PROPOSED REVISION OF THE AMERICAN ASSOCIATION FOR SURGERY OF TRAUMA RENAL TRAUMA ORGAN INJURY SCALE: SECONDARY ANALYSIS OF THE MULTI-INSTITUTIONAL GENITOURINARY TRAUMA STUDY.

BACKGROUND: This study updates the American Association for Surgery of Trauma (AAST) Organ Injury Scale (OIS) for renal trauma using evidence-based criteria for bleeding control intervention. METHODS: This was a secondary analysis of a multi-center retrospective study including patients with high grade renal trauma from 7 Level-1 trauma centers from 2013-2018. All eligible patients were assigned new renal trauma grades based on revised criteria. The primary outcome used to measure injury severity was intervention for renal bleeding. Secondary outcomes included intervention for urinary extravasation, units of packed red blood cells (PRBCs) transfused within 24 hours, and mortality. To test the revised grading system, we performed mixed effect logistic regression adjusted for multiple baseline demographic and trauma covariates. We determined the area under the receiver-operator curve (AUC) to assess accuracy of predicting bleeding interventions from the revised grading system and compared this to 2018 AAST organ injury scale. RESULTS: based on the 2018 OIS grading system, we included 549 patients with AAST Grade III-V injuries and CT scans (III: 52% (n = 284), IV: 45% (n = 249), and V: 3% (n = 16)). Among these patients, 89% experienced blunt injury (n = 491) and 12% (n = 64) underwent intervention for bleeding. After applying the revised grading criteria, 60% (n = 329) of patients were downgraded and 4% (n = 23) were upgraded; 2.8% (n = 7) downgraded from grade V to IV, and 69.5% (n = 173) downgraded from IV to III. The revised renal trauma grading system demonstrated improved predictive ability for bleeding interventions (2018 AUC = 0.805, revised AUC = 0.883; p = 0.001) and number of units of PRBCs transfused. When we removed urinary injury from the revised system, there was no difference in its predictive ability for renal hemorrhage intervention. CONCLUSIONS: A revised renal trauma grading system better delineates the need for hemostatic interventions than the current AAST OIS renal trauma grading system. LEVEL OF EVIDENCE: II.

Management of pediatric renal trauma - Results from the American Association for Surgery and Trauma Multi-Institutional Pediatric Acute Renal Trauma Study (Mi-PARTS).

BACKGROUND: Pediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A non-operative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury is not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This manuscript describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States. METHODS: Retrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010-2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management and outcomes. RESULTS: In total 1216 cases were included in this study. 67.2% were male, and 93.8% had a blunt injury mechanism. 29.3% had isolated renal injuries. 65.6% were high-grade (AAST Grade III-V) injuries. The mean Injury Severity Score (ISS) was 20.5. Most patients were managed non-operatively (86.4%) 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in polytrauma. The rate of avoidable transfer was 28.2%. CONCLUSION: The management and outcomes of pediatric renal trauma lacks data to inform evidence-based guidelines. Non-operative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population, and highlights opportunities for further investigation. With data made available through Mi-PARTS we aim to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries. LEVEL OF EVIDENCE: IV, Epidemiological (prognostic/epidemiological, therapeutic/care management, diagnostic test/criteria, economic/value-based evaluations, and Systematic Review and Meta-Analysis).

Grade V renal trauma management: results from the multi-institutional genito-urinary trauma study.

PURPOSE: To investigate management trends for American Association for the Surgery of Trauma (AAST) grade V renal trauma with focus on non-operative management. METHODS: We used prospectively collected data as part of the Multi-institutional Genito-Urinary Trauma Study (MiGUTS). We included patients with grade V renal trauma according to the AAST Injury Scoring Scale 2018 update. All cases submitted by participating centers with radiology images available were independently reviewed to confirm renal trauma grade. Management was classified as expectant, conservative (minimally invasive, endoscopic or percutaneous procedures), or operative (renal-related surgery). RESULTS: Eighty patients were included, 25 of whom had complete imaging and had independent confirmation of AAST grade V renal trauma. Median age was 35 years (Interquartile range (IQR) 25-50) and 23 (92%) had blunt trauma. Ten patients (40%) were managed operatively with nephrectomy. Conservative management was used in nine patients (36%) of which six received angioembolization and three had a stent or drainage tube placed. Expectant management was followed in six (24%) patients. Transfusion requirements were progressively higher with groups requiring more aggressive treatment, and injury characteristics differed significantly across management groups in terms of hematoma size and laceration size. Vascular contrast extravasation was more likely in operatively managed patients though a statistically significant association was not found. CONCLUSION: Successful use of nonoperative management for grade V injuries is used for a substantial subset of patients. Lower transfusion requirement and less severe injury radiologic phenotype appear to be important characteristics delineating this group.

