Floor-Mounted Robotic Pedicle Screw Placement in Lumbar Spine Surgery: An Analysis of 1,050 Screws.

OBJECTIVE: To analyze the usage of floor-mounted robot in minimally invasive lumbar fusion. METHODS: Patients who underwent minimally invasive lumbar fusion for degenerative pathology using floor-mounted robot (ExcelsiusGPS) were included. Pedicle screw accuracy, proximal level violation rate, pedicle screw size, screw-related complications, and robot abandonment rate were analyzed. RESULTS: Two hundred twenty-nine patients were included. Most surgeries were primary single-level fusion. Sixty-five percent of surgeries had intraoperative computed tomography (CT) workflow, 35% had preoperative CT workflow. Sixty-six percent were transforaminal lumbar interbody fusion, 16% were lateral, 8% were anterior, and 10% were a combined approach. A total of 1,050 screws were placed with robotic assistance (85% in prone position, 15% in lateral position). Postoperative CT scan was available for 80 patients (419 screws). Overall pedicle screw accuracy rate was 96.4% (prone, 96.7%; lateral, 94.2%; primary, 96.7%; revision, 95.3%). Overall poor screw placement rate was 2.8% (prone, 2.7%; lateral, 3.8%; primary, 2.7%; revision, 3.5%). Overall proximal facet and endplate violation rates were 0.4% and 0.9%. Average diameter and length of pedicle screws were 7.1 mm and 47.7 mm. Screw revision had to be done for 1 screw (0.1%). Use of the robot had to be aborted in 2 cases (0.8%). CONCLUSION: Usage of floor-mounted robotics for the placement of lumbar pedicle screws leads to excellent accuracy, large screw size, and negligible screw-related complications. It does so for screw placement in prone/lateral position and primary/revision surgery alike with negligible robot abandonment rates.

The impacts of waiting for surgical correction of Adolescent Idiopathic Scoliosis and its repercussions for publicly funded health systems: systematic review.

PURPOSE: To investigate, through a systematic review, the impact of the waiting time for Adolescent Idiopathic Scoliosis (AIS) surgical correction from the point of view of deformity evolution, treatment cost, and quality of life. METHODS: PubMed, Embase, LILACS, SciELO, Scopus, Web of Science, LIVIVO, and Cochrane Library databases were searched by two researchers to select the articles. The eligibility criteria were: Patients diagnosed with AIS with indication for surgical correction and submitted to waiting lists until treatment. The risks of bias were evaluated using the Risk Of Bias In Non-randomized Studies-Interventions (ROBINS-I) tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to classify the level of the evidence for each outcome. The summary of the available evidence is presented in a narrative synthesis. RESULTS: Six observational studies were included. In a Canadian study, the primary outcome was the need for additional spine surgery in patients who had to wait more than three months due to spine deformity progression. American researchers presented a sample of premenarcheal and skeletally immature patients with AIS showing increased Cobb angle and attributed this to a six-month waiting for the surgical treatment. Another study included 177 patients with AIS with a mean waiting time of 225.7 days. There was a worsening average of 7.7° ± 8.6° in Cobb angle, and there was a change in surgical plan in 28 patients, which increased surgical time. Studies that evaluated the treatment cost showed significantly higher mean costs in those who waited longer than six months. Regarding the quality of life, while waiting for surgery, a retrospective study found that patients who underwent surgery earlier showed better results in a questionnaire that assessed their quality of life compared to those who were still waiting. CONCLUSION: Observational studies show that, in individuals who are on waiting lists for AIS surgery, there is a worsening of the spinal deformity (substantial evidence), an increasing cost of treatment (moderate evidence) and it may negatively impact patients' quality of life (insufficient evidence). Performing better methodological quality studies to investigate these outcomes can violate good research practices since randomized clinical trials on this subject have ethical limitations to be carried out. TRIAL REGISTRATION: The authors declare that the systematic review protocol was registered at the international prospective register of systematic reviews (PROSPERO), CRD42020212134, and it was accepted for publication.

Preoperative opioids before adult spinal deformity surgery associated with increased reoperations and high rates of chronic postoperative opioid use at 3-year follow-up.

