Intraoperative fluid management in adult spinal deformity surgery: variation analysis and association with outcomes.

PURPOSE: To evaluate the variability in intraoperative fluid management during adult spinal deformity (ASD) surgery, and analyze the association with complications, intensive care unit (ICU) requirement, and length of hospital stay (LOS). METHODS: Multicenter comparative cohort study. Patients ≥ 18 years old and with ASD were included. Intraoperative intravenous (IV) fluid data were collected including: crystalloids, colloids, crystalloid/colloid ratio (C/C), total IV fluid (tIVF, ml), normalized total IV fluid (nIVF, ml/kg/h), input/output ratio (IOR), input-output difference (IOD), and normalized input-output difference (nIOD, ml/kg/h). Data from different centers were compared for variability analysis, and fluid parameters were analyzed for possible associations with the outcomes. RESULTS: Seven hundred ninety-eight patients with a median age of 65.2 were included. Among different surgical centers, tIVF, nIVF, and C/C showed significant variation (p < 0.001 for each) with differences of 4.8-fold, 3.7-fold, and 4.9-fold, respectively. Two hundred ninety-two (36.6%) patients experienced at least one in-hospital complication, and ninety-two (11.5%) were IV fluid related. Univariate analysis showed significant relations for: LOS and tIVF (ρ = 0.221, p < 0.001), IOD (ρ = 0.115, p = 0.001) and IOR (ρ = -0.138, p < 0.001); IV fluid-related complications and tIVF (p = 0.049); ICU stay and tIVF, nIVF, IOD and nIOD (p < 0.001 each); extended ICU stay and tIVF (p < 0.001), nIVF (p = 0.010) and IOD (p < 0.001). Multivariate analysis controlling for confounders showed significant relations for: LOS and tIVF (p < 0.001) and nIVF (p = 0.003); ICU stay and IOR (p = 0.002), extended ICU stay and tIVF (p = 0.004). CONCLUSION: Significant variability and lack of standardization in intraoperative IV fluid management exists between different surgical centers. Excessive fluid administration was found to be correlated with negative outcomes. LEVEL OF EVIDENCE: III.

Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI. METHODS: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted. In this international, multicenter clinical trial, eligible participants had moderate-to-severe TBI, were ≥12 months postinjury, and had chronic motor deficits. Participants were randomized in a 1:1:1:1 ratio to stereotactic surgical intracranial implantation of SB623 cells (2.5 × 106, 5.0 × 106, 10 × 106) or surgical sham-controlled procedure. The prespecified primary efficacy end point was significantly greater change from baseline of the Fugl-Meyer Motor Scale (FMMS) score, a measure of motor status, for the SB623 pooled vs control arm at 24 weeks. RESULTS: A total of 211 participants were screened, 148 were excluded, and 63 underwent randomization, of which 61 (97%; mean age, 34 [SD, 12] years; 43 men [70.5%]) completed the trial. Single participants in the SB623 2.5 × 106 and 5.0 × 106 cell dose groups discontinued before surgery. Safety and efficacy (modified intent-to-treat) were assessed in participants who underwent surgery (N = 61; SB623 = 46, controls = 15). The primary efficacy end point (FMMS) was achieved (least squares mean [SE] SB623: +8.3 [1.4]; 95% CI 5.5-11.2 vs control: +2.3 [2.5]; 95% CI -2.7 to 7.3; p = 0.04), with faster improvement of the FMMS score in SB623-treated groups than in controls at 24 weeks and sustained improvement at 48 weeks. At 48 weeks, improvement of function and activities of daily living (ADL) was greater, but not significantly different in SB623-treated groups vs controls. The incidence of adverse events was equivalent in SB623-treated groups and controls. There were no deaths or withdrawals due to adverse events. DISCUSSION: Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02416492. Submitted to registry: April 15, 2015. First participant enrolled: July 6, 2016. Available at: classic.clinicaltrials.gov/ct2/show/NCT02416492. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that intracranial implantation of allogeneic stem (SB623) cells in adults with motor deficits from chronic TBI improves motor function at 24 weeks.

