Identification and characterization of calcium binding protein, spermatid-associated 1 (CABS1)# in selected human tissues and fluids.

Calcium binding protein, spermatid associated 1 (CABS1) is a protein most widely studied in spermatogenesis. However, mRNA for CABS1 has been found in numerous tissues, albeit with little information about the protein. Previously, we identified CABS1 mRNA and protein in human salivary glands and provided evidence that in humans CABS1 contains a heptapeptide near its carboxyl terminus that has anti-inflammatory activities. Moreover, levels of an immunoreactive form of CABS1 were elevated in psychological stress. To more fully characterize human CABS1 we developed additional polyclonal and monoclonal antibodies to different sections of the protein and used these antibodies to characterize CABS1 in an overexpression cell lysate, human salivary glands, saliva, serum and testes using western blot, immunohistochemistry and bioinformatics approaches exploiting the Gene Expression Omnibus (GEO) database. CABS1 appears to have multiple molecular weight forms, consistent with its recognition as a structurally disordered protein, a protein with structural plasticity. Interestingly, in human testes, its cellular distribution differs from that in rodents and pigs, and includes Leydig cells, primary spermatogonia, Sertoli cells and developing spermatocytes and spermatids, Geodata suggests that CABS1 is much more widely distributed than previously recognized, including in the urogenital, gastrointestinal and respiratory tracts, as well as in the nervous system, immune system and other tissues. Much remains to be learned about this intriguing protein.

Justice for Women After Sexual Assault: A Critical Interpretive Synthesis.

Justice after sexual assault is often understood and enacted through the criminal legal system such that the outcomes are binary (i.e., justice is achieved or not achieved). Previous research indicates that survivors have specific wants and needs following an assault in order to experience justice, which may or may not align with current practices. We conducted a critical interpretive synthesis of 5 databases to create a sampling frame of 4,203 records; the final analysis included 81 articles, book chapters, and policy documents. Results indicate that justice is an individualized and dynamic process which may include the experience of voice, connectedness, participating in a process, accountability, and prevention. The experiences of safety and control are central to each of these domains. Survivors may seek and enact these justice domains through several avenues, including the criminal justice and legal systems, restorative justice, medical/mental health spaces, activism, art, and social media. Existing actors within currently available justice systems, including legal, medical, and mental health personnel should encourage survivors to identify and define their own experience of justice, including locating helpful behaviors rooted in safety and control, and resist a binary model of justice. Extant systems should therefore be flexible and accessible to help survivors realize their preferred modes of justice.

Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing.

Fentanyl elicits profound disturbances in ventilatory control processes in humans and experimental animals. The traditional viewpoint with respect to fentanyl-induced respiratory depression is that once the effects on the frequency of breathing (Freq), tidal volume (TV), and minute ventilation (MV = Freq × TV) are resolved, then depression of breathing is no longer a concern. The results of the present study challenge this concept with findings, as they reveal that while the apparent inhibitory effects of fentanyl (75 µg/kg, IV) on Freq, TV, and MV in adult male rats were fully resolved within 15 min, many other fentanyl-induced responses were in full effect, including opposing effects on respiratory timing parameters. For example, although the effects on Freq were resolved at 15 min, inspiratory duration (Ti) and end inspiratory pause (EIP) were elevated, whereas expiratory duration (Te) and end expiratory pause (EEP) were diminished. Since the effects of fentanyl on TV had subsided fully at 15 min, it would be expected that the administration of an opioid receptor (OR) antagonist would have minimal effects if the effects of fentanyl on this and other parameters had resolved. We now report that the intravenous injection of a 1.0 mg/kg dose of the peripherally restricted OR antagonist, methyl-naloxone (naloxone methiodide, NLXmi), did not elicit arousal but elicited some relatively minor changes in Freq, TV, MV, Te, and EEP but pronounced changes in Ti and EIP. In contrast, the injection of a 2.5 mg/kg dose of NLXmi elicited pronounced arousal and dramatic changes in many variables, including Freq, TV, and MV, which were not associated with increases in non-apneic breathing events such as apneas. The two compelling conclusions from this study are as follows: 1) the blockade of central ORs produced by the 2.5 mg/kg dose of NLXmi elicits pronounced increases in Freq, TV, and MV in rats in which the effects of fentanyl had apparently resolved, and 2) it is apparent that fentanyl had induced the activation of two systems with counter-balancing effects on Freq and TV: one being an opioid receptor inhibitory system and the other being a non-OR excitatory system.

Philosophies And Surgical Techniques for Ewing's Sarcoma of Spine with Review of Literature.

