2017. Two investigators independently reviewed search results, identified appropriate studies, and extracted data using standardized spreadsheets. A random effect meta-analysis was carried out. Eleven RCTs were included with a total of 1015 patients. The incorporation of FT-DYN through SVV in surgical patients led to shorter ICU length of stay (weighted mean difference [WMD], -1.43d; 95% confidence interval [CI], -2.09 to -0.78), shorter hospital length of stay (WMD, -1.96d; 95% CI, -2.34 to -1.59), and trended toward improved mortality (odds ratio, 0.55; 95% CI, 0.30-1.03). There was a decrease in daily ICU-related costs per patient for those who received FT-DYN in the perioperative period (WMD, US$ -1619; 95% CI, -2173.68 to -1063.26). Incorporation of FT-DYN through SVV in the perioperative care of surgical ICU patients is associated with decreased ICU length of stay, hospital length of stay, and ICU costs.

Introduction:: With an aging population and increasing numbers of intensive care unit admissions, novel ways of providing quality care at reduced cost are required. Closed neurointensive care units improve outcomes for patients with critical neurological conditions, including decreased mortality and length of stay (LOS). Small studies have demonstrated the safety of intermediate-level units for selected patient populations. However, few studies analyze both cost and safety outcomes of these units. This retrospective study assessed clinical and cost-related outcomes in an intermediate-level neurosciences acute care unit (NACU) before and after the addition of an intensivist to the unit's care team., Methods:: Starting in October 2011, an intensivist-led model was adopted in a 16-bed NACU unit, including daytime coverage by a dedicated intensivist. Data were obtained from all patients admitted 1 year prior to and 2 years after this intervention. Primary outcomes were LOS and hospital costs. Safety outcomes included mortality and readmissions. Descriptive and analytic statistics were calculated. Individual and total patient costs were calculated based on per-day NACU and ward cost estimates and significance measured using bootstrapping., Results:: A total of 2931 patients were included over the study period. Patients were on average 59.5 years and 53% male. The most common reasons for admission were central nervous system (CNS) tumor (27.6%), ischemic stroke (27%), and subarachnoid hemorrhage (11%). Following the introduction of an intensivist, there was a significant reduction in NACU and hospital LOS, by 1 day and 3 days, respectively. There were no differences in readmissions or mortality. Adding an intensivist produced an individual cost savings of US$963 in NACU and US$2687 per patient total hospital stay., Conclusion:: An intensivist-led model of intermediate-level neurointensive care staffed by intensivists is safe, decreases LOS, and produces cost savings in a system increasingly strained to provide quality neurocritical care.

Background: ICU care is costly, and there is a large variation in cost among patients., Methods: This is an observational study conducted at two ICUs in an academic centre. We compared the demographics, clinical data, and outcomes of the highest decile of patients by total costs, to the rest of the population., Results: A total of 7,849 patients were included. The high-cost group had a longer median ICU length of stay (26 versus 4 days, P < 0.001) and amounted to 49% of total costs. In-hospital mortality was lower in the high-cost group (21.1% versus 28.4%, P < 0.001). Fewer high-cost patients were discharged home (23.9% versus 45.2%, P < 0.001), and a large proportion were transferred to long-term care (35.1% versus 12.1%, P < 0.001). Patients with younger age or a diagnosis of subarachnoid hemorrhage, acute respiratory failure, or complications of procedures were more likely to be high cost., Conclusions: High-cost users utilized half of the total costs. While cost is associated with LOS, other drivers include younger age or admission for respiratory failure, subarachnoid hemorrhage, or after a procedural complication. Cost-reduction interventions should incorporate strategies to optimize critical care use among these patients.

