Albuterol delivery via in-line intrapulmonary percussive ventilation superimposed on conventional mechanical ventilation in an adult lung model.

Background: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosols containing medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT) while drug delivery via IPV during conventional mechanical ventilation (IPV/CMV) is not well characterized. We hypothesized that drug delivery via IPV/CMV would take place differently from that via IPV alone due to control of ventilation by CMV. Methods: An adult ventilator circuit was used for IPV/CMV. A normal or diseased lung model was configured to airway resistance (Raw) 5 cm H2O/L/s and lung compliance (CL) 100 mL/cm H2O or Raw 20 cm H2O/L/s and CL 50 mL/cm H2O, respectively. The ventilator settings were: pressure control continuous mandatory ventilation mode, 10 breaths/min, PEEP 5 cm H2O, FIO2 0.21, inspiratory time 1 s, no bias flow, and inspiratory pressure 10 or 15 cm H2O for the normal or diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from Phasitron 5 was captured in a filter placed before the lung model and quantitated by spectrophotometry. Results: The maximal efficiency of albuterol delivery via IPV/CMV was not different from that via IPV alone (3.7 ± 0.2% vs 4.2 ± 0.3%, mean ± SD of loading dose, P= .12). Albuterol delivery efficiency with IPV/CMV was lower for the diseased lung model than for the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%, mean ± SD, P < .001), which increased with decreasing percussion frequency. In contrast, VT was lower for the normal lung model than for the diseased model (401 ± 14 mL vs 470 ± 11 mL, mean ± SD, P < .001). Conclusions: Albuterol delivery via IPV/CMV was modulated by percussion frequency but not increased with increasing VT The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition.

Relationship Between Corticosteroid Administration and Survival Period in Terminal Cancer Patients.

Objective: Corticosteroids are commonly used for symptom relief in patients with terminal cancer, but their use may have an impact on patient survival. We compared the survival of patients with terminal cancer who did and did not receive corticosteroid treatment for symptom relief, stratified by their predicted prognosis. Methods: We retrospectively reviewed consecutive patients with cancer who received corticosteroid treatment for symptom relief in a single palliative care unit. We stratified the patients according to their predicted prognosis using the palliative prognostic (PaP) score either before starting the corticosteroid treatment or at admission for control patients who did not receive a corticosteroid treatment. The 2 groups were compared for survival based on the PaP Scores. Results: We analyzed 204 patients treated with a corticosteroid during the study period and 139 control patients who did not receive corticosteroids during their treatment. No difference was observed in the survival between the treatment and control groups. Conclusion: Corticosteroid treatment for symptom relief in patients with terminal cancer did not affect survival time.

The structure-activity relationship of aryloxyacetylthioureas for the inhibition of Orobanche minor radicle elongation.

Orobanchaceae root parasitic weeds cause significant damage to agriculture and become threats to global food security. Integrated pest management is a key concept in modern agriculture and requires chemicals with various modes of action. Planteose accumulates as a storage carbohydrate in the dry seeds of root parasitic weeds. In Orobanche minor seeds, planteose is hydrolyzed by an α-galactosidase, OmAGAL2, during germination. It was found that the OmAGAL2 inhibitor, PI-28, suppressed the radicle elongation of germinating O. minor seeds. This inhibitory activity against O. minor radicle elongation was evaluated for a series of aryloxyacetylthioureas synthesized based on the structure of PI-28. Compounds with a 3-Cl or 4-Cl substituent on the benzene ring in the phenoxy moiety in PI-28 exhibited more potent activity than the parent PI-28. This is the first report on the effect of aryloxyacetylthioureas on a root parasitic weed and will contribute to the development of control reagents for root parasitic weeds.

