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1.
Article in English | MEDLINE | ID: mdl-38728612

ABSTRACT

BACKGROUND: There is increasing interest in forecasting postoperative complications using bone density metrics. Vertebral Hounsfield unit measurements obtained from CT scans performed for surgical planning or other purposes, known as opportunistic CTs, have shown promise for their ease of measurement and the ability to target density measurement to a particular region of interest. Concomitant with the rising interest in prognostic bone density measurement use has been the increasing adoption of intraoperative advanced imaging techniques. Despite the interest in both outcome prognostication and intraoperative advanced imaging, there is little information regarding the use of CT-based intraoperative imaging as a means to measure bone density. QUESTIONS/PURPOSES: (1) Can vertebral Hounsfield units be reliably measured by physician reviewers from CT scans obtained intraoperatively? (2) Do Hounsfield units measured from intraoperative studies correlate with values measured from preoperative CT scans? METHODS: To be eligible for this retrospective study, patients had to have been treated with the use of an intraoperative CT scan for instrumented spinal fusion for either degenerative conditions or traumatic injuries between January 2015 and December 2022. Importantly, patients without a preoperative CT scan of the fused levels within 180 days before surgery or who were indicated for surgery because of infection, metastatic disease, or who were having revision surgery after prior instrumentation were excluded from the query. Of the 285 patients meeting these inclusion criteria, 53% (151) were initially excluded for the following reasons: 36% (102) had intraoperative CT scans obtained after placement of instrumentation, 16% (47) had undergone intraoperative CT scans but the studies were not accessible for Hounsfield unit measurement, and 0.7% (2) had prior kyphoplasty wherein the cement prevented Hounsfield unit measurement. Finally, an additional 19% (53) of patients were excluded because the preoperative CT and intraoperative CT were obtained at different peak voltages, which can influence Hounsfield unit measurement. This yielded a final population of 81 patients from whom 276 preoperative and 276 intraoperative vertebral Hounsfield unit measurements were taken. Hounsfield unit data were abstracted from the same vertebra(e) from both preoperative and intraoperative studies by two physician reviewers (one PGY3 and one PGY5 orthopaedic surgery resident, both pursuing spine surgery fellowships). For a small, representative subset of patients, measurements were taken by both reviewers. The feasibility and reliability of Hounsfield unit measurement were then assessed with interrater reliability of values measured from the same vertebra by the two different reviewers. To compare Hounsfield unit values from intraoperative CT scans with preoperative CT studies, an intraclass correlation using a two-way random effects, absolute agreement testing technique was employed. Because the data were formatted as multiple measurements from the same vertebra at different times, a repeated measures correlation was used to assess the relationship between preoperative and intraoperative Hounsfield unit values. Finally, a linear mixed model with patients handled as a random effect was used to control for different patient and clinical factors (age, BMI, use of bone density modifying agents, American Society of Anesthesiologists [ASA] classification, smoking status, and total Charlson comorbidity index [CCI] score). RESULTS: We found that Hounsfield units can be reliably measured from intraoperative CT scans by human raters with good concordance. Hounsfield unit measurements of 31 vertebrae from a representative sample of 10 patients, measured by both reviewers, demonstrated a correlation value of 0.82 (95% CI 0.66 to 0.91), indicating good correlation. With regard to the relationship between preoperative and intraoperative measurements of the same vertebra, repeated measures correlation testing demonstrated no correlation between preoperative and intraoperative measurements (r = 0.01 [95% CI -0.13 to 0.15]; p = 0.84). When controlling for patient and clinical factors, we continued to observe no relationship between preoperative and intraoperative Hounsfield unit measurements. CONCLUSION: As intraoperative CT and measurement of vertebral Hounsfield units both become increasingly popular, it would be a natural extension for spine surgeons to try to extract Hounsfield unit data from intraoperative CTs. However, we found that although it is feasible to measure Hounsfield data from intraoperative CT scans, the obtained values do not have any predictable relationship with values obtained from preoperative studies, and thus, these values should not be used interchangeably. With this knowledge, future studies should explore the prognostic value of intraoperative Hounsfield unit measurements as a distinct entity from preoperative measurements. LEVEL OF EVIDENCE: Level III, diagnostic study.

2.
Heliyon ; 10(5): e26547, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38468924

ABSTRACT

Yeasts contain bioactive components that can enhance fish immune robustness and disease resistance. Our study focused on analyzing intestinal immunoregulatory pathways in zebrafish (Danio rerio) using iTRAQ and 2D LC-MS/MS to quantify intestinal proteins. Zebrafish were fed either control diet (C) or diet supplemented with autolyzed Cyberlindnera jadinii (ACJ). KEGG analysis revealed that ACJ yeast diet induced increased abundance of proteins related to arginine and proline metabolism, phagosome, C-lectin receptor signaling, ribosome and PPAR signaling pathways, which can modulate and enhance innate immune responses. ACJ yeast diet also showed decreased abundance of proteins associated with inflammatory pathways, including apoptosis, necroptosis and ferroptosis. These findings indicate boosted innate immune response and control of inflammation-related pathways in zebrafish intestine. Our findings in the well annotated proteome of zebrafish enabled a detailed investigation of intestinal responses and provide insight into health-beneficial effects of yeast species C. jadinii, which is relevant for aquaculture species.