Alignment in motion: Fall risk in spine patients and the effect of vision, support surface, and adaptation on the cone of economy.

Background: Several assessment tools have been developed to estimate a patient's likelihood risk of falling. None of these measures estimate the contributions of the visual, vestibular, and somatosensory systems to fall risk, especially in patients with degenerative lumbar spine disease. Methods: Degenerative lumbar spine patients with radiculopathy (LD) and healthy subjects who were 35-70 years old without spine complaints were recruited. Patient reported outcome measures (PROMs) were collected prior to testing. Fall risk assessment was completed using Computer Dynamic Posturography (CDP), a computer-controlled balance machine that allows cone of economy (CoE) and cone of pressure (CoP) measurements. All patients completed Sensory Organization Tests (SOT) which include normal and perturbed stability, both with and without visual cues. Results: In total, 43 spine patients and 12 healthy controls were included, with mean age 57.8 years, 39.5% females, and mean BMI of 29.3 kg/m2. Nearly all CoE and most CoP dimensions were found to be larger in LD patients compared to controls across nearly all subtests (p<.05), with the largest dimensions generally observed in the surrounding and support sway testing condition. In LD patients, ODI and PROMIS Pain Interference were negatively correlated with CoE and CoP measurements (p<.05). Conclusions: In this prospective study, body sway was assessed as a function of CoE and CoP using the CDP system and was found to be elevated in spine patients, especially when they experienced increasing levels of visual and vestibular stimulation. The ability to identify the primary drivers of balance disorders is essential in spine patients and may be helpful in the development of a patient-specific treatment plan, which may in the future aid with fall-prevention initiatives.

Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

Electrolyte Disturbances and Repletion in Orthopaedic and Spine Surgery Patients.

Electrolyte derangement, defined as disorders of clinically impactful physiologic ions such as potassium, sodium, calcium, magnesium, and phosphate, has a variety of clinical manifestations. These electrolytes have narrow windows of normal in vivo concentration before neurologic, cardiac, renal, or gastrointestinal consequences occur. Perioperative disturbances in electrolyte concentration can lead to increased morbidity and mortality, longer length of stay, and higher rates of short and medium-term readmission in orthopaedic and spine surgery postoperatively. To prevent electrolyte related complications, careful monitoring and repletion of at-risk patients must be undertaken. A systematic approach to repletion allows for a safe and efficacious treatment of these disorders.

L5-S1 Transforaminal Lumbar Interbody Fusion (TLIF) Is Associated with Increased Revisions Compared to L4-L5 TLIF at Two Years.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Compare outcomes in patients undergoing one-level transforaminal lumbar interbody fusion (TLIF) at L4-S1. BACKGROUND: TLIF is frequently performed at L4-S1 to treat degenerative lumbar pathologies. However, the native alignment and biomechanics differ across L4-L5 and L5-S1, and there is limited data regarding comparative radiographic outcomes. METHODS: Patients who underwent one-level TLIF at L4-L5 or L5-S1 at a single academic institution were identified. Baseline demographics, procedural characteristics, change in postoperative spinopelvic alignment and patient-reported outcome measures (PROMs), and two-year postoperative surgical complications were compared. Multivariate regression analyses, accounting for age, gender, Charlson Comorbidity Index (CCI), and body mass index (BMI), were also performed. RESULTS: Across the 175 included patients, 125 had L4-L5 TLIF and 50 had L5-S1 TLIF. The mean age was 57.8 years, 56.6% were female, mean CCI was 0.9, and mean follow-up was 26.7 months. In the hospital, the two cohorts were not statistically different with regards to EBL and LOS. Two years postoperatively, multivariate linear regression analyses revealed that L5-S1 TLIF achieved 6.0° higher correction in L4-S1 lordosis ( P =0.012) than L4-L5 TLIF. At the same time, however, L5-S1 TLIF patients experienced significantly higher rates of pseudoarthrosis (8.0% vs 1.6%, P =0.036) and subsequent spine surgery (18.0% vs. 7.2%, P =0.034), specifically for pseudoarthrosis (6.0% vs. 0.0%, P =0.006), with this cohort having 8.7 times higher odds of subsequent spine surgery for pseudoarthrosis ( P =0.015) than L4-L5 TLIF patients on multivariate logistic analyses. PROMs, on the other hand, were not different across the two cohorts. CONCLUSIONS: Although L5-S1 TLIF yielded good radiographic correction, it was associated with higher rates of subsequent spine surgery for pseudoarthrosis compared to L4-L5 TLIF. These findings may be related to differences in native segmental alignment and biomechanics across the L4-L5 and L5-S1 motion segments and are important to consider during surgical planning. LEVEL OF EVIDENCE: IV.