Shattered Kidney After Renal Trauma: Should It Be Classified As an American Association for the Surgery of Trauma Grade V Injury?

OBJECTIVE: To study the prevalence and management of shattered kidney and to evaluate if the new description of "loss of identifiable renal anatomy" in the 2018 American Association for the Surgery of Trauma (AAST) organ injury scale (OIS) would improve the ability to predict bleeding control interventions. METHODS: We used high-grade renal trauma data from 21 Level-1 trauma centers from 2013 to 2018. Initial CT scans were reviewed to identify shattered kidneys, defined as a kidney having ≥3 parenchymal fragments displaced by blood or fluid on cross-sectional imaging. We further categorized patients with shattered kidney in two models based on loss of identifiable renal parenchymal anatomy and presence or absence of vascular contrast extravasation (VCE). Bleeding interventions were compared between the groups. RESULTS: From 861 high-grade renal trauma patients, 41 (4.8%) had shattered kidney injury. 25 (61%) underwent a bleeding control intervention including 18 (43.9%) nephrectomies and 11 (26.8%) angioembolizations. 18 (41%) had shattered kidney with "loss of identifiable parenchymal renal anatomy" per 2018 AAST OIS (model-1). 28 (68.3%) had concurrent VCE (model-2). Model-2 had a statistically significant improvement in area under the curve over model-1 in predicting bleeding interventions (0.75 vs 0.72; P = .01). CONCLUSION: Shattered kidney is associated with high rates of active bleeding, urinary extravasation, and interventions including nephrectomy. The definition of shattered kidney is vague and subjective and our definition might be simpler and more reproducible. Loss of identifiable renal anatomy per the 2018 AAST OIS did not provide better distinction for bleeding control interventions over presence of VCE.

A multicenter prospective cohort study of endoscopic urethral realignment versus suprapubic cystostomy after complete pelvic fracture urethral injury.

BACKGROUND: Pelvic fracture urethral injury (PFUI) occurs in up to 10% of pelvic fractures. There is mixed evidence supporting early endoscopic urethral realignment (EUR) over suprapubic tube (SPT) placement and delayed urethroplasty. Some studies show decreased urethral obstruction with EUR, while others show few differences. We hypothesized that EUR would reduce the rate of urethral obstruction after PFUI. METHODS: Twenty-six US medical centers contributed patients following either an EUR or SPT protocol from 2015 to 2020. If retrograde cystoscopic catheter placement failed, patients were included and underwent either EUR or SPT placement based on their institution's assigned treatment arm. Endoscopic urethral realignment involved simultaneous antegrade/retrograde cystoscopy to place a catheter across the urethral injury. The primary endpoint was development of urethral obstruction. Fisher's exact test was used to analyze the relationship between PFUI management and development of urethral obstruction. RESULTS: There were 106 patients with PFUI; 69 (65%) had complete urethral disruption and failure of catheter placement with retrograde cystoscopy. Of the 69 patients, there were 37 (54%) and 32 (46%) in the EUR and SPT arms, respectively. Mean age was 37.0 years (SD, 16.3 years) years, and mean follow-up was 463 days (SD, 280 days) from injury. In the EUR arm, 36 patients (97%) developed urethral obstruction compared with 30 patients (94%) in the SPT arm ( p = 0.471). Urethroplasty was performed in 31 (87%) and 29 patients (91%) in the EUR and SPT arms, respectively ( p = 0.784). CONCLUSION: In this prospective multi-institutional study of PFUI, EUR was not associated with a lower rate of urethral obstruction or need for urethroplasty when compared with SPT placement. Given the potential risk of EUR worsening injuries, clinicians should consider SPT placement as initial treatment for PFUI when simple retrograde cystoscopy is not successful in placement of a urethral catheter. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

The Outcomes of Pelvic Fracture Urethral Injuries Stratified by Urethral Injury Severity: A Prospective Multi-institutional Genitourinary Trauma Study (MiGUTS).