3.
J Clin Immunol ; 44(3): 66, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38363477

ABSTRACT

B cells and their secreted antibodies are fundamental for host-defense against pathogens. The generation of high-affinity class switched antibodies results from both somatic hypermutation (SHM) of the immunoglobulin (Ig) variable region genes of the B-cell receptor and class switch recombination (CSR) which alters the Ig heavy chain constant region. Both of these processes are initiated by the enzyme activation-induced cytidine deaminase (AID), encoded by AICDA. Deleterious variants in AICDA are causal of hyper-IgM syndrome type 2 (HIGM2), a B-cell intrinsic primary immunodeficiency characterised by recurrent infections and low serum IgG and IgA levels. Biallelic variants affecting exons 2, 3 or 4 of AICDA have been identified that impair both CSR and SHM in patients with autosomal recessive HIGM2. Interestingly, B cells from patients with autosomal dominant HIGM2, caused by heterozygous variants (V186X, R190X) located in AICDA exon 5 encoding the nuclear export signal (NES) domain, show abolished CSR but variable SHM. We herein report the immunological and functional phenotype of two related patients presenting with common variable immunodeficiency who were found to have a novel heterozygous variant in AICDA (L189X). This variant led to a truncated AID protein lacking the last 10 amino acids of the NES at the C-terminal domain. Interestingly, patients' B cells carrying the L189X variant exhibited not only greatly impaired CSR but also SHM in vivo, as well as CSR and production of IgG and IgA in vitro. Our findings demonstrate that the NES domain of AID can be essential for SHM, as well as for CSR, thereby refining the correlation between AICDA genotype and SHM phenotype as well as broadening our understanding of the pathophysiology of HIGM disorders.


Subject(s)
Cytidine Deaminase , Hyper-IgM Immunodeficiency Syndrome , Immunoglobulin Class Switching , Humans , Cytidine Deaminase/genetics , Cytidine Deaminase/metabolism , Hyper-IgM Immunodeficiency Syndrome/genetics , Immunoglobulin A/genetics , Immunoglobulin Class Switching/genetics , Immunoglobulin G/genetics , Phenotype , Somatic Hypermutation, Immunoglobulin
4.
Arthroplast Today ; 25: 101290, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38298810

ABSTRACT

Dual-mobility (DM) implants have been used in total hip arthroplasty since 1974. Modular DM implants have seen an increase in use in primary and revision total hip arthroplasties given the theoretical decreased dislocation rate. DM constructs have 2 articulation sites, one between the acetabular shell and a polyethylene liner, as well as one between the liner and the femoral head component. However, dislocations with modular DM implant dislocations can still occur. These dislocations occur via an extraprosthetic or intraprosthetic mechanism. Intraprosthetic dislocation is a phenomenon in which the smaller femoral head dissociates from the polyethylene liner. We present a case of intraprosthetic dislocation in an 81-year-old female with migration of the polyethylene liner into her gluteal muscles after 2 attempted closed reductions.

5.
Life Sci Alliance ; 7(3)2024 03.
Article in English | MEDLINE | ID: mdl-38195117

ABSTRACT

Juvenile neuronal ceroid lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 yr and is most commonly caused by mutations in the highly conserved CLN3 gene. Here, we generated cln3 morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant cln3 larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and cholesteryl esters, and a global decrease in bis(monoacylglycero)phosphate species, two of which (GPDs and bis(monoacylglycero)phosphates) were previously proposed as potential biomarkers for CLN3 disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant for CLN3 Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic CLN3 disease.


Subject(s)
Induced Pluripotent Stem Cells , Neuronal Ceroid-Lipofuscinoses , Animals , Humans , Cholesterol Esters , Membrane Glycoproteins/genetics , Metabolomics , Molecular Chaperones , Neuronal Ceroid-Lipofuscinoses/genetics , Zebrafish/genetics
6.
Spine J ; 24(6): 1087-1094, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38262498

ABSTRACT

BACKGROUND CONTEXT: Adolescent idiopathic scoliosis (AIS) is a common condition, often requiring surgical correction. Computed tomography (CT) based navigation technologies, which rely on ionizing radiation, are increasingly being utilized for surgical treatment. Although this population is highly vulnerable to radiation, given their age and female predominance, there is little available information elucidating modeled iatrogenic cancer risk. PURPOSE: To model lifetime cancer risk associated with the use of intraoperative CT-based navigation for surgical treatment of AIS. STUDY DESIGN/SETTING: This retrospective cross-sectional study took place in a quaternary care academic pediatric hospital in the United States. PATIENT SAMPLE: Adolescents aged 10-18 who underwent posterior spinal fusion for a diagnosis of AIS between July 2014 and December 2019. OUTCOMES MEASURES: Effective radiation dose and projected lifetime cancer risk associated with intraoperative doses of ionizing radiation. METHODS: Clinical and radiographic parameters were abstracted, including total radiation dose during surgery from flat plate radiographs, fluoroscopy, and intraoperative CT scans. Multivariable regression analysis was used to assess differences in radiation exposure between patients treated with conventional radiography versus intraoperative navigation. Radiation exposure was translated into lifetime cancer risk using well-established algorithms. RESULTS: In total, 245 patients were included, 119 of whom were treated with navigation. The cohort was 82.9% female and 14.4 years of age. The median radiation exposure (in millisieverts, mSv) for fluoroscopy, radiography, and navigation was 0.05, 4.14, and 8.19 mSv, respectively. When accounting for clinical and radiographic differences, patients treated with intraoperative navigation received 8.18 mSv more radiation (95%CI: 7.22-9.15, p<.001). This increase in radiation projects to 0.90 iatrogenic malignancies per 1,000 patients (95%CI 0.79-1.01). CONCLUSIONS: Ours is the first work to define cancer risk in the setting of radiation exposure for navigated AIS surgery. We project that intraoperative navigation will generate approximately one iatrogenic malignancy for every 1,000 patients treated. Given that spine surgery for AIS is common and occurs in the context of a multitude of other radiation sources, these data highlight the need for radiation budgeting protocols and continued development of lower radiation dose technologies. LEVEL OF EVIDENCE: Therapeutic, III.