First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of DS-7011a, an Anti-TLR7 Antagonistic Monoclonal Antibody for the Treatment of Systemic Lupus Erythematosus.

Toll-like receptor (TLR)7 is a pattern recognition receptor that critically contributes to the pathogenesis of systemic lupus erythematosus (SLE). DS-7011a is an anti-TLR7 monoclonal antibody that prevents TLR7 from signaling. The aim of this first-in-human, double-blind, randomized, and placebo-controlled study was to evaluate the safety, pharmacokinetics, immunogenicity, and pharmacodynamics of single ascending intravenous (IV) and subcutaneous (SC) doses of DS-7011a in healthy subjects (HS) (NCT05203692). On day 1, 80 HS received DS-7011a or placebo 6:2 in 10 cohorts (7 treated IV and 3 SC) of 8 each and were followed for 8 weeks until day 57. Safety was evaluated by recording treatment-emergent adverse events (TEAEs), pharmacokinetics by measuring plasma DS-7011a, immunogenicity by measuring plasma anti-drug antibodies (ADAs), and pharmacodynamics by evaluating the suppression of interleukin-6 production ex vivo in whole blood. DS-7011a was safe and well tolerated across all cohorts. TEAEs were mostly mild in severity and not drug-related. DS-7011a exposure increased with the dose but was not dose proportional, as the elimination of lower doses was accelerated by target-mediated drug disposition. Terminal half-life was about 15-17 days and Tmax upon SC administration was about 5 days. DS-7011a induced ADAs in about half of HS but with no impact on clinical findings and pharmacokinetics. Pharmacodynamic (PD) response also increased with the dose and at the higher doses was of large extent (>90%), early onset, and lasting duration. DS-7011a showed favorable safety, pharmacokinetics, immunogenicity, and PD properties that support its development for the treatment of SLE.