Kinetics of COVID-19 mRNA primary and booster vaccine-associated neutralizing activity against SARS-CoV-2 variants of concern in long-term care facility residents: a prospective longitudinal study in Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a threat to vulnerable populations such as long-term care facility (LTCF) residents, who are often older, severely frail, and have multiple comorbidities. Although associations have been investigated between COVID-19 mRNA vaccine immunogenicity, durability, and response to booster vaccination and chronological age, data on the association of clinical factors such as performance status, nutritional status, and underlying comorbidities other than chronological age are limited. Here, we evaluated the anti-spike IgG level and neutralizing activity against the wild-type virus and Delta and Omicron variants in the sera of LTCF residents, outpatients, and healthcare workers before the primary vaccination; at 8, 12, and 24 weeks after the primary vaccination; and approximately 3 months after the booster vaccination. This 48-week prospective longitudinal study was registered in the UMIN Clinical Trials Registry (Trial ID: UMIN000043558). RESULTS: Of 114 infection-naïve participants (64 LTCF residents, 29 outpatients, and 21 healthcare workers), LTCF residents had substantially lower anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant than outpatients and healthcare workers over 24 weeks after the primary vaccination. In LTCF residents, booster vaccination elicited neutralizing activity against the wild-type virus and Delta variant comparable to that in outpatients, whereas neutralizing activity against the Omicron variant was comparable to that in outpatients and healthcare workers. Multiple regression analyses showed that age was negatively correlated with anti-spike IgG levels and neutralizing activity against the wild-type virus and Delta variant after the primary vaccination. However, multivariate regression analysis revealed that poor performance status and hypoalbuminemia were more strongly associated with a lower humoral immune response than age, number of comorbidities, or sex after primary vaccination. Booster vaccination counteracted the negative effects of poor performance status and hypoalbuminemia on the humoral immune response. CONCLUSIONS: LTCF residents exhibited suboptimal immune responses following primary vaccination. Although older age is significantly associated with a lower humoral immune response, poor performance status and hypoalbuminemia are more strongly associated with a lower humoral immune response after primary vaccination. Thus, booster vaccination is beneficial for older adults, especially those with a poor performance status and hypoalbuminemia.

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

Posterior Spinal Fusion Surgery for Neuromuscular Disease Patients with Severe Scoliosis Whose Cobb Angle Was over 100 Degrees.

Background and objectives: Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre- or intraoperative traction would be effective for severe spinal deformities but would be invasive. This study aimed to evaluate the outcomes of PSF-only surgery for patients with severe NMS with a Cobb angle > 100°. Materials and Methods: Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF-only surgery for scoliosis with a Cobb angle > 100° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings, including Cobb angle and pelvic obliquity (PO) in the sitting position pre- and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. Results: The mean duration of surgery was 338 min, intraoperative blood loss was 1440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group were significantly higher than those in the L5 group. Conclusions: Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF surgery without anterior release or any intra-/preoperative traction showed satisfactory outcomes, including acceptable scoliosis correction and improved clinical findings, even in patients with extremely severe NMS. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

Intraoperative Blood Loss at Different Surgical-Procedure Stages during Posterior Spinal Fusion for Idiopathic Scoliosis.

Background and Objectives: Several predictive factors have been reportedly associated with intraoperative total blood loss (TBL) during posterior spinal fusion (PSF) for idiopathic scoliosis (IS). To reduce TBL, preoperative factors and interoperative factors are considered important. However, there are few reports that have evaluated bleeding patterns according to surgical stages. This study aimed to elucidate bleeding patterns at different surgical stages and determine the predictive factors for TBL during PSF surgery in patients with IS. Materials and Methods: Preoperative data, radiographic parameters, and intraoperative data of patients undergoing PSF for IS were retrospectively collected. We divided the patients into six stages: stage 1, exposure; stage 2, implant placement; stage 3, release; stage 4, correction; stage 5, bone grafting; and stage 6, closure; then we reviewed the blood loss and bleeding speed. Multiple-regression analysis was performed to generate a predictive formula for blood loss using preoperative and intraoperative factors, including blood loss at stage 1, as explanatory variables. Results: Forty-five patients (mean age: 17.6 years) were included. The mean operative time and TBL were 287.9 min and 756.5 mL, respectively. Blood loss was the highest at stage 3, followed by stage 4. Bleeding speed was the highest at stage 4, followed by stage 3. Bleeding speeds at stages 3 and 4 were significantly higher than those at stages 1 and 2. Preoperative Cobb angle, activated partial thromboplastin time (aPTT), number of fused vertebrae, and blood loss at stage 1 were significant contributing factors. Conclusions: Blood loss and bleeding speed during the release and correction stages were high. Specifically, bleeding speed significantly increased during and after the release procedure. The preoperative Cobb angle, aPTT, number of fixed vertebrae, and blood-loss volume during PSF were significantly associated with TBL. Our findings would be helpful for reducing TBL in patients undergoing PSF for IS.