Introduction: Up to 12% of the 800,000 patients who undergo mechanical ventilation in the United States every year require tracheostomies. A recent systematic review showed that early tracheostomy was associated with better outcomes: more ventilator-free days, shorter ICU stays, less sedation and reduced long-term mortality. However, the financial impact of early tracheostomies remain unknown., Objectives: To conduct a cost-analysis on the timing of tracheostomy in mechanically ventilated patients., Methods: We extracted individual length of hospital stay and length of ICU stay data from the studies included in the systematic review from Hosokawa et al. We also searched for any recent randomized control trials on the topic that were published after this review. The weighted length of stay was estimated using a random effects model. Average daily hospital and ICU costs per patients were obtained from a cost study by Kahn et al. We estimated hospital and ICU costs by multiplying LOS with respective average daily cost per patient. We calculated difference in costs by subtracting hospital costs, ICU costs and total direct variable costs from early tracheotomy to late tracheotomy. 95% confidence intervals were estimated using bootstrap re-sampling procedures with 1000 iterations., Results: The average weighted cost of ICU stay in patients with an early tracheostomy was $4316 less when compared to patients with late tracheostomy (95% CI: 403-8229). Subgroup analysis revealed that very early tracheostomies (<4days) cost on average $3672 USD less than late tracheostomies (95% CI: -1309, 10,294) and that early tracheostomies (<10days but >4) cost on average $6385 USD less than late tracheostomies (95% CI: -4396-17,165)., Conclusion: This study shows that early tracheostomy can significantly reduce direct variable and likely total hospital costs in the intensive care unit based on length of stay alone. This is in addition to the already shown benefits of early tracheostomy in terms of ventilator dependent days, reduced length of stays, decreased pain, and improved communication. Further prospective studies on this topic are needed to prove the cost-effectiveness of early tracheostomy in the critically ill population., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: With the introduction of direct entry (0+5) residency programs in addition to the traditional (5+2) programs, the number of vascular surgery graduates across Canada is expected to increase significantly during the next 5 to 10 years. Society's need for these newly qualified surgeons is unclear. This study evaluated the predicted requirement for vascular surgeons across Canada to 2021. A program director survey was also performed to evaluate program directors' perceptions of the 0+5 residency program, the expected number of new trainees, and faculty recruitment and retirement., Methods: The estimated and projected Canadian population numbers for each year between 2013 and 2021 were determined by the Canadian Socio-economic Information and Management System (CANSIM), Statistics Canada's key socioeconomic database. The number of vascular surgery procedures performed from 2008 to 2012 stratified by age, gender, and province was obtained from the Canadian Institute for Health Information Discharge Abstract Database. The future need for vascular surgeons was calculated by two validated methods: (1) population analysis and (2) workload analysis. In addition, a 12-question survey was sent to each vascular surgery program director in Canada., Results: The estimated Canadian population in 2013 was 35.15 million, and there were 212 vascular surgeons performing a total of 98,339 procedures. The projected Canadian population by 2021 is expected to be 38.41 million, a 9.2% increase from 2013; however, the expected growth rate in the age group 60+ years, who are more likely to require vascular procedures, is expected to be 30% vs 3.4% in the age group <60 years. Using population analysis modeling, there will be a surplus of 10 vascular surgeons in Canada by 2021; however, using workload analysis modeling (which accounts for the more rapid growth and larger proportion of procedures performed in the 60+ age group), there will be a deficit of 11 vascular surgeons by 2021. Program directors in Canada have a positive outlook on graduating 0+5 residents' skill, and the majority of programs will be recruiting at least one new vascular surgeon during the next 5 years., Conclusions: Although population analysis projects a potential surplus of surgeons, workload analysis predicts a deficit of surgeons because it accounts for the rapid growth in the 60+ age group in which the majority of procedures are performed, thus more accurately modeling future need for vascular surgeons. This study suggests that there will be a need for newly graduating vascular surgeons in the next 5 years, which could have an impact on resource allocation across training programs in Canada., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Endovascular aneurysm repairs lacking suitable common iliac artery landing zones occasionally require graft limb extension into the external iliac artery, covering the internal iliac artery origin. The purpose of this study was to assess incidence of type II endoleak following simple coverage of internal iliac artery without embolization during endovascular aneurysm repair. Three hundred eighty-nine endovascular aneurysm repairs performed by a single surgeon (2004-2015) were reviewed. Twenty-seven patients underwent simple internal iliac artery coverage. Type II endoleak was assessed from operative reports and follow-up computed tomography imaging. No patient suffered type II endoleak from a covered internal iliac artery in post-operative computed tomography scans. Follow-up ranged from 0.5 to 9 years. No severe pelvic ischemic complications were observed. In conclusion, for selected cases internal iliac artery coverage without embolization is a safe alternative to embolization in endovascular aneurysm repairs, where the graft must be extended into the external iliac artery.

