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The purpose of this study was to identify surgical complications after distal humerus fracture fixation as well as correlations between these complications and patient variables. A total of 132 patients underwent open reduction and internal fixation of traumatic distal humerus fractures between October 2011 and June 2018. Included were adult patients who underwent surgical fixation and had more than 6 months of follow-up. Excluded were patients with inadequate radiographic imaging, less than 6 months of follow-up, and previous distal humerus surgery. Multivariate logistic regression models controlling for age and body mass index were used to determine preoperative factors predictive of postoperative complications. A total of 73 patients were included in this analysis. Surgical complications were reported for 17 patients. Reoperation was required for 13 patients. Open injury at presentation was predictive of delayed union. Predictors of subsequent elbow surgery included younger age, polytrauma, open fracture, and ulnar nerve injury at the time of injury. Radial nerve injury at the time of presentation was also a risk factor for postoperative radial nerve symptoms. Predictors of postoperative heterotopic ossification included older age. Thirty-one patients had an olecranon osteotomy during their open reduction and internal fixation and none went on to nonunion. There were 13 patients with ulnar nerve complications. Of these patients, 3 had undergone an ulnar nerve transposition. None of the other studied variables were predictors of complications, malunion, or nonunion at latest follow-up. Although open reduction and internal fixation is effective in treating distal humerus fractures, its complications cannot be overlooked. Open fractures are more likely to go on to delayed union. Ulnar nerve injury, open fracture, and polytrauma were predictive for reoperation. Older patients were less likely to have subsequent surgery but more likely to develop heterotopic ossification. By identifying at-risk patients, managing physicians can better prognosticate and counsel patients on their recovery. [ Orthopedics . 202x;4x(x):xx–xx.]

The hybrid operating room (HOR) utilizes advanced imaging technology to improve intra-operative visualization and facilitate efficient care in procedures that are relatively image dependent. The robotic C-arm provides improved 2D image quality and is capable of large volume three-dimensional fluoroscopy (3DF) that can rapidly create multiplanar CT like images. Here we discuss on the technique, utility, potential benefits, pitfalls, and complications of using the hybrid suite with and without intra-arterial balloon occlusion for pelvic and acetabular fracture surgery. We also present a case series of patient who underwent pelvic fixation using the HOR. While not advocated for routine use in all pelvic and acetabular fractures; the hybrid suite can be an effective tool in the treatment of complex cases and may facilitate efficient care of the hemodynamically unstable patient. It should be considered when resuscitative stabilization, angioembolization, intra-arterial balloon occlusion, or life-threatening bleeding is anticipated. Additionally, use of the hybrid room allows access to 3D fluoroscopy, and the associated benefits, if a mobile 3D unit is otherwise unavailable. These benefits must be weighed against the cumbersome table, the potential pitfalls with patient size and positioning, and the increased cost to the hospital.

Background The rate of wound complications following traditional open Achilles tendon repair is reported at 7.6%. The purpose of this study is to characterize the rate of wound and other early complications following a specific minimally invasive Achilles tendon repair technique, and to identify any factors associated with increased risk. Methods The postoperative courses of 99 patients who underwent minimally invasive Achilles tendon repair by 2 surgeons at separate academic medical centers were retrospectively reviewed. Mean follow-up was 8.1 months (range 3.0-24.6 months). Repair technique was similar in all cases with the exception that 71 procedures used a longitudinal incision and a tourniquet, while 28 procedures used a transverse incision and no tourniquet (surgeon preference). The rates of complications were compared between patients with differing baseline and procedural characteristics. Results Of the 99 patients included in the study, 2 (2.0%) developed wound complications. There was no statistical difference in the rate of wound complications between patients in the longitudinal incision/tourniquet group and patients in the transverse incision/no tourniquet group (2.8% vs 0%; P = 1.000). Four patients (4.0%) developed sural neuropraxia. One patient developed deep venous thrombosis. There were no cases of rerupture. At final follow-up, all 99 patients had intact Thompson tests and well-healed wounds. Conclusions The rate of wound complications following minimally invasive Achilles tendon repair is low at 2.0%. Patients should be counseled that although risk for wound complications may be lower with this minimally invasive technique, there are risks for sural neuropraxia and deep suture reaction. Levels of Evidence: Level III, Retrospective study

Study Design.Retrospective cohort study.Objective.The aim of this study was to compare clinical and radiographic outcomes of patients who underwent stand-alone lateral lumbar interbody fusion (LLIF) to those who underwent posterolateral fusion (PLF) for symptomatic adjacent segment disease (ASD).Sum

Periprosthetic joint injection (PJI) is a rare, but life-altering complication of total joint arthroplasty (TJA). Though intrawound vancomycin powder (IVP) has been studied in other orthopedic subspecialties, its efficacy and safety in TJA has not been established.PubMed and MEDLINE databases were used to identify studies utilizing IVP in primary and revision total hip (THA) and knee arthroplasty (TKA). Postoperative PJI data were pooled using random effect models with results reported as odds ratios (ORs) and 95% confidence intervals (CIs). Studies were weighted by the inverse variance of their effect estimates.Overall, 16 of the 1871 studies identified were pooled for final analysis, yielding 33,731 patients totally. Of these, 17 164 received IVP. In aggregate, patients who received IVP had a decreased rate of PJI (OR 0.46, P.05). Separately, TKA and THA patients who received IVP had lower rates of PJI (OR 0.41, P.05 and OR 0.45, P.05, respectively). Aggregate analysis of primary TKA and THA patients also revealed a decreased PJI rate (OR 0.44, P.05). Pooled revision TKA and THA patients had a similar decrease in PJI rates (OR 0.30, P.05). Although no publication bias was appreciated, these findings are limited by the low-quality evidence available.While IVP may reduce the risk of PJI in primary and revision TJA, its widespread use cannot be recommended until higher-quality data, such as that obtained from randomized control trials, are available. This study underscores the continued need for more rigorous studies before general adoption of this practice by arthroplasty surgeons.

BACKGROUND: There is increased emphasis on efficiently administering patient-reported outcome measures (PROMs). The International Hip Outcome Tool-12 (iHOT-12) is a short-form version of the iHOT-33, and relatively little is known about clinically significant outcomes using the iHOT-12. QUESTIONS/PURPOSES: The purpose of this study was to define minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) for the iHOT-12 and to identify predictors for achieving these psychometric end points in patients undergoing arthroscopic treatment of femoroacetabular impingement (FAI). METHODS: Data was prospectively collected and retrospectively analyzed as part of an institutional hip preservation repository. One hundred and twenty patients were included; mean age and body mass index (BMI) were 38.7 years and 25.9, respectively. A majority of patients were female (67.5%) and white (81.7%) and participated in recreational sports (79.2%). The iHOT-12 was administered pre-operatively and at 1-year follow-up to patients undergoing primary hip arthroscopy for FAI. The following anchor question was also asked at 1-year follow-up: “Taking into account all the activities you have during your daily life, your level of pain, and also your functional impairment, do you consider that your current state is satisfactory?” MCID was calculated using a distribution-based method. Receiver-operating characteristic analysis with area under the curve was used to confirm the significance of the PASS threshold. RESULTS: Mean iHOT-12 scores improved from 35.6 at pre-operative assessment to 70.7 at 1-year follow-up. Patients indicating satisfaction with their outcome improved from 37.5 pre-operatively to 79.0 at 1-year follow-up. MCID value for the iHOT-12 was 13.0. The PASS threshold was 63.0, indicating an excellent predictive value that patients scoring above this threshold were likely to have met an acceptable symptom state. Worker’s compensation patients and those with increased BMI were less likely to achieve PASS; lower pre-operative iHOT-12 score was predictive for achieving MCID, and achieving MCID was predictive for achieving PASS. CONCLUSION: This is the first study to define PASS and MCID for the iHOT-12, which measures clinically significant outcome improvement comparably to that of other commonly used hip PROMs. As its use becomes more widespread, the iHOT-12 data-points presented in this study can be used to determine clinically significant improvement of patient-reported outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-018-9646-0) contains supplementary material, which is available to authorized users.

