Pre-operative bone quality deficits and risk of complications following spine fusion surgery among postmenopausal women.

Poor bone quality is a risk factor for complications after spinal fusion surgery. This study investigated pre-operative bone quality in postmenopausal women undergoing spine fusion and found that those with small bones, thinner cortices and surgeries involving more vertebral levels were at highest risk for complications. PURPOSE: Spinal fusion is one of the most common surgeries performed worldwide. While skeletal complications are common, underlying skeletal deficits are often missed by pre-operative DXA due to artifact from spinal pathology. This prospective cohort study investigated pre-operative bone quality using high resolution peripheral CT (HRpQCT) and its relation to post-operative outcomes in postmenopausal women, a population that may be at particular risk for skeletal complications. We hypothesized that women with low volumetric BMD (vBMD) and abnormal microarchitecture would have higher rates of post-operative complications. METHODS: Pre-operative imaging included areal BMD (aBMD) by DXA, cortical and trabecular vBMD and microarchitecture of the radius and tibia by high resolution peripheral CT. Intra-operative bone quality was subjectively graded based on resistance to pedicle screw insertion. Post-operative complications were assessed by radiographs and CTs. RESULTS: Among 50 women enrolled (age 65 years), mean spine aBMD was normal and 35% had osteoporosis by DXA at any site. Low aBMD and vBMD were associated with "poor" subjective intra-operative quality. Skeletal complications occurred in 46% over a median follow-up of 15 months. In Cox proportional models, complications were associated with greater number of surgical levels (HR 1.19 95% CI 1.06-1.34), smaller tibia total area (HR 1.67 95% CI1.16-2.44) and lower tibial cortical thickness (HR 1.35 95% CI 1.05-1.75; model p < 0.01). CONCLUSION: Women with smaller bones, thinner cortices and procedures involving a greater number of vertebrae were at highest risk for post-operative complications, providing insights into surgical and skeletal risk factors for complications in this population.

Sex-dependent evolution of whole-body postural alignment with age.

PURPOSE: The goal of this study was to explore sex-related variations of global alignment parameters and their distinct evolution patterns across age groups. METHODS: This multicentric retrospective study included healthy volunteers with full-body biplanar radiographs in free-standing position. All radiographic data were collected from 3D reconstructions: global and lower limb parameters, pelvic incidence (PI) and sacral slope (SS). Lumbar lordosis (LL), thoracic kyphosis (TK) and cervical lordosis (CL) were also assessed as well as the lumbar and thoracic apex, and thoracolumbar inflexion point. The population was divided into five 5 age groups: Children, Adolescents, Young, Middle-Aged and Seniors. RESULTS: This study included 861 subjects (53% females) with a mean age of 34 ± 17 years. Mean PI was 49.6 ± 11.1 and mean LL was - 57.1 ± 11.6°. Females demonstrated a PI increase between Young and Middle-Aged groups (49 ± 11° vs. 55 ± 12°, p < 0.001) while it remained stable in males. SS and LL increased with age in females while remaining constant in males between Children and Middle-aged and then significantly decreased for both sexes between Middle-Aged and Seniors. On average, lumbar apex, inflexion point, and thoracic apex were located one vertebra higher in females (p < 0.001). After skeletal maturity, males had greater TK than females (64 ± 11° vs. 60 ± 12°, p = 0.04), with significantly larger CL (-13 ± 10° vs. -8 ± 10°, p = 0.03). All global spinal parameters indicated more anterior alignment in males. CONCLUSION: Males present more anteriorly tilted spine with age mainly explained by a PI increase in females between Young and Middle-Aged, which may be attributed to childbirth. Consequently, SS and LL increased before decreasing at senior age.

Mechanisms of lumbar spine "flattening" in adult spinal deformity: defining changes in shape that occur relative to a normative population.