Subject(s)
Scoliosis , Spinal Fusion , Humans , Scoliosis/surgery , Adolescent , Female , Male , Child , Spinal Fusion/adverse effects , Spinal Fusion/methods , Retrospective Studies , Cross-Sectional Studies , Surgery, Computer-Assisted/adverse effects , Surgery, Computer-Assisted/methods , Tomography, X-Ray Computed , Radiation Dosage , Radiation Exposure/adverse effects , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/etiology
7.
N Am Spine Soc J ; 17: 100308, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38264152

ABSTRACT

Background: Spinal epidural abscesses (SEAs) are a devastating condition with high levels of associated morbidity and mortality. Hounsfield units (HUs), a marker of radiodensity on CT scans, have previously been correlated with adverse events following spinal interventions. We evaluated whether HUs might also be associated with all-cause complications and/or mortality in this high-risk population. Methods: This retrospective cohort study was carried out within an academic health system in the United States. Adults diagnosed with a SEA between 2006 and 2021 and who also had a CT scan characterizing their SEA within 6 months of diagnosis were considered. HUs were abstracted from the 4 vertebral bodies nearest to, but not including, the infected levels. Our primary outcome was the presence of composite 90-day complications and HUs represented the primary predictor. A multivariable logistic regression analysis was conducted adjusting for demographic and disease-specific confounders. In sensitivity testing, separate logistic regression analyses were conducted (1) in patients aged 65 and older and (2) with mortality as the primary outcome. Results: Our cohort consisted of 399 patients. The overall incidence of 90-day complications was 61.2% (n=244), with a 7.8% (n=31) 90-day mortality rate. Those experiencing complications were more likely to have undergone surgery to treat their SEA (58.6% vs. 46.5%; p=.018) but otherwise the cohorts were similar. HUs were not associated with composite 90-day complications (Odds ratio [OR] 1.00 [95% CI 1.00-1.00]; p=.842). Similar findings were noted in sensitivity testing. Conclusions: While HUs have previously been correlated with adverse events in certain clinical contexts, we found no evidence to suggest that HUs are associated with all-cause complications or mortality in patients with SEAs. Future research hoping to leverage 3-dimensional imaging as a prognostic measure in this patient population should focus on alternative targets. Level of Evidence: Level III; Observational Cohort study.

8.
Epilepsy Res ; 195: 107203, 2023 09.
Article in English | MEDLINE | ID: mdl-37572541

ABSTRACT

Epilepsy is a chronic brain disorder characterized by unprovoked and recurrent seizures, of which 60% are of unknown etiology. Recent studies implicate microglia in the pathophysiology of epilepsy. However, their role in this process, in particular following early-life seizures, remains poorly understood due in part to the lack of suitable experimental models allowing the in vivo imaging of microglial activity. Given the advantage of zebrafish larvae for minimally-invasive imaging approaches, we sought for the first time to describe the microglial responses after acute seizures in two different zebrafish larval models: a chemically-induced epileptic model by the systemic injection of kainate at 3 days post-fertilization, and the didys552 genetic epilepsy model, which carries a mutation in scn1lab that leads to spontaneous epileptiform discharges. Kainate-treated larvae exhibited transient brain damage as shown by increased numbers of apoptotic nuclei as early as one day post-injection, which was followed by an increase in the number of microglia in the brain. A similar microglial phenotype was also observed in didys552-/- mutants, suggesting that microglia numbers change in response to seizure-like activity in the brain. Interestingly, kainate-treated larvae also displayed a decreased seizure threshold towards subsequent pentylenetetrazole-induced seizures, as shown by higher locomotor and encephalographic activity in comparison with vehicle-injected larvae. These results are comparable to kainate-induced rodent seizure models and suggest the suitability of these zebrafish seizure models for future studies, in particular to elucidate the links between epileptogenesis and microglial dynamic changes after seizure induction in the developing brain, and to understand how these modulate seizure susceptibility.