Impact of Prior Cervical Fusion on Patients Undergoing Thoracolumbar Deformity Correction.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: Evaluate the impact of prior cervical constructs on upper instrumented vertebrae (UIV) selection and postoperative outcomes among patients undergoing thoracolumbar deformity correction. BACKGROUND: Surgical planning for adult spinal deformity (ASD) patients involves consideration of spinal alignment and existing fusion constructs. METHODS: ASD patients with (ANTERIOR or POSTERIOR) and without (NONE) prior cervical fusion who underwent thoracolumbar fusion were included. Demographics, radiographic alignment, patient-reported outcome measures (PROMs), and complications were compared. Univariate and multivariate analyses were performed on POSTERIOR patients to identify parameters predictive of UIV choice and to evaluate postoperative outcomes impacted by UIV selection. RESULTS: Among 542 patients, with 446 NONE, 72 ANTERIOR, and 24 POSTERIOR patients, mean age was 64.4 years and 432 (80%) were female. Cervical fusion patients had worse preoperative cervical and lumbosacral deformity, and PROMs (P<0.05). In the POSTERIOR cohort, preoperative LIV was frequently below the cervicothoracic junction (54%) and uncommonly (13%) connected to the thoracolumbar UIV. Multivariate analyses revealed that higher preoperative cervical SVA (coeff=-0.22, 95%CI=-0.43--0.01, P=0.038) and C2SPi (coeff=-0.72, 95%CI=-1.36--0.07, P=0.031), and lower preoperative thoracic kyphosis (coeff=0.14, 95%CI=0.01-0.28, P=0.040) and thoracolumbar lordosis (coeff=0.22, 95%CI=0.10-0.33, P=0.001) were predictive of cranial UIV. Two-year postoperatively, cervical patients continued to have worse cervical deformity and PROMs (P<0.05) but had comparable postoperative complications. Choice of thoracolumbar UIV below or above T6, as well as the number of unfused levels between constructs, did not affect patient outcomes. CONCLUSIONS: Among patients who underwent thoracolumbar deformity correction, prior cervical fusion was associated with more severe spinopelvic deformity and PROMs preoperatively. The choice of thoracolumbar UIV was strongly predicted by their baseline cervical and thoracolumbar alignment. Despite their poor preoperative condition, these patients still experienced significant improvements in their thoracolumbar alignment and PROMs after surgery, irrespective of UIV selection. LEVEL OF EVIDENCE: IV.

Quantified Ataxic Breathing Can Detect Opioid-Induced Respiratory Depression Earlier in Normal Volunteers Infused with Remifentanil.

BACKGROUND: Ataxic breathing (AB) is a well-known manifestation of opioid effects in animals and humans, but is not routinely included in monitoring for opioid-induced respiratory depression (OIRD). We quantified AB in normal volunteers receiving increasing doses of remifentanil. We used a support vector machine (SVM) learning approach with features derived from a modified Poincaré plot. We tested the hypothesis that AB may be found when bradypnea and reduced mental status are not present. METHODS: Twenty-six healthy volunteers (13 female) received escalating target effect-site concentrations of remifentanil with a low baseline dose of propofol to simulate typical breathing patterns in drowsy patients who had received parenteral opioids. We derived respiratory rate (RR) from respiratory inductance plethysmography, mental alertness from the Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S), and AB severity on a 0 to 4 scale (categories ranging from none to severe) from the SVM. The primary outcome measure was sensitivity and specificity for AB to detect OIRD. RESULTS: All respiratory measurements were obtained from unperturbed subjects during steady state in 121 assessments with complete data. The sensitivity of AB for detecting OIRD by the conventional method was 92% and specificity was 28%. As expected, 69 (72%) of the instances not diagnosed as OIRD using conventional measures were observed to have at least moderate AB. CONCLUSIONS: AB was frequently present in the absence of traditionally detected OIRD as defined by reduced mental alertness (MOAA/S score of <4) and bradypnea (RR <8 breaths/min). These results justify the need for future trials to explore replicability with other opioids and clinical utility of AB as an add-on measure in recognizing OIRD.

Whole Gut Transit Scintigraphy for the Assessment of Patients with Symptoms of Chronic Constipation.