PURPOSE: Previous work comparing ASD to a normative population demonstrated that a large proportion of lumbar lordosis is lost proximally (L1-L4). The current study expands on these findings by collectively investigating regional angles and spinal contours. METHODS: 119 asymptomatic volunteers with full-body free-standing radiographs were used to identify age-and-PI models of each Vertebra Pelvic Angle (VPA) from L5 to T10. These formulas were then applied to a cohort of primary surgical ASD patients without coronal malalignment. Loss of lumbar lordosis (LL) was defined as the offset between age-and-PI normative value and pre-operative alignment. Spine shapes defined by VPAs were compared and analyzed using paired t-tests. RESULTS: 362 ASD patients were identified (age = 64.4 ± 13, 57.1% females). Compared to their age-and-PI normative values, patients demonstrated a significant loss in LL of 17 ± 19° in the following distribution: 14.1% had "No loss" (mean = 0.1 ± 2.3), 22.9% with 10°-loss (mean = 9.9 ± 2.9), 22.1% with 20°-loss (mean = 20.0 ± 2.8), and 29.3% with 30°-loss (mean = 33.8 ± 6.0). "No loss" patients' spine was slightly posterior to the normative shape from L4 to T10 (VPA difference of 2°), while superimposed on the normative one from S1 to L2 and became anterior at L1 in the "10°-loss" group. As LL loss increased, ASD and normative shapes offset extended caudally to L3 for the "20°-loss" group and L4 for the "30°-loss" group. CONCLUSION: As LL loss increases, the difference between ASD and normative shapes first occurs proximally and then progresses incrementally caudally. Understanding spinal contour and LL loss location may be key to achieving sustainable correction by identifying optimal and personalized postoperative shapes.

A comparative cohort study of surgical approaches for adult spinal deformity at a minimum 2-year follow-up.

STUDY DESIGN: This study was a retrospective multi-center comparative cohort study. MATERIALS AND METHODS: A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ2 tests. RESULTS: One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5 min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2 years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). CONCLUSION: While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

Trans-sacral interbody fixation in long fusions to the sacrum for adult spinal deformity: complications and fusion rates at minimum two years follow-up.

PURPOSE: This study aims to investigate the fusion rate and complications associated with trans-sacral interbody fusion (TSIF) in long fusions to the sacrum for adult spinal deformity (ASD) over a two year follow-up period. Potential predictor variables associated with pseudarthrosis were also examined. METHODS: A retrospective clinical review was conducted on a consecutive series of ASD patients who underwent long fusions to the sacrum, with TSIF performed as a same-day or staged procedure. Patient demographics, bone mineral density, operative details, perioperative and late complications, and fusion rates were reviewed. Univariate analysis was used to identify the risk factors associated with pseudarthrosis. RESULTS: The study included 43 patients with an average age of 55.3 ± 8.9 years. The perioperative complication rate was 28%, with 12% of the complications directly related to TSIF. The late complication rate was 33%, with 16% related to TSIF. The most common complications were pseudarthrosis (14%) and postoperative ileus (7%). The overall radiographic fusion rate at two years was 86%. Univariate analysis revealed that revision surgery was significantly associated with pseudarthrosis (p = 0.027). Over the follow-up period, patients who underwent TSIF during long posterior fusions to the sacrum showed improvement in overall SRS scores, ODI scores, and SF-36 physical health and mental health (p < 0.05). CONCLUSION: TSIF is a relatively safe and minimally invasive method for achieving interbody fusion at the lumbosacral junction in the treatment of ASD, with acceptable fusion rates and a low complication rate. However, TSIF is not recommended for revision reconstruction in ASD.

Distal junctional kyphosis in adult cervical deformity patients: where does it occur?