Introduction: Ewing sarcoma (ES) is a malignant and aggressive bony tumor affecting the most common age group of 5-20 years. It constitutes 10%-15% of all bone sarcomas and is the second most common primary malignant bone tumor after osteosarcoma. It usually presents with pain, which is typically constant and progressive in nature. The primary source of pain is due to the instability of the spine to support the weight of the body, the vertebral body's expanding cortices due to the growing mass, compression of nerve roots due to tumour mass, pathologic fractures, spinal cord compression, and invasion of tissue by the tumour mass. Methods: We reviewed the literature on Ewing's Sarcoma of the spine to evaluate its etiology, clinical presentations, differential diagnosis, imaging modalities and management with chemotherapy, radiotherapy, and surgical management. PubMed, EMBASE, Google Scholar and Cochrane key articles were searched. Keywords like 'Ewing's Sarcoma,' 'Spine,' 'etiology,' 'treatment,' 'surgical management,' and 'en bloc resection' were used. Discussion: The current management of Ewing's sarcoma of the spine usually involves three primary modalities: combination chemotherapy, surgery and/or radiotherapy. Recent improvements in combination chemotherapy (vincristine, doxorubicin, cyclophosphamide +/- Ifosfamide and etoposide) are among the most significant factors for improving survival. Also, recent advancements in radiotherapy, instrumentation, and fusion techniques in surgical management have been demonstrated to improve local disease control and overall survival. Conclusion: Primary Ewing sarcoma of the spine is a rare condition affecting the most common age group of 5-20 years, accounting for 1-3 cases/million/year. About 5 % of cases have spine involvement. Recent improvements in combination chemotherapy have improved the overall survival rates. Enbloc resection and/or radiotherapy have improved local control of the disease.

Surgeon Preference Regarding Wound Dressing Management in Lumbar Fusion Surgery: An AO Spine Global Cross-Sectional Study.

OBJECTIVE: To evaluate the global practice pattern of wound dressing use after lumbar fusion for degenerative conditions. METHODS: A survey issued by AO Spine Knowledge Forums Deformity and Degenerative was sent out to AO Spine members. The type of postoperative dressing employed, timing of initial dressing removal, and type of subsequent dressing applied were investigated. Differences in the type of surgery and regional distribution of surgeons' preferences were analyzed. RESULTS: Right following surgery, 60.6% utilized a dry dressing, 23.2% a plastic occlusive dressing, 5.7% glue, 6% a combination of glue and polyester mesh, 2.6% a wound vacuum, and 1.2% other dressings. The initial dressing was removed on postoperative day 1 (11.6%), 2 (39.2%), 3 (20.3%), 4 (1.7%), 5 (4.3%), 6 (0.4%), 7 or later (12.5%), or depending on drain removal (9.9%). Following initial dressing removal, 75.9% applied a dry dressing, 17.7% a plastic occlusive dressing, and 1.3% glue, while 12.1% used no dressing. The use of no additional coverage after initial dressing removal was significantly associated with a later dressing change (p < 0.001). Significant differences emerged after comparing dressing management among different AO Spine regions (p < 0.001). CONCLUSION: Most spine surgeons utilized a dry or plastic occlusive dressing initially applied after surgery. The first dressing was more frequently changed during the first 3 postoperative days and replaced with the same type of dressing. While dressing policies tended not to vary according to the type of surgery, regional differences suggest that actual practice may be based on personal experience rather than available evidence.

Post-operative bracing following adult spine deformity surgery: Results from the AO Spine surveillance of post-operative management of patients with adult spine deformity.

STUDY DESIGN: Cross-sectional international survey with a literature review. OBJECTIVES: While some surgeons favor spine bracing after surgery for adult spine deformity (ASD) to help prevent mechanical failures, there is a lack of evidence. The objective of the present study was to better understand the current trend in the use of bracing following ASD surgery based on an international survey. METHODS: An e-mail-based online survey was conducted among over 6000 international AO Spine members regarding the post-operative management of patients with ASD. The details of brace prescription, indications and influencing factors were solicited. Descriptive data were summarized based on different demographic groups and fusion levels for the responding surgeons who annually perform at least 10 long-segment fusions of >5 levels extending to the pelvis. RESULTS: A total of 116 responses were received, including 71 surgeons (61%) who used post-operative bracing for >5 levels of long fusion. The most common reason for bracing was pain management (55%) and bone quality was the strongest influencing factor (69%). Asia-Pacific surgeons had the highest rate of bracing (88%), while North American surgeons had the lowest (45%). The most common type of brace used were TLSO for cases with an uppermost instrumented vertebra (UIV) in the low- or mid-thoracic spine and a cervical brace for UIV at T1-3. The majority (56%) used bracing for 6-12 weeks after surgery. CONCLUSIONS: The present survey demonstrated significant interest in bracing following ASD surgery, however, there is substantial variability in post-operative bracing practice. A formal study on the role of bracing in ASD surgery is needed.

L-NAC and L-NAC methyl ester prevent and overcome physical dependence to fentanyl in male rats.

