Recent developments and challenges in positron emission tomography imaging of gliosis in chronic neuropathic pain.

ABSTRACT: Understanding the mechanisms that underpin the transition from acute to chronic pain is critical for the development of more effective and targeted treatments. There is growing interest in the contribution of glial cells to this process, with cross-sectional preclinical studies demonstrating specific changes in these cell types capturing targeted timepoints from the acute phase and the chronic phase. In vivo longitudinal assessment of the development and evolution of these changes in experimental animals and humans has presented a significant challenge. Recent technological advances in preclinical and clinical positron emission tomography, including the development of specific radiotracers for gliosis, offer great promise for the field. These advances now permit tracking of glial changes over time and provide the ability to relate these changes to pain-relevant symptomology, comorbid psychiatric conditions, and treatment outcomes at both a group and an individual level. In this article, we summarize evidence for gliosis in the transition from acute to chronic pain and provide an overview of the specific radiotracers available to measure this process, highlighting their potential, particularly when combined with ex vivo/in vitro techniques, to understand the pathophysiology of chronic neuropathic pain. These complementary investigations can be used to bridge the existing gap in the field concerning the contribution of gliosis to neuropathic pain and identify potential targets for interventions.

Establishing case volume benchmarks for ACGME-accredited orthopedic surgery of the spine fellowship training.

BACKGROUND CONTEXT: There has been increasing scrutiny on the standardization of surgical training in the US. PURPOSE: This study provides case volume benchmarks for Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopedic spine surgery fellowship training. STUDY DESIGN/SETTING: This was a retrospective cross-sectional study of fellows at ACGME-accredited orthopedic spine surgery fellowships (2017-2022). PATIENT SAMPLE: N/A. OUTCOME MEASURES: Reported case volume during fellowship training. METHODS: Case volume percentiles were calculated across ACGME-defined case categories and temporal changes assessed via linear regression. Variability between the highest and lowest deciles by case volume was calculated as fold-differences (90th percentile/10th percentile). Sensitivity analyses were performed to identify potential targets for case minimum requirements. RESULTS: A total of 163 spine surgery fellows were included in this study. Total mean reported spine surgery case volume increased from 313.2±122 in 2017 to 382.0±164 in 2022 (p=.19). Most cases were classified as adult (range, 97.2%-98.0%) over pediatric cases (range, 2.0%-2.8%). An average of 322.0 cases were reported and most were classified as laminectomy (32%), posterior arthrodesis (29%), and anterior arthrodesis (20%). Overall variability in total case volume was 2.4 and the greatest variability existed for posterior instrumentation (38.1), application of cage (34.6), anterior instrumentation (20.8), and fractures and dislocations (17.3). If case minimum requirements for total reported cases was assumed at 200 cases, then all spine fellows included in this study would achieve this requirement. However, if case minimum requirements were assumed at 250 total cases, then approximately thirty percent of fellows (n=49) would not achieve this requirement for graduation. CONCLUSIONS: Increasingly, national societies and accrediting bodies for surgical education recognize the need for standardized training. This study provides benchmarks to inform potential case minimum requirements and help reduce variability during spine fellowship training. Future studies are needed to establish case minimum requirements for spine surgery fellowship training across comprehensive and granular case categories that cover the full gamut of orthopedic spine surgery.

Infraorbital nerve injury triggers sex-specific neuroimmune responses in the peripheral trigeminal pathway and common pain behaviours.

Trigeminal neuropathic pain is emotionally distressing and disabling. It presents with allodynia, hyperalgesia and dysaesthesia. In preclinical models it has been assumed that cephalic nerve constriction injury shows identical molecular, cellular, and sex dependent neuroimmune changes as observed in extra-cephalic injury models. This study sought empirical evidence for such assumptions using the infraorbital nerve chronic constriction model (ION-CCI). We compared the behavioural consequences of nerve constriction with: (i) the temporal patterns of recruitment of macrophages and T-lymphocytes at the site of nerve injury and in the trigeminal ganglion; and (ii) the degree of demyelination and axonal reorganisation in the injured nerve. Our data demonstrated that simply testing for allodynia and hyperalgesia as is done in extra-cephalic neuropathic pain models does not provide access to the range of injury-specific nociceptive responses and behaviours reflective of the experience of trigeminal neuropathic pain. Similarly, trigeminal neuroimmune changes evoked by nerve injury are not the same as those identified in models of extra-cephalic neuropathy. Specifically, the timing, magnitude, and pattern of ION-CCI evoked macrophage and T-lymphocyte activity differs between the sexes.