PURPOSE: To evaluate the impact of the lowest instrumented vertebra (LIV) on Distal Junctional kyphosis (DJK) incidence in adult cervical deformity (ACD) surgery. METHODS: Prospectively collected data from ACD patients undergoing posterior or anterior-posterior reconstruction at 13 US sites was reviewed up to 2-years postoperatively (n = 140). Data was stratified into five groups by level of LIV: C6-C7, T1-T2, T3-Apex, Apex-T10, and T11-L2. DJK was defined as a kyphotic increase > 10° in Cobb angle from LIV to LIV-1. Analysis included DJK-free survival, covariate-controlled cox regression, and DJK incidence at 1-year follow-up. RESULTS: 25/27 cases of DJK developed within 1-year post-op. In patients with a minimum follow-up of 1-year (n = 102), the incidence of DJK by level of LIV was: C6-7 (3/12, 25.00%), T1-T2 (3/29, 10.34%), T3-Apex (7/41, 17.07%), Apex-T10 (8/11, 72.73%), and T11-L2 (4/8, 50.00%) (p < 0.001). DJK incidence was significantly lower in the T1-T2 LIV group (adjusted residual = -2.13), and significantly higher in the Apex-T10 LIV group (adjusted residual = 3.91). In covariate-controlled regression using the T11-L2 LIV group as reference, LIV selected at the T1-T2 level (HR = 0.054, p = 0.008) or T3-Apex level (HR = 0.081, p = 0.010) was associated with significantly lower risk of DJK. However, there was no difference in DJK risk when LIV was selected at the C6-C7 level (HR = 0.239, p = 0.214). CONCLUSION: DJK risk is lower when the LIV is at the upper thoracic segment than the lower cervical segment. DJK incidence is highest with LIV level in the lower thoracic or thoracolumbar junction.

Eight-Month Follow-up After the Third Dose of BNT162b2 Vaccine in Healthcare Workers: The Question of a Fourth Dose.

BACKGROUND: A fourth dose of vaccination is known to help reduce the severity and mortality rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The South Korean vaccination guidelines for the fourth dose do not include healthcare workers (HCWs) as priority candidates. We investigated the necessity of the fourth dose in South Korean HCWs based on an 8-month follow-up period after the third vaccination. METHODS: Changes in the surrogate virus neutralization test (sVNT) inhibition (%) score were measured at one month, four months and eight months after the third vaccination. The sVNT values were analyzed between infected and uninfected groups, and their trajectories were compared. RESULTS: A total of 43 HCWs were enrolled in this study. In total, 28 cases (65.1%) were confirmed to be infected with SARS-CoV-2 (presumed omicron variant), and all had mild symptoms. Meanwhile, 22 cases (78.6%) were infected within four months of the third dose (median, 97.5 days). Eight months after the third dose, the SARS-CoV-2 (presumed omicron variant)-infected group showed significantly higher sVNT inhibition than that in the uninfected group (91.3% vs. 30.7%; P < 0.001). The antibody response due to hybrid immunity, provided by a combination of infection and vaccination, was maintained at sufficient levels for more than four months. CONCLUSION: For HCWs who had coronavirus disease 2019 infection after completing a third vaccination, a sufficient antibody response was maintained until eight months after the third dose. The recommendation of the fourth dose may not be prioritized in subjects with hybrid immunity.

Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers.

BACKGROUND: Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. METHODS: Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. RESULTS: A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study. Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicron-infected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. CONCLUSION: Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination. Further studies are needed to understand the characteristics of immunogenicity in these populations.

High Expression of Tetraspanin 5 as a Prognostic Marker of Colorectal Cancer.

Cancer is a major disease and the leading cause of death worldwide, with colorectal cancer (CRC) being the third-most common cancer in Korea. The survival rate associated with CRC reduces as the disease stage increases. Therefore, its early detection and treatment can greatly increase patient survival rates. In this study, we identified the tetraspanin 5 (TSPAN5) gene as an important biomarker for predicting the prognosis of patients with CRC. A TMA slide was used for statistical analysis. pN and clinical stage were found to be significant factors according to chi-square analysis, whereas pT, pN, metastasis, clinical stage, and TSPAN5 expression were significant according to Cox regression analysis. In order to prove the usefulness of TSPAN5, which is overexpressed in patients with metastatic CRC, as a biomarker, proliferation, migration, invasion, and tumorigenicity were examined using cell lines inhibited using small interfering RNA. The evaluations confirmed that TSPAN5 suppression, in turn, suppressed proliferation, migration, invasion, and tumorigenesis, which are characteristic of cancer cells. Therefore, the evaluation of TSPAN5 expression may help observe the prognosis of CRC and determine an appropriate treatment method for patients with CRC.