N-acetyl-L-cysteine (L-NAC) is a proposed therapeutic for opioid use disorder. This study determined whether co-injections of L-NAC (500 µmol/kg, IV) or its highly cell-penetrant analogue, L-NAC methyl ester (L-NACme, 500 µmol/kg, IV), prevent acquisition of acute physical dependence induced by twice-daily injections of fentanyl (125 µg/kg, IV), and overcome acquired dependence to these injections in freely-moving male Sprague Dawley rats. The injection of the opioid receptor antagonist, naloxone HCl (NLX; 1.5 mg/kg, IV), elicited a series of withdrawal phenomena (i.e. behavioral and cardiorespiratory responses, hypothermia and body weight loss) in rats that received 5 or 10 injections of fentanyl and similar numbers of vehicle co-injections. With respect to the development of dependence, the NLX-precipitated withdrawal phenomena were reduced in rats that received had co-injections of L-NAC, and more greatly reduced in rats that received co-injections of L-NACme. In regard to overcoming established dependence, the NLX-precipitated withdrawal phenomena in rats that had received 10 injections of fentanyl (125 µg/kg, IV) were reduced in rats that had received co-injections of L-NAC, and more greatly reduced in rats that received co-injections of L-NACme beginning with injection 6 of fentanyl. This study provides compelling evidence that co-injections of L-NAC and L-NACme prevent the acquisition of physical dependence and overcome acquired dependence to fentanyl in male rats. The higher efficacy of L-NACme is likely due to its greater cell penetrability in brain regions mediating dependence to fentanyl and interaction with intracellular signaling cascades, including redox-dependent processes, responsible for the acquisition of physical dependence to fentanyl.

The Reducing Agent Dithiothreitol Modulates the Ventilatory Responses That Occur in Freely Moving Rats during and following a Hypoxic-Hypercapnic Challenge.

The present study examined the hypothesis that changes in the oxidation-reduction state of thiol residues in functional proteins play a major role in the expression of the ventilatory responses in conscious rats that occur during a hypoxic-hypercapnic (HH) gas challenge and upon return to room air. A HH gas challenge in vehicle-treated rats elicited robust and sustained increases in minute volume (via increases in frequency of breathing and tidal volume), peak inspiratory and expiratory flows, and inspiratory and expiratory drives while minimally affecting the non-eupneic breathing index (NEBI). The HH-induced increases in these parameters, except for frequency of breathing, were substantially diminished in rats pre-treated with the potent and lipophilic disulfide-reducing agent, L,D-dithiothreitol (100 µmol/kg, IV). The ventilatory responses that occurred upon return to room air were also substantially different in dithiothreitol-treated rats. In contrast, pre-treatment with a substantially higher dose (500 µmol/kg, IV) of the lipophilic congener of the monosulfide, N-acetyl-L-cysteine methyl ester (L-NACme), only minimally affected the expression of the above-mentioned ventilatory responses that occurred during the HH gas challenge or upon return to room air. The effectiveness of dithiothreitol suggests that the oxidation of thiol residues occurs during exposure to a HH gas challenge and that this process plays an essential role in allowing for the expression of the post-HH excitatory phase in breathing. However, this interpretation is contradicted by the lack of effects of L-NACme. This apparent conundrum may be explained by the disulfide structure affording unique functional properties to dithiothreitol in comparison to monosulfides. More specifically, the disulfide structure may give dithiothreitol the ability to alter the conformational state of functional proteins while transferring electrons. It is also possible that dithiothreitol is simply a more efficient reducing agent following systemic injection, although one interpretation of the data is that the effects of dithiothreitol are not due to its reducing ability.

Laxative use in adults with intellectual disabilities: development of prescribing guidelines.

BACKGROUND: Constipation is overrepresented in people with intellectual disabilities. Around 40% of people with intellectual disabilities who died prematurely were prescribed laxatives. A quarter of people with intellectual disabilities are said to be on laxatives. There are concerns that prescribing is not always effective and appropriate. There are currently no prescribing guidelines specific to this population. AIMS: To develop guidelines to support clinicians with their decision-making when prescribing laxatives to people with intellectual disabilities. METHOD: A modified Delphi methodology, the RAND/UCLA Appropriateness Method, was used. Step 1 comprised development of a bespoke six-item, open-ended questionnaire from background literature and its external validation. Relevant stakeholders, including a range of clinical experts and experts by experience covering the full range of intellectual disability and constipation, were invited to participate in an expert panel. Panel members completed the questionnaire. Responses were divided into 'negative consensus' and 'positive consensus'. Members were then invited to two panel meetings, 2 weeks apart, held virtually over Microsoft Teams, to build consensus. The expert-by-experience group were included in a separate face-to-face meeting. RESULTS: A total of 20 people (ten professional experts and ten experts by experience, of whom seven had intellectual disability) took part. There were five main areas of discussion to reach a consensus i.e. importance of diagnosis, the role of prescribing, practicalities of medication administration, importance of reviewing and monitoring, and communication. CONCLUSIONS: Laxative prescribing guidelines were developed by synthesising the knowledge of an expert panel including people with intellectual disabilities with the existing evidence base, to improve patient care.

Analysis of tranexamic acid usage in adult spinal deformity patients with relative contraindications: does it increase the risk of complications?

