Tiffany Zens

Current outcomes of chronic active antibody mediated rejection – A large single center retrospective review using the updated BANFF 2013 criteria

BACKGROUND The updated BANFF 2013 criteria has enabled a more standardized and complete serologic and histopathologic diagnosis of chronic active antibody mediated rejection (cAMR). Little data exists on the outcomes of cAMR since the initiation of this updated criteria. METHODS 123 consecutive patients with biopsy proven cAMR (BANFF 2013) between 2006 and 2012 were identified. RESULTS Patients identified with cAMR were followed for a median of 9.5 (2.7-20.3) years after transplant and 4.3 (0-8.8) years after cAMR. Ninety-four (76%) recipients lost their grafts with a median survival of 1.9 years after diagnosis with cAMR. Mean C4d and allograft glomerulopathy scores were 2.6 ± 0.7 and 2.2 ± 0.8, respectively. 53.2% had class II DSA, 32.2% had both class I and II, and 14.5% had class I DSA only. Chronicity score >8 (HR 2.9, 95% CI 1-8.4, p=0.05), DSA >2500 MFI (HR 2.8, 95% CI 1.1-6.8, p=0.03), Scr >3mg/dL (HR 3.2, 95% CI 1.6-6.3, p=0.001) and UPC >1g/g (HR 2.5, 95% CI 1.4-4.5, p=0.003) were associated with a higher risk of graft loss. CONCLUSIONS cAMR was associated with poor graft survival after diagnosis. Improved therapies and earlier detection strategies are likely needed to improve outcomes of cAMR in kidney transplant recipients.

A call for a standardized definition of perforated appendicitis.

BACKGROUND Abscess rates have been reported to be as low as 1% and as high as 50% following perforated appendicitis (PA). This range may be because of lack of universal definition for PA. An evidence-based definition (EBD) is crucial for accurate wound classification, risk-stratification, and subsequent process optimization. ACS NSQIP-Pediatric guidelines do not specify a definition of PA. We hypothesize that reported postoperative abscess rates underrepresent true incidence, as they may include low-risk cases in final calculations. METHODS Local institutional records of PA patients were reviewed to calculate the postoperative abscess rate. The ACS NSQIP-Pediatric participant use file (PUF) was used to determine cross-institutional postoperative abscess rates. A PubMed literature review was performed to identify trials reporting PA abscess rates, and definitions and rates were recorded. RESULTS 20.9% of our patients with PA developed a postoperative abscess. The ACS NSQIP-Pediatric abscess rate was significantly lower (7.61%, p<0.001). In the eighteen published studies analyzed, average abscess rate (14.49%) was significantly higher than ACS NSQIP-Pediatric (p<0.001). There was significantly more variation in trials that do not employ an EBD of perforation (Levenes test F-value =6.980, p=0.018). CONCLUSIONS A standard EBD of perforation leads to lower variability in reported postoperative abscess rates following PA. Nonstandard definitions may be significantly altering the aggregate rate of postoperative abscess formation. We advocate for adoption of a standard definition by all institutions participating in ACS NSQIP-Pediatric data submission. LEVEL OF EVIDENCE III.

Number of rib fractures thresholds independently predict worse outcomes in older patients with blunt trauma.

Background. There have been conflicting reports regarding whether the number of rib fractures sustained in blunt trauma is associated independently with worse patient outcomes. We sought to investigate this risk‐adjusted relationship among the lesser‐studied population of older adults. Methods. A retrospective review of the National Trauma Data Bank was performed for patients with blunt trauma who were ≥65 years old and had rib fractures between 2009 and 2012 (N = 67,695). Control data were collected for age, sex, injury severity score, injury mechanism, 24 comorbidities, and number of rib fractures. Outcome data included hospital mortality, hospital and intensive care unit durations of stay, duration of mechanical ventilation, and the occurrence of pneumonia. Multiple logistic and linear regression analyses were performed. Results. Sustaining ≥5 rib fractures was associated with increased intensive care unit admission (odds ratio: 1.14, P < .001) and hospital duration of stay (relative duration: 105%, P < .001). Sustaining ≥7 rib fractures was associated with an increased incidence of pneumonia (odds ratio: 1.32, P < .001) and intensive care unit duration of stay (relative duration: 122%, P < .001). Sustaining ≥8 rib fractures was associated with increased mortality (odds ratio: 1.51, P < .001) and duration of mechanical ventilation (relative duration: 117%, P < .001). Conclusion. In older patients with trauma, sustaining at least 5 rib fractures is a significant predictor of worse outcomes independent of patient characteristics, comorbidities, and trauma burden.