Effects of tumor-infiltrating CD8+ T cells, PD1/PD-L1 axis, and expression patterns of HLA class I on the prognosis of patients with malignant pleural mesothelioma who underwent extra-pleural pneumonectomy.

Programmed cell death protein-1 (PD1), PD1 ligand 1 (PD-L1), and human leukocyte antigen (HLA) class I molecule play pivotal roles in T cell-induced anti-tumor immunity; however, the clinical impact of these parameters in resected malignant pleural mesothelioma (MPM) cases is unknown. We immunohistochemically evaluated the tumor infiltrated lymphocytes (TILs), PD1/PD-L1 axis, and expression of HLA class I in resected specimens from 58 patients with MPM who underwent extra-pleural pneumonectomy (EPP). Higher infiltration of CD3-TIL, CD8-TIL, and PD1-TIL, loss of HLA class I, and overexpression of PD-L1 by tumor cells (PD-L1 TC) or immune cells (PD-L1 IC) were observed in 34 (58.6%), 27 (46.6%), 41 (70.7%), 45 (77.6%), 29 (50.0%), and 33 (56.4%) of 58 cases, respectively. Interestingly, the CD3-TIL score positively correlated with PD-L1 TC and PD1-TIL scores. HLA class I expression level was inversely correlated with the expression levels of PD-L1 TC and PD-L1 IC. Multivariate analysis showed that age, histology, and node metastasis were independent prognostic factors for 5-year overall survival (OS) and loss of HLA class I coincided with a positive prognosis (p = 0.011). The concomitant lack of infiltrating CD8+ T cells with no loss of HLA class I predicted worse 5-year OS (p = 0.007). Moreover, cluster classifications among multiple immunoparameters showed that categories among CD3/PD-L1 TC/HLA class I (p = 0.043), CD8/PD1/HLA class I (p = 0.032), CD8/PD-L1 TC/HLA class I (p = 0.011), and PD1/PD-L1 TC/HLA class I (p = 0.032) predicted 5-year OS in EPP cases for MPM. These immunoparameters could guide surgical indications for patients with MPM.

Decreased muscle mass and strength affected spinal sagittal malalignment.

PURPOSE: Correction surgeries for spinal malalignment showed good clinical outcomes; however, there were concerns including increased invasiveness, complications, and impact on medico-economics. Ideally, an early intervention is needed. To better understand the patho-mechanism and natural course of spinal alignment, the effect of factors such as muscle mass and strength on spinal sagittal imbalance were determined in a multicenter cross-sectional study. METHODS: After excluding metal implant recipients, 1823 of 2551 patients (mean age: 69.2 ± 13.8 years; men 768, women 1055) were enrolled. Age, sex, past medical history (Charlson comorbidity index), body mass index (BMI), grip strength (GS), and trunk muscle mass (TM) were reviewed. Spinal sagittal imbalance was determined by the SRS-Schwab classification. Multiple comparison analysis among four groups (Normal, Mild, Moderate, Severe) and multinomial logistic regression analysis were performed. RESULTS: On multiple comparison analysis, with progressing spinal malalignment, age in both sexes tended to be higher; further, TM in women and GS in both sexes tended to be low. On multinomial logistic regression analysis, age and BMI were positively associated with spinal sagittal malalignment in Mild, Moderate, and Severe groups. TM in Moderate and Severe groups and GS in the Moderate group were negatively associated with spinal sagittal malalignment. CONCLUSION: Aging, obesity, low TM, and low GS are potential risk factors for spinal sagittal malalignment. Especially, low TM and low GS are potentially associated with more progressed spinal sagittal malalignment. Thus, early intervention for muscles, such as exercise therapy, is needed, while the spinal sagittal alignment is normal or mildly affected.