INTRODUCTION: Whole gut transit scintigraphy (WGTS) can detect delayed colonic transit (CT), different types of CT delays, and assess upper GI tract transit. AIM: To delineate the frequency of different types of CT patterns in patients with chronic constipation (CC), determine the relationship between these CT patterns and upper GI tract transit abnormalities, and assess how symptoms relate to different colonic transit patterns. METHODS: Retrospective review of patients who had WGTS for CC. Patients completed a modified PAGI-SYM questionnaire to assess symptoms. Patients ingested a standard solid (Tc-99m egg sandwich)-liquid (In-111 water) meal to assess solid meal gastric emptying (GE), liquid GE, small bowel transit (SBT), and geometric center of colonic activity at 24, 48, and 72h. RESULTS: One hundred and eighty six patients underwent WGTS. Main symptoms were constipation (41%), nausea (24%), and bloating (22%). CT assessment showed 32% of patients had normal transit, 31% colonic inertia (CI), 28% functional rectosigmoid obstruction (FRS0), and 9% generalized slow colonic transit (GSCT). GE was delayed in 36%; more commonly in CI and FRSO. SBT was delayed in 19%; more commonly in GSCT and CI. Patients with CI had less bowel movements per week whereas patients with normal CT had more bm/week. CONCLUSIONS: In this series of patients with symptomatic constipation, WGTS assessment showed delayed colonic transit in 68% of patients, with 31% having colonic inertia, 28% a functional rectosigmoid obstruction pattern, and 9% generalized delay in colonic transit. Abnormalities in GE and SBT were present in 36 and 19%. WGTS is helpful to document delayed colonic transit (CT), assess the pattern of the delay in CT, and determine if there are upper GI transit abnormalities.

Thoracolumbar fusions for adult lumbar deformity show superior QALY gain and lower costs compared with upper thoracic fusions.

PURPOSE: Adult spinal deformity (ASD) patients with sagittal plane deformity (N) or structural lumbar/thoraco-lumbar (TL) curves can be treated with fusions stopping at the TL junction or extending to the upper thoracic (UT) spine. This study evaluates the impact on cost/cumulative quality-adjusted life year (QALY) in patients treated with TL vs UT fusion. METHODS: ASD patients with > 4-level fusion and 2-year follow-up were included. Index and total episode-of-care costs were estimated using average itemized direct costs obtained from hospital records. Cumulative QALY gained were calculated from preoperative to 2-year postoperative change in Short Form Six-Dimension (SF-6D) scores. The TL and UT groups comprised patients with upper instrumented vertebrae (UIV) at T9-T12 and T2-T5, respectively. RESULTS: Of 566 patients with type N or L curves, mean age was 63.2 ± 12.1 years, 72% were female and 93% Caucasians. Patients in the TL group had better sagittal vertical axis (7.3 ± 6.9 vs. 9.2 ± 8.1 cm, p = 0.01), lower surgical invasiveness (- 30; p < 0.001), and shorter OR time (- 35 min; p = 0.01). Index and total costs were 20% lower in the TL than in the UT group (p < 0.001). Cost/QALY was 65% lower (492,174.6 vs. 963,391.4), and 2-year QALY gain was 40% higher, in the TL than UT group (0.15 vs. 0.10; p = 0.02). Multivariate model showed TL fusions had lower total cost (p = 0.001) and higher QALY gain (p = 0.03) than UT fusions. CONCLUSION: In Schwab type N or L curves, TL fusions showed lower 2-year cost and improved QALY gain without increased reoperation rates or length of stay than UT fusions. LEVEL OF EVIDENCE: III.