The purpose of this study was to compare the rates of adjacent segment degeneration (ASD), sagittal alignment parameters, and patient-reported outcomes in patients who underwent multi-level versus single-level anterior cervical discectomy and fusion (ACDF). A retrospective cohort analysis was performed on consecutive patients who underwent an ACDF. Pre- and post-operative radiographic assessment included ASD, change in C2–C7 lordosis, T1 angle, levels fused, sagittal vertical axis (SVA), fusion mass lordosis, proximal and distal adjacent segment lordosis. Patient-reported outcomes were obtained. Of the 404 that underwent an ACDF with a minimum of 6 months of follow-up (average 28 months), there was no significant difference in the rate of radiographic ASD overall (p = 0.479) or in the proximal or distal adjacent segments on multivariate analysis. Secondarily, the multi-level fusions appear to restore significantly greater amounts of lordosis compared to single-level procedures (p

Platelet storage lesions (PSLs) occur during platelet concentrate (PC) storage. Adverse transfusion reactions (ATRs) have been demonstrated to be more frequent in older PCs and removal of the supernatant prior to transfusion reduces their occurrence. Proteomic profiling of PC supernatants was thus performed to identify proteins associated with PSLs and ATRs. Twenty-four PCs were investigated daily from day 0 to day 9 for platelet pre-activation (PPA), platelet-derived extracellular vesicles (PEVs), and platelet function. Using antibody microarrays, 673 extracellular proteins were analysed in PC supernatants on days 0, 3, 5, 7, and 9. During 5 days of storage, PPA and PEVs continuously increased ( P P = 0.1751) and decreased thereafter. Comparison of all time points to day 0 revealed the identification of 136 proteins that were significantly changed in abundance during storage, of which 72 were expressed by platelets. Network analysis identified these proteins to be predominantly associated with exosomes ( P = 4.61 × 10 − 8 , n = 45 genes) and two clusters with distinct functions were found with one being associated with haemostasis and the other with RNA binding. These findings may provide an explanation for ATRs. Significance Changes in platelet concentrate (PC) supernatants during storage have been so far only poorly addressed and high abundant proteins burden the identification of quantitative changes in the secretome. We applied a high-throughput antibody microarray allowing for the sensitive quantification of 673 extracellular factors. PCs account for the highest number of adverse transfusion reactions (ATRs). ATRs have been demonstrated to be more frequent in older PCs and removal of the supernatant prior to transfusion reduces their occurrence. Comprehensive interpretation of the changing proteins in the secretome during platelet storage under blood banking conditions may help to identify mechanisms leading to the occurrence of adverse transfusion reactions.

Study design This is a retrospective cohort study. Objective This study aims to characterize the effect of preoperative symptom duration on postoperative outcomes after minimally invasive lumbar microdiscectomy (MIS LD). Summary of background data It is unknown whether extended nonoperative treatment before MIS LD has implications for long-term clinical outcomes even after surgery is performed. Materials and methods A prospectively maintained surgical registry of patients undergoing MIS LD by a single surgeon between 2013 and 2017 was reviewed. Preoperative symptom duration was dichotomized into 2 groups (≤6 and >6 mo). Only patients with full clinical data at 6 months postoperative follow-up were included in the study. Clinical outcomes were assessed at 6, 12 weeks, and 6 months after surgery. The number of patients obtaining a minimum clinically important difference was assessed. Groups were compared with the χ analysis and the student t tests for categorical and continuous data, respectively. Results In total, 94 patients were identified. A total of 45 patients (47.9%) had symptom duration ≤6 months. No differences in baseline characteristics were found (P>0.05). Patients with shorter symptom duration had significantly greater improvement in Oswestry Disability Index scores at 6 weeks (P=0.004), 12 weeks (P=0.022), and 6 months (P=0.005). Patients with shorter duration of symptoms also obtained minimum clinically important difference for Oswestry Disability Index at a greater rate than those with longer duration of symptoms (P=0.015). Conclusions Although patients who underwent MIS LD within 6 months of symptom onset had similar baseline characteristics compared with patients who underwent surgery after 6 months of symptoms, the patients with longer preoperative symptom duration had worse functional outcomes at 6 months after surgery. These results suggest that earlier MIS lumbar microdiscectomy may provide a functional benefit for patients. Further studies should therefore evaluate the efficacy of nonoperative treatment in the setting of lumbar herniated nucleus pulposus, as prolonged conservative management may potentially impair functional recovery after surgery.

Category: Other Introduction/Purpose: Orthopaedic foot and ankle surgery is a young and rapidly evolving orthopaedic subspecialty. Little is known regarding the authors contributing to the field. The purpose of this study is to characterize the demographics of the authors publishing foot and ankle research since the inception of the research journal of the American Orthopaedic Foot and Ankle Society. Methods: All publications in the journal Foot and Ankle International between 1980 and 2017 were reviewed. Papers were characterized in terms of number of authors, number of institutions, and number of references. The first and corresponding authors were also characterized in terms of country of origin, gender, and degree qualification. Each of these characteristics was tested for trends over time. Results: In total, 5,323 publications were reviewed, including 4,297 research articles, 367 case reports, 262 editorials, 159 letters, and 121 technique tips. The mean number of authors per paper increased from 2.3 during the 1980s to 4.3 during the 2010s (p0.05). The mean number of references to other work increased from 13.8 during the 1980s to 24.4 during the 2010s (pConclusion: The authors of the foot and ankle literature have changed markedly over the past 4 decades. Most notably, there have been shifts towards female and international authorship. The number of authors per paper has also nearly doubled over time. Such trends are likely to continue as the field of foot and ankle grows.

Category: Sports Introduction/Purpose: The rate of wound complications following traditional open Achilles tendon repair is reported at 7-8%. In an effort to reduce the rate of wound complications, orthopaedic surgeons have adopted novel minimally invasive techniques. The purpose of this study is to characterize the rate of wound and other early complications following a minimally invasive Achilles tendon repair, to identify any factors associated with increased risk. Methods: The postoperative courses of 55 patients who underwent minimally invasive Achilles tendon repair by two surgeons at separate academic medical centers were retrospectively reviewed. Repair technique was similar in all cases, making use of the same commercially available suture-guidance jig, silicone-impregnated deep suture material, and locking stitch technique. However, 31 procedures used a longitudinal incision and a tourniquet (one surgeon’s preference), while 24 procedures used a transverse incision and no tourniquet (the second surgeon’s preference). Of the 24 procedures using transverse incisions, 2 had to be converted to L-shaped incisions to achieve better access to the tendon. The rates of early complications within 3 months after surgery were characterized and compared between patients with differing procedural characteristics. Results: Of the 55 patients included in the study, 2 (3.6%) developed wound complications. Both wound complications appeared to be reactions to the deep suture material (see Table 1 for details). There was no statistical difference in the rate of wound complications between patients in the longitudinal incision/tourniquet group and patients in the transverse incision/no tourniquet group (6.5% versus 0.0%; p=0.499). Three patients (5.5%) developed sural neuropraxia, which manifested as mild-to-moderate subjective numbness with sensation remaining intact to light touch. There were no cases of re-rupture. At 3-month follow-up, all 55 patients had intact Thompson tests and well-healed wounds. Conclusion: The rate of wound complications following minimally invasive Achilles repair is low at 3.6%. The present study could not demonstrate a difference in risk for wound complications between patients treated with a longitudinal incision and tourniquet and patients treated with a transverse incision and no tourniquet. The wound complications we observed were primarily attributable to inflammatory reactions to the silicone-impregnated deep suture material. Patients should be counseled that although risk for wound complications may be lower with minimally invasive techniques, such techniques do risk sural neuropraxia and deep suture reaction. Further prospective analysis is warranted.

A retrospective cohort analysis.The aim of this study was to assess whether duration of symptoms (DOS) has an effect on clinical outcomes in patients undergoing lumbar decompression.The success of surgical interventions for lumbar spinal stenosis varies depending on numerous factors, including DOS. However, existing literature does not provide a clear indication of the outcome of lumbar decompression surgery in regard to DOS secondary to nerve root compression.Analysis of patients who underwent primary lumbar laminectomy from 2008 through 2015 by one of two senior orthopedic spine surgeons was conducted. Exclusion criteria were as follows: previous lumbar surgery, patient under 18 years of age at time of surgery, or postoperative follow-up less than 3 months. Patients were divided into groups on the basis of preoperative DOS: less than 1 year and 1 year or greater. Patient-reported outcomes were obtained using Oswestry Disability Index (ODI) scores, Visual Analog Scales (VAS) scores for the back and leg, 12-Item Short Form Mental and Physical Survey (SF-12) scores, and Veterans Rand 12-Item Health Mental and Physical Survey (VR-12) scores. Patients were surveyed about expectations and postoperative satisfaction.Two hundred ten patients were assessed; 108 with DOS of less than 1 year and 102 with DOS of 1 year or more. On multivariate analysis, patients with DOS of 1 year or greater presented with significantly lower SF-12 scores (P = 0.043). No significant differences existed in other outcome survey scores. Reoperation rates were not significantly different (P = 0.904). Both groups reported high levels of satisfaction (odds ratio 0.42, P = 0.483) and that surgery met or exceeded their expectations (odds ratio 1.00, P = 0.308).Symptom chronicity did not significantly affect postoperative clinical outcomes, reoperation rates, or patient satisfaction. Nonoperative treatment of lumbar spinal stenosis is often successful but may delay operative intervention. However, results of this study suggest that the delay does not negatively impact surgical outcomes.3.