A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs.

Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP's pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (-) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (-) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.

Enhanced Immunomodulatory Effect of Intravenous Immunoglobulin by Fc Galactosylation and Nonfucosylation.

Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in the treatment of various autoimmune/inflammatory diseases although its mechanism of action remains elusive. Recently, nonfucosylated IgG has been shown to be preferentially bound to Fcγ receptor IIIa (FcγRIIIa) on circulating natural killer cells; therefore, we hypothesized that nonfucosylated IVIG may modulate immune responses through FcγRIIIa blockade. Here, homogeneous fucosylated or nonfucosylated glycoforms of normal polyclonal IgG bearing sialylated, galactosylated or nongalactosylated Fc oligosaccharides were generated by chemoenzymatic glycoengineering to investigate whether the IgG glycoforms can inhibit antibody-dependent cellular cytotoxicity (ADCC).　Among the six IgG glycoforms, galactosylated, nonfucosylated IgG [(G2)2] had the highest affinity to FcγRIIIa and 20 times higher potency to inhibit ADCC than native IgG. A pilot study of IVIG treatment in mice with collagen antibody-induced arthritis highlighted the low-dose (G2)2 glycoform of IVIG (0.1 g/kg) as an effective immunomodulatory agent as the 10-fold higher dose of native IVIG. These preliminary results suggest that the anti-inflammatory activity of IVIG is in part mediated via activating FcγR blockade by galactosylated, nonfucosylated IgG and that such nonfucosylated IgG glycoforms bound to FcγRs on immune cells play immunomodulatory roles in health and disease. This study provides insights into improved therapeutic strategies for autoimmune/inflammatory diseases using glycoengineered IVIG and recombinant Fc.

Improved Prognostic Prediction by Combination of Early Initiation of Polymyxin B Hemoperfusion with Modified Gender-Age-Physiology Index in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Respiratory failure from acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is associated with high mortality. Direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP) has been reported to have beneficial effects on patients with AE-IPF. Whether patient characteristics influence the extent of this benefit remains unclear. METHODS: We retrospectively examined the records of 30 patients with AE-IPF who underwent PMX-DHP. The favorable factors of survival were determined using Cox proportional hazards analyses. RESULTS: The 1- and 12-month survival rates after PMX-DHP were 70.0% and 50.0%, respectively. The multivariate analysis revealed that low modified Gender-Age-Physiology (GAP) index (≤8 points) (hazard ratio [HR] 0.317, p = 0.015) and PMX-DHP received within 48 h of steroid pulse (HR 0.289, p = 0.012) were favorable factors. Notably, even in the patients with high modified GAP index (>8 points), that is, more advanced IPF, those who received PMX-DHP within 48 h of steroid pulse had a better prognosis than those who did after 48 h of the steroid pulse (p = 0.032). CONCLUSIONS: Early PMX-DHP initiation in patients with AE-IPF, specifically within 48 h after the steroid pulse therapy, may improve prognosis regardless of the severity of chronic phase of IPF before AE-IPF.

Factors associated with pain-related disorders and gait disturbance scores from the Japanese orthopedic association back pain evaluation questionnaire and Oswestry Disability Index in patients with osteoporosis.