Developing a risk score to inform the use of rhBMP-2 in adult spinal deformity surgery.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has not shown superior benefit overall in cost-effectiveness during adult spinal deformity (ASD) surgery. STUDY DESIGN/SETTING: Retrospective PURPOSE: Generate a risk score for pseudarthrosis to inform the utilization of rhBMP-2, balancing costs against quality of life and complications. METHODS: ASD patients with 3-year data were included. Quality of life gained was calculated from ODI to SF-6D and translated to quality-adjusted life years (QALYs). Cost was calculated using the PearlDiver database and CMS definitions for complications and comorbidities. Established weights were generated for predictive variables via logistic regression to yield a predictive risk score for pseudarthrosis that accounted for frailty, diabetes, depression, ASA grade, thoracolumbar kyphosis and three-column osteotomy use. Risk score categories, established via conditional inference tree (CIT)-derived thresholds were tested for cost-utility of rhBMP-2 usage, controlling for age, prior fusion, and baseline deformity and disability. RESULTS: 64% of ASD patients received rhBMP-2 (308/481). There were 17 (3.5%) patients that developed pseudarthrosis. rhBMP-2 use overall did not lower pseudarthrosis rates (OR: 0.5, [0.2-1.3]). Pseudarthrosis rates for each risk category were: No Risk (NoR) 0%; Low-Risk (LowR) 1.6%; Moderate Risk (ModR) 9.3%; High-Risk (HighR) 24.3%. Patients receiving rhBMP-2 had similar QALYs overall to those that did not (0.163 vs. 0.171, p = .65). rhBMP-2 usage had worse cost-utility in the LowR cohort (p < .001). In ModR patients, rhBMP-2 usage had equivocal cost-utility ($53,398 vs. $61,581, p = .232). In the HighR cohort, the cost-utility was reduced via rhBMP-2 usage ($98,328 vs. $211,091, p < .001). CONCLUSION: Our study shows rhBMP-2 demonstrates effective cost-utility for individuals at high risk for developing pseudarthrosis. The generated score can aid spine surgeons in the assessment of risk and enhance justification for the strategic use of rhBMP-2 in the appropriate clinical contexts. LEVEL OF EVIDENCE: III.

Patient Reported Physical and Mental Health Outcomes Following Lumbar Spinal Fusion versus Total Hip and Total Knee Replacement.

BACKGROUND: Total hip and knee arthroplasty (THA/TKA) are reliable surgical procedures for alleviating pain and optimizing function. Spinal fusion has also been shown to be beneficial, however the comparative benefit of THA/TKA to lumbar spinal fusion is incompletely understood. METHODS: This study analyzed a single-center database of patients who underwent primary lumbar spinal fusion, elective primary TKA, or THA. PROMs included Veterans-Rand (VR12) Physical and mental component score (PCS/MCS) for TKA/THA and PROMIS (Patient-Reported Outcomes Measurement Information System) global mental and physical health (GPH/GMH) for spinal fusion. RESULTS: 356 patients who underwent TKA, 290 underwent THA, and 125 underwent spinal fusion were included. Joint replacement patients were older, with higher body mass index in the TKA group. Spine patients had a lower improvement in physical health than the joint patients (TKA: 9.4 ± 11.2, THA: 15.2 ± 11.2, Spine: 6.2 ± 8.7, p<.001) and a lower proportion of patients reaching the minimal clinically important difference (MCID). Spine patients had higher GMH improvements compared to TKA patients (TKA: -1.1 ± 10.7, THA: 1.1 ± 11.9, Spine: 1.8 ± 8.4, p=.009) and the highest proportion of patients reaching the MCID. CONCLUSION: Spinal fusion, total knee arthroplasty, and total hip arthroplasty all significantly improved PROMs at 1-year follow-up. At baseline, spinal fusion patients had better physical function scores and worse mental health scores compared to joint arthroplasty patients, while spinal fusion resulted in mean smaller gains in patient reported physical function and higher gains in patient reported mental health function compared to arthroplasty.

Association of Vitamin D Deficiency With Distal Biceps Injury: A Retrospective Analysis of 336,320 Patients.