Complement inhibition attenuates acute kidney injury after ischemia-reperfusion and limits progression to renal fibrosis in mice

The complement system is an essential component of innate immunity and plays a major role in the pathogenesis of ischemia-reperfusion injury (IRI). In this study, we investigated the impact of human C1-inhibitor (C1INH) on the early inflammatory response to IRI and the subsequent progression to fibrosis in mice. We evaluated structural damage, renal function, acute inflammatory response, progression to fibrosis and overall survival at 90-days post-injury. Animals receiving C1INH prior to reperfusion had a significant improvement in survival rate along with superior renal function when compared to vehicle (PBS) treated counterparts. Pre-treatment with C1INH also prevented acute IL-6, CXCL1 and MCP-1 up-regulation, C5a release, C3b deposition and infiltration by neutrophils and macrophages into renal tissue. This anti-inflammatory effect correlated with a significant reduction in the expression of markers of fibrosis alpha smooth muscle actin, desmin and picrosirius red at 30 and 90 days post-IRI and reduced renal levels of TGF-β1 when compared to untreated controls. Our findings indicate that intravenous delivery of C1INH prior to ischemic injury protects kidneys from inflammatory injury and subsequent progression to fibrosis. We conclude that early complement blockade in the context of IRI constitutes an effective strategy in the prevention of fibrosis after ischemic acute kidney injury.

Pediatric surgeon-directed wound classification improves accuracy.

BACKGROUND Surgical wound classification (SWC) communicates the degree of contamination in the surgical field and is used to stratify risk of surgical site infection and compare outcomes among centers. We hypothesized that by changing from nurse-directed to surgeon-directed SWC during a structured operative debrief, we will improve accuracy of documentation. METHODS An institutional review board-approved retrospective chart review was performed. Two time periods were defined: initially, SWC was determined and recorded by the circulating nurse (before debrief, June 2012-May 2013) and allowing 6 mo for adoption and education, we implemented a structured operative debriefing including surgeon-directed SWC (after debrief, January 2014-August 2014). Accuracy of SWC was determined for four commonly performed pediatric general surgery operations: inguinal hernia repair (clean), gastrostomy ± Nissen fundoplication (clean contaminated), appendectomy without perforation (contaminated), and appendectomy with perforation (dirty). RESULTS One hundred eighty-three cases before debrief and 142 cases after debrief met inclusion criteria. No differences between time periods were noted in regard to patient demographics, ASA class, or case mix. Accuracy of wound classification improved before debrief (42% versus 58.5%, P = 0.003). Before debrief, 26.8% of cases were overestimated or underestimated by more than one wound class, versus 3.5% of cases after debrief (P < 0.001). Interestingly, most after debrief contaminated cases were incorrectly classified as clean contaminated. CONCLUSIONS Implementation of a structured operative debrief including surgeon-directed SWC improves the percentage of correctly classified wounds and decreases the degree of inaccuracy in incorrectly classified cases. However, after implementation of the debriefing, we still observed a 41.5% rate of incorrect documentation, most notably in contaminated cases, indicating further education and process improvement is needed.

Race, insurance status, and traumatic brain injury outcomes before and after enactment of the Affordable Care Act

Background The Affordable Care Act aims to improve patient outcomes. Race/ethnicity and insurance status impact outcomes after traumatic brain injury. We sought to gauge the Affordable Care Acts effect on outcomes after traumatic brain injury, as graded by race/ethnicity and insurance status. Methods The National Trauma Data Bank was utilized to identify traumatic brain injury patients before and after the Affordable Care Act. Patient outcomes comprised of hospital duration of stay, in‐hospital mortality, discharge to rehabilitation, and surgical procedures. Using regression analysis, we evaluated the impact of race/ethnicity and insurance status on traumatic brain injury outcomes, then compared them before and after the Affordable Care Act. Results Mortality decreased for blacks (odds ratio = 0.96 [confidence interval 0.83–1.10] to odds ratio = 0.79 [confidence interval = 0.70–0.89], and Hispanics (odds ratio = 1.03 [confidence interval = 0.90–1.17] to odds ratio = 0.79 [confidence interval = 0.70–0.89]). Mortality increased for the uninsured (odds ratio = 1.28 [confidence interval = 1.11–1.47] to odds ratio = 1.40 [confidence interval = 1.24–1.58]). Medicaid patients underwent decreased duration of stay, (coefficient = 2.75 [confidence interval = 2.49–3.02] to coefficient = 2.17, [confidence interval = 1.98–2.37]), discharge to rehabilitation (odds ratio = 1.15, [confidence interval = 1.04–1.26] to odds ratio = 0.95 [confidence interval = 0.87–1.03]), and surgical procedures (odds ratio = 1.28 [confidence interval = 1.13–1.45] to odds ratio = 1.18, [confidence interval = 1.07–1.30]), while mortality remained unchanged. Conclusion After the Affordable Care Act traumatic brain injury mortality decreased for blacks and Hispanics, but increased for the uninsured. Decreasing trends in resource consumption were also evident, especially for Medicaid patients. These results may illustrate altered delivery of care.