OBJECTIVE: To determine patient outcomes across a range of pelvic fracture urethral injury (PFUI) severity. PFUI is a devastating consequence of a pelvic fracture. No study has stratified PFUI outcomes based on severity of the urethral distraction injury. METHODS: Adult male patients with blunt-trauma-related PFUI were followed prospectively for a minimum of six months at 27 US medical centers from 2015-2020. Patients underwent retrograde cystourethroscopy and retrograde urethrography to determine injury severity and were categorized into three groups: (1) major urethral distraction, (2) minor urethral distraction, and (3) partial urethral injury. Major distraction vs minor distraction was determined by the ability to pass a cystoscope retrograde into the bladder. Simple statistics summarized differences between groups. Multi-variable analyses determined odds ratios for obstruction and urethroplasty controlling for urethral injury type, age, and Injury Severity Score. RESULTS: There were 99 patients included, 72(72%) patients had major, 13(13%) had minor, and 14(14%) had partial urethral injuries. The rate of urethral obstruction differed in patients with major (95.8%), minor (84.6%), and partial injuries (50%) (P < 0.001). Urethroplasty was performed in 90% of major, 66.7% of minor, and 35.7% of partial injuries (P < 0.001). CONCLUSION: In PFUI, a spectrum of severity exists that influences outcomes. While major and minor distraction injuries are associated with a higher risk of developing urethral obstruction and need for urethroplasty, up to 50% of partial PFUI will result in obstruction, and as such need to be closely followed.

Nephrectomy After High-Grade Renal Trauma is Associated With Higher Mortality: Results From the Multi-Institutional Genitourinary Trauma Study (MiGUTS).

OBJECTIVE: To test the hypothesis that undergoing nephrectomy after high-grade renal trauma is associated with higher mortality rates. METHODS: We gathered data from 21 Level-1 trauma centers through the Multi-institutional Genito-Urinary Trauma Study. Patients with high-grade renal trauma were included. We assessed the association between nephrectomy and mortality in all patients and in subgroups of patients after excluding those who died within 24 hours of hospital arrival and those with GCS≤8. We controlled for age, injury severity score (ISS), shock (systolic blood pressure <90 mmHg), and Glasgow Coma Scale (GCS). RESULTS: A total of 1181 high-grade renal trauma patients were included. Median age was 31 and trauma mechanism was blunt in 78%. Injuries were graded as III, IV, and V in 55%, 34%, and 11%, respectively. There were 96 (8%) mortalities and 129 (11%) nephrectomies. Mortality was higher in the nephrectomy group (21.7% vs 6.5%, P <.001). Those who died were older, had higher ISS, lower GCS, and higher rates of shock. After adjusting for patient and injury characteristics nephrectomy was still associated with higher risk of death (RR: 2.12, 95% CI: 1.26-2.55). CONCLUSION: Nephrectomy was associated with higher mortality in the acute trauma setting even when controlling for shock, overall injury severity, and head injury. These results may have implications in decision making in acute trauma management for patients not in extremis from renal hemorrhage.

Development of a Single-Step Antibody-Drug Conjugate Purification Process with Membrane Chromatography.

Membrane chromatography is routinely used to remove host cell proteins, viral particles, and aggregates during antibody downstream processing. The application of membrane chromatography to the field of antibody-drug conjugates (ADCs) has been applied in a limited capacity and in only specialized scenarios. Here, we utilized the characteristics of the membrane adsorbers, Sartobind® S and Phenyl, for aggregate and payload clearance while polishing the ADC in a single chromatographic run. The Sartobind® S membrane was used in the removal of excess payload, while the Sartobind® Phenyl was used to polish the ADC by clearance of unwanted drug-to-antibody ratio (DAR) species and aggregates. The Sartobind® S membrane reproducibly achieved log-fold clearance of free payload with a 10 membrane-volume wash. Application of the Sartobind® Phenyl decreased aggregates and higher DAR species while increasing DAR homogeneity. The Sartobind® S and Phenyl membranes were placed in tandem to simplify the process in a single chromatographic run. With the optimized binding, washing, and elution conditions, the tandem membrane approach was performed in a shorter timescale with minimum solvent consumption and high yield. The application of the tandem membrane chromatography system presents a novel and efficient purification scheme that can be realized during ADC manufacturing.