In the current study, multivariate analyses were performed to determine factors associated with low back pain (LBP) in patients with osteoporosis. Aging, high bone turnover, obesity, low trunk muscle mass, spinal global sagittal malalignment, and a high number of previous vertebral fractures were potential independent risk factors of pain-related disorders, gait disturbance, or ADL deficit due to LBP. PURPOSE: Patients with osteoporosis often experience low back pain (LBP) even in the absence of acute fractures. This study identifies factors that may affect questionnaires about LBP. METHODS: The data of 491 patients with osteoporosis were retrospectively reviewed. Data included patient age, sex, body mass index (BMI), bone mineral density of the lumbar spine, tartrate-resistant acid phosphatase 5b level (TRACP5b), trunk muscle mass, sagittal vertical axis (SVA), previous vertebral fractures, secondary osteoporosis, controlling nutritional status score, pain-related disorders and gait disturbance scores from the Japanese Orthopedic Association Back Pain Evaluation questionnaire (JOABPEQ), and Oswestry disability index (ODI) scores for activities of daily living (ADL) deficit. Patients with scores of 100 for each subsection of the JOABPEQ, or an ODI scores < 12 were considered to not have dysfunction (dysfunction (-) group). Multivariate analyses were used to determine variables associated with dysfunction. RESULTS: Pain-related disorders score of JOABPEQ was associated with aging, high BMI, and high SVA. Aging, high TRACP5b, high BMI, low TM, high SVA, and more previous vertebral fractures were associated with gait disturbance score of JOABPEQ. ODI scores were associated with high BMI, low TM, high SVA, and more previous vertebral fractures. CONCLUSIONS: Aging, high bone turnover, obesity, a low TM, spinal global sagittal malalignment, and a high number of previous VFs were potential independent risk factors of pain-related disorders or gait disturbance according to the JOABPEQ or ODI score in patients with osteoporosis.

Micro-Heterogeneity of Antibody Molecules.

Therapeutic monoclonal antibodies (mAbs) are mostly of the IgG class and constitute highly efficacious biopharmaceuticals for a wide range of clinical indications. Full-length IgG mAbs are large proteins that are subject to multiple posttranslational modifications (PTMs) during biosynthesis, purification, or storage, resulting in micro-heterogeneity. The production of recombinant mAbs in nonhuman cell lines may result in loss of structural fidelity and the generation of variants having altered stability, biological activities, and/or immunogenic potential. Additionally, even fully human therapeutic mAbs are of unique specificity, by design, and, consequently, of unique structure; therefore, structural elements may be recognized as non-self by individuals within an outbred human population to provoke an anti-therapeutic/anti-drug antibody (ATA/ADA) response. Consequently, regulatory authorities require that the structure of a potential mAb drug product is comprehensively characterized employing state-of-the-art orthogonal analytical technologies; the PTM profile may define a set of critical quality attributes (CQAs) for the drug product that must be maintained, employing quality by design parameters, throughout the lifetime of the drug. Glycosylation of IgG-Fc, at Asn297 on each heavy chain, is an established CQA since its presence and fine structure can have a profound impact on efficacy and safety. The glycoform profile of serum-derived IgG is highly heterogeneous while mAbs produced in mammalian cells in vitro is less heterogeneous and can be "orchestrated" depending on the cell line employed and the culture conditions adopted. Thus, the gross structure and PTM profile of a given mAb, established for the drug substance gaining regulatory approval, have to be maintained for the lifespan of the drug. This review outlines our current understanding of common PTMs detected in mAbs and endogenous IgG and the relationship between a variant's structural attribute and its impact on clinical performance.

Importance and Monitoring of Therapeutic Immunoglobulin G Glycosylation.

The complex diantennary-type oligosaccharides at Asn297 residues of the IgG heavy chains have a profound impact on the safety and efficacy of therapeutic IgG monoclonal antibodies (mAbs). Fc glycosylation of a mAb is an established critical quality attribute (CQA), and its oligosaccharide profile is required to be thoroughly characterized by state-of-the-art analytical methods. The Fc oligosaccharides are highly heterogeneous, and the differentially glycosylated species (glycoforms) of IgG express unique biological activities. Glycoengineering is a promising approach for the production of selected mAb glycoforms with improved effector functions, and non- and low-fucosylated mAbs exhibiting enhanced antibody-dependent cellular cytotoxicity activity have been approved or are under clinical evaluation for treatment of cancers, autoimmune/chronic inflammatory diseases, and infection. Recently, the chemoenzymatic glycoengineering method that allows for the transfer of structurally defined oligosaccharides to Asn-linked GlcNAc residues with glycosynthase has been developed for remodeling of IgG-Fc oligosaccharides with high efficiency and flexibility. Additionally, various glycoengineering methods have been developed that utilize the Fc oligosaccharides of IgG as reaction handles to conjugate cytotoxic agents by "click chemistry", providing new routes to the design of antibody-drug conjugates (ADCs) with tightly controlled drug-antibody ratios (DARs) and homogeneity. This review focuses on current understanding of the biological relevance of individual IgG glycoforms and advances in the development of next-generation antibody therapeutics with improved efficacy and safety through glycoengineering.