Subject(s)
Epilepsy , Zebrafish , Animals , Microglia , Kainic Acid/toxicity , Seizures/chemically induced , Brain , Pentylenetetrazole/toxicity , Disease Models, Animal
9.
J Bone Joint Surg Am ; 105(18): 1403-1409, 2023 09 20.
Article in English | MEDLINE | ID: mdl-37410854

ABSTRACT

BACKGROUND: The Stopping Opioids after Surgery (SOS) score was developed to identify patients at risk for sustained opioid use following surgery. The SOS score has not been specifically validated for patients in a general orthopaedic context. Our primary objective was to validate the SOS score within this context. METHODS: In this retrospective cohort study, we considered a broad array of representative orthopaedic procedures performed between January 1, 2018, and March 31, 2022. These procedures included rotator cuff repair, lumbar discectomy, lumbar fusion, total knee and total hip arthroplasty, open reduction and internal fixation (ORIF) of ankle fracture, ORIF of distal radial fracture, and anterior cruciate ligament reconstruction. The performance of the SOS score was evaluated by calculating the c-statistic, receiver operating characteristic curve, and the observed rates of sustained prescription opioid use (defined as uninterrupted prescriptions of opioids for ≥90 days) following surgery. For our sensitivity analysis, we compared these metrics among various time epochs related to the COVID-19 pandemic. RESULTS: A total of 26,114 patients were included, of whom 51.6% were female and 78.1% were White. The median age was 63 years. The observed prevalence of sustained opioid use was 1.3% (95% confidence interval [CI], 1.2% to 1.5%) in the low-risk group (SOS score of <30), 7.4% (95% CI, 6.9% to 8.0%) in the medium-risk group (SOS score of 30 to 60), and 20.8% (95% CI, 17.7% to 24.2%) in the high-risk group (SOS score of >60). The performance of the SOS score in the overall group was strong, with a c-statistic of 0.82. The performance of the SOS score showed no evidence of worsening over time. The c-statistic was 0.79 before the COVID-19 pandemic and ranged from 0.77 to 0.80 throughout the waves of the pandemic. CONCLUSIONS: We validated the use of the SOS score for sustained prescription opioid use following a diverse array of orthopaedic procedures across subspecialties. This tool is easy to implement for the purpose of prospectively identifying patients in musculoskeletal service lines who are at higher risk for sustained opioid use, thereby enabling the future implementation of upstream interventions and modifications to avert opioid abuse and to combat the opioid epidemic. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , COVID-19 , Opioid-Related Disorders , Orthopedics , Humans , Female , Middle Aged , Male , Analgesics, Opioid/therapeutic use , Retrospective Studies , Pandemics , Pain, Postoperative/etiology , COVID-19/epidemiology , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/prevention & control , Prescriptions , Diskectomy/adverse effects
10.
Global Spine J ; : 21925682231188816, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37452005

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Up to 30% of Multiple Myeloma (MM) patients are expected to experience Epidural Spinal Cord Compression (ESCC) during the course of their disease. To prevent irreversible neurological damage, timely diagnosis and treatment are important. However, debate remains regarding the optimal treatment regimen. The aim of this study was to investigate the neurological outcomes and frequency of retreatments for MM patients undergoing isolated radiotherapy and surgical interventions for high-grade (grade 2-3) ESCC. METHODS: This study included patients with MM and high-grade ESCC treated with isolated radiotherapy or surgery. Pre- and post-treatment American Spinal Injury Association (ASIA) impairment scale and retreatment rate were compared between the 2 groups. Adjusted multivariable logistic regression was utilized to examine differences in neurologic compromise, pain, and retreatments. RESULTS: A total of 247 patients were included (Radiotherapy: n = 154; Surgery: n = 93). After radiotherapy, 82 patients (53%) achieved full neurologic function (ASIA E) at the end of follow-up. Of the surgically treated patients, 67 (64%) achieved full neurologic function. In adjusted analyses, patients treated with surgery were less likely to experience neurologic deterioration within 2 years (OR = .15; 95%CI .05-.44; P = .001) and had less pain (OR = .29; 95%CI .11-.74; P = .010). Surgical treatment was not associated with an increased risk of retreatments (OR = .64; 95%CI .28-1.47; P = .29) or death (HR = .62, 95%CI .28-1.38; P = .24). CONCLUSIONS: After adjusting for baseline differences, surgically treated patients with high-grade ESCC showed better neurologic outcomes compared to patients treated with radiotherapy. There were no differences in risk of retreatment or death.

11.
J Ethnopharmacol ; 317: 116740, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37315641

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy is one of the most prevalent neurological human diseases, affecting 1% of the population in all age groups. Despite the availability of over 25 anti-seizure medications (ASMs), which are approved in most industrialized countries, approximately 30% of epilepsy patients still experience seizures that are resistant to these drugs. Since ASMs target only limited number of neurochemical mechanisms, drug-resistant epilepsy (DRE) is not only an unmet medical need, but also a formidable challenge in drug discovery. AIM: In this review, we examine recently approved epilepsy drugs based on natural product (NP) such as cannabidiol (CBD) and rapamycin, as well as NP-based epilepsy drug candidates still in clinical development, such as huperzine A. We also critically evaluate the therapeutic potential of botanical drugs as polytherapy or adjunct therapy specifically for DRE. METHODS: Articles related to ethnopharmacological anti-epileptic medicines and NPs in treating all forms of epilepsy were collected from PubMed and Scopus using keywords related to epilepsy, DRE, herbal medicines, and NPs. The database clinicaltrials.gov was used to find ongoing, terminated and planned clinical trials using herbal medicines or NPs in epilepsy treatment. RESULTS: A comprehensive review on anti-epileptic herbal drugs and natural products from the ethnomedical literature is provided. We discuss the ethnomedical context of recently approved drugs and drug candidates derived from NPs, including CBD, rapamycin, and huperzine A. Recently published studies on natural products with preclinical efficacy in animal models of DRE are summarized. Moreover, we highlight that natural products capable of pharmacologically activating the vagus nerve (VN), such as CBD, may be therapeutically useful to treat DRE. CONCLUSIONS: The review highlights that herbal drugs utilized in traditional medicine offer a valuable source of potential anti-epileptic drug candidates with novel mechanisms of action, and with clinical promise for the treatment of drug-resistant epilepsy (DRE). Moreover, recently developed NP-based anti-seizure medications (ASMs) indicate the translational potential of metabolites of plant, microbial, fungal and animal origin.