OBJECTIVE: Complex spinal deformity surgeries may involve significant blood loss. The use of antifibrinolytic agents such as tranexamic acid (TXA) has been proven to reduce perioperative blood loss. However, for patients with a history of thromboembolic events, there is concern of increased risk when TXA is used during these surgeries. This study aimed to assess whether TXA use in patients undergoing complex spinal deformity correction surgeries increases the risk of thromboembolic complications based on preexisting thromboembolic risk factors. METHODS: Data were analyzed for adult patients who received TXA during surgical correction for spinal deformity at 21 North American centers between August 2018 and October 2022. Patients with preexisting thromboembolic events and other risk factors (history of deep venous thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], stroke, peripheral vascular disease, or cancer) were identified. Thromboembolic complication rates were assessed during the postoperative 90 days. Univariate and multivariate analyses were performed to assess thromboembolic outcomes in high-risk and low-risk patients who received intravenous TXA. RESULTS: Among 411 consecutive patients who underwent complex spinal deformity surgery and received TXA intraoperatively, 130 (31.6%) were considered high-risk patients. There was no significant difference in thromboembolic complications between patients with and those without preexisting thromboembolic risk factors in univariate analysis (high-risk group vs low-risk group: 8.5% vs 2.8%, p = 0.45). Specifically, there were no significant differences between groups regarding the 90-day postoperative rates of DVT (high-risk group vs low-risk group: 1.5% vs 1.4%, p = 0.98), PE (2.3% vs 1.8%, p = 0.71), acute MI (1.5% vs 0%, p = 0.19), or stroke (0.8% vs 1.1%, p > 0.99). On multivariate analysis, high-risk status was not a significant independent predictor for any of the thromboembolic complications. CONCLUSIONS: Administration of intravenous TXA during the correction procedure did not change rates of thromboembolic events, acute MI, or stroke in this cohort of adult spinal deformity surgery patients.

Stronger association of objective physical metrics with baseline patient-reported outcome measures than preoperative standing sagittal parameters for adult spinal deformity patients.

OBJECTIVE: Sagittal alignment measured on standing radiography remains a fundamental component of surgical planning for adult spinal deformity (ASD). However, the relationship between classic sagittal alignment parameters and objective metrics, such as walking time (WT) and grip strength (GS), remains unknown. The objective of this work was to determine if ASD patients with worse baseline sagittal malalignment have worse objective physical metrics and if those metrics have a stronger relationship to patient-reported outcome metrics (PROMs) than standing alignment. METHODS: The authors conducted a retrospective review of a multicenter ASD cohort. ASD patients underwent baseline testing with the timed up-and-go 6-m walk test (seconds) and for GS (pounds). Baseline PROMs were surveyed, including Oswestry Disability Index (ODI), Patient-Reported Outcomes Measurement Information System (PROMIS), Scoliosis Research Society (SRS)-22r, and Veterans RAND 12 (VR-12) scores. Standard spinopelvic measurements were obtained (sagittal vertical axis [SVA], pelvic tilt [PT], and mismatch between pelvic incidence and lumbar lordosis [PI-LL], and SRS-Schwab ASD classification). Univariate and multivariable linear regression modeling was performed to interrogate associations between objective physical metrics, sagittal parameters, and PROMs. RESULTS: In total, 494 patients were included, with mean ± SD age 61 ± 14 years, and 68% were female. Average WT was 11.2 ± 6.1 seconds and average GS was 56.6 ± 24.9 lbs. With increasing PT, PI-LL, and SVA quartiles, WT significantly increased (p < 0.05). SRS-Schwab type N patients demonstrated a significantly longer average WT (12.5 ± 6.2 seconds), and type T patients had a significantly shorter WT time (7.9 ± 2.7 seconds, p = 0.03). With increasing PT quartiles, GS significantly decreased (p < 0.05). SRS-Schwab type T patients had a significantly higher average GS (68.8 ± 27.8 lbs), and type L patients had a significantly lower average GS (51.6 ± 20.4 lbs, p = 0.03). In the frailty-adjusted multivariable linear regression analyses, WT was more strongly associated with PROMs than sagittal parameters. GS was more strongly associated with ODI and PROMIS Physical Function scores. CONCLUSIONS: The authors observed that increasing baseline sagittal malalignment is associated with slower WT, and possibly weaker GS, in ASD patients. WT has a stronger relationship to PROMs than standing alignment parameters. Objective physical metrics likely offer added value to standard spinopelvic measurements in ASD evaluation and surgical planning.

