Clinical outcomes and complications after biportal endoscopic spine surgery: a comprehensive systematic review and meta-analysis of 3673 cases.

PURPOSE: Current literature suggests that biportal spinal endoscopy is safe and effective in treating lumbar spine pathology such as lumbar disc herniation, lumbar stenosis, and degenerative spondylolisthesis. No prior study has investigated the postoperative outcomes or complication profile of the technique as a whole. This study serves as the first comprehensive systematic review and meta-analysis of biportal spinal endoscopy in the lumbar spine. METHODS: A PubMed literature search provided over 100 studies. 42 papers were reviewed and 3673 cases were identified with average follow-up time of 12.5 months. Preoperative diagnoses consisted of acute disc herniation (1098), lumbar stenosis (2432), and degenerative spondylolisthesis (229). Demographics, operative details, complications, and perioperative outcome and satisfaction scores were analyzed. RESULTS: Average age was 61.32 years, 48% male. 2402 decompressions, 1056 discectomies, and 261 transforaminal lumbar Interbody fusions (TLIFs) were performed. Surgery was performed on 4376 lumbar levels, with L4-5 being most common(61.3%). 290 total complications occurred, 2.23% durotomies, 1.29% inadequate decompressions, 3.79% epidural hematomas, and < 1% transient nerve root injuries, infections, and iatrogenic instability. Significant improvement in VAS-Back, VAS-Leg, ODI, and Macnab Scores were seen across the cohort. CONCLUSION: Biportal spinal endoscopy is a novel method to address pathology in the lumbar spine with direct visualization through an endoscopic approach. Complications are comparable to previously published rates. Clinical outcomes demonstrate effectiveness. Prospective studies are required to assess the efficacy of the technique as compared to traditional techniques. This study demonstrates that the technique can be successful in the lumbar spine.

What are the indications and survivorship of tumor endoprosthetic reconstructions for patients with extremity metastatic bone disease?

BACKGROUND AND OBJECTIVES: Given advances in therapies, endoprosthetic reconstruction (EPR) in metastatic bone disease (MBD) may be increasingly indicated. The objectives were to review the indications, and implant and patient survivorship in patients undergoing EPR for MBD. METHODS: A review of patients undergoing EPR for extremity MBD between 1992 and 2022 at two centers was performed. Surgical data, implant survival, patient survival, and implant failure modes were examined. RESULTS: One hundred fifteen patients were included with a median follow-up of 14.9 months (95% confidence interval [CI]: 9.2-19.3) and survival of 19.4 months (95% CI: 13.6-26.1). The most common diagnosis was renal cell carcinoma (34/115, 29.6%) and the most common location was proximal femur (43/115, 37.4%). Indications included: actualized fracture (58/115, 50.4%), impending fracture (30/115, 26.1%), and failed fixation (27/115, 23.5%). Implant failure was uncommon (10/115, 8.7%). Patients undergoing EPR for failed fixation were more likely to have renal or lung cancer (p = 0.006). CONCLUSIONS: EPRs were performed most frequently for renal cell carcinoma and in patients with a relatively favorable survival. EPR was indicated for failed previous fixation in 23.5% of cases, emphasizing the importance of predictive survival modeling. EPR can be a reliable and durable surgical option for patients with MBD.

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.

Influenza-induced thrombotic microangiopathy in a patient with cancer on proteasome inhibitor: a diagnostic dilemma.

Thrombotic microangiopathy (TMA) in a cancer patient is a common complication of either cancer itself or anticancer therapy. Incidence of TMA from anticancer therapy was found to be > 15%, since the introduction of anti-angiogenic drugs like anti-vascular endothelial growth factor agents. It is, however, important to not ignore other causes of TMA such as bacteria, viruses, antiplatelet drugs, hereditary complement mutations, and autoimmune disorders. We present such a diagnostic dilemma in our patient who was admitted with influenza and was found to have TMA on renal biopsy, while on proteasome inhibitor (PI) therapy. With this case, we would like to highlight the importance of understanding the true cause of TMA to avoid unwarranted long-term discontinuation of life saving anti-cancer drugs after TMA resolution.

Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge.

Implant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an in situ coupling reaction of branched poly(ethylene glycol) and poly(allyl mercaptan) (PEG-PAM) polymers to generate an amphiphilic polymeric coating. We show in vivo efficacy in preventing implant infection in both post-arthroplasty infection and post-spinal surgery infection mouse models. Our technology displays efficacy with or without systemic antibiotics, the standard of care. Our coating technology is applied in a clinically relevant time frame, does not require modification of implant manufacturing process, and does not change the implant shelf life.

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.

Novel in vivo mouse model of shoulder implant infection.