PURPOSE: To determine the association of preoperative opioid prescriptions with reoperations and postoperative opioid prescriptions after adult spina deformity (ASD) surgery. With the current opioid crisis, patients undergoing surgery for ASD are at particular risk for opioid-related complications due to significant preoperative disability and surgical morbidity. No previous studies consider preoperative opioids in this population. METHODS: A retrospective cohort study of patients undergoing posterior spinal fusion (7 or more levels) for ASD was performed. All patients had at least 3 years of postoperative follow-up 3 years postoperatively. Prescriptions for 4 different opioid medications (hydromorphone, oxycodone, hydrocodone, and tramadol) were identified within 3 months preoperatively and up to 3 years postoperatively. Multivariate regression was utilized to determine the association of preoperative use with reoperations and with postoperative opioid use, controlling for both patient and surgery-related confounding factors. RESULTS: A total of 743 patients were identified and 59.6% (443) had opioid prescriptions within 3 months preoperatively. Postoperative opioid prescriptions were identified in 66.9% of patients at 12 months postoperatively, and in 54.8% at 36 months postoperatively. The 3-year reoperation rate was 11.0% in patients without preoperative prescriptions, 16.0% in patients with preoperative any opioid prescriptions (P = 0.07), and 34.8% in patients with preoperative hydromorphone prescriptions (P < 0.01). In multivariate analysis, preoperative opioid prescriptions were associated with increased reoperations (odds ratio [OR]: 1.62, P = 0.04), and chronic postoperative opioid use (OR: 4.40, P < 0.01). Preoperative hydromorphone prescriptions had the strongest association with both reoperations (OR: 4.96; P < 0.01) and chronic use (OR: 5.19: P = 0.03). CONCLUSION: In the ASD population, preoperative opioids are associated with both reoperations and chronic opioid use, with hydromorphone having the strongest association. Further investigation of the benefits of preoperative weaning programs is warranted.

Does robot-assisted navigation influence pedicle screw selection and accuracy in minimally invasive spine surgery?

OBJECTIVE: The accuracy of percutaneous pedicle screw placement has increased with the advent of robotic and surgical navigation technologies. However, the effect of robotic intraoperative screw size and trajectory templating remains unclear. The purpose of this study was to compare pedicle screw sizes and accuracy of placement using robotic navigation (RN) versus skin-based intraoperative navigation (ION) alone in minimally invasive lumbar fusion procedures. METHODS: A retrospective cohort study was conducted using a single-institution registry of spine procedures performed over a 4-year period. Patients who underwent 1- or 2-level primary or revision minimally invasive surgery (MIS)-transforaminal lumbar interbody fusion (TLIF) with pedicle screw placement, via either robotic assistance or surgical navigation alone, were included. Demographic, surgical, and radiographic data were collected. Pedicle screw type, quantity, length, diameter, and the presence of endplate breach or facet joint violation were assessed. Statistical analysis using the Student t-test and chi-square test was performed to evaluate the differences in pedicle screw sizes and the accuracy of placement between both groups. RESULTS: Overall, 222 patients were included, of whom 92 underwent RN and 130 underwent ION MIS-TLIF. A total of 403 and 534 pedicle screws were placed with RN and ION, respectively. The mean screw diameters were 7.25 ± 0.81 mm and 6.72 ± 0.49 mm (p < 0.001) for the RN and ION groups, respectively. The mean screw length was 48.4 ± 4.48 mm in the RN group and 45.6 ± 3.46 mm in the ION group (p < 0.001). The rates of "ideal" pedicle screws in the RN and ION groups were comparable at 88.5% and 88.4% (p = 0.969), respectively. The overall screw placement was also similar. The RN cohort had 63.7% screws rated as good and 31.4% as acceptable, while 66.1% of ION-placed screws had good placement and 28.7% had acceptable placement (p = 0.661 and p = 0.595, respectively). There was a significant reduction in high-grade breaches in the RN group (0%, n = 0) compared with the ION group (1.2%, n = 17, p = 0.05). CONCLUSIONS: The results of this study suggest that robotic assistance allows for placement of screws with greater screw diameter and length compared with surgical navigation alone, although with similarly high accuracy. These findings have implied that robotic platforms may allow for safe placement of the "optimal screw," maximizing construct stability and, thus, the ability to obtain a successful fusion.

Extra-Axial Fluid Collections After Decompressive Craniectomy: Management, Outcomes, and Treatment Algorithm.