Clinical and Radiographic Factors Associated With Failed Renal Angioembolization: Results From the Multi-institutional Genitourinary Trauma Study (Mi-GUTS).

OBJECTIVE: To find clinical or radiographic factors that are associated with angioembolization failure after high-grade renal trauma. MATERIAL AND METHODS: Patients were selected from the Multi-institutional Genito-Urinary Trauma Study. Included were patients who initially received renal angioembolization after high-grade renal trauma (AAST grades III-V). This cohort was dichotomized into successful or failed angioembolization. Angioembolization was considered a failure if angioembolization was followed by repeat angiography and/or an exploratory laparotomy. RESULTS: A total of 67 patients underwent management initially with angioembolization, with failure in 18 (27%) patients. Those with failed angioembolization had a larger proportion ofgrade IV (72% vs 53%) and grade V (22% vs 12%) renal injuries. A total of 53 patients underwent renal angioembolization and had initial radiographic data for review, with failure in 13 cases. The failed renal angioembolization group had larger perirenal hematoma sizes on the initial trauma scan. CONCLUSION: Angioembolization after high-grade renal trauma failed in 27% of patients. Failed angioembolization was associated with higher injury grade and a larger perirenal hematoma. Likely these characteristics are associated with high-grade renal trauma that may be less amenable to successful treatment after a single renal angioembolization.

Current Management of Extraperitoneal Bladder Injuries: Results from the Multi-Institutional Genito-Urinary Trauma Study (MiGUTS).

PURPOSE: We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach. MATERIALS AND METHODS: We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications. RESULTS: From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01). CONCLUSIONS: In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

The American Association for the Surgery of Trauma renal injury grading scale: Implications of the 2018 revisions for injury reclassification and predicting bleeding interventions.

BACKGROUND: In 2018, the American Association for the Surgery of Trauma (AAST) published revisions to the renal injury grading system to reflect the increased reliance on computed tomography scans and non-operative management of high-grade renal trauma (HGRT). We aimed to evaluate how these revisions will change the grading of HGRT and if it outperforms the original 1989 grading in predicting bleeding control interventions. METHODS: Data on HGRT were collected from 14 Level-1 trauma centers from 2014 to 2017. Patients with initial computed tomography scans were included. Two radiologists reviewed the scans to regrade the injuries according to the 1989 and 2018 AAST grading systems. Descriptive statistics were used to assess grade reclassifications. Mixed-effect multivariable logistic regression was used to measure the predictive ability of each grading system. The areas under the curves were compared. RESULTS: Of the 322 injuries included, 27.0% were upgraded, 3.4% were downgraded, and 69.5% remained unchanged. Of the injuries graded as III or lower using the 1989 AAST, 33.5% were upgraded to grade IV using the 2018 AAST. Of the grade V injuries, 58.8% were downgraded using the 2018 AAST. There was no statistically significant difference in the overall areas under the curves between the 2018 and 1989 AAST grading system for predicting bleeding interventions (0.72 vs. 0.68, p = 0.34). CONCLUSION: About one third of the injuries previously classified as grade III will be upgraded to grade IV using the 2018 AAST, which adds to the heterogeneity of grade IV injuries. Although the 2018 AAST grading provides more anatomic details on injury patterns and includes important radiologic findings, it did not outperform the 1989 AAST grading in predicting bleeding interventions. LEVEL OF EVIDENCE: Prognostic and Epidemiological Study, level III.

The associations between initial radiographic findings and interventions for renal hemorrhage after high-grade renal trauma: Results from the Multi-Institutional Genitourinary Trauma Study.