The relationship of global sagittal malalignment to fatty infiltration in the aging spine.

PURPOSE: To investigate associations between muscle size, fat infiltration (FI), and global sagittal alignment in patients with adult spinal deformity (ASD). METHODS: Retrospective cohort study was conducted on a single-institution database of ASD patients with preoperative radiographs and CTs. Following multiplanar reconstructions of CTs, images in the plane of each vertebra were generated. The posterior vertebral musculature (PVM) was contoured on axial images at three vertebral levels (T2, T10, L3). FI was calculated by comparing Hounsfield units within muscles to the normative values of fat. Correlation analyses were conducted between demographics, alignment, and muscle characteristics. RESULTS: 107 patients underwent preoperative spine CT (58yo, 79%F, BMI 27 kg/m2). Muscle data were available for 49 pts at T2, 39 pts at T10, and 81 pts at L3. Mean FI was T2 = 33% ± 18, T10 = 28% ± 19, L3_Erector = 39% ± 19, and L3_Psoas = 19% ± 9. FI correlated across levels (T2 vs. T10 r = 0.698; T10 vs L3_Erector r = 0.506; L3_Erector vs Psoas r = 0.419) and with demographics; older pts had greater fat percentages (r = 0.31-0.45) and BMIs (r = 0.24-0.51). Increased FI at T2, T10, and L3 was associated with increased pelvic retroversion (PT: r = 0.25-0.43), global deformity (TPA: r = 0.27-0.45), and anterior malalignment (SVA: r = 0.23-0.41). The degree of FI in the PVM increased with the severity of SRS-Schwab PT and SVA modifiers. CONCLUSION: In ASD patients, global sagittal malalignment is related to FI of the PVM throughout the lumbar and thoracic spine, as identified through CT. Future research should investigate how FI relates to ASD pathogenesis.

Artificial intelligence clustering of adult spinal deformity sagittal plane morphology predicts surgical characteristics, alignment, and outcomes.

PURPOSE: AI algorithms have shown promise in medical image analysis. Previous studies of ASD clusters have analyzed alignment metrics-this study sought to complement these efforts by analyzing images of sagittal anatomical spinopelvic landmarks. We hypothesized that an AI algorithm would cluster preoperative lateral radiographs into groups with distinct morphology. METHODS: This was a retrospective review of a multicenter, prospectively collected database of adult spinal deformity. A total of 915 patients with adult spinal deformity and preoperative lateral radiographs were included. A 2 × 3, self-organizing map-a form of artificial neural network frequently employed in unsupervised classification tasks-was developed. The mean spine shape was plotted for each of the six clusters. Alignment, surgical characteristics, and outcomes were compared. RESULTS: Qualitatively, clusters C and D exhibited only mild sagittal plane deformity. Clusters B, E, and F, however, exhibited marked positive sagittal balance and loss of lumbar lordosis. Cluster A had mixed characteristics, likely representing compensated deformity. Patients in clusters B, E, and F disproportionately underwent 3-CO. PJK and PJF were particularly prevalent among clusters A and E. Among clusters B and F, patients who experienced PJK had significantly greater positive sagittal balance than those who did not. CONCLUSIONS: This study clustered preoperative lateral radiographs of ASD patients into groups with highly distinct overall spinal morphology and association with sagittal alignment parameters, baseline HRQOL, and surgical characteristics. The relationship between SVA and PJK differed by cluster. This study represents significant progress toward incorporation of computer vision into clinically relevant classification systems in adult spinal deformity. LEVEL OF EVIDENCE IV: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Use of rhBMP-2 for adult spinal deformity surgery: patterns of usage and changes over the past decade.

OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to increase fusion rates; however, cost, limited FDA approval, and possible complications impact its use. Decisions regarding rhBMP-2 use and changes over time have not been well defined. In this study, the authors aimed to assess changes in rhBMP-2 use for adult spinal deformity (ASD) surgery over the past decade. METHODS: A retrospective review of the International Spine Study Group prospective multicenter database was performed to identify ASD patients treated surgically from 2008 to 2018. For assessment of rhBMP-2 use over time, 3 periods were created: 2008-2011, 2012-2015, and 2016-2018. RESULTS: Of the patients identified, 1180 met inclusion criteria, with a mean age 60 years and 30% of patients requiring revision surgery; rhBMP-2 was used in 73.9% of patients overall. The mean rhBMP-2 dose per patient was 23.6 mg. Patients receiving rhBMP-2 were older (61 vs 58 years, p < 0.001) and had more comorbidities (Charlson Comorbidity Index 1.9 vs 1.4, p < 0.001), a higher rate of the Scoliosis Research Society-Schwab pelvic tilt modifier (> 0; 68% vs 62%, p = 0.026), a greater deformity correction (change in pelvic incidence minus lumbar lordosis 15° vs 12°, p = 0.01), and more levels fused (8.9 vs 7.9, p = 0.003). Over the 3 time periods, the overall rate of rhBMP-2 use increased and then stabilized (62.5% vs 79% vs 77%). Stratified analysis showed that after an overall increase in rhBMP-2 use, only patients who were younger than 50 years, those who were smokers, those who received a three-column osteotomy (3CO), and patients who underwent revision sustained an increased rate of rhBMP-2 use between the later two periods. No similar increases were noted for older patients, nonsmokers, primary surgery patients, and patients without a 3CO. The total rhBMP-2 dose decreased over time (26.6 mg vs 24.8 mg vs 20.7 mg, p < 0.001). After matching patients by preoperative alignment, 215 patients were included, and a significantly lower rate of complications leading to revision surgery was observed within the 2012-2015 period compared with the 2008-2011 (21.4% vs 13.0%, p = 0.029) period, while rhBMP-2 was increasingly used (80.5% vs 66.0%, p = 0.001). There was a trend toward a lower rate of pseudarthrosis for patients in the 2012-2015 period, but this difference did not reach statistical significance (7% vs 4.2%, p = 0.283). CONCLUSIONS: The authors found that rhBMP-2 was used in the majority of ASD patients and was more commonly used in those with greater deformity correction. Additionally, over the last 10 years, rhBMP-2 was increasingly used for ASD patients, but the dose has decreased.

Morphometric analysis of cervical interlaminar space for posterior surgical approach and decompression.

PURPOSE: The purpose of this study is to provide a morphometric description of the bony margins of the interlaminar spaces by level in the cervical spine for guidance of safe posterior cervical surgical dissection and decompression. We also aim to describe the impact of increasing static cervical lordosis on the overlap between the lamina. METHODS: Morphometric measurements of the interlaminar space were performed on 100 consecutive cervical spine CT scans of patients ranging in age from 18 to 50 years were selected. Three raters performed measurements of the interlaminar height measured using two techniques (true interlaminar height and surgical interlaminar height), and interlaminar width from C2-C3 to C7-T1. RESULTS: In total, 100 patients were included. The true interlaminar height was greatest at C2-3, C3-4, C4-5 (5.2 ± 1.4-1.8 mm) and smallest at C6-7 (4.4 ± 1.3 mm). Surgical interlaminar height was greatest at C3-4 (4.2 ± 1.7) and smallest at C6-7 (3.0 ± 1.3 mm). The widest interlaminar space was observed at C3-4 (27.1 ± 2.1 mm) and most narrow at C7-T1 (20.9 ± 2.4 mm). Following multivariate regression, male gender was associated with greater interlaminar widths at each cervical level between C4 and T1 (Table 2). While greater patient height was associated with larger interlaminar height (true and surgical) and width at C2-3 and C4-5, weight was not independently associated with the interlaminar measurements. Increasing C2-C7 lordosis was significantly associated with decreasing true and surgical interlaminar heights at all levels except C7-T1, but was not associated with differences between interlaminar width. CONCLUSION: The study provides a morphometric analysis of interlaminar anatomy in the cervical spine. Surgeons can apply this information in their pre-operative plan to safely approach the posterior cervical spine.