Musculoskeletal health: an ecological study assessing disease burden and research funding.

Background: Exacerbated by an aging population, musculoskeletal diseases are a chronic and growing problem in the United States that impose significant health and economic burdens. The objective of this study was to analyze the correlation between the burden of diseases and the federal funds assigned to health-related research through the National Institutes of Health (NIH). Methods: An ecological study design was used to examine the relationship between NIH research funding and disease burden for 60 disease categories. We used the Global Burden of Disease (GBD) Study 2019 to measure disease burden and the NIH Research, Condition, and Disease Categories (RCDC) data to identify 60 disease categories aligned with available GBD data. NIH funding data was obtained from the RCDC system and the NIH Office of Budget. Using linear regression models, we observed that musculoskeletal diseases were among the most underfunded (i.e., negative residuals from the model) with respect to disease burden. Findings: Musculoskeletal diseases were underfunded, with neck pain being the most underfunded at only 0.83% of expected funding. Low back pain, osteoarthritis, and rheumatoid arthritis were also underfunded at 13.88%, 35.08%, and 66.26%, respectively. Musculoskeletal diseases were the leading cause of years lived with disability and the third leading cause in terms of prevalence and disability-adjusted life years. Despite the increasing burden of these diseases, the allocation of NIH funding to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has remained low compared to other institutes. Interpretation: Despite the increasing health burden and economic cost of $980 billion annually, the allocation of NIH funding to the NIAMS has remained low compared to other institutes. These findings suggest that the NIH may need to reassess its allocation of research funding to align with the current health challenges of our country. Furthermore, these clinically relevant observations highlight the need to increase research funding for musculoskeletal diseases and improve their prevention, diagnosis, and treatment. Funding: No funding.

Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.

Background: Low back pain is a global health problem that originated mainly from intervertebral disc degeneration (IDD). Autophagy, negatively regulated by the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, prevents metabolic and degenerative diseases by removing and recycling damaged cellular components. Despite growing evidence that autophagy occurs in the intervertebral disc, the regulation of disc cellular autophagy is still poorly understood. Methods: Annulus fibrosus (rAF) cell cultures derived from healthy female rabbit discs were used to test the effect of autophagy inhibition or activation on disc cell fate and matrix homeostasis. Specifically, different chemical inhibitors including rapamycin, 3-methyladenine, MK-2206, and PP242 were used to modulate activities of different proteins in the PI3K/Akt/mTOR signaling pathway to assess IL-1ß-induced cellular senescence, apoptosis, and matrix homeostasis in rAF cells grown under nutrient-poor culture condition. Results: Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), reduced the phosphorylation of mTOR and its effector p70/S6K in rAF cell cultures. Rapamycin also induced autophagic flux as measured by increased expression of key autophagy markers, including LC3 puncta number, LC3-II expression, and cytoplasmic HMGB1 intensity and decreased p62/SQSTM1 expression. As expected, IL-1ß stimulation promoted rAF cellular senescence, apoptosis, and matrix homeostatic imbalance with enhanced aggrecanolysis and MMP-3 and MMP-13 expression. Rapamycin treatment effectively mitigated IL-1ß-mediated inflammatory stress changes, but these alleviating effects of rapamycin were abrogated by chemical inhibition of Akt and mTOR complex 2 (mTORC2). Conclusions: These findings suggest that rapamycin blunts adverse effects of inflammation on disc cells by inhibiting mTORC1 to induce autophagy through the PI3K/Akt/mTOR pathway that is dependent on Akt and mTORC2 activities. Hence, our findings identify autophagy, rapamycin, and PI3K/Akt/mTOR signaling as potential therapeutic targets for IDD treatment.

Trends in ACGME Accreditation of Orthopedic Surgery Fellowship Training.

