Intraoperative Hypothermia is Common, but not Associated With Blood Loss or Transfusion in Pediatric Posterior Spinal Fusion.

BACKGROUND: Intraoperative hypothermia may be associated with increased blood loss due to the effects of temperature on clotting but this has not been evaluated in the setting of pediatric posterior spinal fusion (PSF). The purpose of this study was to determine if a correlation exists between intraoperative hypothermia and estimated blood loss (EBL) or transfusion requirements in pediatric patients undergoing PSF. METHODS: A retrospective review of consecutive patients undergoing PSF for scoliosis at a single institution between 6/2004 and 3/2012 was performed. Exclusion criteria were fewer than 10 levels fused, anterior spinal fusion, and patients below 9 years old at time of surgery. Temperature was measured every 15 seconds using esophageal temperature probe. Input variable of hypothermia was analyzed as a binary variable Tmin ≤35°C at any point during anesthesia and as integrated temperature area under the curve (TAUC). RESULTS: A total of 510 with an average age of 14.6 years (range, 9.0 to 24.3 y) met inclusion criteria. Totally, 56% (287/510) had idiopathic scoliosis (IS) and 44% (223/510) were non-IS. Hypothermia (Tmin≤35°C) was experienced by 45% (230/510) of all patients [48% (137/287) of IS; 42% (93/223) of non-IS]. A total of 63% (323/510) of patients were transfused with packed red blood cells (PRBC) [49% (141/287) of IS patients; 82% (182/223) of non-IS patients]. There was no correlation between Tmin≤35°C and transfusion of PRBC in all included patients (P=0.49); (IS patients P=0.45, non-IS patients P=0.61). There was no significant difference in EBL between patients who experienced hypothermia and those who did not (P=0.33; IS patients P=0.21, non-IS patients P=0.87). There was no significant correlation between TAUC and transfusion of PRBC for all patients (P=0.35), IS patients (P=0.26) and non-IS patients (P=0.54) or between TAUC and EBL (P=0.80); (IS patients P=0.57. non-IS patients P=0.62). CONCLUSIONS: There was no significant correlation between intraoperative hypothermia and EBL or transfusion of PRBC in pediatric patients undergoing PSF. LEVEL OF EVIDENCE: Level III.

Reconstructive Science in Orthopedic Oncology.

Limb salvage is widely practiced as standard of care in most cases of extremity bone sarcoma. Allograft and endoprosthesis reconstructions are the most widely utilized modalities for the reconstruction of large segment defects, however complication rates remain high. Aseptic loosening and infection remain the most common modes of failure. Implant integration, soft-tissue function, and infection prevention are crucial for implant longevity and function. Macro and micro alterations in implant design are reviewed in this manuscript. Tissue engineering principles using nanoparticles, cell-based, and biological augments have been utilized to develop implant coatings that improve osseointegration and decrease infection. Similar techniques have been used to improve the interaction between soft tissues and implants. Tissue engineered constructs (TEC) used in combination with, or in place of, traditional reconstructive techniques may represent the next major advancement in orthopaedic oncology reconstructive science, although preclinical results have yet to achieve durable translation to the bedside.

Prevalence of specific gait abnormalities in children with cerebral palsy revisited: influence of age, prior surgery, and Gross Motor Function Classification System level.

AIM: To examine the impact of age, surgery, and Gross Motor Function Classification System (GMFCS) level on the prevalence of gait problems in children with cerebral palsy (CP). METHOD: Gait analysis records were retrospectively reviewed for ambulatory patients with CP. Gait abnormalities were identified using physical exam and kinematic data. Relationships among age, sex, previous surgery, GMFCS level, and prevalence of gait abnormalities associated with crouch and out-toeing, and equinus and in-toeing were assessed using univariable and multivariable logistic regression. RESULTS: One-thousand and five records were reviewed. The most common gait problems were in-toeing, excessive knee flexion, stiff knee, hip flexion, internal rotation, adduction, and equinus (all >50%). Odds ratios (OR) for various gait problems associated with crouch and out-toeing increased (OR 1.07-1.32), and those associated with equinus and in-toeing decreased (OR 0.80-0.94) significantly with increasing age for patients in GMFCS levels I to III. The same trends were seen with prior surgery (OR for crouch and out-toeing: 1.86-7.14; OR for equinus and in-toeing: 0.16-0.59). INTERPRETATION: The prevalence of gait abnormalities varies by GMFCS level, but similarities exist among levels. The study results suggest that in younger children, particularly those in GMFCS levels III and IV, treatments for equinus and in-toeing should be undertaken with caution because these problems tend to decrease with age even without orthopedic intervention. Such children may end up with the 'opposite' deformities of calcaneal crouch and out-toeing, which tend to increase in prevalence with age.