Enhanced Recovery after Lumbar Spine Fusion: A Randomized Controlled Trial to Assess the Quality of Patient Recovery.

BACKGROUND: Prospective trials of enhanced recovery after spine surgery are lacking. We tested the hypothesis that an enhanced recovery pathway improves quality of recovery after one- to two-level lumbar fusion. METHODS: A patient- and assessor-blinded trial of 56 patients randomized to enhanced recovery (17 evidence-based pre-, intra-, and postoperative care elements) or usual care was performed. The primary outcome was Quality of Recovery-40 score (40 to 200 points) at postoperative day 3. Twelve points defined the clinically important difference. Secondary outcomes included Quality of Recovery-40 at days 0 to 2, 14, and 56; time to oral intake and discharge from physical therapy; length of stay; numeric pain scores (0 to 10); opioid consumption (morphine equivalents); duration of intravenous patient-controlled analgesia use; complications; and markers of surgical stress (interleukin 6, cortisol, and C-reactive protein). RESULTS: The analysis included 25 enhanced recovery patients and 26 usual care patients. Significantly higher Quality of Recovery-40 scores were found in the enhanced recovery group at postoperative day 3 (179 ± 14 vs. 170 ± 16; P = 0.041) without reaching the clinically important difference. There were no significant differences in recovery scores at days 0 (175 ± 16 vs. 162 ± 22; P = 0.059), 1 (174 ± 18 vs. 164 ± 15; P = 0.050), 2 (174 ± 18 vs. 167 ± 17; P = 0.289), 14 (184 ± 13 vs. 180 ± 12; P = 0.500), and 56 (187 ± 14 vs. 190 ± 8; P = 0.801). In the enhanced recovery group, subscores on the Quality of Recovery-40 comfort dimension were higher (longitudinal mean score difference, 4; 95% CI, 1, 7; P = 0.008); time to oral intake (-3 h; 95% CI, -6, -0.5; P = 0.010); and duration of intravenous patient-controlled analgesia (-11 h; 95% CI, -19, -6; P < 0.001) were shorter; opioid consumption was lower at day 1 (-57 mg; 95% CI, -130, -5; P = 0.030) without adversely affecting pain scores (-2; 95% CI, -3, 0; P = 0.005); and C-reactive protein was lower at day 3 (6.1; 95% CI, 3.8, 15.7 vs. 15.9; 95% CI, 6.6, 19.7; P = 0.037). CONCLUSIONS: Statistically significant gains in early recovery were achieved by an enhanced recovery pathway. However, significant clinical impact was not demonstrated.

Global alignment and proportion (GAP) scores in an asymptomatic, nonoperative cohort: a divergence of age-adjusted and pelvic incidence-based alignment targets.

PURPOSE: To investigate GAP scores in an asymptomatic cohort of adults, including older adults with age-expected changes in spinal alignment. METHODS: One hundred and twenty asymptomatic volunteers underwent full-body radiographic scans. Demographics and sagittal radiographic parameters (pelvic incidence, sacral slope, L1-S1 lordosis, L4-S1 lordosis, and global tilt) were measured and GAP scores calculated ( www.gapcalculator.com ). Mann-Whitney U test compared groups. RESULTS: Eighty-five individuals (65 female, average age 48 ± 16 years, BMI 27 ± 6 kg/cm2) were analyzed. The median GAP score was that of a proportioned spine (0, range 0-10). 20% were moderately disproportioned and 6% were severely disproportioned. The mean relative pelvic version, relative lumbar lordosis (RLL), lumbar distribution index (LDI), and relative spinopelvic alignment were all considered aligned, although the mean RLL and LDI scores were both greater than 1. When categorized by age (< 60 years, ≥ 60 years), the median GAP score of the younger group was 0 (normal), while the median GAP score of the older cohort was 1 (normal) and different from the younger group (p < 0.001). CONCLUSION: Most patients in this asymptomatic, nonoperative cohort were normally proportioned. However, a large percentage of asymptomatic volunteers were moderately or severely disproportioned. Older patients had higher scores, indicating some disproportion. There was also a small number of severely sagittally misaligned and poorly proportioned, yet asymptomatic, volunteers. Further refinement of individualized targets is needed to determine the effect on mechanical complications and quality of life given the divergent recommendations of age-adjusted targets and GAP targets.