Subject(s)
Biological Products , Cannabidiol , Drug Resistant Epilepsy , Epilepsy , Plants, Medicinal , Animals , Humans , Ethnopharmacology , Biological Products/therapeutic use , Epilepsy/drug therapy , Epilepsy/metabolism , Anticonvulsants/pharmacology , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Drug Resistant Epilepsy/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Evidence-Based Medicine
12.
Clin Orthop Relat Res ; 481(12): 2343-2351, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37159263

ABSTRACT

BACKGROUND: The Stopping Opioids After Surgery (SOS) score is a validated tool that was developed to determine the risk of sustained opioid use after surgical interventions, including orthopaedic procedures. Despite prior investigations validating the SOS score in diverse contexts, its performance across racial, ethnic, and socioeconomic subgroups has not been assessed. QUESTIONS/PURPOSES: In a large, urban, academic health network, did the performance of the SOS score differ depending on (1) race and ethnicity or (2) socioeconomic status? METHODS: This retrospective investigation was conducted using data from an internal, longitudinally maintained registry of a large, urban, academic health system in the Northeastern United States. Between January 1, 2018, and March 31, 2022, we treated 26,732 adult patients via rotator cuff repair, lumbar discectomy, lumbar fusion, TKA, THA, ankle or distal radius open reduction and internal fixation, or ACL reconstruction. We excluded 1% of patients (274 of 26,732) because of missing length of stay information, 0.06% (15) for missing discharge information, 1% (310) for missing medication information related to loss to follow-up, and 0.07% (19) who died during their hospital stay. Based on these inclusion and exclusion criteria, 26,114 adult patients were left for analysis. The median age in our cohort was 63 years (IQR 52 to 71), and most patients were women (52% [13,462 of 26,114]). Most patients self-reported their race and ethnicity as non-Hispanic White (78% [20,408 of 26,114]), but the cohort also included non-Hispanic Black (4% [939]), non-Hispanic Asian (2% [638]), and Hispanic (1% [365]) patients. Five percent (1295) of patients were of low socioeconomic status, defined by prior SOS score investigations as patients with Medicaid insurance. Components of the SOS score and the observed frequency of sustained postoperative opioid prescriptions were abstracted. The performance of the SOS score was compared across racial, ethnic, and socioeconomic subgroups using the c-statistic, which measures the capacity of the model to differentiate between patients with and without sustained opioid use. This measure should be interpreted on a scale between 0 and 1, where 0 represents a model that perfectly predicts the wrong classification, 0.5 represents performance no better than chance, and 1.0 represents perfect discrimination. Scores less than 0.7 are generally considered poor. The baseline performance of the SOS score in past investigations has ranged from 0.76 to 0.80. RESULTS: The c-statistic for non-Hispanic White patients was 0.79 (95% CI 0.78 to 0.81), which fell within the range of past investigations. The SOS score performed worse for Hispanic patients (c-statistic 0.66 [95% CI 0.52 to 0.79]; p < 0.001), where it tended to overestimate patients' risks of sustained opioid use. The SOS score for non-Hispanic Asian patients did not perform worse than in the White patient population (c-statistic 0.79 [95% CI 0.67 to 0.90]; p = 0.65). Similarly, the degree of overlapping CIs suggests that the SOS score did not perform worse in the non-Hispanic Black population (c-statistic 0.75 [95% CI 0.69 to 0.81]; p = 0.003). There was no difference in score performance among socioeconomic groups (c-statistic 0.79 [95% CI 0.74 to 0.83] for socioeconomically disadvantaged patients; 0.78 [95% CI 0.77 to 0.80] for patients who were not socioeconomically disadvantaged; p = 0.92). CONCLUSION: The SOS score performed adequately for non-Hispanic White patients but performed worse for Hispanic patients, where the 95% CI nearly included an area under the curve value of 0.5, suggesting that the tool is no better than chance at predicting sustained opioid use for Hispanic patients. In the Hispanic population, it commonly overestimated the risk of opioid dependence. Its performance did not differ among patients of different sociodemographic backgrounds. Future studies might seek to contextualize why the SOS score overestimates expected opioid prescriptions for Hispanic patients and how the utility performs among more specific Hispanic subgroups. CLINICAL RELEVANCE: The SOS score is a valuable tool in ongoing efforts to combat the opioid epidemic; however, disparities exist in terms of its clinical applicability. Based on this analysis, the SOS score should not be used for Hispanic patients. Additionally, we provide a framework for how other predictive models should be tested in various lesser-represented populations before implementation.