BACKGROUND: Animal models are used to guide management of periprosthetic implant infections. No adequate model exists for periprosthetic shoulder infections, and clinicians thus have no preclinical tools to assess potential therapeutics. We hypothesize that it is possible to establish a mouse model of shoulder implant infection (SII) that allows noninvasive, longitudinal tracking of biofilm and host response through in vivo optical imaging. The model may then be employed to validate a targeting probe (1D9-680) with clinical translation potential for diagnosing infection and image-guided débridement. METHODS: A surgical implant was press-fit into the proximal humerus of c57BL/6J mice and inoculated with 2 µL of 1 × 103 (e3), or 1 × 104 (e4), colony-forming units (CFUs) of bioluminescent Staphylococcus aureus Xen-36. The control group received 2 µL sterile saline. Bacterial activity was monitored in vivo over 42 days, directly (bioluminescence) and indirectly (targeting probe). Weekly radiographs assessed implant loosening. CFU harvests, confocal microscopy, and histology were performed. RESULTS: Both inoculated groups established chronic infections. CFUs on postoperative day (POD) 42 were increased in the infected groups compared with the sterile group (P < .001). By POD 14, osteolysis was visualized in both infected groups. The e4 group developed catastrophic bone destruction by POD 42. The e3 group maintained a congruent shoulder joint. Targeting probes helped to visualize low-grade infections via fluorescence. DISCUSSION: Given bone destruction in the e4 group, a longitudinal, noninvasive mouse model of SII and chronic osteolysis was produced using e3 of S aureus Xen-36, mimicking clinical presentations of chronic SII. CONCLUSION: The development of this model provides a foundation to study new therapeutics, interventions, and host modifications.

The Use of a Novel Antimicrobial Implant Coating In Vivo to Prevent Spinal Implant Infection.

STUDY DESIGN: A controlled, interventional animal study. OBJECTIVE: Spinal implant infection (SII) is a devastating complication. The objective of this study was to evaluate the efficacy of a novel implant coating that has both a passive antibiotic elution and an active-release mechanism triggered in the presence of bacteria, using an in vivo mouse model of SII. SUMMARY OF BACKGROUND DATA: Current methods to minimize the frequency of SII include local antibiotic therapy (vancomycin powder), betadine irrigation, silver nanoparticles, and passive release from antibiotic-loaded poly(methyl methacrylate) cement beads, all of which have notable weaknesses. A novel implant coating has been developed to address some of these limitations but has not been tested in the environment of a SII. METHODS: A biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics. The in vivo performance of this coating was tested in the delivery of either vancomycin or tigecycline in a previously established mouse model of SII. Noninvasive bioluminescence imaging was used to quantify the bacterial burden, and implant sonication was used to determine bacterial colony-forming units (CFUs) from the implant and surrounding bone and soft tissue. RESULTS: The PEG-PPS-vancomycin coating significantly lowered the infection burden from postoperative day 3 onwards (P < 0.05), whereas PEG-PPS-tigecycline only decreased the infection on postoperative day 5 to 10 (P < 0.05). CFUs were lower on PEG-PPS-vancomycin pins than PEG-PPS-tigecycline and PEG-PPS pins alone on both the implants (2.4 × 10, 8.5 × 10, and 1.0 × 10 CFUs, respectively) and surrounding bone and soft tissue (1.3 × 10, 4.8 × 10, and 5.4 × 10 CFUs, respectively) (P < 0.05). CONCLUSION: The biodegradable PEG-PPS coating demonstrates promise in decreasing bacterial burden and preventing SII. The vancomycin coating outperformed the tigecycline coating in this model compared to prior work in arthroplasty models, highlighting the uniqueness of the paraspinal infection microenvironment. LEVEL OF EVIDENCE: N/A.

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.

A Comparison of Defense and Plaintiff Expert Witnesses in Orthopaedic Surgery Malpractice Litigation.

BACKGROUND: According to the American Academy of Orthopaedic Surgeons (AAOS) Standards of Professionalism, the responsible testimony of expert witnesses in orthopaedic surgery malpractice lawsuits is important to the public interest. However, these expert witnesses are recruited and compensated without established standards, and their testimony can potentially sway court opinion, with substantial consequences. The objective of this study was to characterize defense and plaintiff expert orthopaedic surgeon witnesses in orthopaedic surgery malpractice litigation. METHODS: Utilizing the WestlawNext legal database, defense and plaintiff expert witnesses involved in orthopaedic surgery malpractice lawsuits from 2013 to 2017 were identified. Each witness's subspecialty, mean years of experience, involvement in academic or private practice, fellowship training, and scholarly impact, as measured by the Hirsch index (h-index), were determined through a query of professional profiles, the Scopus database, and a PubMed search. Statistical comparisons were made for each parameter among defense and plaintiff expert witnesses. RESULTS: Between 2013 and 2017, 306 expert medical witnesses for orthopaedic cases were identified; 174 (56.9%) testified on behalf of the plaintiff, and 132 (43.1%) testified on behalf of the defense. Orthopaedic surgeons who identified themselves as general orthopaedists comprised the largest share of expert witnesses on both the plaintiff (n = 61) and defense (n = 25) sides. The plaintiff witnesses averaged 36 years of experience versus 31 years for the defense witnesses (p < 0.001); 26% of the plaintiff witnesses held an academic position versus 43% of the defense witnesses (p = 0.013). Defense witnesses exhibited a higher proportion of fellowship training in comparison to plaintiff expert witnesses (80.5% versus 64.5%, respectively, p = 0.003). The h-index for the plaintiff group was 6.6 versus 9.1 for the defense group (p = 0.04). Two witnesses testified for both the plaintiff and defense sides. CONCLUSIONS: Defense expert witnesses held higher rates of academic appointments and exhibited greater scholarly impact than their plaintiff counterparts, with both sides averaging >30 years of experience. These data collectively show that there are differences in characteristics between plaintiff and defense witnesses. Additional study is needed to illuminate the etiology of these differences.