BACKGROUND: Indications for intervention after high-grade renal trauma (HGRT) remain poorly defined. Certain radiographic findings can be used to guide the management of HGRT. We aimed to assess the associations between initial radiographic findings and interventions for hemorrhage after HGRT and to determine hematoma and laceration sizes predicting interventions. METHODS: The Genitourinary Trauma Study is a multicenter study including HGRT patients from 14 Level I trauma centers from 2014 to 2017. Admission computed tomography scans were categorized based on multiple variables, including vascular contrast extravasation (VCE), hematoma rim distance (HRD), and size of the deepest laceration. Renal bleeding interventions included angioembolization, surgical packing, renorrhaphy, partial nephrectomy, and nephrectomy. Mixed-effect Poisson regression was used to assess the associations. Receiver operating characteristic analysis was used to define optimal cutoffs for HRD and laceration size. RESULTS: In the 326 patients, injury mechanism was blunt in 81%. Forty-seven (14%) patients underwent 51 bleeding interventions, including 19 renal angioembolizations, 16 nephrectomies, and 16 other procedures. In univariable analysis, presence of VCE was associated with a 5.9-fold increase in risk of interventions, and each centimeter increase in HRD was associated with 30% increase in risk of bleeding interventions. An HRD of 3.5 cm or greater and renal laceration depth of 2.5 cm or greater were most predictive of interventions. In multivariable models, VCE and HRD were significantly associated with bleeding interventions. CONCLUSION: Our findings support the importance of certain radiographic findings in prediction of bleeding interventions after HGRT. These factors can be used as adjuncts to renal injury grading to guide clinical decision making. LEVEL OF EVIDENCE: Prognostic and Epidemiological Study, Level III and Therapeutic/Care Management, Level IV.

A nomogram predicting the need for bleeding interventions after high-grade renal trauma: Results from the American Association for the Surgery of Trauma Multi-institutional Genito-Urinary Trauma Study (MiGUTS).

BACKGROUND: The management of high-grade renal trauma (HGRT) and the indications for intervention are not well defined. The American Association for the Surgery of Trauma (AAST) renal grading does not incorporate some important clinical and radiologic variables associated with increased risk of interventions. We aimed to use data from a multi-institutional contemporary cohort to develop a nomogram predicting risk of interventions for bleeding after HGRT. METHODS: From 2014 to 2017, data on adult HGRT (AAST grades III-V) were collected from 14 level 1 trauma centers. Patients with both clinical and radiologic data were included. Data were gathered on demographics, injury characteristics, management, and outcomes. Clinical and radiologic parameters, obtained after trauma evaluation, were used to predict renal bleeding interventions. We developed a prediction model by applying backward model selection to a logistic regression model and built a nomogram using the selected model. RESULTS: A total of 326 patients met the inclusion criteria. Mechanism of injury was blunt in 81%. Median age and injury severity score were 28 years and 22, respectively. Injuries were reported as AAST grades III (60%), IV (33%), and V (7%). Overall, 47 (14%) underwent interventions for bleeding control including 19 renal angioembolizations, 16 nephrectomies, and 12 other procedures. Of the variables included in the nomogram, a hematoma size of 12 cm contributed the most points, followed by penetrating trauma mechanism, vascular contrast extravasation, pararenal hematoma extension, concomitant injuries, and shock. The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.81-0.85). CONCLUSION: We developed a nomogram that integrates multiple clinical and radiologic factors readily available upon assessment of patients with HGRT and can provide predicted probability for bleeding interventions. This nomogram may help in guiding appropriate management of HGRT and decreasing unnecessary interventions. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Optimal timing of delayed excretory phase computed tomography scan for diagnosis of urinary extravasation after high-grade renal trauma.

BACKGROUND: Excretory phase computed tomography (CT) scan is used for diagnosis of renal collecting system injuries and accurate grading of high-grade renal trauma. However, optimal timing of the excretory phase is not well established. We hypothesized that there is an association between excretory phase timing and diagnosis of urinary extravasation and aimed to identify the optimal excretory phase timing for diagnosis of urinary extravasation. METHODS: The Genito-Urinary Trauma Study collected data on high-grade renal trauma (grades III-V) from 14 Level I trauma centers between 2014 and 2017. The time between portal venous and excretory phases at initial CT scans was recorded. Poisson regression was used to measure the association between excretory phase timing and diagnosis of urinary extravasation. Predictive receiver operating characteristic analysis was used to identify a cutoff point optimizing detection of urinary extravasation. RESULTS: Overall, 326 patients were included; 245 (75%) had excretory phase CT scans for review either initially (n = 212) or only at their follow-up (n = 33). At initial CT with excretory phase, 46 (22%) of 212 patients were diagnosed with urinary extravasation. Median time between portal venous and excretory phases was 4 minutes (interquartile range, 4-7 minutes). Time of initial excretory phase was significantly greater in those diagnosed with urinary extravasation. Increased time to excretory phase was positively associated with finding urinary extravasation at the initial CT scan after controlling for multiple factors (risk ratio per minute, 1.15; 95% confidence interval, 1.09-1.22; p < 0.001). The optimal delay for detection of urinary extravasation was 9 minutes. CONCLUSION: Timing of the excretory phase is a significant factor in accurate diagnosis of renal collecting system injury. A 9-minute delay between the early and excretory phases optimized detection of urinary extravasation. LEVEL OF EVIDENCE: Diagnostic tests/criteria study, level III.