Subject(s)
Analgesics, Opioid , Opioid-Related Disorders , Socioeconomic Factors , Adult , Aged , Female , Humans , Male , Middle Aged , Analgesics, Opioid/therapeutic use , Ethnicity , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/prevention & control , Retrospective Studies , United States , Racial Groups
13.
Spine (Phila Pa 1976) ; 48(13): 893-900, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37040462

ABSTRACT

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: (1) To determine the incremental increase in intraoperative ionizing radiation conferred by computed tomography (CT) as compared with conventional radiography; and (2) to model different lifetime cancer risks contextualized by the intersection between age, sex, and intraoperative imaging modality. SUMMARY OF BACKGROUND DATA: Emerging technologies in spine surgery, like navigation, automation, and augmented reality, commonly utilize intraoperative CT. Although much has been written about the benefits of such imaging modalities, the inherent risk profile of increasing intraoperative CT has not been well evaluated. MATERIALS AND METHODS: Effective doses of intraoperative ionizing radiation were extracted from 610 adult patients who underwent single-level instrumented fusion for lumbar degenerative or isthmic spondylolisthesis from January 2015 through January 2022. Patients were divided into those who received intraoperative CT (n=138) and those who underwent conventional intraoperative radiography (n=472). Generalized linear modeling was utilized with intraoperative CT use as a primary predictor and patient demographics, disease characteristics, and preference-sensitive intraoperative considerations ( e.g. surgical approach and surgical invasiveness) as covariates. The adjusted risk difference in radiation dose calculated from our regression analysis was used to prognosticate the associated cancer risk across age and sex strata. RESULTS: (1) After adjusting for covariates, intraoperative CT was associated with 7.6 mSv (interquartile range: 6.8-8.4 mSv; P <0.001) more radiation than conventional radiography. (2) For the median patient in our population (a 62-year-old female), intraoperative CT use increased lifetime cancer risk by 2.3 incidents (interquartile range: 2.1-2.6) per 10,000. Similar projections for other age and sex strata were also appreciated. CONCLUSIONS: Intraoperative CT use significantly increases cancer risk compared with conventional intraoperative radiography for patients undergoing lumbar spinal fusions. As emerging technologies in spine surgery continue to proliferate and leverage intraoperative CT for cross-sectional imaging data, strategies must be developed by surgeons, institutions, and medical technology companies to mitigate long-term cancer risks.


Subject(s)
Neoplasms , Spinal Fusion , Adult , Female , Humans , Middle Aged , Retrospective Studies , Cross-Sectional Studies , Tomography, X-Ray Computed/adverse effects , Tomography, X-Ray Computed/methods , Risk , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion/adverse effects , Spinal Fusion/methods
14.
Spine J ; 23(6): 791-798, 2023 06.
Article in English | MEDLINE | ID: mdl-36870450

ABSTRACT

BACKGROUND CONTEXT: The use of intraoperative CT has continued to grow in recent years, as various techniques leverage the promise of improved instrumentation accuracy and the hope for decreased complications. Nonetheless, the literature regarding the short- and long-term complications associated with such techniques remains scant and/or confounded by indication and selection bias. PURPOSE: To use causal inference techniques to determine whether intraoperative CT use is associated with an improved complication profile as compared to conventional radiography for single-level lumbar fusions, an increasingly commonplace application for this technology. STUDY DESIGN/SETTING: Inverse probability weighted retrospective cohort study carried out within a large integrated health care network. PATIENT SAMPLE: Adult patients who underwent surgical treatment of spondylolisthesis via lumbar fusion from January 2016 to December 2021. OUTCOME MEASURES: Our primary outcome was the incidence rate of revision surgery. Our secondary outcome was the incidence of composite 90-day complications (deep and superficial surgical site infection, venous thromboembolic events, and unplanned readmissions). METHODS: Demographics, intraoperative information, and postoperative complications were abstracted from electronic health records. A propensity score was developed utilizing a parsimonious model to account for covariate interaction with our primary predictor, intraoperative imaging technique. This propensity score was utilized in the creation of inverse probability weights to adjust for indication and selection bias. The rate of revisions within 3 years as well as the rate of revisions at any time-point were compared between cohorts using Cox regression analysis. The incidence of composite 90-day complications were compared using negative binomial regression. RESULTS: Our patient population consisted of 583 patients, with 132 who underwent intraoperative CT and 451 who underwent conventional radiographic techniques. There were no significant differences between cohorts following inverse probability weighting. No significant differences were detected in 3-year revision rates (HR, 0.74 [95% CI 0.29, 1.92]; p=.5), overall revision rates (HR, 0.54 [95% CI 0.20, 1.46]; p=.2), or 90-day complications (RC -0.24 [95% CI -1.35, 0.87]; p=.7). CONCLUSIONS: Intraoperative CT use was not associated with an improved complication profile in either the short- or long-term for patients undergoing single-level instrumented fusion. This observed clinical equipoise should be weighed against resource and radiation-related costs when considering intraoperative CT for low complexity fusions.