Currently, most surgeons pursue subspecialty fellowship training. This study answers the following questions: (1) How does the rate of fellowship training in orthopedic surgery compare with that in other surgical specialties? (2) To what extent did adoption of Accreditation Council for Graduate Medical Education (ACGME) accreditation change from 2013 to 2021? Orthopedic subspecialties were analyzed for total number of fellowship programs and positions in the 2013 and 2021 Match. Rates of ACGME accreditation were analyzed via chi-square tests. In 2021, orthopedic surgery had the highest rate of fellowship selection (94%) relative to general surgery (77%), ophthalmology (66%), plastic surgery (63%), and otolaryngology (55%). Across all orthopedic subspecialties, the percentage of ACGME accreditation decreased among fellowship programs (53% in 2013 to 48% in 2021, P=.166) and positions (58% in 2013 to 50% in 2021, P<.001). Orthopedic sports medicine had the highest adoption of ACGME accreditation (100%), followed by hand surgery (99%), musculoskeletal oncology (67%), and pediatric orthopedics (56%). Significant increases in the adoption of ACGME accreditation were noted for orthopedic sports medicine (93% in 2013 to 100% in 2021, P=.016) and hand surgery (81% in 2013 to 99% in 2021, P<.001). There was a significant decrease in ACGME accreditation for adult reconstructive orthopedics (40% in 2013 to 24% in 2021, P=.042), driven by the increase in unaccredited fellowship programs. Accreditation of orthopedic subspecialty fellowship training has decreased with respect to the proportion of accredited training positions. More research is needed to understand the benefits of ACGME accreditation for fellowship training in orthopedic surgery. [Orthopedics. 2024;47(1):57-63.].

Analysis of Academic Accomplishments and Demographics for Elected Presidents of National Orthopedic Surgery Organizations in the United States.

This study analyzed the academic accomplishments and demographics of elected presidents of the American Academy of Orthopaedic Surgeons (AAOS), American Orthopaedic Association (AOA), and American Board of Orthopaedic Surgery (ABOS). Curriculum vitae and internet-based resources were reviewed to collect demographics, training characteristics, bibliometrics, and National Institutes of Health (NIH) research funding of contemporary presidents (1990-2020). Eighty presidents were included. Most presidents were men (97%), and 4% of presidents were non-White (3% Black and 1% Hispanic). Few had an additional graduate degree (4% MBA, 3% MS, 1% MPH, 1% PhD). Ten orthopedic surgery residency programs trained 47% of these presidents. Most had fellowship training (59%), and the top three were hand surgery (11%), pediatric orthopedics (11%), and adult reconstruction (10%). Twenty-nine presidents (36%) participated in a traveling fellowship. The mean age at appointment was 58±5 years, which was 27 years since residency graduation. The mean h-index was 36±23, resulting from 150±126 peer-reviewed manuscripts. Orthopedic surgery presidents had more peer-reviewed manuscripts (150±126) than chairs (73±81) and program directors (27±32) (P<.001). AOA presidents had the highest mean h-index (42±21) compared with AAOS (38±27) and ABOS (25±16) presidents (P=.035). Nineteen presidents had NIH funding (24%). More presidents had NIH funding in the AOA (39%) and AAOS (25%) than the ABOS (0%) (P=.007). Orthopedic surgery presidents possess high levels of scholarly output. AOA presidents had the highest h-index values and prevalence of NIH funding. Females and racial minorities remain underrepresented at the highest levels of leadership. [Orthopedics. 2024;47(1):e45-e51.].

Biological Therapeutic Modalities for Intervertebral Disc Diseases: An Orthoregeneration Network (ON) Foundation Review.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the spine, including lower back pain, with or without numbness and/or dysfunction in the lower extremities, disc herniation, spinal stenosis, and spondylolisthesis. Promising and established treatment modalities include repair of the annulus fibrosis, injection of expanded or nonexpanded autologous or allogenic cells that are chondrogenic or from a stem cell lineage used to promote matrix tissue regeneration of the intervertebral disc, including nucleus pulpous cells and mesenchymal stem cells isolated from bone marrow, umbilical cord blood, or adipose tissue; and injection of platelet-rich plasma, platelet-rich fibrin, or fibrin sealant. Early clinical studies show promise for pain reduction and functional recovery. LEVEL OF EVIDENCE: Level V, expert opinion.

Cellular behavior and extracellular matrix turnover in bovine annulus fibrosus cells under hydrostatic pressure and deviatoric strain.