Background. Spontaneous breathing trials (SBTs) are standard of care in assessing extubation readiness; however, there are no universally accepted guidelines regarding their precise performance and reporting. Objective. To investigate variability in SBT practice across centres. Methods. Data from 680 patients undergoing 931 SBTs from eight North American centres from the Weaning and Variability Evaluation (WAVE) observational study were examined. SBT performance was analyzed with respect to ventilatory support, oxygen requirements, and sedation level using the Richmond Agitation Scale Score (RASS). The incidence of use of clinical extubation criteria and changes in physiologic parameters during an SBT were assessed. Results. The majority (80% and 78%) of SBTs used 5 cmH2O of ventilator support, although there was variability. A significant range in oxygenation was observed. RASS scores were variable, with RASS 0 ranging from 29% to 86% and 22% of SBTs performed in sedated patients (RASS < -2). Clinical extubation criteria were heterogeneous among centres. On average, there was no change in physiological variables during SBTs. Conclusion. The present study highlights variation in SBT performance and documentation across and within sites. With their impact on the accuracy of outcome prediction, these results support efforts to further clarify and standardize optimal SBT technique.

Introduction: Prolonged ventilation and failed extubation are associated with increased harm and cost. The added value of heart and respiratory rate variability (HRV and RRV) during spontaneous breathing trials (SBTs) to predict extubation failure remains unknown., Methods: We enrolled 721 patients in a multicenter (12 sites), prospective, observational study, evaluating clinical estimates of risk of extubation failure, physiologic measures recorded during SBTs, HRV and RRV recorded before and during the last SBT prior to extubation, and extubation outcomes. We excluded 287 patients because of protocol or technical violations, or poor data quality. Measures of variability (97 HRV, 82 RRV) were calculated from electrocardiogram and capnography waveforms followed by automated cleaning and variability analysis using Continuous Individualized Multiorgan Variability Analysis (CIMVA™) software. Repeated randomized subsampling with training, validation, and testing were used to derive and compare predictive models., Results: Of 434 patients with high-quality data, 51 (12%) failed extubation. Two HRV and eight RRV measures showed statistically significant association with extubation failure (P <0.0041, 5% false discovery rate). An ensemble average of five univariate logistic regression models using RRV during SBT, yielding a probability of extubation failure (called WAVE score), demonstrated optimal predictive capacity. With repeated random subsampling and testing, the model showed mean receiver operating characteristic area under the curve (ROC AUC) of 0.69, higher than heart rate (0.51), rapid shallow breathing index (RBSI; 0.61) and respiratory rate (0.63). After deriving a WAVE model based on all data, training-set performance demonstrated that the model increased its predictive power when applied to patients conventionally considered high risk: a WAVE score >0.5 in patients with RSBI >105 and perceived high risk of failure yielded a fold increase in risk of extubation failure of 3.0 (95% confidence interval (CI) 1.2 to 5.2) and 3.5 (95% CI 1.9 to 5.4), respectively., Conclusions: Altered HRV and RRV (during the SBT prior to extubation) are significantly associated with extubation failure. A predictive model using RRV during the last SBT provided optimal accuracy of prediction in all patients, with improved accuracy when combined with clinical impression or RSBI. This model requires a validation cohort to evaluate accuracy and generalizability., Trial Registration: ClinicalTrials.gov NCT01237886. Registered 13 October 2010.