Purpose To characterize the 3-dimensional muscular, musculotendinous, and neurovascular anatomy about the pubic symphysis relevant to core muscle injury (CMI). Methods Ten cadaveric hips were dissected to characterize the musculotendinous insertion of the rectus abdominis and inguinal ligament, origins of the adductor longus and adductor brevis, and the pubic cartilage plate. A 3-dimensional coordinate measuring system and data acquisition software were used to calculate structure cross-sectional area, and the landmark anatomical relationships to 1 another and relevant neurovascular structures. Results All specimens were male with an average age of 62 ± 2 years. The mean footprints of the rectus abdominis, inguinal ligament, adductor longus, and adductor brevis were 8.4 ± 3.1, 1.2 ± 0.5, 3.8 ± 1.6, and 2.9 ± 1.3 cm2, respectively. The mean pectineus and gracilis footprints were 6.3 ± 2.4 and 3.4 ± 0.9 cm2, respectively. The mean cross-sectional area of the cartilage plate was 24.8 ± 5.6 cm2. The adductor longus was an average 1.5 ± 0.25 cm from the adductor brevis and 0.69 ± 0.52 cm from the rectus abdominis. The genital branch of the genitofemoral nerve was an average of 4.3 cm (range, 2.8-6.4) lateral to the insertion of the inguinal ligament. The femoral vein and artery were 3.0 cm (range, 2.5-3.6) and 3.7 cm (range, 2.5-5.9) lateral to the inguinal ligament footprint. The obturator nerve was 2.5 cm (range, 1.6-3.4) lateral to the adductor longus. Conclusions Familiarity with the anatomy of the pubic symphysis is essential for surgeons treating patients with CMI. We have shown that this relatively small area is the site of many muscular, musculotendinous, and neurovascular structures with various sized footprints and described the 3-dimensional anatomy of the anterior pubic symphysis. The origin of the adductor longus lies in close proximity to other structures, such as the adductor brevis, the insertion of the rectus abdominis, and the obturator nerve. These findings should be considered when operating in this region and treating patients with chronic groin pain. Clinical Relevance The anatomy of the pelvic region and pubic symphysis has not been well characterized. Intimate knowledge of relevant anatomy is essential to treating CMI, also known as athletic pubalgia or sports hernia.

Background: Since the inception of CrossFit in 2000, the popularity of high-intensity interval training (HIIT) in the United States has risen dramatically. While HIIT is a highly efficient exercise for weight loss and improved conditioning, some literature reports injuries in up to 34% of HIIT participants. We sought to evaluate the functional and sports-specific results of hip arthroscopic surgery in recreational HIIT participants. Purpose: To evaluate patients’ ability to return to HIIT after hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS). Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients with FAIS who had identified themselves as participating in HIIT and had undergone hip arthroscopic surgery for the treatment of FAIS by a single fellowship-trained surgeon between 2012 and 2015 were reviewed. Demographic data; preoperative physical examination findings; preoperative imaging results; preoperative patient-reported outcome (PRO) scores including the modified Harris Hip Score (mHHS), Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sports-Specific Subscale (HOS-SSS), and visual analog scale (VAS) for pain; and postoperative examination and PRO scores at a minimum 2 years after surgery, including a HIIT-specific questionnaire, were assessed for all patients. Results: Thirty-two patients (13 male, 19 female) with a mean age of 34.7 ± 6.9 years (range, 21-49 years) were identified with a minimum 24-month follow-up. Among these, 22 participated in CrossFit, 4 in Shred415, 3 in Orangetheory, and 3 in self-directed cross-training including plyometrics. Preoperatively, 14 patients had discontinued HIIT because of activity-related hip complaints, 17 patients had scaled back involvement in HIIT, and 1 patient maintained her baseline routine. Postoperatively, 28 of 32 patients (88%) returned to HIIT at a mean of 9.8 ± 5.7 months after surgery (range, 3-24 months); 96% returned to HIIT at the same level as or better than before the injury. Fear of reinjury was the most common reason for cessation (3/4). Preinjury and postoperative involvement in HIIT were comparable (5.3 vs 5.1 h/wk, respectively; P = .8). All patients had significant improvements in the HOS-ADL score (69.7 ± 17.3 to 94.2 ± 8.4; P < .001), HOS-SSS score (49.2 ± 21.2 to 83.3 ± 21.4; P < .001), mHHS score (59.9 ± 14.2 to 85.4 ± 11.6; P < .001), and VAS for pain score (7.5 ± 1.8 to 1.1 ± 1.3; P < .001) from preoperatively to postoperatively. Conclusion: Arthroscopic treatment of FAIS in recreational HIIT participants resulted in significant improvements in hip function and predictably high rates of patient satisfaction. Postoperatively, 88% of patients returned to HIIT, 44% noted improvement from preinjury HIIT performance, and the mean weekly participation was comparable with before the injury.

Background Total hip arthroplasty (THA) is projected to increase in prevalence and associated complications will impose significant cost on the US healthcare system. The purpose of this study is to validate a predictive model for postoperative complications utilizing a novel 11-component hip-specific questionnaire encompassing preoperatively available clinical and radiographic data. Methods Consecutive primary THA patients between January 2014 and January 2016 were included. Exclusion criteria included patients without questionnaire scoring variables and less than 1-year follow-up. Patients were stratified into 4 tiers based on their questionnaire score: low risk (>74), mild risk (57-73), moderate risk (41-56), and high risk ( Results Four hundred fifty patients were included in the final analysis with a mean (range) follow-up of 2.1 years (1.0-5.9), age of 63.1 years (25.7-9.17), and body mass index of 31.7 kg/m2 (17.8-64.5). The complication rate was 13.6%. A hip questionnaire score of 73.8 conferred a 98.5% sensitivity and 98.5% negative predictive value for complications. The questionnaire score was the strongest predictor of a decreased complication likelihood (odds ratio 0.94, 95% confidence interval 0.90-0.97, P Conclusion This novel hip questionnaire demonstrated a high sensitivity and negative predictive value to identify patients at risk for postoperative complications. Future studies should attempt to prospectively validate the use of this questionnaire.

STUDY DESIGN Literature review. OBJECTIVE To examine changes in authorship characteristics for Spine publications from the year 2000 to 2015. SUMMARY OF BACKGROUND DATA Scientific publications are considered an indication of academic achievement for physicians. Recently, authorship trends have been investigated; however, limited information is available on this topic within spine-specific literature. METHODS Original research articles published in Spine in the years 2000, 2005, 2010, and 2015 were evaluated. Authorship characteristics were collected for each article, including the number of authors and institutions per publication, first and last authors' sex, publication origin, and highest degree held by the first and last author. Trends over time were analyzed using numeric and visual descriptive analyses including percentages, means, standard deviations, and graphs. RESULTS An average of 506 articles per year was published in Spine during the years 2000, 2005, 2010, and 2015. The number of articles written by 10 or more authors increased during this time (0.9%-14.4%). There was a substantial increase in the number of multiple institutional affiliations (33.6%-68.7%) and articles originating from outside North America (47.6%-55.7%) from 2000 to 2015. The percentage of first authors with bachelor's degrees was higher in 2015 (6.6%) as compared to 2000 (1.4%), and more last authors were identified as MD/PhDs in 2015 (19.2%) than in 2000 (10.0%). Similar female representation was noted for first and last authorship for all years evaluated. CONCLUSION The results of this study demonstrate increases in authors per article published in Spine from 2000 to 2015. In addition, first authors were more likely to hold bachelor's degrees over time. This may be attributed to increasing competition in spine-related fields, necessitating earlier research exposure to aid in academic achievement. Interestingly, the percentage of female authorship has not changed significantly over time, in contrast with much of the previous literature. LEVEL OF EVIDENCE 2.