Subject(s)
Lumbar Vertebrae , Spinal Fusion , Adult , Humans , Retrospective Studies , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Tomography, X-Ray Computed , Treatment Outcome
15.
Arch Orthop Trauma Surg ; 143(9): 5985-5992, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36905425

ABSTRACT

INTRODUCTION: Arthroplasty care delivery is facing a growing supply-demand mismatch. To meet future demand for joint arthroplasty, systems will need to identify potential surgical candidates prior to evaluation by orthopaedic surgeons. MATERIALS AND METHODS: Retrospective review was conducted at two academic medical centers and three community hospitals from March 1 to July 31, 2020 to identify new patient telemedicine encounters (without prior in-person evaluation) for consideration of hip or knee arthroplasty. The primary outcome was surgical indication for joint replacement. Five machine learning algorithms were developed to predict likelihood of surgical indication and assessed by discrimination, calibration, overall performance, and decision curve analysis. RESULTS: Overall, 158 patients underwent new patient telemedicine evaluation for consideration of THA, TKA, or UKA and 65.2% (n = 103) were indicated for operative intervention prior to in-person evaluation. The median age was 65 (interquartile range 59-70) and 60.8% were women. Variables found to be associated with operative intervention were radiographic degree of arthritis, prior trial of intra-articular injection, trial of physical therapy, opioid use, and tobacco use. In the independent testing set (n = 46) not used for algorithm development, the stochastic gradient boosting algorithm achieved the best performance with AUC 0.83, calibration intercept 0.13, calibration slope 1.03, Brier score 0.15 relative to a null model Brier score of 0.23, and higher net benefit than the default alternatives on decision curve analysis. CONCLUSION: We developed a machine learning algorithm to identify potential surgical candidates for joint arthroplasty in the setting of osteoarthritis without an in-person evaluation or physical examination. If externally validated, this algorithm could be deployed by various stakeholders, including patients, providers, and health systems, to direct appropriate next steps in patients with osteoarthritis and improve efficiency in identifying surgical candidates. LEVEL OF EVIDENCE: III.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Osteoarthritis , Humans , Female , Aged , Male , Algorithms , Machine Learning , Retrospective Studies
16.
Spine (Phila Pa 1976) ; 48(6): 436-443, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36728030

ABSTRACT

STUDY DESIGN: Narrative review. OBJECTIVE: To describe the evolution of acute traumatic thoracolumbar (TL) injury classification systems; to promote standardization of concepts and vocabulary with respect to TL injuries. SUMMARY OF BACKGROUND DATA: Over the past century, numerous TL classification systems have been proposed and implemented, each influenced by the thought, imaging modalities, and surgical techniques available at the time. While much progress has been made in our understanding and management of these injuries, concepts, and terms are often intermixed, leading to potential confusion and miscommunication. METHODS: We present a narrative review of the current state of the literature regarding classification systems for TL trauma. RESULTS: The evolution of TL classification systems has broadly been characterized by a transition away from descriptive categorizations of fracture patterns to schema incorporating morphology, stability, and neurological function. In addition to these features, more recent systems have demonstrated the importance of predictive/prognostic capability, reliability, validity, and generalizability. The Arbeitsgemeinschaft fur Osteosynthesenfragen Spine Thoracolumbar Injury Classification System/Thoracolumbar Arbeitsgemeinschaft fur Osteosynthesenfragen Spine Injury Score represents the most modern and recently updated system, retiring past concepts and terminology in favor of clear, internationally agreed upon descriptors. CONCLUSIONS: Advancements in our understanding of blunt TL trauma injuries have led to changes in management. Such advances are reflected in modern, dedicated classification systems. Over time, various key factors have been acknowledged and incorporated. In an effort to promote standardization of thought and language, past ideas and terminology should be retired.


Subject(s)
Spinal Injuries , Wounds, Nonpenetrating , Humans , Reproducibility of Results , Thoracic Vertebrae/surgery , Lumbar Vertebrae/surgery , Language , Reference Standards
18.
Spine J ; 23(6): 824-831, 2023 06.
Article in English | MEDLINE | ID: mdl-36736738

ABSTRACT

BACKGROUND CONTEXT: Radiographs, fluoroscopy, and computed tomography (CT) are increasingly utilized in the diagnosis and management of various spine pathologies. Such modalities utilize ionizing radiation, a known cause of carcinogenesis. While the radiation doses such studies confer has been investigated previously, it is less clear how such doses translate to projected cancer risks, which may be a more interpretable metric. PURPOSE: (1) Calculate the lifetime cancer risk and the relative contributions of preference-sensitive selection of imaging modalities associated with the surgical management of a common spine pathology, isthmic spondylolisthesis (IS); (2) Investigate whether the use of intraoperative CT, which is being more pervasively adopted, increases the risk of cancer. STUDY DESIGN/SETTING: Retrospective cross-sectional study carried out within a large integrated health care network. PATIENT SAMPLE: Adult patients who underwent surgical treatment of IS via lumbar fusion from January 2016 through December 2021. OUTCOME MEASURES: (1) Effective radiation dose and lifetime cancer risk associated with each exposure to ionizing radiation; (2) Difference in effective radiation dose (and lifetime cancer risk) among patients who received intraoperative CT compared to other intraoperative imaging techniques. METHODS: Baseline demographics and differences in surgical techniques were characterized. Radiation exposure data were collected from the 2-year period centered on the operative date. Projected risk of cancer from this radiation was calculated utilizing each patient's effective radiation dose in combination with age and sex. Generalized linear modeling was used to adjust for covariates when determining the comparative risk of intraoperative CT as compared to alternative imaging modalities. RESULTS: We included 151 patients in this cohort. The range in calculated cancer risk exclusively from IS management was 1.3-13 cases of cancer per 1,000 patients. During the intraoperative period, CT imaging was found to significantly increase radiation exposure as compared to alternate imaging modalities (adjusted risk difference (ARD) 12.33mSv; IQR 10.04, 14.63mSv; p<.001). For a standardized 40 to 49-year-old female, this projects to an additional 0.72 cases of cancer per 1,000. For the entire 2-year perioperative care episode, intraoperative CT as compared to other intraoperative imaging techniques was not found to increase total ionizing radiation exposure (ARD 9.49mSv; IQR -0.83, 19.81mSv; p=.072). The effect of intraoperative imaging choice was mitigated in part due to preoperative (ARD 13.1mSv, p<.001) and postoperative CTs (ARD 22.7mSv, p<.001). CONCLUSIONS: Preference-sensitive imaging decisions in the treatment of IS impart substantial cancer risk. Important drivers of radiation exposure exist in each phase of care, including intraoperative CT and/or CT scans during the perioperative period. Knowledge of these data warrant re-evaluation of current imaging protocols and suggest a need for the development of radiation-sensitive approaches to perioperative imaging.