Factors Associated with the Maintenance of Cost-Effectiveness at 5 Years in Adult Spinal Deformity Corrective Surgery.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate factors associated with the long-term durability of cost-effectiveness (CE) in ASD patients. BACKGROUND: A substantial increase in costs associated with the surgical treatment for adult spinal deformity (ASD) has given precedence to scrutinize the value and utility it provides. METHODS: We included 327 operative ASD patients with 5-year (5 Y) follow-up. Published methods were used to determine costs based on CMS.gov definitions and were based on the average DRG reimbursement rates. Utility was calculated using quality-adjusted life-years (QALY) utilizing the Oswestry Disability Index (ODI) converted to Short-Form Six-Dimension (SF-6D), with a 3% discount applied for its decline with life expectancy. The CE threshold of $150,000 was used for primary analysis. RESULTS: Major and minor complication rates were 11% and 47% respectively, with 26% undergoing reoperation by 5 Y. The mean cost associated with surgery was $91,095±$47,003, with a utility gain of 0.091±0.086 at 1Y, QALY gained at 2 Y of 0.171±0.183, and at 5 Y of 0.42±0.43. The cost per QALY at 2 Y was $414,885, which decreased to $142,058 at 5 Y.With the threshold of $150,000 for CE, 19% met CE at 2 Y and 56% at 5 Y. In those in which revision was avoided, 87% met cumulative CE till life expectancy. Controlling analysis depicted higher baseline CCI and pelvic tilt (PT) to be the strongest predictors for not maintaining durable CE to 5 Y (CCI OR: 1.821 [1.159-2.862], P=0.009) (PT OR: 1.079 [1.007-1.155], P=0.030). CONCLUSIONS: Most patients achieved cost-effectiveness after four years postoperatively, with 56% meeting at five years postoperatively. When revision was avoided, 87% of patients met cumulative cost-effectiveness till life expectancy. Mechanical complications were predictive of failure to achieve cost-effectiveness at 2 Y, while comorbidity burden and medical complications were at 5 Y.

Pedicle screw accuracy placed with assistance of machine vision technology in patients with neuromuscular scoliosis.

INTRODUCTION: Pedicle screws are the primary method of vertebral fixation in scoliosis surgery, but there are lingering concerns over potential malposition. The rates of pedicle screw malposition in pediatric spine surgery vary from 10% to 21%. Malpositioned screws can lead to potentially catastrophic neurological, vascular, and visceral complications. Pedicle screw positioning in patients with neuromuscular scoliosis is challenging due to a combination of large curves, complex pelvic anatomy, and osteopenia. This study aimed to determine the rate of pedicle screw malposition, associated complications, and subsequent revision from screws placed with the assistance of machine vision navigation technology in patients with neuromuscular scoliosis undergoing posterior instrumentation and fusion. METHOD: A retrospective analysis of the records of patients with neuromuscular scoliosis who underwent thoracolumbar pedicle screw insertion with the assistance of machine-vision image guidance navigation was performed. Screws were inserted by either a staff surgeon, orthopaedic fellow, or orthopaedic resident. Post-operative ultra-low dose CT scans were used to assess pedicle screw accuracy. The Gertzbein classification was used to grade any pedicle breaches (grade 0, no breach; grade 1, <2 mm; grade 2, 2-4 mm; grade 3, >4 mm). A screw was deemed accurate if no breach was identified (grade 0). RESULTS: 25 patients were included in the analysis, with a mean age of 13.6 years (range 11 to 18 years; 13/25 (52.0%) were female. The average pre-operative supine Cobb angle was 90.0 degrees (48-120 degrees). A total of 687 screws from 25 patients were analyzed (402 thoracic, 241 lumbosacral, 44 S2 alar-iliac (S2AI) screws). Surgical trainees (fellows and orthopaedic residents) inserted 46.6% (320/687) of screws with 98.8% (4/320) accuracy. The overall accuracy of pedicle screw insertion was 98.0% (Grade 0, no breach). All 13 breaches that occurred in the thoracic and lumbar screws were Grade 1. Of the 44 S2AI screws placed, one screw had a Grade 3 breach (2.3%) noted on intra-operative radiographs following rod placement and correction. This screw was subsequently revised. None of the breaches resulted in neuromonitoring changes, vessel, or visceral injuries. CONCLUSION: Machine vision navigation technology combined with careful free-hand pedicle screw insertion techniques demonstrated high levels of pedicle screw insertion accuracy, even in patients with challenging anatomy.

Impact of Hip and Knee Osteoarthritis on Full Body Sagittal Alignment and Compensation for Sagittal Spinal Deformity.

STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To investigate the effect of lower extremity osteoarthritis on sagittal alignment and compensatory mechanisms in adult spinal deformity (ASD). BACKGROUND: Spine, hip, and knee pathologies often overlap in ASD patients. Limited data exists on how lower extremity osteoarthritis impacts sagittal alignment and compensatory mechanisms in ASD. PATIENTS AND METHODS: In total, 527 preoperative ASD patients with full body radiographs were included. Patients were grouped by Kellgren-Lawrence grade of bilateral hips and knees and stratified by quartile of T1-Pelvic Angle (T1PA) severity into low-, mid-, high-, and severe-T1PA. Full-body alignment and compensation were compared across quartiles. Regression analysis examined the incremental impact of hip and knee osteoarthritis severity on compensation. RESULTS: The mean T1PA for low-, mid-, high-, and severe-T1PA groups was 7.3°, 19.5°, 27.8°, and 41.6°, respectively. Mid-T1PA patients with severe hip osteoarthritis had an increased sagittal vertical axis and global sagittal alignment ( P <0.001). Increasing hip osteoarthritis severity resulted in decreased pelvic tilt ( P =0.001) and sacrofemoral angle ( P <0.001), but increased knee flexion ( P =0.012). Regression analysis revealed that with increasing T1PA, pelvic tilt correlated inversely with hip osteoarthritis and positively with knee osteoarthritis ( r2 =0.812). Hip osteoarthritis decreased compensation through sacrofemoral angle (ß-coefficient=-0.206). Knee and hip osteoarthritis contributed to greater knee flexion (ß-coefficients=0.215, 0.101; respectively). For pelvic shift, only hip osteoarthritis significantly contributed to the model (ß-coefficient=0.100). CONCLUSIONS: For the same magnitude of spinal deformity, increased hip osteoarthritis severity was associated with worse truncal and full body alignment with posterior translation of the pelvis. Patients with severe hip and knee osteoarthritis exhibited decreased hip extension and pelvic tilt but increased knee flexion. This examines sagittal alignment and compensation in ASD patients with hip and knee arthritis and may help delineate whether hip and knee flexion is due to spinal deformity compensation or lower extremity osteoarthritis.

Persistent Lower Extremity Compensation for Sagittal Imbalance After Surgical Correction of Complex Adult Spinal Deformity: A Radiographic Analysis of Early Impact.

BACKGROUND AND OBJECTIVES: Achieving spinopelvic realignment during adult spinal deformity (ASD) surgery does not always produce ideal outcomes. Little is known whether compensation in lower extremities (LEs) plays a role in this disassociation. The objective is to analyze lower extremity compensation after complex ASD surgery, its effect on outcomes, and whether correction can alleviate these mechanisms. METHODS: We included patients with complex ASD with 6-week data. LE parameters were as follows: sacrofemoral angle, knee flexion angle, and ankle flexion angle. Each parameter was ranked, and upper tertile was deemed compensation. Patients compensating and not compensating postoperatively were propensity score matched for body mass index, frailty, and T1 pelvic angle. Linear regression assessed correlation between LE parameters and baseline deformity, demographics, and surgical details. Multivariate analysis controlling for baseline deformity and history of total knee/hip arthroplasty evaluated outcomes. RESULTS: Two hundred and ten patients (age: 61.3 ± 14.1 years, body mass index: 27.4 ± 5.8 kg/m2, Charlson Comorbidity Index: 1.1 ± 1.6, 72% female, 22% previous total joint arthroplasty, 24% osteoporosis, levels fused: 13.1 ± 3.8) were included. At baseline, 59% were compensating in LE: 32% at hips, 39% knees, and 36% ankles. After correction, 61% were compensating at least one joint. Patients undercorrected postoperatively were less likely to relieve LE compensation (odds ratio: 0.2, P = .037). Patients compensating in LE were more often undercorrected in age-adjusted pelvic tilt, pelvic incidence, lumbar lordosis, and T1 pelvic angle and disproportioned in Global Alignment and Proportion (P < .05). Patients matched in sagittal age-adjusted score at 6 weeks but compensating in LE were more likely to develop proximal junctional kyphosis (odds ratio: 4.1, P = .009) and proximal junctional failure (8% vs 0%, P = .035) than those sagittal age-adjusted score-matched and not compensating in LE. CONCLUSION: Perioperative lower extremity compensation was a product of undercorrecting complex ASD. Even in age-adjusted realignment, compensation was associated with global undercorrection and junctional failure. Consideration of lower extremities during planning is vital to avoid adverse outcomes in perioperative course after complex ASD surgery.

L-cysteine ethylester reverses the adverse effects of morphine on breathing and arterial blood-gas chemistry while minimally affecting antinociception in unanesthetized rats.

L-cysteine ethylester (L-CYSee) is a membrane-permeable analogue of L-cysteine with a variety of pharmacological effects. The purpose of this study was to determine the effects of L-CYSee on morphine-induced changes in ventilation, arterial-blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient (i.e., a measure of the index of alveolar gas-exchange), antinociception and sedation in male Sprague Dawley rats. An injection of morphine (10 mg/kg, IV) produced adverse effects on breathing, including sustained decreases in minute ventilation. L-CYSee (500 µmol/kg, IV) given 15 min later immediately reversed the actions of morphine. Another injection of L-CYSee (500 µmol/kg, IV) after 15 min elicited more pronounced excitatory ventilatory responses. L-CYSee (250 or 500 µmol/kg, IV) elicited a rapid and prolonged reversal of the actions of morphine (10 mg/kg, IV) on ABG chemistry (pH, pCO2, pO2, sO2) and A-a gradient. L-serine ethylester (an oxygen atom replaces the sulfur; 500 µmol/kg, IV), was ineffective in all studies. L-CYSee (500 µmol/kg, IV) did not alter morphine (10 mg/kg, IV)-induced sedation, but slightly reduced the overall duration of morphine (5 or 10 mg/kg, IV)-induced analgesia. In summary, L-CYSee rapidly overcame the effects of morphine on breathing and alveolar gas-exchange, while not affecting morphine sedation or early-stage analgesia. The mechanisms by which L-CYSee modulates morphine depression of breathing are unknown, but appear to require thiol-dependent processes.