BACKGROUND CONTEXT Recent studies have suggested that lateral lumbar interbody fusion (LLIF) can successfully treat adjacent segment disease (ASD), however, there are no studies to date that compare LLIF with the traditional open posterolateral fusion (PLF) in this cohort. PURPOSE Compare clinical and radiographic outcomes of patients who underwent stand-alone LLIF to those who underwent PLF for symptomatic ASD. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE Forty-seven consecutive patients who underwent a single- or two-level LLIF or open posterior decompression and PLF for symptomatic ASD between January 2007 and August 2016 after failure of conservative management. Exclusion criteria included: under the age of 18, follow-up of less than 24 months, presentation with adjacent level pathology that showed a spondylolisthesis greater than grade 1, active infection, active malignancy, or acute trauma. OUTCOME MEASURES Patient-reported outcomes (PRO) were collected on all patients preoperatively and postoperatively at intervals of 2 weeks, 6 weeks, 3 months, 1 year after surgery, and at the most recent postoperative visit using the Oswestry Disability Index (ODI), Visual Analog Scale (VAS)–Back, and VAS–Leg surveys. Preoperative, immediate postoperative (day 1 or 2 after surgery) and most recent postoperative radiographs were assessed for: pelvic incidence, fusion, intervertebral disc height (average between anterior and posterior measurements of the distance between inferior end plate of the cephalad vertebral body and superior end plate of the caudal vertebral body), segmental and overall lordosis. METHODS Patients undergoing a single- or two-level LLIF or open posterior decompression and PLF for symptomatic ASD after failure of conservative management were included. Symptomatic ASD was diagnosed if back pain, neurogenic claudication, or lower extremity radiculopathy presented following a previous LF. Preoperative plain radiographs were evaluated for the presence of pathology associated with adjacent segment degeneration. RESULTS Forty-seven patients (23 LLIF, 24 PLF) met inclusion criteria. The LLIF group had significantly more male patients (p=0.028); however, there were no other differences in demographics between groups. Operative times (p CONCLUSIONS Stand-alone LLIF appears to be a safe and effective approach with substantially less perioperative morbidity, shorter length of hospitalization, acceptable complication rates, significantly better restoration of radiographic sagittal alignment parameters, and similar successful PRO compared to patients undergoing open PLF for symptomatic ASD. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND CONTEXT While attention to sagittal parameters in the cervical spine is increasing, the relationship between these radiographic measurements and clinical outcomes is less clear. PURPOSE The aim of the present study was to characterize independent associations between cervical spine radiographic parameters and clinical outcomes following anterior cervical discectomy and fusion (ACDF). STUDY DESIGN/SETTING Retrospective cohort analysis. PATIENT SAMPLE Analysis of consecutive patients who underwent a single-level ACDF at an academic institution between 2008 and 2015 for cervical radiculopathy and/or myelopathy, with a minimum of 6 months of clinical and radiographic follow-up. OUTCOME MEASURES Disc height was measured as the anterior vertebral distance (AVD), mid-vertebral distance (MVD), and posterior vertebral distance (PVD) on preoperative and immediate postoperative radiographs. Sagittal parameters were also measured, and included C2-C7 lordosis, T1 angle, fusion segment lordosis, sagittal vertical axis (SVA), proximal and distal adjacent segment lordosis. Preoperative and final visual analog scale (VAS) neck, VAS arm, and Neck Disability Index (NDI) scores were collected. The rates of reoperation, successful fusion, and subsidence (postoperative disc space collapse >2 mm) were determined. METHODS Preoperative, postoperative, and final radiographs were reviewed. Radiographic parameters were tested for association with patient-reported outcomes, reoperation, fusion, and subsidence using multivariate linear regression and multivariate logistic regression for continuous and binary outcomes, respectively. Multivariate regressions controlled for potential confounding variables in order to identify independent risk factors for each outcome. The Sidak-Holm method was used to adjust p-values in order to correct for multiple statistical comparisons. The threshold for statistical significance was set at p RESULTS A total of 381 patients met inclusion criteria. Average follow-up length was 28 months, average age was 50.2 years, average body mass index was 28.7, and 49.2% of patients were female. Of these patients, 93.7% achieved successful fusion, 6.6% had graft subsidence, and 4.99% had a reoperation. Preoperative and postoperative radiographic measurements and patient-reported outcomes were collected. Preoperative radiographic measurements poorly predicted clinical outcomes. Increased preoperative lordosis at the adjacent unfused segment proximal to the eventual fusion mass was found to be associated with increased final NDI (corrected p=0.018), and increased final proximal lordosis was associated with increased final NDI (corrected p=0.049). However, no other radiographic parameters were associated with any patient-reported clinical outcomes. Subsidence rates were increased with greater change in proximal lordosis from preoperative to postoperative (OR 1.30, corrected p=0.007) and from preoperative to final follow-up (OR 1.17, corrected p=0.044). Subsidence was negatively associated with increased change in lordosis across the fused segments from preoperative to postoperative (OR 0.88, corrected p=0.032) and from preoperative to final follow-up (OR 0.86, corrected p=0.017). CONCLUSIONS The present study found that sagittal parameters were poorly predictive of clinical outcomes. Increased preoperative lordosis at the adjacent segment proximal to the fusion mass was associated with worse final NDI scores, and was the only preoperative radiographic parameter associated with clinical outcomes. Further research should attempt to identify other preoperative factors or radiographic parameters that are more closely associated with clinical outcomes. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Purpose To evaluate the safety and efficacy of hip arthroscopy for femoroacetabular impingement syndrome by assessing complications, comprehensive procedure survivorship, and the influence of labral and capsular management on procedure survivorship. Methods A systematic review of multiple medical databases was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist. All clinical outcome studies that reported on the presence or absence of reoperation after hip arthroscopy for femoroacetabular impingement syndrome were eligible for inclusion. Data pertaining to patient demographic characteristics, surgical technique (specifically labral and capsular management), patient-reported outcomes, complications, reoperation, and conversion to arthroplasty were extracted from each study. Results A total of 68 studies (7,241 hips) were included. Most were Level IV studies (63%). Complications occurred in 1.9% of cases. The most common complications were neurologic (53%), heterotopic ossification (24%), infection (15%), and thromboembolic (7%). Conversion to total hip arthroplasty (456 cases) was the most common reason for reoperation, followed by revision hip arthroscopy (226 cases) and periacetabular osteotomy (7 cases). The rate of arthroplasty conversion was lower than 10% in 43 of 59 studies reporting this outcome. The average interval to arthroplasty conversion was 58 months. Between 2009 and 2017, the performance of labral repair increased from 19% to 81% of cases and capsular closure increased from 7% to 58% of cases. Conclusions Arthroplasty conversion occurred in fewer than 10% of cases in the clear majority of series. Labral repair (compared with labral debridement) and capsular closure (compared with unrepaired capsulotomy) were associated with a lower risk of conversion to arthroplasty. Throughout the study interval, there were shifts in surgical technique favoring labral repair over debridement and capsular repair over unrepaired capsulotomy. The study is limited by selection bias because cases in which labral and capsular repair was performed may have had superior tissue that was more amenable to repair. Level of Evidence Level IV, systematic review.

Hernia is a common complication following radical cystectomy and urinary diversion. We investigated the clinical and radiological evidence for parastomal and incisional hernias, and their risk factors in a large cohort.Using an institutional review board approved prospective database we reviewed the records of 1,101 patients who underwent radical cystectomy from 2003 to 2013. Followup (median 57 months) was available for 670 patients. Of the 670 patients 92 underwent ileal conduit diversion using Turnbull stomas with a median followup 34 months. Patients were followed with computerized tomography cancer surveillance. Standardized criteria were used to define parastomal and incisional hernias by an expert radiologist. Multivariate logistic regression was done to identify independent predictors.Parastomal hernia was diagnosed in 21 of 92 patients (23%) with a mean age at diagnosis of 76.5 years. Incisional hernia was present in 125 of 670 patients (18.7%) with a mean age at diagnosis of 68.6 years. Five patients had both hernia types. Of patients with parastomal and incisional hernias 11 (53%) and 111 (88.8%), respectively, were male. Mean body mass index was 27.5 and 27.3 kg/m(2) in patients with parastomal and incisional hernias, respectively. Mean parastomal and incisional defect sizes were 3.8 and 2.4 cm, respectively. In 18 patients (85%) parastomal hernias were clinically and radiologically evident, 5 patients were symptomatic and 2 underwent repair. In 51 patients (40%) incisional hernias were clinically and radiologically evident, 34 were symptomatic and 48 underwent repair. Multivariate logistic regression showed significant associations of incisional hernia with age, gender, incision length, orthotopic diversion and body mass index. Parastomal hernia had no significant association.Hernia is common after cystectomy and diversion. Age, gender, body mass index, incision length and diversion type are risk factors for incisional hernia. Multi-institutional prospective studies may better identify patients at high risk.

Based on the impressive results from the IRIS trial (International Randomized Interferon vs. STI-571), the tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) has become the recommended first-li...