Fever is common postoperatively following posterior spinal fusion: infection is an uncommon cause.

OBJECTIVE: To determine the frequency and clinical significance of postoperative fever in pediatric patients undergoing posterior spinal fusion (PSF). STUDY DESIGN: A retrospective chart review was performed for consecutive patients undergoing PSF at a single institution between June 2005 and April 2011, with a minimum of 2-year follow up. Exclusion criteria were previous spine surgery, a combined anterior-posterior approach, and delayed wound closure at the time of surgery. RESULTS: Two hundred and seventy-eight patients with an average age of 13 years (1-22 years) met inclusion criteria, with the following diagnoses: adolescent idiopathic scoliosis 43%, neuromuscular/syndromic scoliosis 39%, congenital scoliosis 11%, spondylolisthesis 4%, and Scheuermann kyphosis 3%. Seventy-two percent (201/278) of patients had a maximum temperature (Tmax) >38(°) postoperatively, and 9% (27/278) Tmax >39(°). The percentage of febrile patients trended down following the first postoperative day. Infection rate was 4% (12/278). There was no correlation between Tmax >38(°) or Tmax >39(°), and timing of fever, positive blood or urine cultures, pneumonia, or surgical site infection. CONCLUSION: Seventy-two percent of pediatric patients undergoing PSF experienced postoperative fever, and 9% of patients had Tmax>39(°). There was no significant correlation between fever and positive blood culture, urine culture, pneumonia, or surgical site infection. This information may help relieve stress for families and healthcare providers, and obviate routine laboratory evaluation for fever alone.

Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model.

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

A Risk Calculator for the Prediction of C5 Nerve Root Palsy After Instrumented Cervical Fusion.

BACKGROUND: C5 palsy is a common postoperative complication after cervical fusion and is associated with increased health care costs and diminished quality of life. Accurate prediction of C5 palsy may allow for appropriate preoperative counseling and risk stratification. We primarily aim to develop an algorithm for the prediction of C5 palsy after instrumented cervical fusion and identify novel features for risk prediction. Additionally, we aim to build a risk calculator to provide the risk of C5 palsy. METHODS: We identified adult patients who underwent instrumented cervical fusion at a tertiary care medical center between 2013 and 2020. The primary outcome was postoperative C5 palsy. We developed ensemble machine learning, standard machine learning, and logistic regression models predicting the risk of C5 palsy-assessing discrimination and calibration. Additionally, a web-based risk calculator was built with the best-performing model. RESULTS: A total of 1024 patients were included, with 52 cases of C5 palsy. The ensemble model was well-calibrated and demonstrated excellent discrimination with an area under the receiver-operating characteristic curve of 0.773. The following features were the most important for ensemble model performance: diabetes mellitus, bipolar disorder, C5 or C4 level, surgical approach, preoperative non-motor neurologic symptoms, degenerative disease, number of fused levels, and age. CONCLUSIONS: We report a risk calculator that generates patient-specific C5 palsy risk after instrumented cervical fusion. Individualized risk prediction for patients may facilitate improved preoperative patient counseling and risk stratification as well as potential intraoperative mitigating measures. This tool may also aid in addressing potentially modifiable risk factors such as diabetes and obesity.

In vitro and in vivo methods to study bacterial colonization of hydrogel dermal fillers.