Lumbar Lordosis Redistribution and Segmental Correction in Adult Spinal Deformity (ASD): Does it Matter?

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: Evaluate the impact of correcting to normative segmental lordosis values on post-operative outcomes. BACKGROUND: Restoring lumbar lordosis magnitude is crucial in adult spinal deformity surgery, but the optimal location and segmental distribution remains unclear. METHODS: Patients were grouped based on offset to normative segmental lordosis values, extracted from recent publications. Matched patients were within 10% of the cohort's mean offset, less than or over 10% were under- and over-corrected. Surgical technique, PROMs, and surgical complications were compared across groups at baseline and 2-year. RESULTS: 510 patients with an average age of 64.6, mean CCI 2.08, and average follow-up of 25 months. L4-5 was least likely to be matched (19.1%), while L4-S1 was the most likely (24.3%). More patients were overcorrected at proximal levels (T10-L2; Undercorrected, U: 32.2% vs. Matched, M: 21.7% vs. Overcorrected, O: 46.1%) and undercorrected at distal levels (L4-S1: U: 39.0% vs. M: 24.3% vs. O: 36.8%). Postoperative ODI was comparable across correction groups at all spinal levels except at L4-S1 and T10-L2/L4-S1, where overcorrected patients and matched were better than undercorrected (U: 32.1 vs. M: 25.4 vs. O: 26.5, P=0.005; U: 36.2 vs. M: 24.2 vs. O: 26.8, P=0.001; respectively). Patients overcorrected at T10-L2 experienced higher rates of proximal junctional failure (PJF) (U: 16.0% vs. M: 15.6% vs. O: 32.8%, P<0.001) and had greater posterior inclination of the upper instrumented vertebra (UIV) (U: -9.2±9.4° vs. M: -9.6±9.1° vs. O: -12.2±10.0°, P<0.001), whereas undercorrection at these levels led to higher rates of revision for implant failure (U: 14.2% vs. M: 7.3% vs. O: 6.4%, P=0.025). CONCLUSIONS: Patients undergoing fusion for adult spinal deformity suffer higher rates of PJF with overcorrection and increased rates of implant failure with undercorrection based on normative segmental lordosis. LEVEL OF EVIDENCE: IV.

Selective neural inhibition via photobiomodulation alleviates behavioral hypersensitivity associated with small sensory fiber activation.

OBJECTIVE: Photobiomodulation at higher irradiances has great potential as a pain-alleviating method that selectively inhibits small diameter nerve fibers and corresponding sensory experiences, such as nociception and heat sensation. The longevity and magnitude of these effects as a function of laser irradiation parameters at the nerve was explored. METHODS: In a rodent chronic pain model (spared nerve injury-SNI), light was applied directly at the sural nerve with four delivery schemes: two irradiance levels (7.64 and 2.55 W/cm2 ) for two durations each, corresponding to either 4.8 or 14.4 J total energy, and the effect on sensory hypersensitivities was evaluated. RESULTS: At emitter irradiances of 7.64 W/cm2 (for 240 s), 2.55 W/cm2 (for 720 s), and 7.64 W/cm2 (for 80 s) the heat hypersensitivity was relieved the day following photobiomodulation (PBM) treatment by 37 ± 8.1% (statistically significant, p < 0.001), 26% ± 6% (p = 0.072), and 28 ± 6.1% (statistically significant, p = 0.032), respectively, and all three treatments reduced the hypersensitivity over the course of the experiment (13 days) at a statistically significant level (mixed-design analysis of variance, p < 0.05). The increases in tissue temperature (5.3 ± 1.0 and 1.3 ± 0.4°C from 33.3°C for the higher and lower power densities, respectively) at the neural target were well below those typically associated with permanent action potential disruption. CONCLUSIONS: The data from this study support the use of direct PBM on nerves of interest to reduce sensitivities associated with small-diameter fiber activity.

Predicting the spatial distribution of wintering golden eagles to inform full annual cycle conservation in western North America.