Guidelines for the management of a brain death donor in the rhesus macaque: A translational transplant model

Introduction The development of a translatable brain death animal model has significant potential to advance not only transplant research, but also the understanding of the pathophysiologic changes that occur in brain death and severe traumatic brain injury. The aim of this paper is to describe a rhesus macaque model of brain death designed to simulate the average time and medical management described in the human literature. Methods Following approval by the Institutional Animal Care and Use Committee, a brain death model was developed. Non-human primates were monitored and maintained for 20 hours after brain death induction. Vasoactive agents and fluid boluses were administered to maintain hemodynamic stability. Endocrine derangements, particularly diabetes insipidus, were aggressively managed. Results A total of 9 rhesus macaque animals were included in the study. The expected hemodynamic instability of brain death in a rostral to caudal fashion was documented in terms of blood pressure and heart rate changes. During the maintenance phase of brain death, the animal’s temperature and hemodynamics were maintained with goals of mean arterial pressure greater than 60mmHg and heart rate within 20 beats per minute of baseline. Resuscitation protocols are described so that future investigators may reproduce this model. Conclusion We have developed a reproducible large animal primate model of brain death which simulates clinical scenarios and treatment. Our model offers the opportunity for researchers to have translational model to test the efficacy of therapeutic strategies prior to human clinical trials.

Thoracoscopic, minimally invasive rib fixation after trauma:

Rib fractures and flail chest are associated with significant morbidity and mortality. Operative rib fixation has been shown to improve patient outcomes. In an attempt to decrease postoperative pain and wound infection rates, we performed rib fixation using a thoracoscopic approach. A 43-year-old trauma patient underwent thoracoscopic rib fixation with placement of a bioabsorbable plate. Postoperatively, the patient was extubated on post-operative day (POD) 1 and no longer required supplemental oxygen on POD5. This case demonstrates that thoracoscopic rib fixation is technically feasible and safe.

Indications for Rib Fixation

There are no clear, absolute, and universally accepted indications or contraindications for operative rib fixation. Furthermore, although the majority of experts believe patients benefit most from early operative fixation, there is no consensus agreement regarding optimal timing of surgery. The most common and well-accepted indication for operative rib fixation is the presence of a flail chest segment in a patient on mechanical ventilation with no underlying pulmonary contusion. This indication is in concordance with the clinical practice guidelines issued by the Eastern Association for the Surgery of Trauma. Additional relative indications supported by the literature and recommended by experts in the field include severe chest wall deformity, symptomatic rib fracture nonunion, acute pulmonary herniation, failure to wean from mechanical ventilation or poor pulmonary mechanics in a patient with severe chest wall trauma, need for acute or chronic pain/symptom control, and thoracotomy for another reason. Surgeons should take into consideration possible contraindications for operative repair including the location of rib fractures and presence of either pulmonary contusion or traumatic brain injury.

Socioeconomic disparities in the thoracic trauma population

BACKGROUND Health-care disparities based on socioeconomic status have been well documented in the trauma literature; however, there is a paucity of data on how these factors affect outcomes in patients experiencing severe thoracic trauma. This study aims to identify the effect of insurance status and race on patient mortality and disposition after thoracic trauma. METHODS The National Trauma Data Bank was queried from 2007 to 2012 for patients with sternal fractures, rib fractures, and flailed chest. Demographics data were examined for the cohort based on insurance status. Univariate and multivariate logistic regression models were used, controlling for patient comorbidities, age, injury severity score, and associated injuries, to determine the impact of race and insurance status on length of stay, mortality, and discharge disposition. RESULTS A total of 152,655 thoracic traumas were included in our analysis. As compared to privately insured patients, uninsured patients with thoracic trauma were 1.9 times more likely to die (odds ratio [OR]: 1.91, confidence interval [CI]: 1.76-2.09) and 4.6 times more likely to leave against medical advice (OR: 4.61, CI: 3.14-6.79). When compared to Caucasians, Hispanics had slightly higher in-hospital mortality (OR: 1.14, CI: 1.02-1.27), but there was no survival difference seen in black patients (OR: 0.95, CI: 0.86-1.05). CONCLUSIONS Insurance status appears to have a more significant effect on thoracic trauma patient outcomes than race, but substantial socioeconomic disparities were seen in this patient population. Further studies are needed to show reproducibility of our findings and to investigate the impact of universal health care and expansion of insurance availability on thoracic trauma outcomes. LEVEL OF EVIDENCE Level 3, economic/decision.