Preclinical in vitro and in vivo methods to study bacterial interactions with dermal fillers and infection pathogenesis are lacking. In this work, first in vitro methods to assess protein biofouling and effective pore size of commercial dermal fillers, including degradable hyaluronic acid (HA)-based fillers and other semi-degradable or permanent fillers (non-HA), were developed. The results were then related to Staphylococcus aureus (S. aureus) adhesion rates in vitro. HA fillers had less protein sorption than non-HA fillers and overall had smaller effective pore sizes. The properties correlated with levels of bacterial adhesion, where the control glass surface had the most rapid increase in bacterial cell adhesion, with a slope of 0.29 cm-2  min-1 , three unique non-HA fillers had intermediate adhesion with slopes of 0.11 and 0.06 cm-2  min-1 , and three unique HA fillers had the least adhesion with slopes of 0.02, 0.02, and 0.01 cm-2  min-1 . S. aureus had greater motility on the HA fillers than on non-HA fillers. Next, a mouse model for dermal filler biofilm and infection was developed. Mice were inoculated with a controlled amount of bioluminescent bacteria (Xen36 S. aureus) and polyacrylamide hydrogels of different stiffness were injected. In vivo bioluminescence was monitored longitudinally for 35 days to ensure that lasting colonization was established. The inoculum was optimized to achieve adequate bioluminescent signal, and bacterial bioburden over time and inter-animal variability in bioburden were determined. These in vitro and in vivo approaches can be used for future studies of antimicrobial interventions for dermal fillers.

Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients.

Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R(-) ) of a SOT from a seropositive donor (D(+) ). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is over expressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D(+) R(-) patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D(+) R(-) patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which, however, showed exhaustion phenotypes.

Genicular Artery Embolization for the Treatment of Symptomatic Knee Osteoarthritis.

Genicular artery embolization (GAE) is a novel therapy to treat patients with symptomatic knee osteoarthritis (OA) by reducing synovial arterial hypervascularity. This study evaluates the safety and efficacy of GAE for the treatment of symptomatic knee OA. METHODS: A prospective, single-center, open-label U.S. Food and Drug Administration-approved investigational device exemption study was conducted. Patients enrolled in the study were 40 to 80 years old, with moderate or severe knee OA (Kellgren-Lawrence grade 2, 3, or 4), who previously had failure of conservative therapy. Baseline pain (visual analog scale [VAS]) and symptom scores (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were assessed. After femoral arterial access was achieved, GAE of 1, 2, or 3 genicular arteries supplying the location of the subject's pain, as determined by digital subtraction angiography and cone-beam computed tomography, was performed using 100-µm particles. Adverse events and symptoms scores were assessed at 1 week, 1 month, 3 months, 6 months, and 1 year after GAE. RESULTS: Over a 10-month period, 40 subjects were enrolled. The median age was 69 years (range, 49 to 80 years). The median body mass index was 29 kg/m2 (range, 19 to 44 kg/m2). Knee OA severity was grade 2 in 18% of the patients, grade 3 in 43%, and grade 4 in 40%. Technical success was achieved in 100% of the subjects. Transient skin discoloration and transient mild knee pain after the procedure were common and expected. Treatment-related adverse events included a groin hematoma requiring overnight observation in 1 subject, self-resolving focal skin ulceration in 7 subjects, and an asymptomatic small bone infarct on magnetic resonance imaging at 3 months in 2 subjects. The WOMAC total and VAS pain scores decreased by 61% and 67% at 12 months from a median baseline of 52 (of 96) and 8 (of 10), respectively. Twenty-seven patients (68%) had a reduction of ≥50% in both WOMAC total and VAS pain scores. CONCLUSIONS: This prospective trial demonstrates that GAE is effective and durable in reducing pain symptoms from moderate or severe knee OA that is refractory to other conservative therapy, with an acceptable safety profile. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Severity and location of lumbar spine stenosis affects the outcome of total knee arthroplasty.