Wildlife conservation strategies focused on one season or population segment may fail to adequately protect populations, especially when a species' habitat preferences vary among seasons, age-classes, geographic regions, or other factors. Conservation of golden eagles (Aquila chrysaetos) is an example of such a complex scenario, in which the distribution, habitat use, and migratory strategies of this species of conservation concern vary by age-class, reproductive status, region, and season. Nonetheless, research aimed at mapping priority use areas to inform management of golden eagles in western North America has typically focused on territory-holding adults during the breeding period, largely to the exclusion of other seasons and life-history groups. To support population-wide conservation planning across the full annual cycle for golden eagles, we developed a distribution model for individuals in a season not typically evaluated-winter-and in an area of the interior western U.S. that is a high priority for conservation of the species. We used a large GPS-telemetry dataset and library of environmental variables to develop a machine-learning model to predict spatial variation in the relative intensity of use by golden eagles during winter in Wyoming, USA, and surrounding ecoregions. Based on a rigorous series of evaluations including cross-validation, withheld and independent data, our winter-season model accurately predicted spatial variation in intensity of use by multiple age- and life-history groups of eagles not associated with nesting territories (i.e., all age classes of long-distance migrants, and resident non-adults and adult "floaters", and movements of adult territory holders and their offspring outside their breeding territories). Important predictors in the model were wind and uplift (40.2% contribution), vegetation and landcover (27.9%), topography (14%), climate and weather (9.4%), and ecoregion (8.7%). Predicted areas of high-use winter habitat had relatively low spatial overlap with nesting habitat, suggesting a conservation strategy targeting high-use areas for one season would capture as much as half and as little as one quarter of high-use areas for the other season. The majority of predicted high-use habitat (top 10% quantile) occurred on private lands (55%); lands managed by states and the Bureau of Land Management (BLM) had a lower amount (33%), but higher concentration of high-use habitat than expected for their area (1.5-1.6x). These results will enable those involved in conservation and management of golden eagles in our study region to incorporate spatial prioritization of wintering habitat into their existing regulatory processes, land-use planning tasks, and conservation actions.

Predictors of pelvic tilt normalization: a multicenter study on the impact of regional and lower-extremity compensation on pelvic alignment after complex adult spinal deformity surgery.

OBJECTIVE: The objective was to determine the degree of regional decompensation to pelvic tilt (PT) normalization after complex adult spinal deformity (ASD) surgery. METHODS: Operative ASD patients with 1 year of PT measurements were included. Patients with normalized PT at baseline were excluded. Predicted PT was compared to actual PT, tested for change from baseline, and then compared against age-adjusted, Scoliosis Research Society-Schwab, and global alignment and proportion (GAP) scores. Lower-extremity (LE) parameters included the cranial-hip-sacrum angle, cranial-knee-sacrum angle, and cranial-ankle-sacrum angle. LE compensation was set as the 1-year upper tertile compared with intraoperative baseline. Univariate analyses were used to compare normalized and nonnormalized data against alignment outcomes. Multivariable logistic regression analyses were used to develop a model consisting of significant predictors for normalization related to regional compensation. RESULTS: In total, 156 patients met the inclusion criteria (mean ± SD age 64.6 ± 9.1 years, BMI 27.9 ± 5.6 kg/m2, Charlson Comorbidity Index 1.9 ± 1.6). Patients with normalized PT were more likely to have overcorrected pelvic incidence minus lumbar lordosis and sagittal vertical axis at 6 weeks (p < 0.05). GAP score at 6 weeks was greater for patients with nonnormalized PT (0.6 vs 1.3, p = 0.08). At baseline, 58.5% of patients had compensation in the thoracic and cervical regions. Postoperatively, compensation was maintained by 42% with no change after matching in age-adjusted or GAP score. The patients with nonnormalized PT had increased rates of thoracic and cervical compensation (p < 0.05). Compensation in thoracic kyphosis differed between patients with normalized PT at 6 weeks and those with normalized PT at 1 year (69% vs 35%, p < 0.05). Those who compensated had increased rates of implant complications by 1 year (OR [95% CI] 2.08 [1.32-6.56], p < 0.05). Cervical compensation was maintained at 6 weeks and 1 year (56% vs 43%, p = 0.12), with no difference in implant complications (OR 1.31 [95% CI -2.34 to 1.03], p = 0.09). For the lower extremities at baseline, 61% were compensating. Matching age-adjusted alignment did not eliminate compensation at any joint (all p > 0.05). Patients with nonnormalized PT had higher rates of LE compensation across joints (all p < 0.01). Overall, patients with normalized PT at 1 year had the greatest odds of resolving LE compensation (OR 9.6, p < 0.001). Patients with normalized PT at 1 year had lower rates of implant failure (8.9% vs 19.5%, p < 0.05), rod breakage (1.3% vs 13.8%, p < 0.05), and pseudarthrosis (0% vs 4.6%, p < 0.05) compared with patients with nonnormalized PT. The complication rate was significantly lower for patients with normalized PT at 1 year (56.7% vs 66.1%, p = 0.02), despite comparable health-related quality of life scores. CONCLUSIONS: Patients with PT normalization had greater rates of resolution in thoracic and LE compensation, leading to lower rates of complications by 1 year. Thus, consideration of both the lower extremities and thoracic regions in surgical planning is vital to preventing adverse outcomes and maintaining pelvic alignment.