Impact of malnutrition on mortality and neurological recovery of older patients with spinal cord injury.

This retrospective cohort study established malnutrition's impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan-Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p < 0.05). In conclusion, 6% of older patients with cervical SCI had major nutrition-related risks; they showed a significantly higher 1 year mortality rate, shorter survival time, poorer neurological improvement, and lower ADL at 1 year post-injury than matched controls.

Neurological recovery rate and predictive factors of incomplete AIS grade C spinal cord injury in the older aged population.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To define the prognosis and predictive factors for neurological improvement in older patients with incomplete spinal cord injury (SCI) of American Spinal Injury Association Impairment Scale grade C (AIS-C). SETTINGS: Multi-institutions in Japan. METHODS: We included patients aged ≥65 years with traumatic SCI of AIS-C who were treated conservatively or surgically with >3 follow-up months. To identify factors related to neurological improvement, patients were divided into three groups according to their neurological status at the final follow-up, with univariate among-group comparisons of demographics, radiographic, and therapeutic factors. Significant variables were included in the multivariate logistic regression analysis. RESULTS: Overall, 296 older patients with SCI of AIS-C on admission were identified (average age: 75.2 years, average follow-up: 18.7 months). Among them, 190 (64.2%) patients improved to AIS-D and 21 (7.1%) patients improved to AIS-E at final follow-up. There were significant among-group differences in age (p = 0.026), body mass index (p = 0.007), status of pre-traumatic activities of daily living (ADL) (p = 0.037), and serum albumin concentrations (p = 0.011). Logistic regression analysis showed no significant differences in variables in the stratified group of patients who improved to AIS-D. Meanwhile, serum albumin was a significant variable in patients who improved to AIS-E (p = 0.026; OR: 6.20, pre-traumatic ADL was omitted due to data skewness). CONCLUSIONS: Most older patients with incomplete AIS-C SCI demonstrated at least 1 grade of neurological improvement. However, <10% of patients achieved complete recovery. Key predictors of complete recovery were high serum albumin levels on admission and independent pre-traumatic ADL. SPONSORSHIP: No funding was received for this study.

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.

In situ-formed hyaluronan gel/BMP-2/hydroxyapatite composite promotes bone union in refractory fracture model mice.

BACKGROUND: A combination of synthetic porous materials and BMP-2 has been used to promote fracture healing. For bone healing to be successful, it is important to use growth factor delivery systems that enable continuous release of BMP-2 at the fracture site. We previously reported that in situ-formed gels (IFGs) consisting of hyaluronan (HyA)-tyramine (TA), horseradish peroxidase and hydrogen peroxide enhance the bone formation ability of hydroxyapatite (Hap)/BMP-2 composites in a posterior lumbar fusion model. OBJECTIVE: We examined the effectiveness of IFGs-HyA/Hap/BMP-2 composites for facilitating osteogenesis in refractory fracture model mice. METHODS: After establishing the refractory fracture model, animals were either treated at the site of fracture with Hap harboring BMP-2 (Hap/BMP-2) or IFGs-HyA with Hap harboring BMP-2 (IFGs-HyA/Hap/BMP-2) (n = 10 each). Animals that underwent the fracture surgery but did not receive any treatment were considered the control group (n = 10). We determined the extent of bone formation at the fracture site according to findings on micro-computed tomography and histological studies four weeks following treatment. RESULTS: Animals treated with IFGs-HyA/Hap/BMP-2 demonstrated significantly greater bone volume, bone mineral content and bone union than those treated with vehicle or IFG-HyA/Hap alone. CONCLUSIONS: IFGs-HyA/Hap/BMP-2 could be an effective treatment option for refractory fractures.

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.

Prognostic impact of respiratory dysfunction in elderly patients with cervical spinal cord injury and/or fractures: a multicenter survey.

PURPOSE: To investigate the impact of early post-injury respiratory dysfunction for neurological and ambulatory ability recovery in patients with cervical spinal cord injury (SCI) and/or fractures. METHODS: We included 1,353 elderly patients with SCI and/or fractures from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were included in the respiratory dysfunction group, which was further classified into mild and severe respiratory groups based on respiratory weaning management. Patient characteristics, laboratory data, neurological impairment scale scores, complications at injury, and surgical treatment were evaluated. We performed a propensity score-matched analysis to compare neurological outcomes and mobility between groups. RESULTS: Overall, 104 patients (7.8%) had impaired respiratory function. In propensity score-matched analysis, the respiratory dysfunction group had a lower home discharge and ambulation rates (p = 0.018, p = 0.001, respectively), and higher rate of severe paralysis (p < 0.001) at discharge. At the final follow-up, the respiratory dysfunction group had a lower ambulation rate (p = 0.004) and higher rate of severe paralysis (p < 0.001). Twenty-six patients with severe disability required respiratory management for up to 6 months post-injury and died of respiratory complications. The mild and severe respiratory dysfunction groups had a high percentage of severe paraplegic cases with low ambulatory ability; there was no significant difference between them. The severe respiratory dysfunction group tended to have a poorer prognosis. CONCLUSION: Respiratory dysfunction in elderly patients with SCI and/or cervical fracture in the early post-injury period reflects the severity of the condition and may be a useful prognostic predictor.