BACKGROUND: Recent studies have noted that patients with pre-existing lumbar spinal stenosis (LSS) have lower functional outcomes after total knee arthroplasty (TKA). Given that LSS manifests heterogeneously in location and severity, its influence on knee replacement merits a radiographically targeted analysis. We hypothesize that patients with more severe LSS will have diminished knee mobility before and after TKA. METHODS: This retrospective case series assessed all TKAs performed at our institution for primary osteoarthritis from 2017-2020. Preoperative lumbar magnetic resonance image (MRI) with no prior lumbar spine surgery was necessary for inclusion. Stenosis severity was demonstrated by (1) anterior-posterior (AP) diameter of the thecal sac and (2) morphological grade. TKA outcomes in 103 cases (94 patients) were assessed by measuring preoperative and postoperative arc of motion (AOM), postoperative flexion contracture, and need for manipulation under anesthesia. RESULTS: Patients with mild stenosis did significantly better in terms of postoperative knee AOM. As AP diameter decreased at levels L1-2, L2-3, L3-4, and L4-5, there was a significant reduction in preoperative-AOM (p < 0.001 for each), with a 16 degree decrease when using patients' most stenotic level (p < 0.001). The same was noted with respect to increased morphological grade (p < 0.001), with a 5 degree decrease for patients' most stenotic level (p < 0.001). CONCLUSION: Severe LSS, which is readily demonstrated by a reduction in the AP diameter of the thecal sac or increased morphological grade on MRI, correlated with a significant reduction in preoperative AOM that was not improved after TKA. Persistent postoperative reductions in AOM may contribute to reduced patient satisfaction and recovery. LEVEL OF EVIDENCE: Level 4.

Predictors of Medical Malpractice Outcomes After Spine Surgery: A Comprehensive Analysis From 2010 to 2019.

STUDY DESIGN: Retrospective review of spine surgery malpractice cases. OBJECTIVES: The aim was to compare medical malpractice outcomes among different types of spine surgery and identify predictors of litigation outcomes. SUMMARY OF BACKGROUND DATA: Spine surgery is highly litigious in the United States with data suggesting favorable outcomes for defendant surgeons. However, factor specific data and explanations for plaintiff verdicts are lacking. METHODS: Westlaw legal database was queried for spine surgery malpractice outcomes from 2010 to 2019. Clinical data, reasons for litigation, and legal outcomes were tabulated. Statistical analysis was performed to identify factors associated with litigation outcomes. RESULTS: A total of 257 cases were identified for inclusion. There were 98 noninstrumented and 148 instrumented cases; 110 single-level and 99 multilevel; 83 decompressions, 95 decompression and fusions, and 47 fusion only. In all, 182 (71%) resulted in a defendant verdict, 44 (17%) plaintiff verdict, and 31 (12%) settlement. Plaintiff verdicts resulted in payouts of $2.03 million, while settlements resulted in $1.11 million (P=0.34). Common reasons for litigation were intraoperative error, hardware complication, and improper postoperative management. Cases were more likely to result for the plaintiff if postoperative cauda equina syndrome (55% vs. 26%, P<0.01), a surgical site infection (46% vs. 27%, P=0.03), or other catastrophic injury (40% vs. 26%, P=0.03) occurred. Higher monetary awards were associated with multi versus single-level (median: $2.61 vs. $0.92 million, P=0.01), improper postoperative management cited (median: $2.29 vs. $1.12 million, P=0.04), and permanent neurological deficits ($2.29 vs. $0.78 million, P<0.01). Plaintiff payouts were more likely if defendant specialty was neurosurgery versus orthopedic surgery (33% vs. 18%, P=0.01). CONCLUSIONS: Spine surgery is a litigious field with multiple factors associated with outcomes. Efforts to reduce intraoperative errors and complications may improve patient care and decrease the risk of litigation.

Comparison of two fluorescent probes in preclinical non-invasive imaging and image-guided debridement surgery of Staphylococcal biofilm implant infections.

Implant-associated infections are challenging to diagnose and treat. Fluorescent probes have been heralded as a technologic advancement that can improve our ability to non-invasively identify infecting organisms, as well as guide the inexact procedure of surgical debridement. This study's purpose was to compare two fluorescent probes for their ability to localize Staphylococcus aureus biofilm infections on spinal implants utilizing noninvasive optical imaging, then assessing the broader applicability of the more successful probe in other infection animal models. This was followed by real-time, fluorescence image-guided surgery to facilitate debridement of infected tissue. The two probe candidates, a labelled antibiotic that targets peptidoglycan (Vanco-800CW), and the other, a labelled antibody targeting the immunodominant Staphylococcal antigen A (1D9-680), were injected into mice with spine implant infections. Mice were then imaged noninvasively with near infrared fluorescent imaging at wavelengths corresponding to the two probe candidates. Both probes localized to the infection, with the 1D9-680 probe showing greater fidelity over time. The 1D9-680 probe was then tested in mouse models of shoulder implant and allograft infection, demonstrating its broader applicability. Finally, an image-guided surgery system which superimposes fluorescent signals over analog, real-time, tissue images was employed to facilitate debridement of fluorescent-labelled bacteria.