BACKGROUND CONTEXT The success of surgical interventions for lumbar spinal stenosis can vary significantly depending on various factors, one of which is the duration of symptoms. Literature does not provide a clear indication of when lumbar decompression surgery become less effective in the setting of acute versus chronic symptoms from nerve root compression. PURPOSE The main objective of this study was to assess whether the duration of symptoms has an effect on clinical outcomes, especially resolution of radicular symptoms due to pathology compressing the lumbar nerve roots in patients undergoing lumbar decompression-only procedures. STUDY DESIGN/SETTING Retrospective cohort series. PATIENT SAMPLE We performed a retrospective cohort analysis of patients who underwent a primary lumbar laminectomy, discectomy or a combination of the two between 2009 and 2015 by one of two senior orthopedic spine surgeons. Patients were excluded from analysis if they had any previous lumbar surgery were under 18years of age at the time of surgery or had postoperative follow-up less than 3 months. Patients were divided into two groups: those with lumbar radicular symptoms for less than one year prior to surgery, and those who experienced symptoms for one year or greater before undergoing surgery. OUTCOME MEASURES Patient reported outcomes were obtained in the form of Oswestry Disability Index scores, Visual Analog Scales (VAS) scores for the back and leg, 12-Item Short Form Mental and Physical Survey (SF-12) scores, and the Veterans Rand 12-Item Health Mental and Physical Survey (VR-12) scores. Patients were also surveyed about their expectations and satisfactions following surgery. METHODS Baseline patient characteristics were compared using chi-squared analysis and independent sample t-tests for categorical and continuous data, respectively. Bivariate and multivariate regressions were subsequently used to compare clinical outcomes between procedure groups. Multivariate analyses controlled for differences in baseline patient characteristics. RESULTS Overall, 210 consecutive patients who fulfilled our inclusion criteria were assessed. Average follow-up was 24.14 months (range 3–78 months). There were 108 patients that experienced radicular symptoms for less than one year, while 102 patients experienced radicular symptoms for one year or more. Patients who experienced radicular symptoms for less than one year had a significantly higher rate of a herniated nucleus pulposus present (75.9% vs. 49.0%; p 1 year 7.9%; p=.904). Patients presented with high levels of satisfaction (pain 1 year 82.4%; OR1.06, p=.904) and expressed that the surgery met or exceeded their expectations (pain 1 year 96.1%; OR1.06, p=.904). CONCLUSIONS Overall, patients present with similar clinical outcome scores, despite the differences in the duration of their lumbar radicular symptoms prior to surgery. At approximately 2years following lumbar decompression-only surgery, all patients, despite their symptom chronicity, appear to show similar improvement in their clinical outcome scores. Re-operation rates were low and similar between the two groups of patients. Most patients report being satisfied with their outcome and with their expectations being met or exceeded to similar degrees. Given the various options available for nonoperative management of lumbar spinal stenosis and/or a lumbar herniated nucleus pulposus, the extended effort of these conservative treatments or delay of operative intervention do not appear to negatively impact the eventual outcome of surgery. Patients report significant improvement in their symptoms, based on clinical outcome surveys, regardless of their symptom chronicity.

BACKGROUND CONTEXT Osteoporosis is a significant comorbidity that can increase the risk, technical difficulty, and outcomes following spine surgery. Surgical treatment for adult spinal deformity may reliably lead to improvement in radiographical and clinical outcomes. However, proximal junctional kyphosis (PJK) remains a common complication after long instrumented spinal fusion surgery and may occur more often in osteoporotic patients. PURPOSE The goal of this study was to compare patients diagnosed with osteoporosis to nonosteoporotic patients and evaluate the occurrence of PJK following deformity correction spine fusion surgery for adult spinal deformity. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE Consecutive patients who underwent elective posterior spinal fusion for adult deformity at a single academic institution from 2008 to 2014 with a minimum of 2 years of follow-up were identified. Patients were considered osteoporotic if their bone mineral density (BMD) score revealed T OUTCOME MEASURES Radiographic assessments included: sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL), thoracic kyphosis (TK), T1 pelvic angle (TPA), and kyphosis at one- and two-levels above the upper instrumented vertebra (UIV+1, UIV+2). At two levels above the upper instrumented vertebra (UIV+2), kyphosis greater than 10° and more than a 10° increase from the preoperative film was defined as PJK. At UIV+1, PJK was defined as a greater than 15° increase from the preoperative film Multivariate logistic regression was used to test the association between osteoporosis and development of PJK while controlling for differences in patient and operative characteristics. METHODS Multivariate logistic regression was used to test the association between osteoporosis and development of PJK while controlling for differences in patient and operative characteristics. RESULTS A total of 214 patients fulfilled inclusion criteria. Average follow up was (52.8±29.1 months). Patients with osteoporosis were older (64.7+/−12.6 years vs. 56.7 +/−8.6 years; p CONCLUSIONS Patients diagnosed with osteoporosis may be at risk for developing PJK following deformity-correction spine fusion for adult spinal deformity compared to those with more robust bone mineral density. These concerns and the effect on sagittal alignment, and ultimate health-related quality of life, provide additional support towards the importance of preoperative bone mineral density optimization and expectations prior to surgery.

BACKGROUND CONTEXT Proximal junctional kyphosis (PJK) is a significant concern following long posterior spinal fusion. Biomechanically, proximal hook placement at the upper instrumented vertebra have been shown to allow a more gradual transition to normal motion compared with pedicle screws in a long posterior instrumented spinal fusion. PURPOSE The purpose of this study was to evaluate the risk of developing proximal junctional kyphosis with sublaminar hooks versus pedical screw fixation at the upper instrumented vertebra of a posterior spine fusion for adult spinal deformity. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE Consecutive patients who underwent elective posterior spinal fusion for adult deformity at a single academic institution from 2008 to 2014 with a minimum of 2years of follow-up were identified. Patients with proximal hooks and those with proximal screws were separated into 2 groups. OUTCOME MEASURES Preoperative, first postoperative, and final postoperative standing radiographs were reviewed. Radiographic assessments included: sagittal vertical axis (SVA), pelvic incidence, lumbar lordosis, thoracic kyphosis, T1 pelvic angle (TPA) and kyphosis at one- and two-levels above the upper instrumented vertebra (UIV+1, UIV+2). Two common methods of assessing PJK were used. At two levels above the upper instrumented vertebra (UIV+2), kyphosis greater than 10° and more than a 10° increase from the preoperative film was defined as PJK. At UIV+1, PJK was defined as a greater than 15° increase from the preoperative film. METHODS Multivariate logistic regression was used to test the association between proximal hooks and development of PJK while controlling for differences in patient and operative characteristics. RESULTS A total of 142 patients fulfilled inclusion criteria. Average follow-up was (52.8 ±29.1 months). There were no significant differences in demographic characteristics between the 2 groups. Patients with sublaminar hooks at the UIV presented with significantly fewer instances of PJK using UIV+1 (44.0% vs. 63.1%; p=.029) and UIV+2 (52.0% vs. 76.1%; p=.048) measurements compared to those who received pedicle screws at the UIV. Patients with laminar hooks experienced a significantly greater increase in SVA from preoperative to immediate postoperative (13.6±11.6 mm vs. 1.8±12.4 mm; p CONCLUSIONS Laminar hooks at the upper instrumented vertebra were associated with reduced rates of PJK compared with pedicle screws in patients who undergo deformity-correcting spine fusion for adult spinal deformity. This information may be useful for operative planning to minimize the occurrence of PJK after adult deformity surgery.

In recent years, human dendritic cells (DCs) could be subdivided into CD304+ plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter encompassing the CD1c+, CD16+, and CD141+ DC subsets. To date, the low frequency of these DCs in human blood has essentially prevented functional studies defining their specific contribution to antigen presentation. We have established a protocol for an effective isolation of pDC and cDC subsets to high purity. Using this approach, we show that CD141+ DCs are the only cells in human blood that express the chemokine receptor XCR1 and respond to the specific ligand XCL1 by Ca2+ mobilization and potent chemotaxis. More importantly, we demonstrate that CD141+ DCs excel in cross-presentation of soluble or cell-associated antigen to CD8+ T cells when directly compared with CD1c+ DCs, CD16+ DCs, and pDCs from the same donors. Both in their functional XCR1 expression and their effective processing and presentation of exogenous antigen in the context of major histocompatibility complex class I, human CD141+ DCs correspond to mouse CD8+ DCs, a subset known for superior antigen cross-presentation in vivo. These data define CD141+ DCs as professional antigen cross-presenting DCs in the human.