Background: Current Canadian and international guidelines suggest patients with transient ischemic attack (TIA) or nondisabling stroke and ipsilateral internal carotid artery stenosis of 50% to 99% should be offered carotid endarterectomy (CEA) ≤ 2 weeks of the incident TIA or stroke. The objective of the study was to identify whether these goals are being met and the factors that most influence wait times., Methods: Patients who underwent CEA at the Ottawa Hospital for symptomatic carotid artery stenosis from 2008 to 2010 were identified. Time intervals based on the dates of initial symptoms, referral to and visit with a vascular surgeon, the decision to operate, and the date of surgery were recorded for each patient. The influence of various factors on wait times was explored, including age, sex, type of index event, referring physician, distance from the surgical center, degree of stenosis, and surgeon assigned., Results: Of the 117 patients who underwent CEA, 92 (78.6%) were symptomatic. The median time from onset of symptoms to surgery for all patients was 79 days (interquartile range [IQR], 34-161). The shortest wait times were observed in stroke patients (49 [IQR, 27-81] days) and inpatient referrals (66 [IQR, 25-103] days). Only 7 of the 92 symptomatic patients (8%) received care within the recommended 2 weeks. The median surgical wait time for all patients was 14 days (IQR, 8-25 days). In the multivariable analysis, significant predictors of longer wait times included retinal TIA (P = .003), outpatient referrals (P = .004), and distance from the center (P = .008). Patients who presented to the emergency department had the shortest delays in seeing a vascular surgeon and subsequently undergoing CEA (P < .0001). There was no difference between surgeons for wait times to be seen in the clinic; however, there were significant differences among surgeons once the decision was made to proceed with CEA., Conclusions: Our wait times for CEA currently do not fall within the recommended 2-week guideline nor does it appear feasible within the current system. Important factors contributing to delays include outpatient referrals, living farther from the hospital, and presenting with a retinal TIA (amaurosis fugax). Our findings also suggest better scheduling practices once a decision is made to operate can modestly improve overall and surgical wait times for CEA., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Innate immunity provides obstacles to successful organ transplantation, which cannot be prevented by cyclosporine (CsA). Here we have determined the potential of a myxoma viral serpin, Serp-1, with proven anti-inflammatory and antiatherogenic actions, to modulate innate immunity and contribute synergistically with CsA in the prevention of acute cardiac allograft rejection., Methods: Brown-Norway rat hearts were heterotopically transplanted into Lewis rats and given either a monotherapy treatment of Serp-1, a subtherapeutic dose of CsA, or the two drugs in combination., Results: A brief treatment of Serp-1 alone, or a subtherapeutic dose of CsA, resulted in a marked decrease in intragraft macrophage infiltration and downregulation of toll-like receptor (TLR)-2, TLR4 and MyD88 at 48 hours posttransplantation, which was associated with significantly reduced numbers of mature dendritic cells. A significant reduction in intragraft T-lymphocyte infiltration was observed with both Serp-1 monotherapy and Serp-1 and CsA combination therapy, with the combination treatment achieving indefinite graft survival (>100 days) with normal histology. The CsA monotherapy group displayed partially reduced lymphocyte infiltration compared to the untreated controls, but failed to inhibit early innate immune graft recognition events such as macrophage infiltration and TLR 2, TLR4, and MyD88, and was ultimately unsuccessful in preventing rejection (36.3+/-7.8 days)., Conclusion: Observed suppressive effects of Serp-1 on early innate immune response components such as TLR-2 and 4, and on adaptive responses such as T-cell intragraft infiltration suggests that Serp-1 may modulate the transition from innate to adaptive immunity, exhibiting a synergistic effect on allograft survival when used in combination with a subtherapeutic dose of CsA.