Randomized Trial of a Virtual Reality Tool to Teach Surgical Technique for Tibial Shaft Fracture Intramedullary Nailing.

INTRODUCTION: Active learning methods have accumulated popularity due to improved results in knowledge acquisition as opposed to passive learning methods. For surgical resident physicians with limited training opportunities outside of the operating room due to time constraints, virtual reality (VR) is a relatively inexpensive and time-efficient active training method for procurement of surgical skills. We conducted a simulated intramedullary nailing (IMN) of a tibia to demonstrate VR training programs as a more effective modality of learning orthopedic surgical techniques compared to passive learning tools such as a standard guide (SG) through trained novice medical students performing a SawBones simulation of intramedullary nail fixation. MATERIALS AND METHODS: First and second-year medical students without prior experience of procedure were recruited and randomized to SG or VR training. Participants were observed performing simulated tibia IMN procedure immediately after training and evaluated by a blinded attending surgeon using procedure-specific checklist and 5-point global assessment scale. Participants returned after 2-weeks for repeat training and evaluation. RESULTS: 20 participants were recruited and randomized into VR (n = 10) and SG (n = 10) groups. All 20 participants completed the first phase and 17 completed the second phase of the study. Aggregate global assessment scores were significantly higher for VR than SG group (17.5 vs. 7.5, p < 0.001), including scores in all individual categories. The percentage of steps completed correctly was significantly higher in the VR group compared to the SG group (63% vs. 25%, p < 0.002). Average improvement between the first and second phases of the study were higher in the VR group compared to SG group across all 5-categories of the global assessment scale, and significantly higher for knowledge of instruments (50% vs. 11%, p, 0.01). DISCUSSION: VR training was more effective than a passive SG in our model of simulated tibia IMN for novice medical students. Virtual reality training may be a useful method to augment orthopedic education.

Progress not panacea: vancomycin powder efficacy and dose evaluated in an in vivo mouse model of spine implant infection.

BACKGROUND: Intrawound vancomycin powder (VP) has been rapidly adopted in spine surgery with apparent benefit demonstrated in limited, retrospective studies. Randomized trials, basic science, and dose response studies are scarce. PURPOSE: This study aims to test the efficacy and dose effect of VP over an extended time course within a randomized, controlled in vivo animal experiment. STUDY DESIGN/SETTING: Randomized controlled experiment utilizing a mouse model of spine implant infection with treatment groups receiving vancomycin powder following bacterial inoculation. METHODS: Utilizing a mouse model of spine implant infection with bioluminescent Staphylococcus aureus, 24 mice were randomized into 3 groups: 10 infected mice with VP treatment (+VP), 10 infected mice without VP treatment (No-VP), and 4 sterile controls (SC). Four milligrams of VP (mouse equivalent of 1 g in a human) were administered before wound closure. Bioluminescence imaging was performed over 5 weeks to quantify bacterial burden. Electron microscopy (EM), bacterial colonization assays (Live/Dead) staining, and colony forming units (CFU) analyses were completed. A second dosing experiment was completed with 34 mice randomized into 4 groups: control, 2 mg, 4 mg, and 8 mg groups. RESULTS: The (+VP) treatment group exhibited significantly lower bacterial loads compared to the control (No-VP) group, (p<.001). CFU analysis at the conclusion of the experiment revealed 20% of mice in the +VP group and 67% of mice in the No-VP group had persistent infections, and the (+VP) treatment group had significantly less mean number of CFUs (p<.03). EM and Live/Dead staining revealed florid biofilm formation in the No-VP group. Bioluminescence was suppressed in all VP doses tested compared with sterile controls (p<.001). CFU analysis revealed a 40%, 10%, and 20% persistent infection rate in the 2 mg, 4 mg, and 8 mg dose groups, respectively. CFU counts across dosing groups were not statistically different (p=.56). CONCLUSIONS: Vancomycin powder provided an overall infection prevention benefit but failed to eradicate infection in all mice. Furthermore, the dose when halved also demonstrated an overall protective benefit, albeit at a lower rate. CLINICAL SIGNIFICANCE: Vancomycin powder is efficacious but should not be viewed as a panacea for perioperative infection prevention. Dose alterations can be considered, especially in patients with kidney disease or at high risk for seroma.