SummaryPatients with refractory autoimmune thrombocytopenia (ITP) may develop life-threatening bleeding that cannot be immediately controlled by drug administration. To date, there have been no studies conducted to evaluate the efficacy of platelet transfusion alone in such cases. Ten patients with refractory ITP and bleeding or a high bleeding risk were consecutively transfused (one unit/30 min) with apheresis platelet concentrates (APC) without the administration of new drugs. The used APCs (average 3 – 7 units) contained 2.7 × 1011 (medium) platelets and were leukodepleted (≤1 × 106 leukocytes/unit).Platelet serology was performed using standard techniques. Platelet transfusion resulted in an increase in the platelet count to 84 – 157 × 103/µl, and the cessation of bleeding in all patients without any serious adverse effects. Although platelet counts gradually decreased within a few days post-transfusion, bleeding was stopped in all cases. These findings indicate that consecutive platelet transfusion using APCs is a rapidly effective emergency treatment in patients with refractory ITP.

BACKGROUND: This multicenter study was performed with the intention to evaluate the exactness of the predicted CD34+ cell yield calculated by two leukapheresis programs of the cell separator COM.TEC upon the number of donor's circulating CD34+ cells and the blood volume processed. STUDY DESIGN AND METHODS: Patients and healthy donors (n = 166) received mobilization by chemotherapy and/or granulocyte colony-stimulating factor and underwent CD34+ cell harvest by the leukapheresis programs MNC or RV-PBSC (n = 203). RESULTS: CD34+ cells were collected by 112 harvests on MNC and by 91 collections on RV-PBSC. The median collection efficiency of CD34+ cells was significantly better for the program MNC than for RV-PBSC (p

INTRODUCTION AND OBJECTIVES: The Survival Prediction After Radical Cystectomy (SPARC) score incorporates clinical and pathologic features to predict cancer specific survival (CSS) for urothelial carcinoma of the bladder after radical cystectomy (RC). Validation of this model would improve its generalizability. METHODS: Using the IRB-approved bladder cancer database at the University of Southern California, we identified patients who underwent RC for urothelial carcinoma of the bladder for curative intent from 1971-2009. Clinical factors (Charlson comorbidity index, ECOG performance status, hydronephrosis, adjuvant chemotherapy, smoking status) and pathologic factors (pathologic T stage, nodal status, multifocality, and lymphovascular invasion) included in the SPARC score were obtained. Patients were excluded if there were missing variables or if they underwent neoadjuvant chemotherapy. Associations between clinicopathologic factors and CSS were evaluated using Cox proportional hazards. Calibration plots were generated comparing actuarial CSS with SPARC predicted CSS by deciles. A c-index was generated to determine accuracy of the prediction. Kaplan Meier curves estimated CSS stratified by SPARC score and were compared with the log rank test. RESULTS: A total of 2045 patients underwent RC and 1123 (55%) met inclusion criteria with a median follow-up of 4.7 years (IQR 2.0-8.9 years). Of the 1123 patients, 332 (30%) died of bladder cancer. All the clinical and pathologic variables used in the SPARC scoring model were associated with CSS except for smoking status and tumor multifocality. Calibration plots demonstrated concordance between the SPARC-predicted and actuarial CSS with a c-index of 0.75. Kaplan Meier curves demonstrated significant differences in CSS based upon SPARC score, p

Objective To evaluate the risk factors, management, and outcomes of benign ureteroenteric strictures (UES) in patients undergoing open radical cystectomy (RC) and urinary diversion for urothelial bladder carcinoma. Materials and Methods Using our institutional review board–approved institutional bladder cancer database, we identified 1964 patients who underwent RC for urothelial bladder carcinoma between 1971 and 2008. Patients underwent a uniform refluxing ureteroenteric anastomosis technique to ileum. In patients with UES, we reviewed clinicopathologic, management, and outcome variables. A multivariate logistic regression model was used to identify independent UES predictors. Results Forty-nine patients and 51 renal units were retrospectively identified with benign UES (2.6%). Median follow-up was 12.4 years (0.2-27.3 years) and median time from RC to UES diagnosis was 10 months (2 months-10 years). Although one-third were asymptomatic, common presentations included flank pain (22%) and urinary tract infection (9%). Thirty-one patients underwent primary endoscopic treatments, including dilatation and stenting, of whom, 13 patients (42%) underwent secondary endoscopic treatment and 9 patients (29%) underwent open revision. Three patients underwent primary open management. Median glomerular filtration rate did not change after management (49-48 mL/min); however, imaging showed improvement in 50% of cases. A multivariate logistic regression model revealed no association with age, body mass index, Charlson comorbidity index, perioperative radiation or chemotherapy, or preoperative serum albumin in predicting UES. Conclusion Benign UES are uncommon after RC and urinary diversion using a consistent meticulous surgical approach. More commonly on the left, UES generally present a few months after RC. Although no specific predisposing factor was determined, surgical technique plays an important role.

Therapy with imatinib mesylate is limited by cellular resistance in chronic myeloid leukaemia (CML). Further, the limited availability of matching stem cell donors or an unfavourable risk profile for allogeneic stem cell transplantation (SCT) reduces the number of therapeutic options in a number of patients. To assess the possibility of stem cell mobilization (SCM) during imatinib therapy we performed granulocyte colony-stimulating factor (filgrastim)-induced SCM and subsequent aphaeresis in 15 chronic phase and three accelerated phase CML patients. Aphaeresis was successful in 13 patients (72%) (> or =2.0 x 10(6) CD34+ cells/kg body weight) and five (28%) harvests could be obtained, which were negative for BCR/ABL mRNA as assessed by nested-reverse transcription polymerase chain reaction (RT-PCR). All harvests, except one, were negative after first round RT-PCR, implicating a low level of CML cell contamination. There was no significant change in peripheral BCR/ABL transcript load after SCM as assessed by quantitative real-time RT-PCR. Fifteen patients remained stable in complete cytogenetic remission (CCR) during a median observation period of 9.3 months. One patient achieved a molecular remission shortly after SCM. Another patient who exhibited rising BCR/ABL mRNA levels before SCM achieved CCR after autologous SCT with the generated harvest. One patient with a Philadelphia chromosome-negative, BCR/ABL-positive CML showed a cytogenetic relapse 6 months after SCM. We conclude that filgrastim-induced CD34+ cell aphaeresis under simultaneous imatinib medication is safe and feasible in CML patients. Additionally, we found evidence that this procedure could generate stem cell harvests that exhibit non-detectable levels of BCR/ABL mRNA.

BACKGROUND: Patients undergoing high-dose radio- and/or chemotherapy and autologous or allogeneic PBPC transplantation are at high risk for infections owing to profound immunosuppression. In this study, the rate of microbial contamination of ex vivo processed PBPC products was analyzed, comparing preparation under clean room conditions to standard laboratory conditions. STUDY DESIGN AND METHODS: After implementation of good manufacturing practice conditions in the two participating institutions, the microbial contamination rate of 366 PBPC harvests from 198 patients was determined under certified clean room conditions (Group A) from 2000 until 2002. To investigate influence of improved environmental conditions along with other parameters, this set of samples was compared with a historical control set of 1413 PBPC products, which have been processed ex vivo under a clean bench in a regular laboratory room and were harvested from 626 patients (Group B) from 1989 until 2000. RESULTS: In Group B microbial contamination was found in 74 PBPC products (5.2%) from 57 patients. In Group A microbial growth was detected in 3 leukapheresis products (0.8%) from 3 patients. After exclusion of PBPC products, which were probably contaminated before manipulation, statistical analysis showed a significant difference (χ2= 10.339; p < 0.001). CONCLUSION: These data suggest an impact of clean room conditions on the bacterial contamination rate of PBPC products. To identify confounding variables, variables like technique of leukapheresis, culture methodology, and microbial colonization of central venous catheters were taken into account. Further variables might be identified in following studies.

B-cell immune dysfunction contributes to the risk of severe infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed B-cell regeneration is found in patients with systemic graft-versus-host disease (GVHD) and is often accompanied by bone marrow (BM) suppression. Little is known about human BM GVHD. We analyzed the reconstitution kinetics of B-cell subsets in adult leukemic patients within 6 months after allo-HSCT. B-cell deficiency already existed before transplant and was aggravated after transplant. Onset of B-cell reconstitution characterized by transitional B-cell recovery occurred either early (months 2-3) or late (from month 6 on) and correlated highly positively with reverse transcription-polymerase chain reaction quantified numbers of κ-deleting recombination excision circles (KRECs). Delayed recovery was associated with systemic acute GVHD and full-intensity conditioning therapy. Histological analysis of BM trephines revealed increased T-cell infiltration in late recovering patients, which was associated with reduced numbers of osteoblasts. Functionally, late recovering patients displayed less pneumococcal polysaccharide-specific immunoglobin M-producing B cells on ex vivo B-cell activation than early recovering patients. Our results provide evidence for acute BM GVHD in allo-HSCT patients with infiltrating donor T cells and osteoblast destruction. This is associated with delayed B-cell reconstitution and impaired antibody response. Herein, KREC appears suitable to monitor BM B-cell output after transplant.