Prevalence and location of endplate fracture and subsidence after oblique lumbar interbody fusion for adult spinal deformity.

BACKGROUND: Recently, Oblique lumbar interbody fusion (OLIF) is commonly indicated to correct the sagittal and coronal alignment in adult spinal deformity (ASD). Endplate fracture during surgery is a major complication of OLIF, but the detailed location of fracture in vertebral endplate in ASD has not yet been determined. We sought to determine the incidence and location of endplate fracture and subsidence of the OLIF cage in ASD surgery, and its association with fusion status and alignment. METHODS: We analyzed 75 levels in 27 patients were analyzed using multiplanar CT to detect the endplate fracture immediately after surgery and subsidence at 1 year postoperatively. The prevalence was compared between anterior and posterior, approach and non-approach sides, and concave and convex side. Their association with fusion status, local and global alignment, and complication was also investigated. RESULTS: Endplate fracture was observed in 64 levels (85.3%) in all 27 patients, and the incidence was significantly higher in the posterior area compared with the anterior area (85.3 vs. 68.0%, p=0.02) of affected vertebra in the sagittal plane. In the coronal plane, there was no significant difference in incidence between left (approach) and right (non-approach) sides (77.3 and 81.3%, respectively), or concave and convex sides (69.4 and 79.6%) of wedged vertebra. By contrast, cage subsidence at 1 year postoperatively was noted in 14/75 levels (18.7%), but was not associated with endplate fracture. Fusion status, local and global alignment, and complications were not associated with endplate fracture or subsidence. CONCLUSION: Endplate fracture during OLIF procedure in ASD cases is barely avoidable, possibly induced by the corrective maneuver with ideal rod counter and cantilever force, but is less associated with subsequent cage subsidence, fusion status, and sustainment of corrected alignment in long fusion surgery performed even for elderly patients.

Prevalence and Characteristics of Spinal Sagittal Malalignment in Patients with Osteoporosis.

Spinal sagittal malalignment due to vertebral fractures (VFs) induces low back pain (LBP) in patients with osteoporosis. This study aimed to elucidate spinal sagittal malalignment prevalence based on VF number and patient characteristics in individuals with osteoporosis and spinal sagittal malalignment. Spinal sagittal alignment, and VF number were measured in 259 patients with osteoporosis. Spinal sagittal malalignment was defined according to the SRS-Schwab classification of adult spinal deformity. Spinal sagittal malalignment prevalence was evaluated based on VF number. In patients without VFs, bone mineral density, bone turnover markers, LBP scores and health-related quality of life (HRQoL) scores of normal and sagittal malalignment groups were compared. In 205 of the 259 (79.2%) patients, spinal sagittal malalignment was detected. Sagittal malalignment prevalence in patients with 0, 1, or ≥2 VFs was 72.1%, 86.0%, and 86.3%, respectively. All LBP scores and some subscale of HRQoL scores in patients without VFs were significantly worse for the sagittal malalignment group than the normal alignment group (p < 0.05). The majority of patients with osteoporosis had spinal sagittal malalignment, including ≥70% of patients without VFs. Patients with spinal sagittal malalignment reported worse LBP and HRQoL. These findings suggest that spinal sagittal malalignment is a risk factor for LBP and poor HRQoL in patients with osteoporosis.

Incidence of Unintentional Intraoperative Hypothermia in Pediatric Scoliosis Surgery and Associated Preoperative Risk Factors.