Evading the host response: Staphylococcus "hiding" in cortical bone canalicular system causes increased bacterial burden.

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this "limb salvage" surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar-canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

Multimodal imaging guides surgical management in a preclinical spinal implant infection model.

Spine implant infections portend disastrous outcomes, as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. Current imaging modalities can detect anatomical alterations and anomalies but cannot differentiate between infection and aseptic loosening, diagnose specific pathogens, or delineate the extent of an infection. Herein, a fully human monoclonal antibody 1D9, recognizing the immunodominant staphylococcal antigen A on the surface of Staphylococcus aureus, was assessed as a nuclear and fluorescent imaging probe in a preclinical model of S. aureus spinal implant infection, utilizing bioluminescently labeled bacteria to confirm the specificity and sensitivity of this targeting. Postoperative mice were administered 1D9 probe dual labeled with 89-zirconium (89Zr) and a near infrared dye (NIR680) (89Zr-NIR680-1D9), and PET-CT and in vivo fluorescence and bioluminescence imaging were performed. The 89Zr-NIR680-1D9 probe accurately diagnosed both acute and subacute implant infection and permitted fluorescent image-guided surgery for selective debridement of infected tissue. Therefore, a single probe could noninvasively diagnose an infection and facilitate image-guided surgery to improve the clinical management of implant infections.

Ambulatory anterior cervical discectomy and fusion is associated with a higher risk of revision surgery and perioperative complications: an analysis of a large nationwide database.

BACKGROUND CONTEXT: With the changing landscape of health care, outpatient spine surgery is being more commonly performed to reduce cost and to improve efficiency. Anterior cervical discectomy and fusion (ACDF) is one of the most common spine surgeries performed and demand is expected to increase with an aging population. PURPOSE: The objective of this study was to determine the nationwide trends and relative complication rates associated with outpatient ACDF. STUDY DESIGN/SETTING: This is a large-scale retrospective case control study. PATIENT SAMPLE: The patient sample included Humana-insured patients who underwent one- to two-level ACDF as either outpatients or inpatients from 2011 to 2016 OUTCOME MEASURES: The outcome measures included incidence and the adjusted odds ratio (OR) of postoperative medical and surgical complications within 1 year of the index surgery. MATERIALS AND METHODS: A retrospective review was performed of the PearlDiver Humana insurance records database to identify patients undergoing one- to two-level ACDF (Current Procedural Terminology [CPT]-22551 and International Classification of Diseases [ICD]-9-816.2) as either outpatients or inpatients from 2011 to 2016. The incidence of perioperative medical and surgical complications was determined by querying for relevant ICD and CPT codes. Multivariate logistic regression adjusting for age, gender, and Charlson Comorbidity Index was used to calculate ORs of complications among outpatients relative to inpatients undergoing ACDF. RESULTS: Cohorts of 1,215 patients who underwent outpatient ACDF and 10,964 patients who underwent inpatient ACDF were identified. The median age was in the 65-69 age group for both cohorts. The annual relative incidence of outpatient ACDF increased from 0.11 in 2011 to 0.22 in 2016 (R2=0.82, p=.04). Adjusting for age, gender, and comorbidities, patients undergoing outpatient ACDF were more likely to undergo revision surgery for posterior fusion at both 6 months (OR 1.58, confidence interval [CI] 1.27-1.96, p<.001) and 1 year (OR 1.79, CI 1.51-2.13, p<.001) postoperatively. Outpatient ACDF was also associated with a higher likelihood of revision anterior fusion at 1 year postoperatively (OR 1.46, CI 1.26-1.70, p<.001). Among medical complications, postoperative acute renal failure was more frequently associated with outpatient ACDF than inpatient ACDF (OR 1.25, CI 1.06-1.49, p=.010). Adjusted rates of all other queried surgical and medical complications were comparable. CONCLUSIONS: Outpatient ACDF is increasing in frequency nationwide over the past several years. Nationwide data demonstrate a greater risk of perioperative surgical complications, including revision anterior and posterior fusion, as well as a higher risk of postoperative acute renal failure. Candidates for outpatient ACDF should be counseled and carefully selected to reduce these risks.