Intervertebral disc herniation is a common spinal disorder that is often treated with discectomy when conservative measures fail. To devise therapeutic strategies for tears in the annulus fibrosus (AF), the regenerative capability of AF cells under spinal loading needs to be addressed. We hypothesized that the compressive loading associated with deformation in AF cells reduces synthetic and degradative activities in extracellular matrix and cell proliferation. We evaluated expression of key matrix molecules and cell proliferation by RT-PCR and immunohistochemistry by inner and outer bovine AF cells incubated under hydrostatic pressure (HP), arc-bending strain (Strain), and combined HP and Strain (HP/Strain) mimicking spinal loading. Inner AF cells showed significantly increased levels of aggrecan core protein, chondroitin sulfate N-acetylgalactosaminyltransferase-1, and tissue inhibitor of metalloproteinases-2 by 6 days under HP (p < 0.05), with a tendency toward increased matrix metalloproteinase-13. Outer AF cells demonstrated a significant decline in collagen type-2 under Strain and HP/Strain (p < 0.05) and a tendency toward suppression of collagen type-1 and elastin expression compared to HP and unloaded control. On the other hand, proliferating cell nucleus antigen increased significantly under Strain and HP/Strain in inner AF and declined under unloaded and HP in outer AF (p < 0.05). Immunohistology findings supported reductions in gene expressions of matrix molecules. Thus, changes in HP/Strain in AF appear to diminish synthetic and degradative activities while increasing cell proliferation. To promote regeneration, continuous overloading should be avoided, as it converts the synthetic activity to a state in which tissue repair is limited.

Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome.

Surgery is a major challenge for the immune system, but little is known about the immune response of geriatric patients to surgery. We therefore investigated the impact of surgery on the molecular signature of circulating CD14+ monocytes, cells implicated in clinical recovery from surgery, in older patients. We enrolled older patients having elective joint replacement (N = 19) or spine (N = 16) surgery and investigated pre- to postoperative expression changes in 784 immune-related genes in monocytes. Joint replacement altered the expression of 489 genes (adjusted p < 0.05), of which 38 had a |logFC| > 1. Spine surgery changed the expression of 209 genes (adjusted p < 0.05), of which 27 had a |logFC| > 1. In both, the majority of genes with a |logFC| > 1 change were downregulated. In the combined group (N = 35), 471 transcripts were differentially expressed (adjusted p < 0.05) after surgery; 29 had a |logFC| > 1 and 72% of these were downregulated. Notably, 21 transcripts were common across procedures. Thus, elective surgery in older patients produces myriad changes in the immune gene transcriptome of monocytes, with many suggesting development of an immunocompromised/hypoactive phenotype. Because monocytes are strongly implicated in the quality of surgical recovery, this signature provides insight into the cellular and molecular mechanisms of the immune response to surgery and warrants further study as a potential biomarker for predicting poor outcomes in older surgical patients.

Recurrent Primary Hyperparathyroidism in Hyperparathyroid Jaw Tumor Syndrome: A Case Report.

Hyperparathyroidism occasionally develops secondary to genetic disorders, though CDC73-related diseases such as hyperparathyroid jaw tumor syndrome (HPT-JT) are among the least common. Typically, patients are identified in the third decade of life by characteristically early development of hyperparathyroidism, atypical pathology on histologic evaluation of parathyroid adenomas, or presence of concomitant tumors in the jaw, renal, or uterine anatomy. We report a case of a 60-year-old male who was identified as having hyperparathyroidism jaw tumor syndrome after presenting with recurrent hyperparathyroidism 10 years after parathyroid adenoma resection, which is likely the oldest age to date for diagnosis. We also review his clinical presentation, pathophysiology, genetic significance, and surveillance criteria relating to HPT-JT.

Limited number of spine surgeons among recipients of National Institutes of Health grants awarded for degenerative spine disease research.

OBJECTIVE: Surgeon scientists remain underrepresented among recipients of National Institutes of Health (NIH) grants despite their unique ability to perform translational research. This study elucidates the portfolio of NIH grants awarded for degenerative spine diseases and the role of spine surgeons in this portfolio. METHODS: The most common diagnoses and surgical procedures for degenerative spine diseases were queried on the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) database (2011-2021). Total NIH funding was extracted for 20 additional clinical areas and compound annual growth rates (CAGRs) were calculated. A retrospective cohort study of principal investigators (PIs) was conducted. NIH grants and funding totals were extracted and compared to those from other clinical areas. RESULTS: The total NIH research budget increased from $31 to $43 billion over the 10-year period (CAGR 3.4%). A total of 273 unique grants equaling $91 million (CAGR 0%) were awarded for degenerative spine diseases. Diabetes ($11.8 billion, CAGR 0%), obesity ($10.6 billion, CAGR 3%), and chronic pain ($5.6 billion, CAGR 7%) received the most funding. Most NIH funding for degenerative spine disease research was awarded through the R01 (66%) and R44 (8%) grant mechanisms. The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded the most NIH funding (64%). Departments of orthopedic surgery were awarded the most funding (32%). NIH funding supported clinical (28%), translational (37%), and basic science (35%) research. Disease mechanisms (58%), imaging modalities (20%), and emerging technologies (16%) received the most funding. Nineteen spine surgeons were identified as PIs (16%). There were no significant differences in NIH funding totals by PI demographic and academic characteristics (p > 0.05)-except for full professors, who had the most NIH funding (p = 0.007) and highest h-index values (p < 0.001). CONCLUSIONS: Few spine surgeons receive NIH grants for degenerative spine disease research. Future opportunities may exist for spine surgeons to collaborate in identified areas of clinical interest. Additional strategies are needed to increase NIH funding in spine surgery.