INTRODUCTION: Intraoperative hypothermia is associated with perioperative complications such as blood loss and wound infection. Thus, perioperative heat retention methods to prevent perioperative hypothermia such as providing a warmed blanket and active patients' warming are important. Although major surgery and pediatric patient age are noted as risk factors, only a few studies focus on hypothermia as an intraoperative complication in pediatric scoliosis surgery. The aim of this study is to investigate the incidence of intraoperative hypothermia in pediatric scoliosis surgery and the associated preoperative risk factors. METHODS: We retrospectively reviewed the records of pediatric patients who underwent posterior spinal fusion at a single institution between 2015 and 2019. We recorded the background data, perioperative data, lowest recorded core temperature, and perioperative complications. Patients were divided into those whose temperature decreased below 36°C (Group H) and those who maintained a temperature of 36°C or greater (Group N) during surgery. We compared the two groups and performed multivariate analysis to identify preoperative risk factors for intraoperative hypothermia. RESULTS: A total of 103 patients underwent posterior spinal fusion; 56 for adolescent idiopathic scoliosis and 47 for neuromuscular scoliosis. Hypothermia was observed in 40 patients (38.8%). Group H had more non-adolescent idiopathic scoliosis (AIS) patients, lower mean body mass index, greater mean blood loss, greater number of fused vertebrae, larger preoperative Cobb angle, and lower initial core body temperature (immediately after induction of anesthesia). On multivariate analysis, a diagnosis of neuromuscular scoliosis, a lower body mass index, and a lower initial core body temperature were identified as independent risk factors for intraoperative hypothermia. CONCLUSIONS: The incidence of hypothermia in pediatric posterior scoliosis surgery is 38.8%. Diagnosis of non-AIS, lower body mass index, and lower core body temperature at the time of anesthesia induction are preoperative risk factors for intraoperative hypothermia.

Posterior Spinal Correction and Fusion Surgery in Patients with Spinal Muscular Atrophy-Associated Scoliosis for Whom Treatment with Nusinersen Was Planned.

INTRODUCTION: Spinal muscular atrophy (SMA) is defined as a neuromuscular disorder induced by progressive weakness of the skeletal muscle and is usually accompanied by progressive spinal deformity including scoliosis. The newly developed Nusinersen, which is the first approved drug worldwide for SMA, requires accurate intrathecal injection, which is sometimes difficult in patients with severe spinal deformity. TECHNICAL NOTE: For an accurate intrathecal approach in patients who have spinal fusion surgery to treat neuromuscular scoliosis, we have combined an L3 laminectomy with spinal correction and fusion surgery. Here, we review four cases of SMA in patients who underwent the additional L3 laminectomy during surgery to treat spinal scoliosis. A successful intrathecal approach was made using fluoroscopic guidance in all four patients, who were then administered with Nusinersen. CONCLUSIONS: Our findings show that additional lumbar laminectomy during surgery for spinal scoliosis has effectively allowed for intrathecal injection of Nusinersen.

Chylous retroperitoneum following 720 degree anteroposterior-combined corrective surgery for adult spinal deformity with split vertebral fracture subluxation: a case report.

STUDY DESIGN: Clinical case report. PURPOSE: To report the rare case with post-operative chylous retroperitoneum after corrective surgery for adult spinal deformity. METHODS: We present a case of a 73-year-old woman with Parkinson's disease. She sustained a severe split fracture subluxation of the L3 vertebra with AO Spine Thoracolumbar classification type CN2M2, resulting in severe kyphoscoliosis in global alignment. She underwent a two-stage 720-degree anteroposterior-combined corrective surgery with anterior vertebral column resection of L3 and posterior fusion from T4 to the pelvis. On post-operative day 1, milky fluid in the drainage tube was noted, which was diagnosed as post-operative chylous retroperitoneum. RESULTS: Oral intake was discontinued immediately and peripheral parenteral nutrition was started. A low-fat, high-protein diet was started on post-operative day 4, and drainage was removed on day 6. A low-fat diet was continued until 3 months post-operatively, with dietary counselling by a nutritionist. The chylous retroperitoneum resolved without recurrence at the final follow-up evaluation at 3 years. CONCLUSION: Surgeons should recognize this rare complication, which might be induced by direct damage to the lymphatic flow during an operative maneuver anterior to the lumbar vertebral body and indirect damage due to shearing force during correction of a subluxated vertebra, especially in cases with a severe deformity.