INTRODUCTION AND OBJECTIVES: The incidence of ureteral anastomotic strictures (UAS) after cystectomy ranges from 4-8%. We examined whether renal function and overall survival outcomes varied by operative (i.e., ureteral reimplantation) versus non-operative management approaches. METHODS: We identified patients with UAS following cystectomy and urinary diversion for any cause through our IRB-approved institutional database. Demographic, perioperative, renal function and survival data were abstracted. We compared time to stricture from initial cystectomy, renal functional outcomes, and overall survival by nonoperative versus operative management for patients with UAS. We used the Student’s t-test and chi-square testing for continuous and categorical variables, respectively. A multivariable Cox proportional hazard model was used to examine whether ureteral reimplantation was associated with improved overall survival. RESULTS: We identified 69 patients who developed benign UAS. Twenty-five patients (36.2%) were treated with ureteral reimplantation on a total of 86 obstructed renal units, 63% of cases occurred on the left. Demographic data including age at cystectomy (62.0 reimplant vs. 67.4 no reimplant, p1⁄40.06), gender (p1⁄40.92) and Charlson comorbidity (p1⁄40.08) were similar between the operative and nonoperative groups. However, Karnofsky performance status was worse in non-operative patients (p1⁄40.04). The differences between baseline and follow-up creatinine (+0.41 mg/dL reimplant vs. +0.72 mg/dL no reimplant, p1⁄40.38) and GFR (-14.7 reimplant vs. -16.7 no reimplant, mL/min/1.73 m2, p1⁄40.80) were not statistically different between groups. Two patients from the non-surgical group progressed to dialysis and 30 patients died during follow up (16.0% reimplant vs. 59.1% no reimplant, p1⁄40.001). Compared to patients with non-surgical management, patients undergoing reimplantation appeared to have better survival after adjusting for demographic factors, chemotherapy, comorbidity and performance status (Adjusted hazard ratio (aHR) 0.25, 95% CI 0.08-0.76) (Figure). CONCLUSIONS: Surgical intervention does not appear to impact renal functional outcomes in patients experiencing UAS following cystectomy. However, patients with UAS managed with nonsurgical approaches have worse overall survival after controlling for comorbidity and disease status suggesting that potential complications of non-surgical management may affect longevity.

In approximately 25% of patients with testicular germ cell tumor (GCT), the cancer metastasizes to lymph nodes and distant organs. The initial lymphatic drainage site of GCTs is the retroperitoneum. GCTs rarely involve mesenteric lymph nodes. In this study, we report a case of a 32-year-old male patient with GCT and associated mesenteric lymphadenopathy.

Multi-kinase inhibitors have been established for the treatment of advanced renal cell cancer, but long-term results are still disappointing and immunotherapeutic approaches remain an interesting experimental option particularly in patients with a low tumor burden. DC are crucial for antigen-specific MHC-restricted T cell immunity. Furthermore, allogeneic HLA-molecules pose a strong immunogenic signal and may help to induce tumor-specific T cell responses. In this phase I/II trial, 7 patients with histologically confirmed progressive metastatic RCC were immunized repetitively with 1 × 10 (7) allogeneic partially HLA-matched DC pulsed with autologous tumor lysate following a schedule of 8 vaccinations over 20 weeks. Patients also received 3 Mio IE IL-2 s.c. once daily starting in week 4. Primary endpoints of the study were feasibility and safety. Secondary endpoints were immunological and clinical responses. Vaccination was feasible and safe with no severe toxicity being observed. No objective response could be documented. However, while all patients had documented progress at study entry, 29% of the patients showed SD throughout the study with a mean TTP of 24.6 weeks (range 5 to 96 weeks). In 3/7 patients, TH1-polarized immune responses against RCC-associated antigens were observed. In one patient showing a minimal clinical response and a TTP of 96 weeks, clonally proliferated T cells against yet undefined antigens were induced by the vaccine. Vaccination with tumor antigen loaded DC remains an interesting experimental approach, but should rather be applied in the situation of minimal residual disease after systemic therapy. Additional depletion of regulatory cells might be a promising strategy.

326 Background: The Survival Prediction After Radical Cystectomy (SPARC) score (Eisenberg et al, J Urol 2013) incorporates clinical and pathologic features to predict cancer specific survival (CSS) for urothelial carcinoma of the bladder. Validation of this model would improve its generalizability. Methods: Using the IRB-approved bladder cancer database at the University of Southern California (USC), we identified patients who underwent radical cystectomy (RC) for urothelial carcinoma of the bladder for curative intent from 1971-2009. Clinical factors (Charlson comorbidity index, ECOG performance status, hydronephrosis, adjuvant chemotherapy, smoking status) and pathologic factors (pathologic T stage, nodal status, multifocality, and lymphovascular invasion) included in the SPARC score were obtained. Patients were excluded if there were missing variables or if they underwent neoadjuvant chemotherapy. Associations between clinicopathologic factors and CSS were evaluated using Cox proportional hazards. Calibration plots were generated comparing actuarial CSS with SPARC predicted CSS by deciles. A c-index was generated to determine accuracy of the prediction. Kaplan Meier curves estimated CSS stratified by SPARC score and were compared with the log rank test. Results: A total of 2,045 patients underwent RC and 1,123 (55%) met inclusion criteria with a median follow-up of 4.7 years (IQR 2.0-8.9 years). Of the 1,123 patients, 332 (30%) died of bladder cancer. All the clinical and pathologic variables used in the SPARC scoring model were associated with CSS except for smoking status and tumor multifocality. Calibration plots demonstrated concordance between the SPARC-predicted and actuarial CSS with a c-index of 0.75. Kaplan Meier curves demonstrated significant differences in CSS based upon SPARC score, p

In patients with multiple myeloma, irradiation of bone marrow prior to mobilization of autologous peripheral blood progenitor cells (PBPCs) may lead to a reduced yield of CD34+ cells. Quantitative effects have not been sufficiently assessed. We retrospectively performed a multivariate analysis in 114 patients (67 men, 47 women) with multiple myeloma, of whom 53 (47%) patients had been irradiated prior to mobilization chemotherapy. High-dose cyclophosphamide followed by granulocyte colony-stimulating factor was used for mobilization in 84% of patients. In addition to previous chemotherapy, we quantitatively evaluated the dose and fractionation of prior irradiation, the volume of the irradiated bone marrow, and the time interval between radiation therapy and mobilization of PBPCs. The median volume of irradiated bone marrow was 9% (range 1-30%) of the estimated total hematopoietic bone marrow. The irradiated bone marrow volume and the number of CD34+ cells per kilogram of body weight in the first leukapheresis product showed no correlation. However, the time between irradiation and mobilization seemed to influence the yield of CD34+ cells. A comparison of irradiated patients with nonirradiated patients revealed no differences with respect to the CD34+ cell counts. We did not find a significant influence of the extent or the total dose of irradiation on the yield of CD34+ cells in the first leukapheresis product in patients with multiple myeloma. However, there may be an inverse correlation between the time elapsed since the last irradiation and the number of mobilized CD34+ cells.

Therapy with imatinib mesylate is limited by cellular resistance in chronic myeloid leukaemia (CML). Further, the limited availability of matching stem cell donors or an unfavourable risk profile for allogeneic stem cell transplantation (SCT) reduces the number of therapeutic options in a number of patients. To assess the possibility of stem cell mobilization (SCM) during imatinib therapy we performed granulocyte colony-stimulating factor (filgrastim)-induced SCM and subsequent aphaeresis in 15 chronic phase and three accelerated phase CML patients. Aphaeresis was successful in 13 patients (72%) (or =2.0 x 10(6) CD34+ cells/kg body weight) and five (28%) harvests could be obtained, which were negative for BCR/ABL mRNA as assessed by nested-reverse transcription polymerase chain reaction (RT-PCR). All harvests, except one, were negative after first round RT-PCR, implicating a low level of CML cell contamination. There was no significant change in peripheral BCR/ABL transcript load after SCM as assessed by quantitative real-time RT-PCR. Fifteen patients remained stable in complete cytogenetic remission (CCR) during a median observation period of 9.3 months. One patient achieved a molecular remission shortly after SCM. Another patient who exhibited rising BCR/ABL mRNA levels before SCM achieved CCR after autologous SCT with the generated harvest. One patient with a Philadelphia chromosome-negative, BCR/ABL-positive CML showed a cytogenetic relapse 6 months after SCM. We conclude that filgrastim-induced CD34+ cell aphaeresis under simultaneous imatinib medication is safe and feasible in CML patients. Additionally, we found evidence that this procedure could generate stem cell harvests that exhibit non-detectable levels of BCR/ABL mRNA.