Injectable Lipid Emulsion and Clinical Outcomes in Patients Exclusively Receiving Parenteral Nutrition in an ICU: A Retrospective Cohort Study Using a Japanese Medical Claims Database.

Guidelines for the nutritional management of critically ill patients recommend the use of injectable lipid emulsion (ILE) as part of parenteral nutrition (PN). The ILE's impact on outcomes remains unclear. Associations between prescribed ILE and in-hospital mortality, hospital readmission, and hospital length of stay (LOS) in critically ill patients in the intensive care unit (ICU) were investigated. Patients who were ≥18 years old in an ICU from January 2010 through June 2020, receiving mechanical ventilation, and fasting for >7 days, were selected from a Japanese medical claims database and divided, based on prescribed ILE during days from 4 to 7 of ICU admission, into 2 groups, no-lipid and with-lipid. Associations between the with-lipid group and in-hospital mortality, hospital readmission, and hospital LOS were evaluated relative to the no-lipid group. Regression analyses and the Cox proportional hazards model were used to calculate the odds ratios (OR) and regression coefficients, and hazard ratios (HR) were adjusted for patient characteristics and parenteral energy and amino acid doses. A total of 20,773 patients were evaluated. Adjusted OR and HR (95% confidence interval) for in-hospital mortality were 0.66 (0.62-0.71) and 0.68 (0.64-0.72), respectively, for the with-lipid group relative to the no-lipid group. No significant differences between the two groups were observed for hospital readmission or hospital LOS. The use of ILE for days 4 to 7 in PN prescribed for critically ill patients, who were in an ICU receiving mechanical ventilation and fasting for more than 7 days, was associated with a significant reduction in in-hospital mortality.

Effects of Dementia on Outcomes after Cervical Spine Injuries in Elderly Patients: Evaluation of 1512 Cases in a Nationwide Multicenter Study in Japan.

We aimed to retrospectively investigate the demographic characteristics and short-term outcomes of traumatic cervical spine injuries in patients with dementia. We enrolled 1512 patients aged ≥ 65 years with traumatic cervical injuries registered in a multicenter study database. Patients were divided into two groups according to the presence of dementia, and 95 patients (6.3%) had dementia. Univariate analysis revealed that the dementia group comprised patients who were older and predominantly female and had lower body mass index, higher modified 5-item frailty index (mFI-5), lower pre-injury activities of daily living (ADLs), and a larger number of comorbidities than patients without dementia. Furthermore, 61 patient pairs were selected through propensity score matching with adjustments for age, sex, pre-injury ADLs, American Spinal Injury Association Impairment Scale score at the time of injury, and the administration of surgical treatment. In the univariate analysis of the matched groups, patients with dementia had significantly lower ADLs at 6 months and a higher incidence of dysphagia up to 6 months than patients without dementia. Kaplan-Meier analysis revealed that patients with dementia had a higher mortality than those without dementia until the last follow-up. Dementia was associated with poor ADLs and higher mortality rates after traumatic cervical spine injuries in elderly patients.

Delirium Risk Score in Elderly Patients with Cervical Spinal Cord Injury and/or Cervical Fracture.

The number of elderly patients with cervical trauma is increasing. Such patients are considered to be at high risk for delirium, which is an acute neuropsychological disorder that reduces the patient's capacity to interact with their environment due to impairments in cognition. This study aimed to establish a risk score that predicts delirium in elderly patients with cervical SCI and/or cervical fracture regardless of treatment type. This retrospective cohort study included 1512 patients aged ≥65 years with cervical SCI and/or cervical fracture. The risk factors for delirium according to treatment type (surgical or conservative) were calculated using multivariate logistic regression. A delirium risk score was established as the simple arithmetic sum of points assigned to variables that were significant in the multivariate analyses. Based on the statistical results, the delirium risk score was defined using six factors: old age (≥80 years), hypoalbuminemia, cervical fracture, major organ injury, dependence on pre-injury mobility, and comorbid diabetes. The score's area under the curve for the prediction of delirium was 0.66 (p < 0.001). Although the current scoring system must be validated with an independent dataset, the system remains beneficial because it can be used after screening examinations upon hospitalization and before deciding the treatment strategy.