The spino-pelvic ratio: a novel global sagittal parameter associated with clinical outcomes in adult spinal deformity patients.

PURPOSE: Analysis of interactions of spinal alignment metrics may uncover novel alignment parameters, similar to PI-LL. This study utilized a data-driven approach to hypothesis generation by testing all possible division interactions between spinal alignment parameters. METHODS: This study was a retrospective cohort analysis. In total, 1439 patients with baseline ODI were included for hypothesis generation. In total, 666 patients had 2-year postoperative follow-up and were included for validation. All possible combinations of division interactions between baseline metrics were assessed with linear regression against baseline ODI. RESULTS: From 247 raw alignment metrics, 32,398 division interactions were considered in hypothesis generation. Conceptually, the TPA divided by PI is a measure of the relative alignment of the line connecting T1 to the femoral head and the line perpendicular to the sacral endplate. The mean TPA/PI was 0.41 at baseline and 0.30 at 2 years postoperatively. Higher TPA/PI was associated with worse baseline ODI (p < 0.0001). The change in ODI at 2 years was linearly associated with the change in TPA/PI (p = 0.0172). The optimal statistical grouping of TPA/PI was low/normal (≤ 0.2), medium (0.2-0.4), and high (> 0.4). The R-squared for ODI against categorical TPA/PI alone (0.154) was directionally higher than that for each of the individual Schwab modifiers (SVA: 0.138, PI-LL 0.111, PT 0.057). CONCLUSION: This study utilized a data-driven approach for hypothesis generation and identified the spino-pelvic ratio (TPA divided by PI) as a promising measure of sagittal spinal alignment among ASD patients. Patients with SPR > 0.2 exhibited inferior ODI scores. LEVEL OF EVIDENCE: III.

Prognostic Relevance of HJURP Expression in Patients with Surgically Resected Colorectal Cancer.

HJURP is a key factor for CENP-A deposition and maintenance in centromeres. The role of mis-regulation of histone chaperones in cancer initiation and progression has been studied. However, its role in colorectal cancer is still unclear. In this study, we aimed to evaluate the expression of HJURP in 162 colorectal cancer tissue. To investigate the function of HJURP in the colorectal cancer cell, we suppressed HJURP expression by siRNA and confirmed proliferation, migration, invasion, and anchorage independent of colony forming ability. The association between HJURP expression levels and clinicopathological factors was evaluated in 162 CRC tissues using immunohistochemistry. The overall survival rate in patients of HJURP high expression was higher than those in HJURP low expression in CRC. Suppressing HJURP expression decreased cellular proliferation, invasion, and migration in four CRC cell lines: HT29, HCT116, SW480, SW620 in vitro study. Our findings revealed that the knockdown of HJURP suppressed the proliferation, migration, invasion, and tumorigenicity in CRC cells. Due to its strong association with CRC, HJURP could be a potential prognostic biomarker and a novel target for drug discovery.

Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial.

BACKGROUND: Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. METHODS: This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival. FINDINGS: Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9-22), median progression-free survival was 20·1 months (95% CI 14·2-21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1-17·0) in the capecitabine group (hazard ratio 0·659 [95% CI 0·437-0·994], one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 [75%] of 92 vs 14 [16%] of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen. FUNDING: Pfizer, Shinpoong, and Daewoong Korea and Takeda.

Thoracolumbar junction orientation: its impact on thoracic kyphosis and sagittal alignment in both asymptomatic volunteers and symptomatic patients.