Patients undergoing high-dose radio- and/or chemotherapy and autologous or allogeneic PBPC transplantation are at high risk for infections owing to profound immunosuppression. In this study, the rate of microbial contamination of ex vivo processed PBPC products was analyzed, comparing preparation under clean room conditions to standard laboratory conditions.After implementation of good manufacturing practice conditions in the two participating institutions, the microbial contamination rate of 366 PBPC harvests from 198 patients was determined under certified clean room conditions (Group A) from 2000 until 2002. To investigate influence of improved environmental conditions along with other parameters, this set of samples was compared with a historical control set of 1413 PBPC products, which have been processed ex vivo under a clean bench in a regular laboratory room and were harvested from 626 patients (Group B) from 1989 until 2000.In Group B microbial contamination was found in 74 PBPC products (5.2%) from 57 patients. In Group A microbial growth was detected in 3 leukapheresis products (0.8%) from 3 patients. After exclusion of PBPC products, which were probably contaminated before manipulation, statistical analysis showed a significant difference (chi2= 10.339; p0.001).These data suggest an impact of clean room conditions on the bacterial contamination rate of PBPC products. To identify confounding variables, variables like technique of leukapheresis, culture methodology, and microbial colonization of central venous catheters were taken into account. Further variables might be identified in following studies.

BACKGROUND: Peripheral blood progenitor cells (PBPCs) can be collected on various cell separators. Two leukapheresis programs (LP-MNC and LP-PBSC-Lym) were evaluated for computerized collection of PBPCs on a new cell separator. STUDY DESIGN AND METHODS: Leukapheresis assisted by the LP-MNC or LP-PBSC-Lym software was performed for the harvesting of PBPCs in 52 oncology patients after chemotherapy plus G-CSF treatment and in 18 healthy subjects after G-CSF mobilization alone. RESULTS: A total of 38 components from 33 donors via LP-MNC and 43 components from 37 donors via LP-PBSC-Lym were collected with a median of one (range, one to two) standard-volume leukapheresis procedures (9.2-13.3 L) per donor. There were no significant differences between the two groups concerning median counts of WBCs, CD34+ cells, CD34+ cell yields per harvest, and CD34+ cell yields of cumulative harvests. The blood cell counts after leukapheresis revealed that the LP-MNC resulted in significantly higher platelet loss than LP-PBSC-Lym (p = 0.024): 35.9 percent (range, 19.2%-66.1%) versus 29.7 percent (11.6%-52.3%). Regarding the CD34+ cell collection efficiency, the LP-MNC program was significantly better than the LP-PBSC-Lym program (p < 0.001): 77.5 percent (range, 35.5%-98.9%) versus 58.3 percent (range, 20.4%-98.9%). However, concentrates collected by the LP-PBSC-Lym program had significantly higher percentages of MNCs (p < 0.001) and CD34+ cells (p = 0.028) than harvests with the LP-MNC program: 90 percent (range, 69%-99%) versus 70 percent (range, 35%-98%) and 1.2 percent (range, 0.2%-7.3%) versus 0.7 percent (range, 0.2%-6.0%), respectively. No leukapheresis-related serious adverse events were seen, and time for hematopoietic engraftment was equivalent to data published in the literature. CONCLUSION: The LP-MNC program shows a significantly better CD34+ cell collection efficiency than the LP-PBSC-Lym program. However, collections with the LP-MNC program result in PBPC components with a lower MNC and CD34+ cell concentrations and a higher apheresis-related loss of patient's platelets.

e15053 Background: Despite novel kinase inhibitors, prognosis of metastatic RCC remains poor and new experimental approaches are warranted. Our aim was to evaluate a DC-based vaccine, which exploits alloreactivity as a means to amplify specific anti-tumor immune responses. Methods: Allogeneic, partially HLA-matched DC were generated in our GMP facility. DC were loaded with autologous tumor lysate. 8 patients with progressive mRCC were included, 7 patients were immunized repetitively with 107 DC s.c. over 20 weeks. Low-dose IL-2 (3 Mio U s.c. qd) was used concomitantly. Endpoints of the study were feasibility, safety, immunological and clinical responses. T cell responses against HLA-A2-restricted RCC-associated antigens were evaluated by proliferation assays, ELISpot and cytokine bead array (CBA). T cell repertoire was analysed by T cell receptor γ and –β PCR. Results: Vaccination was feasible and safe, no treatment-related grade 3/4 toxicity or clinically relevant autoimmunity was observed. No objective responses were observed, however, 2/7 patients showed stable disease, one a minimal clinical response. The mean TTP was 24.6 weeks (range 5 to 96). Delayed-type hypersensitivity was detected in 3/7 and HLA antibodies were induced in 3/7 patients. In 3/7 patients T cell responses against RCC-associated antigens such as TYMS, G250, vimentin, surviving and cyclin-D1 were induced by vaccination. These antigen-specific T cells showed a predominant TH1-cytokine profile. Interestingly, a clonally expanded T cell population could be detected by γ- and –β PCR in one patient with both a minimal clinical response and a T cell response. This clone is currently persisting for more than 80 months, its specificity is under investigation. Conclusions: Vaccination with allogeneic tumor-lysate-loaded DC was feasible, safe and was able to induce TH1-polarized immune responses against RCC-associated antigens. Tumor vaccination might be a promising approach in minimal residual disease, possibly in combination with antibodies against CTLA-4 or PD-1.

Abstract 3418 Introduction: Mobilisation and collection of in vivo-purged CD34+ stem cells for chronic myeloid leukemia (CML) patients while in complete cytogenetic remission (CCyR) may offer a therapeutic option for those who develop resistance to the tyrosine kinase inhibitor imatinib mesylate (IM), the recommended first line therapy. Indeed, several groups have reported on retrospective studies showing autologous stem cell mobilisation to be safe and efficacious during IM therapy. However, assessing the clinical utility of managing patients using this approach is difficult as long-term follow-up is lacking. Here, we report the clinical outcome for 22 CML patients with a median of 99.5 months follow-up post G-CSF induced stem cell mobilisation. We assessed the efficacy and the the impact on BCR-ABL1 expression levels in these individuals. Material and Methods: Stem cell mobilisation was achieved by administering 10 mg/kg body weight (bw)/day filgrastim (granulocyte-colony stimulating factor, G-CSF) subcutaneously. Stem cell apheresis was performed if the absolute number of circulating CD34+ cells exceeded 5/ml. Target stem cell yield was 32×106 CD34+ cells/kg body weight. BCR-ABL1 transcripts were quantified by real time PCR (Q-PCR) of reverse transcribed total RNA using LightCycler® with β-actin as endogenous control gene. Results: For the twenty-two patients included in the present study, median age was 47 years (range, 24 – 71) and median disease duration was 20 months (range, 1 – 77). At the start of IM, 19 patients were in chronic phase (CP), and 3 in accelerated phase (AP). With a median duration on IM of 16 months (range, 2 – 29), time to first CCyR was 6 months (range, 0 – 25) and time from CCyR to apheresis was 8.5 months (range, 1 – 20). Mobilisation was performed once in 16 patients and twice in 6 patients, of whom eighteen patients (82 %) proceeded to apheresis. Overall, mobilisation was successful in 17 of 22 patients (78 %) with a median CD34+ cell number of 3.1×106/kg body weight (range, 0,7 - 6). BCR-ABL1 transcripts were undetectable in 12 of 22 peripheral blood samples (55 %) at the time of apheresis and 7 of 14 stem cell harvests (50 %) without discernible correlation with matched peripheral blood samples. Progression-free survival at 5 and 8 years was determined to be 63 %, and overall survival at 5 years and 8 years was 95 % and 90 %, respectively. Sixteen of 22 patients (73 %) continue to be treated with IM and twelve of 22 patients (55 %) are without detectable BCR-ABL1 transcripts, i.e. in complete molecular remission (CMR). Of the six patients that stopped IM (3 resistant and 3 intolerant), all received nilotinib as second-line TKI. Five of these six patients are still alive (1 in CHR; 1 in MCyR; 1 in MMR; and 2 in CMR), and one patient who subsequently received dasatinib died after progressing to blast crisis. Conclusion: These observations show G-CSF induced stem cell mobilisation and collection during IM therapy for autologous transplantation to be safe and efficient with a favourable long-term outcome. Disclosures: No relevant conflicts of interest to declare.