Postpartum Thyroiditis Mimicking Central Hypothyroidism: The Perfect Thyming.

Hypothyroidism can be seen in postpartum women as a result of central or primary hypothyroidism. Postpartum thyroiditis is a primary hypothyroid condition in which there is likely autoimmune dysfunction leading to damage to the thyroid gland. Patients with postpartum thyroiditis often present with little to no symptoms, and the key to establishing this diagnosis is a comprehensive endocrine workup. We report the case of a 24-year-old postpartum female patient who was diagnosed with postpartum thyroiditis after initial evaluation demonstrated findings concerning central hypothyroidism.

A Comprehensive Review on Machine Learning in Healthcare Industry: Classification, Restrictions, Opportunities and Challenges.

Recently, various sophisticated methods, including machine learning and artificial intelligence, have been employed to examine health-related data. Medical professionals are acquiring enhanced diagnostic and treatment abilities by utilizing machine learning applications in the healthcare domain. Medical data have been used by many researchers to detect diseases and identify patterns. In the current literature, there are very few studies that address machine learning algorithms to improve healthcare data accuracy and efficiency. We examined the effectiveness of machine learning algorithms in improving time series healthcare metrics for heart rate data transmission (accuracy and efficiency). In this paper, we reviewed several machine learning algorithms in healthcare applications. After a comprehensive overview and investigation of supervised and unsupervised machine learning algorithms, we also demonstrated time series tasks based on past values (along with reviewing their feasibility for both small and large datasets).

Impact of Specialty on Cases Performed During Spine Surgery Training in the United States.

OBJECTIVE: Two general pathways exist for spine surgery training in the United States: orthopedic surgery and neurological surgery. Previous studies have not quantified the impact of fellowship training when comparing case volumes between these 2 training pathways. This study compares reported spine surgery case volume upon graduation from orthopedic surgery and neurological surgery training. METHODS: This was a retrospective cohort study of recent graduates from orthopedic surgery and neurological Surgery training programs in the United States (2018-2021). The Accreditation Council for Graduate Medical Education provided case logs for residents in neurological surgery and orthopedic surgery as well as fellows in orthopedic spine surgery. Case volumes were compared for adult and pediatric spine surgery cases using parametric tests. RESULTS: Case logs from 3146 orthopedic surgery residents, 107 orthopedic spine surgery fellows, and 766 neurological surgery residents were included in this study. Across each cohort, neurological surgery trainees reported more total adult spine surgery cases than orthopedic surgery trainees (514 ± 206 vs. 383 ± 171, P < 0.001). Orthopedic surgery trainees reported more total pediatric spine surgery cases (21 ± 14 vs. 17 ± 12, P = 0.006). CONCLUSIONS: Neurological surgery training affords a greater volume of adult spine surgery cases, but orthopedic surgery affords more pediatric spine surgery cases. Identification of relative strengths and weaknesses can help facilitate multidisciplinary training experiences in spine surgery.

Regenerative Capability of Human Nucleus Pulposus Cells in Degenerated Disc Under Hydrostatic Pressure Mimicking Physiologically Relevant Intradiscal Pressure In Vitro.