Background: The present study was undertaken to determine the role of preformed and induced anti-non-Gal antibodies in the rejection of hDAF pig-to-baboon kidney xenotransplants after anti-Gal antibody neutralization therapy., Methods: Seven baboons received life-supporting kidney transplants from hDAF transgenic pigs. Anti-Gal antibodies were neutralized by GAS914 or TPC (a Gal PEG glycoconjugate polymer). Group 1 (n=5) underwent a conventional immunosuppressive therapy with FK506, rabbit anti-thymocyte serum/immunoglobulin, mycophenolate mofetil, and steroids. Group 2 (n=2) received an anti-humoral immunity regimen with LF15-0195, Rituxan and cobra venom factor in addition to ATG, FK506 and steroids. Levels of anti-non-Gal antibodies and their mediated complement-dependent cytotoxic activities (CDC) were detected by flow cytometry using Gal knockout (k/o) pig lymphocytes (LC) or endothelial cells (EC) as targets., Results: Continuous infusion of GAS914/TPC significantly reduced anti-Gal antibodies. In Group 1, four of five baboons developed severe acute humoral xenograft rejection (AHXR) and the rejection was associated with either a high level of preformed anti-non-Gal IgG or a marked elevation in induced anti-non-Gal IgG and IgM. Sera collected at the time of AHXR had a high level of CDC to porcine LC/EC from Gal k/o animals. The intensive anti-humoral therapy in Group 2 completely inhibited both anti-Gal and non-Gal antibody production and prevented AHXR. However, this therapy was not well tolerated by the baboons., Conclusion: In a pig-to-baboon kidney transplant model, both preformed and induced anti-non-Gal antibodies are strongly associated with the pathogenesis of AHXR when anti-Gal antibodies are neutralized.

Background: Transgenic pigs expressing human decay accelerating factor (hDAF) have been widely used as donors in various non-human primate transplant models. Despite the use of similar immunosuppressive protocols, there is marked variation in graft survival among centres. The present study was undertaken to determine whether the level of hDAF expression in the pig kidney correlates with the degree of rejection and duration of graft survival., Methods: hDAF transgenic pigs were provided from two suppliers: Guelph Imutran Centre (G) and Harlan Sprague Dawley (H). Following a bilateral nephrectomy, a single hDAF pig kidney was implanted in the baboon, which was subsequently treated with conventional immunosuppressive protocols. The pig's contralateral kidney was collected to provide baseline data. The severity of acute humoral xenograft rejection (AHXR) was graded as stage I-III. hDAF expression was measured using morphologic analysis comparing the contralateral and grafted kidneys at the endpoint., Results: Baseline hDAF expression in kidneys from pigs provided by supplier G was significantly higher than that from supplier H (P<0.01). Furthermore, the survival of baboons receiving grafts from G pigs was significantly longer than those receiving grafts from H pigs (P<0.05). In addition, reduction of hDAF expression at the endpoint was associated with a higher degree of AHXR. Severe apoptosis or necrosis was found in grafts with AHXR II-III., Conclusions: Pig kidneys from different suppliers have variable baseline hDAF expression, which may have an influence on graft survival. Reduced expression of hDAF in the terminal graft was associated with the severity of rejection.

Background: Inhibition of the complement cascade at C5 prevents formation of pro-inflammatory molecules C5a and C5b-9, which play a key role in allograft rejection. The present study was undertaken to determine whether blocking terminal complement with anti-C5 monoclonal antibody (mAb) alone or combined with cyclosporine (CsA) would prevent acute vascular rejection (AVR) in a mouse cardiac allograft model., Methods: C3H mouse hearts were transplanted into BALB/c mice and randomized into five groups with the following treatments: (1) no treatment; (2) CsA alone; (3) control mAb; (4) anti-C5 mAb alone; and (5) anti-C5 mAb and CsA., Results: Allografts in untreated or control mAb-treated recipients were rapidly rejected at 8.0+/-0.6 and 8.2+/-0.8 days, respectively. These grafts exhibited typical AVR, characterized by vasculitis, hemorrhage, and thrombosis. A high level of complement activity was also demonstrated in these animals. High-dose CsA was not able to inhibit complement activation or AVR, and grafts were rejected in 15.5+/-1.1 days. Anti-C5 monotherapy completely inhibited complement activation and attenuated AVR, but grafts were rejected in 8.3+/-0.5 days by acute cellular rejection. In contrast, a combination of anti-C5 mAb and CsA successfully achieved indefinite graft survival (>100 days). This combined therapy completely inhibited terminal complement activation and prevented both humoral- and cellular-mediated rejection., Conclusions: Combination therapy of anti-C5 mAb and CsA achieves indefinite graft survival in a mouse cardiac allograft model. These data suggest that inhibition of terminal complement using anti-C5 mAb may be an effective therapeutic adjunct to prevent AVR in clinical transplantation.