An American Association for the Surgery of Trauma (AAST) prospective multi-center research protocol: outcomes of urethral realignment versus suprapubic cystostomy after pelvic fracture urethral injury.

BACKGROUND: Pelvic fracture urethral injuries (PFUI) occur in up to 10% of pelvic fractures. It remains controversial whether initial primary urethral realignment (PR) after PFUI decreases the incidence of urethral obstruction and the need for subsequent urethral procedures. We present methodology for a prospective cohort study analyzing the outcomes of PR versus suprapubic cystostomy tube (SPT) after PFUI. METHODS: A prospective cohort trial was designed to compare outcomes between PR (group 1) and SPT placement (group 2). Centers are assigned to a group upon entry into the study. All patients will undergo retrograde attempted catheter placement; if this fails a cystoscopy exam is done to confirm a complete urethral disruption and attempt at gentle retrograde catheter placement. If catheter placement fails, group 1 will undergo urethral realignment and group 2 will undergo SPT. The primary outcome measure will be the rate of urethral obstruction preventing atraumatic passage of a flexible cystoscope. Secondary outcome measures include: subsequent urethral interventions, post-injury complications, urethroplasty complexity, erectile dysfunction (ED) and urinary incontinence rates. RESULTS: Prior studies demonstrate PR is associated with a 15% to 50% reduction in urethral obstruction. Ninety-six men (48 per treatment group) are required to detect a 15% treatment effect (80% power, 0.05 significance level, 20% loss to follow up/death rate). Busy trauma centers treat complete PFUI approximately 1-6 times per year, thus our goal is to recruit 25 trauma centers and enroll patients for 3 years with a goal of 100 or more total patients with complete urethral disruption. CONCLUSIONS: The proposed prospective multi-institutional cohort study should determine the utility of acute urethral realignment after PFUI.

Fluctuations in dissolved oxygen concentration during a CHO cell culture process affects monoclonal antibody productivity and the sulfhydryl-drug conjugation process.

During a CHO cell culture production process, important parameters are generally well controlled by a feedback mechanism (PID loop) in order to ensure consistency in both productivity and product quality. These parameters typically include pH, dissolved oxygen (DO), and temperature. While most of these parameters are very well controlled within their specific deadband, stable DO control can be challenging. Oscillations in DO concentration are not uncommon and these fluctuations can be exacerbated with an efficient mass transfer aeration strategy. In this study, where an IgG2 producing cell line was used, we observed increased lactate accumulation accompanied by decreased titer production in lots with fluctuations in DO concentration (DOF ) when compared with lots with stable DO control (DOS ). We demonstrate that DOF had a greater impact on performance with respect to titer production and lactate accumulation than DO setpoint. Furthermore, we report that estimated specific oxygen uptake rates (qOURs) were lower in DOF lots when compared with DOS lots. We also report that purified mAb sourced from DOF lots yielded lower drug-to-antibody ratio (DAR) after the sulfhydryl-targeted maleimide conjugation process when equivalent reducing agent was used. All mAb lots were within the analytical specifications for release, though a slight increase in measureable trisulfides were observed in DOF mAb lots. DO control aimed to minimize fluctuations around DO setpoint was essential for us to produce consistent DAR without adjusting the conjugation process. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1427-1437, 2018.

Contemporary management of high-grade renal trauma: Results from the American Association for the Surgery of Trauma Genitourinary Trauma study.