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 amino acids and albumin administration on albumin metabolism in surgically stressed rats: A basic nutritional study.

BACKGROUND: Nutrition therapy and administration of albumin preparations are common in postsurgical patients. However, the effects of these interventions on albumin metabolism are unclear. We elucidated the effect of postoperative albumin and/or parenteral nutrition administration on it. METHODS: Sprague-Dawley rats underwent surgery involving intestinal rubbing followed by intestinal exposure. Subsequently, they were administered experimental solutions for 48 h, their blood samples were collected at 24 and 48 h, and livers were excised at 48 h. Based on experimental solutions, rats were divided into five groups: non-surgical (Non-surg); glucose and electrolyte solution (GE); amino acid, glucose, and electrolyte solution (AGE); GE + rat serum albumin (Alb) (GE + Alb); and AGE + Alb. Their plasma albumin concentrations; albumin fractional synthesis rate (ALB FSR); mercaptoalbumin/total albumin ratio (MA ratio); and messenger RNA (mRNA) expressions of albumin and hepatocyte nuclear factor-1 (HNF-1) in the liver were measured. RESULTS: The GE and AGE groups showed significant decline in albumin concentrations. ALB FSR was significantly enhanced in the AGE group compared with the GE group. The mRNA expression of albumin was similar to ALB FSR in all groups and that of HNF-1 was significantly decreased in the GE + Alb and AGE + Alb groups compared with the Non-surg group. The MA ratio in the AGE group was similar to the Non-surg group. CONCLUSION: The administration of amino acids comprising parenteral nutrition after surgery augmented ALB FSR and maintained the MA ratio only without simultaneous albumin administration.

Risk Factors for Early Mortality in Older Patients with Traumatic Cervical Spine Injuries-A Multicenter Retrospective Study of 1512 Cases.

For older patients with decreased reserve function, traumatic cervical spine injuries frequently lead to early mortality. However, the prognostic factors for early mortality remain unclear. This study included patients aged ≥65 years and hospitalized for treatment of traumatic cervical spine injuries in 78 hospitals between 2010 and 2020. Early mortality was defined as death within 90 days after injury. We evaluated the relationship between early mortality and the following factors: age, sex, body mass index, history of drinking and smoking, injury mechanisms, presence of a cervical spine fracture and dislocation, cervical ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, American Spinal Injury Association Impairment Scale, concomitant injury, pre-existing comorbidities, steroid administration, and treatment plan. Overall, 1512 patients (mean age, 75.8 ± 6.9 years) were included in the study. The early mortality rate was 4.0%. Multivariate analysis identified older age (OR = 1.1, p < 0.001), male sex (OR = 3.7, p = 0.009), cervical spine fracture (OR = 4.2, p < 0.001), complete motor paralysis (OR = 8.4, p < 0.001), and chronic kidney disease (OR = 5.3, p < 0.001) as risk factors for early mortality. Older age, male sex, cervical spine fracture, complete motor paralysis, and chronic kidney disease are prognostic factors for early mortality in older patients with traumatic cervical spine injuries.

Effect of spheroid size on gene expression profiles of a mouse mesenchymal stem cell line in spheroid culture.

BACKGROUND: Mesenchymal stem cell (MSC)-based therapies offer potential for bone repair. MSC spheroid cultures may harbor enhanced therapeutic potential over MSC monolayers through increased secretion of trophic factors. However, the impact of spheroid size on trophic factor expression is unclear. OBJECTIVE: We investigated the effect of spheroid size on trophic factor-related gene expression. METHODS: KUM10, a murine MSC line was used. RNA-seq was used to screen the transcriptional profiles of MSC monolayer and spheroid cultures. Differentially expressed genes identified in RNA-seq were evaluated by q-PCR in cultures of 5 × 104 (S group), 5 × 105 (M group), 5 × 106 (L group) cells/well. RESULTS: Comparison of expression levels between KUM10 monolayer and spheroid cultures identified 2140 differentially expressed genes, of which 1047 were upregulated and 1093 were downregulated in KUM10 spheroids. Among these, 12 upregulated genes (Bmp2, Fgf9, Fgf18, Ngf, Pdgfa, Pdgfb, Tgfb1, Vegfa, Vegfc, Wnt4, Wnt5a, Wnt10a) were associated with secretory growth factors. Of these, expression of Fgf9, Fgf18, Vegfa and Vegfc was elevated in the L group, and Pdgfb and Tgfb1 was elevated in the S group. CONCLUSIONS: Spheroid size may impact trophic factor expression. Our results will be useful for future studies assessing the utility of MSC spheroids for treating bone injury.