BACKGROUND: This study explores the association between vitamin D deficiency and distal biceps tendon injuries, illustrating that, although vitamin D deficiency is associated with prolonged hospital stays and various musculoskeletal problems, its connection to distal biceps tendon injuries is unknown. HYPOTHESIS: Vitamin D deficiency is associated with an elevated risk of distal biceps injury but not with increased rates of subsequent surgery or revision surgery. STUDY DESIGN: Case-control study. LEVEL OF EVIDENCE: Level 3. METHODS: A 1:1 matched retrospective comparative study of 336,320 vitamin-D-deficient patients was performed using PearlDiver data (between January 1, 2011 and October 31, 2018). Cohorts, with a mean age of 55.7 ± 13.2 years, underwent multivariate logistic regression to calculate distal biceps tendon injury and surgical repair incidence according to age and sex, while controlling for demographics and comorbidities. RESULTS: The 1-year incidence of distal biceps tendinopathy in vitamin-D-deficient patients was 118 per 100,000 person-years (95% CI) compared with 44.3 per 100,000 person-years in matched controls. Male patients with vitamin D deficiency were at a greater risk for distal biceps tendinopathy after 1 and 2 years (adjusted odds ratio [aOR] = 2.81, 2.08-3.83; aOR = 2.80, 2.21-3.56). Female patients were also at a greater risk after both years (aOR = 1.69, 1.27-2.27; aOR = 1.57, 1.26-1.96). Vitamin D deficiency was not associated with an elevated risk of surgical repair or revision surgery. CONCLUSION: In a nationwide cohort, a diagnosis of vitamin D deficiency elevated the risk of distal biceps tendinopathy but did not raise the rate of surgical repair or revision. As a result, prevention strategies in the form of vitamin supplementation should be increased for athletes.Clinical Relevance: These findings emphasize the clinical relevance of monitoring vitamin D levels in patients at risk for musculoskeletal injuries, and providing adequate care to those involved in high-demand physical activities.Strength of Recommendation: B.

Crossing the Cervicothoracic Junction: A Biomechanical Investigation of C7 vs T1 Caudal Selection's Effect on Adjacent Segment Motion in Posterior Cervical Fusion.

STUDY DESIGN: Biomechanical Study. OBJECTIVE: This study aims to evaluate the biomechanical adjacent segment effects of multi-level posterior cervical fusion constructs that terminate at C7 compared to those that terminate at T1 in cadaveric specimens. BACKGROUND: The cervicothoracic junction poses unique challenges for spine surgeons. Deciding to terminate multi-level posterior cervical fusion constructs at C7 or extend them across the cervicothoracic junction remains a controversial issue. METHODS: Six cadaveric specimens underwent biomechanical testing in the intact state and after instrumentation with constructs from C3 and terminating at either C7 or T1. Range of motion (ROM) was assessed in flexion-extension, lateral bending, and axial rotation globally and at cranial and caudal adjacent segments. RESULTS: There was a significant decrease in overall flexion/extension by both C7 (-35.5°, P=0.002) and T1 (-39.8°, P=0.002) instrumentation compared to the intact spine. T1 instrumentation had significantly lower (-4.3°, P=0.008) flexion/extension ROM compared to C7 instrumentation. There were significant decreases in axial rotation by both C7 (-31.4°, P=0.009) and T1 (-36.8°, P=0.009) instrumentation compared to the intact spine, but no significant differences were observed between the two. There were also significant decreases in lateral bending by both C7 (-27.9°, P=0.022) and T1 (-33.7°, P=0.022) instrumentation compared to the intact spine, but no significant differences were observed between the two. No significant differences were observed in ROM at cranial or caudal adjacent segments between constructs terminating at C7 and those extending to T1. CONCLUSION: This biomechanical investigation demonstrates that constructs that cross the cervicothoracic junction experience less overall spinal motion in flexion-extension compared to those that terminate at C7. However, contrary to prior studies there is no difference in cranial and caudal adjacent segment motion. Surgeons should make clinical decisions regarding the caudal extent of fusion in multi-level posterior cervical fusions without major concerns about adjacent segment motion.