BACKGROUND: The rarity of renal trauma limits its study and the strength of evidence-based guidelines. Although management of renal injuries has shifted toward a nonoperative approach, nephrectomy remains the most common intervention for high-grade renal trauma (HGRT). We aimed to describe the contemporary management of HGRT in the United States and also evaluate clinical factors associated with nephrectomy after HGRT. METHODS: From 2014 to 2017, data on HGRT (American Association for the Surgery of Trauma grades III-V) were collected from 14 participating Level-1 trauma centers. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Management was classified into three groups-expectant, conservative/minimally invasive, and open operative. Descriptive statistics were used to report management of renal trauma. Univariate and multivariate logistic mixed effect models with clustering by facility were used to look at associations between proposed risk factors and nephrectomy. RESULTS: A total of 431 adult HGRT were recorded; 79% were male, and mechanism of injury was blunt in 71%. Injuries were graded as III, IV, and V in 236 (55%), 142 (33%), and 53 (12%), respectively. Laparotomy was performed in 169 (39%) patients. Overall, 300 (70%) patients were managed expectantly and 47 (11%) underwent conservative/minimally invasive management. Eighty-four (19%) underwent renal-related open operative management with 55 (67%) of them undergoing nephrectomy. Nephrectomy rates were 15% and 62% for grades IV and V, respectively. Penetrating injuries had significantly higher American Association for the Surgery of Trauma grades and higher rates of nephrectomy. In multivariable analysis, only renal injury grade and penetrating mechanism of injury were significantly associated with undergoing nephrectomy. CONCLUSION: Expectant and conservative management is currently utilized in 80% of HGRT; however, the rate of nephrectomy remains high. Clinical factors, such as surrogates of hemodynamic instability and metabolic acidosis, are associated with nephrectomy for HGRT; however, higher renal injury grade and penetrating trauma remain the strongest associations. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; Therapeutic study, level IV.

Surgical Site Infections after Open Reduction Internal Fixation for Trauma in Low and Middle Human Development Index Countries: A Systematic Review.

BACKGROUND: Musculoskeletal trauma represents a large source of morbidity in low and middle human development index countries (LMHDICs). Open reduction and internal fixation (ORIF) of traumatic long bone fractures definitively manages these injuries and restores function when conducted safely and effectively. Surgical site infections (SSIs) are a common complication of operative fracture fixation, although the risks of infection are ill-defined in LMHDIC. PATIENTS AND METHODS: This study reviewed systematically all studies describing SSI after ORIF in LMDHICs. Studies were reviewed based on their qualitative characteristics, after which a quantitative synthesis of weighted pooled infection rates based on available patient-level data was performed to estimate published incidence of SSI. RESULTS: Forty-two studies met criteria for qualitative review and 32 studies comprising 3,084 operations were included in the quantitative analysis. Among 3,084 operations, the weighted pooled SSI rate was 6.4 infections per 100 procedures (95% confidence interval [CI] 4.6-8.2 infections per 100 procedures). Higher rates of infection were noted among the sub-group of open fractures (95% CI 13.9-23.0 infections per 100 procedures). Lower extremity injuries and procedures utilizing intra-medullary nails also had slightly higher rates of infection versus upper extremity procedures and other fixation devices. CONCLUSIONS: Reported rates of SSI after ORIF are higher in LMHDICs, and may be driven by high rates of infection in the sub-group of open fractures. This study provides a baseline SSI rate obtained from literature produced from LMHDICs. Infection rates are highly dependent on fracture sub-types.

Reducing Unnecessary Blood Chemistry Testing in the Emergency Department: Implementation of Choosing Wisely.

Point of care (POC) laboratory testing is used to improve emergency department (ED) throughput but often overuses resources by duplicating formal laboratory testing. This study sought to evaluate the effect of a multimodal intervention on duplicate chemistry testing. This pre-post analysis included all visits to 2 urban EDs between June 2014 and June 2016. The multimodal intervention including provider education, signage, electronic health record redesign, and audit and feedback focused on reducing duplicate chemistry testing. The primary outcome was the number of duplicate chemistry tests per 100 visits. Autoregressive integrated moving-average models were used to account for secular changes. A total of 299 701 ED visits were included. The daily number of duplicate chemistry and POC chemistry tests significantly decreased following the intervention (3.3 fewer duplicates and 10.2 fewer POC per 100 ED visits, P < .0001). This implementation of a multimodal quality improvement intervention yielded substantial reductions in the overuse of blood chemistry testing in the ED.