Associations between In-Hospital Mortality and Prescribed Parenteral Energy and Amino Acid Doses in Critically Ill Patients: A Retrospective Cohort Study Using a Medical Claims Database.

Some critically ill patients completely rely on parenteral nutrition (PN), which often cannot provide sufficient energy/amino acids. We investigated the relationship between PN doses of energy/amino acids and clinical outcomes in a retrospective cohort study using a medical claims database (≥10.5 years, from Japan, and involving 20,773 adult intensive care unit (ICU) patients on mechanical ventilation and exclusively receiving PN). Study patients: >70 years old, 63.0%; male, 63.3%; and BMI < 22.5, 56.3%. Initiation of PN: third day of ICU admission. PN duration: 12 days. In-hospital mortality: 42.5%. Patients were divided into nine subgroups based on combinations of the mean daily doses received during ICU days 4-7: (1) energy (very low <10 kcal/kg/day; low ≥10, <20; and moderate ≥20); (2) amino acids (very low <0.3 g/kg/day; low ≥0.3, <0.6; and moderate ≥0.6). For each subgroup, adjusted odds ratios (AORs) of in-hospital mortality with 95% confidence intervals (CIs) were calculated by regression analysis. The highest odds of mortality among the nine subgroups was in the moderate calorie/very low amino acid (AOR = 2.25, 95% CI 1.76-2.87) and moderate calorie/low amino acid (AOR = 1.68, 95% CI 1.36-2.08) subgroups, meaning a significant increase in the odds of mortality by between 68% and 125% when an amino acid dose of <0.6 g/kg/day was prescribed during ICU days 4-7, even when ≥20 kcal/kg/day of calories was prescribed. In conclusion, PN-dependent critically ill patients may have better outcomes including in-hospital mortality when ≥0.6 g/kg/day of amino acids is prescribed.

Clinical impact of lipid injectable emulsion in internal medicine inpatients exclusively receiving parenteral nutrition: a propensity score matching analysis from a Japanese medical claims database.

BACKGROUND: Although guidelines recommend lipid injectable emulsions (ILEs) be used as a part of parenteral nutrition, many patients in Japan receive lipid-free parenteral nutrition. Furthermore, little is known about the effect of ILEs on clinical outcomes in medical inpatients managed with parenteral nutrition. The aim of this study was to investigate the clinical impact of ILEs on internal medicine inpatients receiving parenteral nutrition. METHODS: A propensity score matching (PSM) analysis was performed using a medical claims database covering 451 hospitals in Japan. Participants included the following internal medicine inpatients, ages ≥ 18 years, fasting > 10 days, and receiving exclusively parenteral nutrition, between 2011 and 2020. Participants were divided into 2 groups: those who did and did not receive ILEs. The primary endpoint was in-hospital mortality. The secondary endpoints included intravenous catheter infection, activities of daily living (ADL), hospital length of stay (LOS), and total medical costs. To adjust for energy doses, logistic or multiple regression analyses were performed using energy dose as an additional explanatory variable. RESULTS: After PSM, 19,602 matched pairs were formed out of 61,437 patients. The ILE group had significantly lower incidences than the non-ILE group of in-hospital mortality (20.3% vs. 26.9%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72; p < 0.001), deteriorated ADL (10.8% vs. 12.5%; OR, 0.85; 95% CI, 0.79-0.92; p < 0.001), and shorter LOS (regression coefficient, - 0.8; 95% CI, - 1.6-0.0; p = 0.045). After adjusting for energy dose, these ORs or regression coefficients demonstrated the same tendencies and statistical significance. The mean total medical costs were $21,009 in the ILE group and $21,402 in the non-ILE group (p = 0.08), and the adjusted regression coefficient for the ILE vs. the non-ILE group was - $860 (95% CI, - $1252 to - $47). CONCLUSIONS: ILE use was associated with improved clinical outcomes, including lower in-hospital mortality, in internal medicine inpatients receiving parenteral nutrition.

Dose-Dependent Effects of Amino Acids on Clinical Outcomes in Adult Medical Inpatients Receiving Only Parenteral Nutrition: A Retrospective Cohort Study Using a Japanese Medical Claims Database.