One-Level versus Two-Level Anterior Lumbar Interbody Fusion (ALIF) from L4-S1: Comparison of Complications, Alignment, and Patient Outcomes.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Compare outcomes in patients undergoing one-level or two-level anterior lumbar interbody fusion (ALIF) at L4-S1. BACKGROUND: Although ALIF may deliver restoration of lumbar lordosis and improvement in clinical outcomes, it also carries risk of complications including major vascular injury. Whether one-level and two-level ALIF offers similar outcomes is not known. METHODS: Adults who underwent one-level L4-L5 or L5-S1 ALIF and two-level L4-S1 ALIF at a single academic institution were identified. Patient demographics, procedural characteristics, improvement in spinopelvic alignment, and one-year postoperative patient-reported outcome measures (PROMs) and complications were compared. Multivariate regression analyses, accounting for age, gender, and Charlson Comorbidity Index (CCI), were also performed. RESULTS: In total, 158 ALIF patients (111 one-level and 47 two-level) were included, with mean age of 51.4 years, 57.0% female, mean CCI of 1.2, and mean follow-up of 27.0 months. Surgical time (147.3 min vs. 124.6 min, P=0.002) and hospital length of stay (3.5 d vs. 2.9 d, P=0.036) were higher for two-level ALIF. One-year postoperatively, two-level ALIF patients had more caudal apex of lordosis (P=0.016) and 4.1 mm (P=0.002) and 2.0 mm (P=0.019) higher L4-L5 anterior and posterior disc heights, respectively. PROMs were not statistically different across groups (P>0.05). Finally, two-level ALIF patients were 10.9 times more likely to have in-hospital complications (P=0.040), such as intraoperative vascular injury (11.1% vs. 1.5%, P=0.040) or postoperative ileus (7.4% vs. 0.0%, P=0.027), than one-level ALIF patients. CONCLUSION: In this investigation with greater than one-year follow-up, two-level ALIF in the L4-S1 spine had higher procedural time, length of stay, and approach-related complications than one-level ALIF. Although there were minor improvements in alignment with two-level ALIF, PROMs were comparable with improvements from baseline to last follow-up. These findings may help surgeons carefully weigh the risks and benefits of one- versus two-level ALIF when determining surgical plans for patients. LEVEL OF EVIDENCE: IV.

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation.

BACKGROUND: Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks' gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. METHODS: Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122-125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. RESULTS: Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration ("Prion Disease", "Alzheimer's Disease", "Arachidonic Acid metabolism"). Adverse changes were independent of respiratory function during ventilation. CONCLUSIONS: Our data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Sagittal spinal alignment measurements and evaluation: Historical perspective.

Spinal alignment analysis play an important role in evaluating patients and planning surgical corrections for adult spinal deformity. The history of these parameters is relatively short with the first parameter, the Cobb angle, introduced in 1948 as part of an effort to improve scoliosis evaluation. New developments in the field were limited for nearly 30 years before better imaging technology encouraged new theories and later data about spinal alignment and the relationship between the spine and pelvis. These efforts would ultimately contribute to the creation of foundational spinal alignment parameters, including pelvic incidence, pelvic tilt, and sacral slope. By the 1990s, spinal alignment had become a sustained area of investigation for spinal surgeons and researchers. Novel alignment parameters have since been introduced as our knowledge has evolved and has allowed for valuable research that demonstrates the clinical and surgical value of alignment measurement. This manuscript will explore the history of spinal alignment analysis over the decades.

The association of the room air challenge with long-term outcomes in extremely preterm infants.

OBJECTIVE: Evaluate the association between results of the room air (RA) challenge and death, respiratory morbidity, and neurodevelopmental impairment (NDI) at 2 years' corrected age. STUDY DESIGN: Cohort study of infants born <27 weeks' gestational age who underwent a RA challenge to determine BPD diagnosis at 36 weeks postmenstrual age. RESULTS: Of 1022 infants eligible for the RA challenge, 554 underwent testing and 223 passed. Test result was not associated with death or serious respiratory morbidities [adjusted relative risk (aRR) 1.01, 95% confidence interval (CI) 0.65-1.56] or death or moderate/severe NDI (aRR 1.06, 95% CI 0.81-1.39) at 2 years. CONCLUSION: Results of the RA challenge were not associated with differences in respiratory or neurodevelopmental morbidity at 2 years, suggesting the RA challenge does not add prognostic value in contemporary extremely preterm infants. GOV ID: Generic Database: NCT00063063.