Single-Dose, Preoperative Vitamin-D Supplementation Decreases Infection in a Mouse Model of Periprosthetic Joint Infection.

BACKGROUND: Despite recent advances, infection remains the most common etiology of arthroplasty failure. Recent work suggests that 25-hydroxyvitamin D (25D) deficiency correlates with the frequency of periprosthetic joint infection (PJI). We endeavored to examine whether 25D3 deficiency leads to increased bacterial burden in vivo in an established mouse model of PJI and, if so, whether this effect can be reversed by preoperative 25D3 supplementation. METHODS: Mice (lys-EGFP) possessing fluorescent neutrophils were fed a vitamin D3-sufficient (n = 20) or deficient (n = 40) diet for 6 weeks. A group of 25D3-deficient mice (n = 20) were "rescued" with 1 intraperitoneal dose of 25D3 at 3 days before surgery. A stainless steel implant was inserted into the knee joint and the joint space was inoculated with bioluminescent Staphylococcus aureus (1 × 10 colony forming units [CFUs]). In vivo imaging was used to monitor bacterial burden and neutrophil infiltration. Blood was drawn to confirm 25D3 levels 3 days before surgery and on postoperative days (PODs) 0 and 14. Mice were killed at POD 21, and CFUs were quantified after culture. Myeloperoxidase (MPO) and ß-N-acetylglucosaminidase (NAG) were assayed to look at neutrophil infiltration and activated tissue macrophage recruitment, respectively. RESULTS: Serum values confirmed 25D3 deficiency and repletion of the 25D3-rescued group. Bacterial bioluminescence and neutrophil fluorescence were significantly greater (p < 0.05) in the 25D3-deficient group. CFU counts from the joint tissue and implant were also significantly greater in this group (p < 0.05). Rescue treatment significantly decreased bacterial burden and neutrophil infiltration (p < 0.05). Compared with the 25D3-sufficient and 25D3-rescued groups, MPO activity was higher (p < 0.02) and NAG activity was lower (p < 0.03) in the 25D3-deficient group. CONCLUSIONS: This study demonstrated in vivo in a mouse model of PJI that (1) 25D3 deficiency results in increased bacterial burden and neutrophil infiltration, and (2) this effect can be reversed with preoperative repletion of 25D3. CLINICAL RELEVANCE: Considering that >65% of patients undergoing arthroplasty have insufficient or low levels of total 25D and that 25D levels can be replenished with ease using a U.S. Food and Drug Administration (FDA)-approved, oral 25D3 product, 25D deficiency may be an important modifiable risk factor in humans undergoing joint replacement.

Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection.

BACKGROUND: Management of spine implant infections (SII) are challenging. Explantation of infected spinal hardware can destabilize the spine, but retention can lead to cord compromise and biofilm formation, complicating management. While vancomycin monotherapy is commonly used, in vitro studies have shown reduced efficacy against biofilm compared to combination therapy with rifampin. Using an established in vivo mouse model of SII, we aim to evaluate whether combination therapy has increased efficacy compared to both vancomycin alone and infected controls. METHODS: An L-shaped, Kirschner-wire was transfixed into the L4 spinous process of 12-week-old C57BL/6 mice, and inoculated with bioluminescent Staphylococcus aureus. Mice were randomized into a vancomycin group, a combination group with vancomycin plus rifampin, or a control group receiving saline. Treatment began on post-operative day (POD) 7 and continued through POD 14. In vivo imaging was performed to monitor bioluminescence for 35 days. Colony-forming units (CFUs) were cultured on POD 35. RESULTS: Bioluminescence peaked around POD 7 for all groups. The combination group had a 10-fold decrease in signal by POD 10. The vancomycin and control groups reached similar levels on POD 17 and 21, respectively. On POD 25 the combination group dropped below baseline, but rebounded to the same level as the other groups, demonstrating a biofilm-associated infection by POD 35. Quantification of CFUs on POD 35 confirmed an ongoing infection in all three groups. CONCLUSIONS: Although both therapies were initially effective, they were not able to eliminate implant biofilm bacteria, resulting in a rebound infection after antibiotic cessation. This model shows, for the first time, why histologic-based, static assessments of antimicrobials can be misleading, and the importance of longitudinal tracking of infection. Future studies can use this model to test combinations of antibiotic therapies to see if they are more effective in eliminating biofilm prior to human trials.