Subject(s)
Neoplasms , Spinal Fusion , Spondylolisthesis , Adult , Female , Humans , Middle Aged , Spondylolisthesis/diagnostic imaging , Spondylolisthesis/surgery , Spondylolisthesis/etiology , Retrospective Studies , Cross-Sectional Studies , Radiation Dosage , Neoplasms/etiology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion/adverse effects
19.
Injury ; 54(2): 280-287, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36586813

ABSTRACT

INTRODUCTION: Iliopsoas hematoma with femoral nerve palsy is a rare phenomenon with no consensus treatment algorithm. The objective of this study was to perform a systematic review of all reported cases of femoral nerve palsy secondary to iliopsoas hematoma to better elucidate it's optimal treatment. MATERIALS AND METHODS: Queries of the PubMed, Embase, and Cochrane databases were performed for reports available in English of femoral nerve palsy secondary to iliopsoas, psoas, or iliacus hematoma. 1491 articles were identified. After removal of duplicated publications and review of abstract titles via a majority reviewer consensus, 217 articles remained for consideration. Dedicated review of the remaining articles (including their reference sections) yielded 122 articles representing 174 distinct cases. Clinical data including patient age, sex, medical history, use of pharmacologic anticoagulation, sensory and motor examination at presentation and follow-up, hematoma etiology and location, time to intervention, and type of intervention were collected. Descriptive statistics were generated for each variable. RESULTS: Femoral nerve palsy secondary to iliopsoas hematoma occurred at a mean age of 44.5 years old. A majority of patients (60%) were male, and a majority of hematomas (54%) occurred due to pharmacologic anticoagulation. Most hematomas (57%) were treated conservatively, and almost half (49%) - regardless of treatment modality - resulted in persistent motor deficits at final follow-up. A minority of patients treated surgically (34%) had residual motor deficit at final follow-up, while 66% of those treated medically had resultant motor deficits, although no direct statistical comparison was able to be performed. DISCUSSION AND CONCLUSIONS: The disparate available data on iliopsoas hematoma with femoral nerve palsy precludes the completion of a true metanalysis, and therefore any conclusions on an optimal treatment algorithm. Based on review of the literature, small to moderate hematomas are often treated conservatively, while larger hematomas with progressive neurological symptoms are usually managed with a percutaneous decompression or surgery. LEVEL OF EVIDENCE: IV.


Subject(s)
Femoral Nerve , Psoas Muscles , Humans , Male , Female , Adult , Hematoma/epidemiology , Hematoma/surgery , Paralysis , Anticoagulants/adverse effects
20.
Clin Spine Surg ; 36(7): E317-E323, 2023 08 01.
Article in English | MEDLINE | ID: mdl-35943872

ABSTRACT

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: To characterize the variability in cost for anterior cervical discectomy and fusion (ACDF) constructs and to identify key predictors of procedural cost. SUMMARY OF BACKGROUND DATA: ACDF is commonly performed for surgical treatment of cervical radiculopathy and myelopathy. Numerous biomechanical constructs and graft/biological options are available, with most demonstrating relatively equivalent clinical results. Despite the substantial focus on value in spine care, the differences and contributions to procedural cost in ACDF have not been well defined. MATERIALS AND METHODS: We evaluated the records of patients who underwent a single level ACDF from 2016 to 2020 at 4 hospitals in a major metropolitan area. We abstracted demographics, insurance status, operative time, diagnosis, surgeon, institution, and components of procedural costs. Costs based on construct were compared using multivariable adjusted analyses using negative binomial regression. The primary outcome measures were cost differences between ACDF techniques. RESULTS: Two hundred sixty-four patients were included, with procedures by 13 surgeons across 4 institutions. The total procedural cost for ACDF had a mean of US$2317 with wide variation (range, US$967-US$7370). Multivariable analysis revealed body mass index and use of polyether ether ketone to be correlated with increased cost while carbon fiber and autograft correlated with decreased cost. When comparing standalone device constructs to cases with anterior instrumentation (plate/screws), the total cost was significantly higher in the plate/screw group (US$2686±US$921 vs. US$1466±US$878, P <0.001). CONCLUSIONS: We encountered wide variation in procedural costs associated with ACDF, including as much as an 8-fold difference in the cost of constructs. The most important drivers included instrumentation type and implant materials. Here, we identify potential targets of opportunity for health care organizations that are looking to reduce variance in procedural expenditures to improve health care savings associated with the performance of ACDF.


Subject(s)
Spinal Fusion , Humans , Retrospective Studies , Spinal Fusion/methods , Treatment Outcome , Diskectomy/methods , Bone Plates , Cervical Vertebrae/surgery
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