PURPOSE: The thoracolumbar junction (TLJ) has not been explored in regard to its contribution to global sagittal alignment. This study aims to define novel sagittal parameters of the TLJ and to assess their roles within global sagittal alignment. METHODS: Included for cross-sectional, retrospective analysis were asymptomatic volunteers and symptomatic patients who had undergone operation for adult spinal deformity. Unique sagittal parameters of the TLJ were measured using the midline of the T12-L1 disk space: The TLJ orientation [TLJO; thoracolumbar tilt (TLT) and slope (TLS)]. Thoracic kyphosis (TK; T5-12), C7-S1 sagittal vertical axis (SVA), lumbar lordosis (LL; L1-S1), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI) were measured. Continuous variables were compared using the independent t test. Pearson correlations examined relationships between the parameters in each group. The asymptomatic TK was calculated using the measurement of the asymptomatic volunteer's TLJO by linear regression. RESULTS: One hundred fifteen asymptomatic volunteers and 127 symptomatic patients were included. Only LL among the lumbopelvic parameters correlated with TK (asymptomatic volunteers: r = - 0.42; symptomatic patients: r = - 0.40). All the pelvic parameters have no direct correlation with TK in both groups. TLJO had stronger correlation with TK [asymptomatic volunteers: r = - 0.68 (TLS), r = 0.41 (TLT); symptomatic patients: r = - 0.56 (TLS), r = 0.44 (TLT)] than the lumbopelvic parameters. TLS correlated with LL (asymptomatic volunteers: r = 0.78; symptomatic patients: r = 0.73). Most pelvic parameters correlated with TLJO except for PI. The asymptomatic TK was estimated by the derived formula: 20.847 + TLS × (- 1.198). CONCLUSION: The TLJO integrates the status of the lumbopelvic sagittal parameters and simultaneously correlates with thoracic and global sagittal alignment. These slides can be retrieved under Electronic Supplementary Material.

Anterior cervical discectomy and fusion can restore cervical sagittal alignment in degenerative cervical disease.

OBJECTIVE: The purpose of this study was to evaluate its effect on the restoration and maintenance of cervical sagittal alignment in usual cervical degenerative diseases without preoperative sagittal malalignment. MATERIALS AND METHODS: We retrospectively evaluated 108 patients who were diagnosed with degenerative cervical disease and underwent ACDF (allograft and plating) with > 1-year follow-up. For radiographic evaluation, we analysed segmental and C2-7 cervical lordosis, disc height, C2-7 sagittal vertical axis (SVA), T1 slope, and T1 slope minus C2-7 lordosis (T1S - CL) in lateral X-ray. Clinical assessment was based on arm VAS, neck VAS, and NDI scores. Correlation analysis was performed across the pre-post-changes in radiological parameters. Correlations between the changes in radiological and clinical parameters at final follow-up were also analysed. RESULTS: C2-7 lordosis was 7.13° preoperatively and increased to 13.06° (p < 0.001) and maintained at 10.08° at final follow-up (p = 0.007). Segmental lordosis increased from 0.66° to 8.33° and maintained at 5.19° (p < 0.001). Segmental disc height was 4.67 mm preoperatively (increased to 7.13 mm postoperatively and decreased to 5.74 mm at final follow-up) (p < 0.001). SVA distance (31.53 mm to 30.02 mm) (p = 0.750) and T1 slope (30.03° to 31.37°) did not show meaningful change after surgery. Increase in segmental lordosis was correlated to an increase in C2-7 lordosis (p < 0.001). C2-7 SVA change correlated with both the T1 slope change (p < 0.001) and T1S - CL (p = 0.012). Change in SVA was correlated to a change in segmental lordosis and T1 slope (p = 0.003, p = 0.014). Clinical outcomes did not correlate with radiological findings. CONCLUSION: ACDF for the treatment of degenerative cervical disease without preoperative deformity was effective in restoring cervical sagittal alignment. Improvement of segmental lordosis related to an improvement in C2-7 lordosis and SVA. Radiological sagittal alignment did not show any relation with clinical outcomes in usual degenerative cases.