The majority of inpatients requiring parenteral nutrition (PN) do not receive adequate amino acid, which may negatively impact clinical outcomes. We investigated the influence of amino acid doses on clinical outcomes in medical adult inpatients fasting >10 days and receiving only PN, using Japanese medical claims database. The primary endpoint was in-hospital mortality, and the secondary endpoints included deterioration of activities of daily living (ADL), intravenous catheter infection, hospital readmission, hospital length of stay (LOS), and total medical costs. Patients were divided into four groups according to their mean prescribed daily amino acid doses from Days 4 to 10 of fasting: Adequate (≥0.8 g/kg/day), Moderate (≥0.6−<0.8 g/kg/day), Low (≥0.4−<0.6 g/kg/day), and Very low (<0.4 g/kg/day). Multivariate logistic or multiple regression analyses were performed with adjustments for patient characteristics (total n = 86,702). The Adequate group was used as the reference in all analyses. For the Moderate, Low, and Very low groups, adjusted ORs (95% CI) of in-hospital mortality were 1.20 (1.14−1.26), 1.43 (1.36−1.51), and 1.72 (1.62−1.82), respectively, and for deterioration of ADL were 1.21 (1.11−1.32), 1.34 (1.22−1.47), and 1.22 (1.09−1.37), respectively. Adjusted regression coefficients (95% CI) of hospital LOS were 1.2 (0.4−2.1), 1.5 (0.6−2.4), and 2.9 (1.8−4.1), respectively. Lower prescribed doses of amino acids were associated with worse clinical outcomes including higher in-hospital mortality.

Effect of Bone Morphogenetic Protein-2 (BMP-2)/Hydroxyapatite/In Situ-Formed Hyaluronan Hydrogel Composites on Bone Formation in a Murine Model of Posterolateral Lumbar Fusion.

Several types of calcium phosphate (CaP) biomaterial carriers have been designed to deliver bone morphogenetic protein-2 (BMP-2) to augment spinal fusion in spinal surgery. Here, we evaluated an in situ-formed hydrogel (IFH) constructed from hyaluronan (IFH-HA) combined with a BMP2/hydroxyapatite (HAP) composite in bone formation in a murine model of posterolateral lumbar fusion (PLF). HAP was submerged in HA-tyramine (TA) polymer solution containing horseradish peroxidase (HRP) and 2 µg BMP-2 (BMP2/HA-TA/HRP solution). H2O2 was added to initiate the curing reaction (BMP-2/IFH-HA). phosphate-buffered saline (PBS) was added to the BMP2/HA-TA/HRP solution (BMP-2/HA-TA) instead of H2O2 to evaluate the effectiveness of the curing reaction. HAP immersed in PBS was used as a control. PLF model mice were randomly assigned to receive one these composites (n = 10 each). X-ray images were taken to assess the bone fusion, and microcomputed tomography analysis was conducted to examine new bone formation at the graft site four weeks following surgery. No evidence of fusion was observed four weeks after surgery in the Control or BMP2/HA-TA group. In contrast, the BMP2/IFH-HA group exhibited newly formed bone between the transverse processes and bone union in coronal sections. Relative to the Control and BMP2/HA-TA groups, the BMP2/IFH-HA group showed significantly greater bone volume. The BMP2/IFH-HA group also showed significantly elevated bone mineral content relative to the BMP2/HA-TA group. A composite comprising BMP2/HAP and IFH-HA, thus, enhanced the new bone formation in a murine model of PLF, suggesting its promise for augmenting spinal fusion.

Computational Analysis of the SARS-CoV-2 RBD-ACE2-Binding Process Based on MD and the 3D-RISM Theory.

The binding process of angiotensin-converting enzyme 2 (ACE2) to the receptor-binding domain (RBD) of the severe acute respiratory syndrome-like coronavirus 2 spike protein was investigated using molecular dynamics simulation and the three-dimensional reference interaction-site model theory. The results suggested that the protein-binding process consists of a protein-protein approaching step, followed by a local structural rearrangement step. In the approaching step, the interprotein interaction energy decreased as the proteins approached each other, whereas the solvation free energy increased. As the proteins approached, the glycan of ACE2 first established a hydrogen bond with the RBD. Thereafter, the number of interprotein hydrogen bonds increased rapidly. The solvation free energy increased because of the desolvation of the protein as it approached its partner. The spatial distribution function of the solvent revealed the presence of hydrogen bonds bridged by water molecules on the RBD-ACE2 interface. Finally, principal component analysis revealed that ACE2 showed a pronounced conformational change, whereas there was no significant change in RBD.

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.

Investigations into the Potential of Using Open Source CFD to Analyze the Differences in Hemodynamic Parameters for Aortic Dissections (Healthy versus Stanford Type A and B).

BACKGROUND: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. METHODS: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. RESULTS: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. CONCLUSIONS: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.