STUDY DESIGN: Isolated human nucleus pulposus (hNP) cells from the degenerated intervertebral disc (IVD) were incubated under hydrostatic pressure (HP) and evaluated for regenerative potential. OBJECTIVES: To characterize metabolic turnover in hNP cells isolated from degenerated IVDs classified by Pfirrmann grade under physiologically relevant HP at high osmolality in vitro. SUMMARY OF BACKGROUND DATA: We demonstrated that bovine caudal nucleus pulposus cells isolated from healthy cows produced more extracellular matrix under cyclic HP followed by constant pressure (mimicking physiological intradiscal pressure in humans) than under no pressure in vitro. We assessed the effects of pressure on human degenerated cells isolated under the same regimen of pressure used for bovine cells. MATERIALS AND METHODS: hNP cells isolated from discarded tissue classified as Pfirrmann grade 2 to 3 (n = 13: age, 46.7 ± 14.0) and grade 4 (n = 13: age, 53.0 ± 11.5) were incubated under cyclic HP at 0.2 to 0.7 MPa, 0.5 Hz for 2 days followed by constant pressure at 0.3 MPa for 1 day, repeated twice over 6 days. The gene expression and immunohistology of matrix molecules and catabolic and anticatabolic proteins were evaluated. RESULTS: Aggrecan and collagen type II expression were significantly more upregulated under HP in grades 2 to 3 than in grade 4 tissues (both, P < 0.01). Linear regression analysis showed a positive correlation between matrix metalloproteinase 13 and tissue inhibitor for metalloproteinase 2 expression in grades 2 to 3, whereas a negative correlation was found in grade 4 ( P < 0.05). Immunohistological staining revealed the activation of a mechanoreceptor, transient receptor potential vanilloid 4, under HP. CONCLUSIONS: Resident cells in mild-moderate degenerated discs classified as Pfirrmann grade 2 to 3 have the potential to promote extracellular matrix production and maintain adequate cell viability under physiological spinal loading. RELEVANCE: This study explored the potential of degenerated remnant nucleus pulposus cells under a physiological environment, possibly leading to establishing strategies for IVD regeneration.

Serotonin and Dopamine Show Different Response Profiles to Acute Stress in the Nucleus Accumbens and Medial Prefrontal Cortex of Rats with Neuropathic Pain.

The ability to adaptively guide behaviour requires the integration of external information with internal motivational factors. Decision-making capabilities can be impaired by acute stress and is often exacerbated by chronic pain. Chronic neuropathic pain patients often present with cognitive dysfunction, including impaired decision-making. The mechanisms underlying these changes are not well understood but may include altered monoaminergic transmission in the brain. In this study we investigated the relationships between dopamine, serotonin, and their metabolites in key brain regions that regulate motivated behaviour and decision-making. The neurochemical profiles of the medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens were analysed using HPLC in rats that received a chronic constriction injury (CCI) of the right sciatic nerve and an acute stress (15-min restraint), prior to an outcome devaluation task. CCI alone significantly decreased dopamine but not serotonin concentrations in the medial prefrontal cortex. By contrast, restraint stress acutely increased dopamine in the medial prefrontal cortex, and the nucleus accumbens; and increased serotonin in the medial prefrontal cortex 2 h later. The sustained dopaminergic and serotonergic responses to acute stress highlight the importance of an animal's ability to mount an effective coping response. In addition, these data suggest that the impact of nerve injury and acute stress on outcome-devaluation occurs independently of dopaminergic and serotonergic transmission in the medial prefrontal cortex, orbital prefrontal cortex and nucleus accumbens of rats.

Utility of Spine Surgery Fellowship Training for Orthopaedic Surgeons in the United States.

INTRODUCTION: Orthopaedic spine surgeons gain surgical experience through cases conducted during residency and fellowship training. This study elucidates the incremental benefit in spine surgery volume from orthopaedic spine surgery fellowship training. METHODS: This was a retrospective national cohort study of orthopaedic surgery residents and orthopaedic spine surgery fellows graduating from US Accreditation Council for Graduate Medical Education-accredited training programs during the 2017 to 2020 academic years. Comparisons in spine surgery case volume were made with parametric tests. RESULTS: One hundred fourteen spine surgery fellows and 3,000 orthopaedic surgery residents were included. There was a 3.5-fold increase in total spine surgery cases conducted during fellowship versus residency (314 ± 129 vs. 89 ± 61, P < 0.001). Spine surgery fellows one standard deviation more than the mean reported 443 total spine cases. The largest differences between fellows and residents were Decompression (104 ± 48 vs. 28 ± 23, P < 0.001), Posterior Arthrodesis (94 ± 46 vs. 21 ± 18, P < 0.001), Anterior Arthrodesis (64 ± 31 vs. 13 ± 13, P < 0.001), and Instrumentation (43 ± 25 vs. 22 ± 12, P < 0.001). DISCUSSION: Spine surgery fellowship training affords orthopaedic surgeons the opportunity to increase spine surgery case volume by over threefold. The greatest increases in case volume were reported for Decompression, Posterior Arthrodesis, Anterior Arthrodesis, and Instrumentation.