Outpatient Posterior Lumbar Fusion: A Population-Based Analysis of Trends and Complication Rates.

STUDY DESIGN: A retrospective case-control study. OBJECTIVE: The aim of this study was to determine the nationwide trends and complication rates associated with outpatient posterior lumbar fusion (PLF). SUMMARY OF BACKGROUND DATA: Outpatient lumbar spine fusion is now possible secondary to minimally invasive techniques that allow for reduced hospital stays and analgesic requirements. Limited data are currently available regarding the clinical outcome of outpatient lumbar fusion. METHODS: The Humana administrative claims database was queried for patients who underwent one to two-level PLF (CPT-22612 or CPT-22633 AND ICD-9-816.2) as either outpatients or inpatients from Q1 2007 to Q2 2015. The incidence of perioperative medical and surgical complications was determined by querying for relevant International Classification of Diseases and Current Procedural Terminology codes. Multivariate logistic regression adjusting for age, gender, and Charlson Comorbidity Index was used to calculate odds ratios (ORs) of complications among outpatients relative to inpatients undergoing PLF. RESULTS: Cohorts of 770 patients who underwent outpatient PLF and 26,826 patients who underwent inpatient PLF were identified. The median age was in the 65 to 69 years age group for both cohorts. The annual relative incidence of outpatient PLF remained stable across the study period (R = 0.03, P = 0.646). Adjusting for age, gender, and comorbidities, patients undergoing outpatient PLF had higher likelihood of revision/extension of posterior fusion [(OR 2.33, confidence interval (CI) 2.06-2.63, P < 0.001], anterior fusion (OR 1.64, CI 1.31-2.04, P < 0.001), and decompressive laminectomy (OR 2.01, CI 1.74-2.33, P < 0.001) within 1 year. Risk-adjusted rates of all other postoperative surgical and medical complications were statistically comparable. CONCLUSION: Outpatient lumbar fusion is uncommonly performed in the United States. Data collected from a national private insurance database demonstrate a greater risk of postoperative surgical complications including revision anterior and posterior fusion and decompressive laminectomy. Surgeons should be cautious in performing PLF in the outpatient setting, as the risk of revision surgery may increase in these cases. LEVEL OF EVIDENCE: 3.

Effect of Delta-9-tetrahydrocannabinol on mouse resistance to systemic Candida albicans infection.

Delta-9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, is known to suppress the immune responses to bacterial, viral and protozoan infections, but its effects on fungal infections have not been studied. Therefore, we investigated the effects of chronic Δ9-THC treatment on mouse resistance to systemic Candida albicans (C. albicans) infection. To determine the outcome of chronic Δ9-THC treatment on primary, acute systemic candidiasis, c57BL/6 mice were given vehicle or Δ9-THC (16 mg/kg) in vehicle on days 1-4, 8-11 and 15-18. On day 19, mice were infected with 5×10(5) C. albicans. We also determined the effect of chronic Δ9-THC (4-64 mg/kg) treatment on mice infected with a non-lethal dose of 7.5×10(4) C. albicans on day 2, followed by a higher challenge with 5×10(5) C. albicans on day 19. Mouse resistance to the infection was assessed by survival and tissue fungal load. Serum cytokine levels were determine to evaluate the immune responses. In the acute infection, chronic Δ9-THC treatment had no effect on mouse survival or tissue fungal load when compared to vehicle treated mice. However, Δ9-THC significantly suppressed IL-12p70 and IL-12p40 as well as marginally suppressed IL-17 versus vehicle treated mice. In comparison, when mice were given a secondary yeast infection, Δ9-THC significantly decreased survival, increased tissue fungal burden and suppressed serum IFN-γ and IL-12p40 levels compared to vehicle treated mice. The data showed that chronic Δ9-THC treatment decreased the efficacy of the memory immune response to candida infection, which correlated with a decrease in IFN-γ that was only observed after the secondary candida challenge.