BACKGROUND: Extra-axial fluid collections (EACs) frequently develop after decompressive craniectomy. Management of EACs remains poorly understood, and information on how to predict their clinical course is inadequate. We aimed to better characterize EACs, understand predictors of their resolution, and delineate the best treatment paradigm for patients. METHODS: We reviewed patients who developed EACs after undergoing decompressive craniectomy for treatment of refractory intracranial pressure elevations. We excluded patients who had an ischemic stroke, as EACs in these patients have a different clinical course. We performed univariate analysis and multiple linear regression to find variables associated with earlier resolution of EACs and stratified our analyses by EAC phenotype (complicated vs. uncomplicated). We conducted a systematic review to compare our findings with the literature. RESULTS: Of 96 included patients, 73% were male, and median age was 42.5 years. EACs resolved after a median of 60 days. Complicated EACs were common (62.5%) and required multiple drainage methods before cranioplasty. These were not associated with a protracted course or increased risk of death (P > 0.05). Early bone flap restoration with simultaneous drainage was independently associated with earlier resolution of EACs (ß = 0.56, P < 0.001). Systematic review confirmed lack of standardized direction with respect to EAC management. CONCLUSIONS: Our analyses reveal 2 clinically relevant phenotypes of EAC: complicated and uncomplicated. Our proposed treatment algorithm involves replacing the bone flap as soon as it is safe to do so and draining refractory EACs aggressively. Further studies to assess long-term clinical outcomes of EACs are warranted.

Current Concepts in the Management of Advanced Trigger Finger: A Critical Analysis Review.

¼: While the majority of patients with trigger finger obtain excellent outcomes from nonoperative treatment or release of the A1 pulley, a subset of patients with advanced trigger finger, defined as trigger finger with loss of active or passive range of motion, may have incomplete symptom relief and warrant specific attention. ¼: Advanced trigger finger is more refractory to complete symptom resolution from corticosteroid injection, and particular attention should be paid to incomplete improvement of flexion contractures. ¼: Unlike simple trigger finger, the pathology in advanced trigger finger involves not only the A1 pulley but also the flexor tendon, including thickening and degeneration. ¼: Progression toward surgical intervention should not be delayed when nonoperative measures fail, and specific attention should be paid to persistent inability to achieve full extension following A1 pulley release. ¼: Facing substantial residual flexion contracture, reduction flexor tenoplasty and partial or complete resection of the superficialis tendon followed by hand therapy and splinting may be needed to allow patients to regain reliable full range of motion.

Correction to: At the US Epicenter of the COVID-19 Pandemic, an Orthopedic Residency Program Reorganizes.

[This corrects the article DOI: 10.1007/s11420-020-09765-5.].

Interleukin-8 blockade prevents activated endothelial cell mediated proliferation and chemoresistance of acute myeloid leukemia.

One of the greatest challenges in treating acute myeloid leukemia (AML) is chemotherapy refractory disease. Previously, we demonstrated a novel mechanism whereby AML-induced endothelial cell (EC) activation leads to subsequent leukemia cell adherence, quiescence and chemoresistance, identifying activated ECs as potential mediators of relapse. We now show mechanistically that EC activation induces the secretion of interleukin-8 (IL-8) leading to significant expansion of non-adherent AML cells and resistance to cytarabine (Ara-C). Through crystallography and computational modeling, we identified a pocket within IL-8 responsible for receptor binding, screened for small molecules that fit within this pocket, and blocked IL-8 induced proliferation and chemo-protection of AML cells with a hit compound. Results from this study show a new therapeutic strategy for targeting the sanctuary of an activated leukemia microenvironment.

Use of Intraoperative Ultrasound During Spinal Surgery.

STUDY DESIGN: Review and technical report. OBJECTIVE: Intraoperative ultrasound has been used by spine surgeons since the early 1980s. Since that time, more advanced modes of intraoperative imaging and navigation have become widely available. Although the use of ultrasound during spine surgery has fallen out of favor, it remains the only true real-time imaging modality that allows surgeons to visualize soft tissue anatomy instantly and continuously while operating. It is our objective to demonstrate that for this reason, ultrasound is a useful adjunctive technique for spine surgeons, especially when approaching intradural lesions or when addressing pathology in the ventral spinal canal via a posterior approach. METHODS: Using PubMed, the existing literature regarding the use of intraoperative ultrasound during spinal surgery was evaluated. Also, surgical case logs were reviewed to identify spinal operations during which intraoperative ultrasound was used. Illustrative cases were selected and reviewed in detail. RESULTS: This article provides a brief review of the history of intraoperative ultrasound in spine surgery and describes certain surgical scenarios during which this technique might be useful. Several illustrative cases are provided from our own experience. CONCLUSIONS: Surgeons should consider the use of intraoperative ultrasound when approaching intradural lesions or when addressing pathology ventral to the thecal sac via a posterior approach.

Structural Elements Recognized by Abacavir-Induced T Cells.

Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976-984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230-238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.

Validation of an International Classification of Disease, Ninth Revision coding algorithm to identify decompressive craniectomy for stroke.

BACKGROUND: Although International Classification of Disease, Ninth Revision, Clinical Modification (ICD9-CM) coding is the basis of administrative claims data, no study has validated an ICD9-CM algorithm to identify patients undergoing decompressive craniectomy for space-occupying supratentorial infarction. METHODS: Patients who underwent decompressive craniectomy for stroke at our institution were retrospectively identified and their associated ICD9-CM codes were extracted from billing data. An ICD9-CM algorithm was generated and its accuracy compared against physician review. RESULTS: A total of 10,925 neurosurgical operations were performed from December 2008 to March 2015, of which 46 (0.4%) were decompressive craniectomy for space-occupying stroke. The ICD9-CM procedure code for craniectomy (01.25) was only encoded in 67.4% of patients, while craniotomy (01.24) was used in 19.6% and lobectomy (01.39, 01.53, 01.59) in 13.1%. The ICD-9-CM algorithm included patients with a diagnosis codes for cerebral infarction (433.11, 434.01, 434.11, and 434.91) and a procedure code for craniotomy, craniectomy, or lobectomy. Patients were excluded with an ICD9-CM diagnosis code for brain tumor, intracranial abscess, subarachnoid hemorrhage, vertebrobasilar infarction, intracranial aneurysm, Moyamoya disease, intracranial venous sinus thrombosis, vertebral artery dissection, congenital cerebrovascular anomaly, head trauma or an ICD9-CM procedure code for laminectomy. This algorithm had a sensitivity of 97.8%, specificity of 99.9%, positive predictive value of 88.2%, and negative predictive value of 99.9%. The majority of false-positive results were patients who underwent evacuation of a primary intracerebral hematoma. CONCLUSION: An ICD-9-CM algorithm based on diagnosis and procedure codes can effectively identify patients undergoing decompressive craniectomy for supratentorial stroke.

Fever, rash, and systemic symptoms: understanding the role of virus and HLA in severe cutaneous drug allergy.

Drug hypersensitivity syndromes such as abacavir hypersensitivity and the severe cutaneous adverse drug reactions have been associated with significant short- and long-term morbidity and mortality. More recently, these immunologically mediated and previously unpredictable diseases have been shown to be associated with primarily class I but also class II HLA alleles. The case of the association of HLA-B*57:01 and abacavir hypersensitivity has created a translational roadmap for how this knowledge can be used in the clinic to prevent severe reactions. Although many hurdles exist to the widespread translation of such HLA screening approaches, our understanding of how drugs interact with the major histocompatibility complex has contributed to the discovery of new models that have provided considerable insights into the immunopathogenesis of severe cutaneous adverse drug reactions and other T-cell-mediated drug hypersensitivity syndromes. Future translation of this knowledge will facilitate the development of preclinical toxicity screening to significantly improve efficacy and safety of drug development and design.

The structural basis of HLA-associated drug hypersensitivity syndromes.

Recent data suggest alternative mechanisms that promote human leukocyte antigen (HLA)-associated drug syndromes. Hypersensitive responses have been attributed to drug interactions with HLA molecules, peptides presented by HLA molecules and T-cell antigen receptors. Definition of an increasing number of HLA-associated drug syndromes suggests that polymorphism in the antigen-binding cleft residues influence recognition of specific drugs. Recent data demonstrate that small molecule drugs bind within the antigen-binding cleft of HLA in a manner that alters the repertoire of HLA-bound peptide ligands. This drug recognition mechanism permits presentation of self-peptides to which the host has not been tolerized. This altered repertoire mechanism is analogous to massive polyclonal T-cell responses occurring in mismatched HLA organ transplantation in which the drug in effect creates a novel HLA allele. Alteration of the self-peptide repertoire by HLA-binding small molecules may be the mechanistic basis for a diverse set of deleterious T-cell responses since the antigen-binding cleft has structural features that are compatible with binding drug-like small molecules. Small molecule drugs that bind elements of the trimolecular complex (T-cell receptor, peptide, and HLA) may cause short- and long-term adverse effects by a diverse set of mechanisms.

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire.

Idiosyncratic adverse drug reactions are unpredictable, dose-independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8(+) T cells that required HLA-B*57:01 molecules for their function; however, the mechanism by which abacavir induces this pathologic T-cell response remains unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional compounds with suspected HLA-linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA-linked hypersensitivities, and guide the development of safer drugs.