A case of delayed dyspnea after corrective posterior fusion of the middle and lower cervical spine for dropped head syndrome.

Dyspnea has been reported to occur following posterior occipitocervical fusion. However, there are no documented cases of dyspnea following posterior fixation of the middle and lower cervical spine without posterior occipitocervical fusion. An 80-year-old woman underwent corrective fusion from T4 to the ilium for kyphoscoliosis. Sixteen months later, the patient developed cervical kyphosis (dropped head syndrome) with proximal junctional kyphosis, leading to a pedicle subtraction osteotomy at T4 and an extended fixation to C2. On the sixth postoperative day, the patient experienced respiratory arrest, prompting a reoperation to reduce cervical lordosis, ultimately resolving the respiratory dysfunction. Excessive correction of cervical kyphosis should be avoided to prevent the occurrence of postoperative dyspnea, even in cases where posterior occipitocervical fusion has not been performed.

Long-term psychiatric disorders in families of severe COVID-19 patients.

Aim: The present study aimed to describe in detail the changes to and assess the risk factors for poor long-term outcomes of psychiatric disorders in families of COVID-19 patients. Methods: A single-center, retrospective study using questionnaires. Family members of patients admitted to the intensive care unit (ICU) with severe COVID-19 participated. Psychiatric disorders refer to the psychological distress such as anxiety, depression, and posttraumatic stress disorder (PTSD) experienced by the patient's family. Results: Forty-six family members completed the survey and were analyzed. Anxiety, depression, and PTSD occurred in 24%, 33%, and 2% of family members, respectively, and psychiatric disorders occurred in 39%. On multivariable analysis, living in the same house with the patient was independently associated with a lower risk of psychiatric disorders in families of COVID-19 patients (OR, 0.180; 95% CI, 0.036-0.908; p = 0.038). Furthermore, four family members overcame psychiatric disorders, and six family members newly developed psychiatric disorders during the one-year follow-up period. Conclusion: Approximately 40% of family members had long-term psychiatric disorders, and some of them overcame the psychiatric disorders, and some newly developed psychiatric disorders over the one-year follow-up. Living in the same house with the patient was possibly significantly associated with the reduction of long-term symptoms of psychiatric disorders, but this result must be interpreted with care. Further large studies are needed to examine the factors associated with the long-term mental status of family members.

The efficacy of anatomic resection for hepatocellular carcinoma within Milan criteria: A retrospective single-institution case-matched study.

INTRODUCTION: Still now, the efficacy of anatomic resection (AR) for hepatocellular carcinoma (HCC) is controversial. The aim of this study is to examine it in our cohort and detect an optimal indicator for AR. METHODS: The present study included 656 patients with primary HCC within Milan criteria who underwent hepatectomy from 2000 to 2019. Our cohort was divided into AR (n = 378) and non-anatomic resection (NAR) (n = 278) groups, and 1:1 propensity score matching (PSM) was performed to minimize the effect of potential confounders. Recurrence-free survival (RFS), overall survival (OS), and a preoperative indicator for AR were examined. RESULTS: 210 patients from each group were well-matched, and preoperative confounding factors were balanced between the two groups. There was no significant difference in RFS and OS between the two groups before (RFS; HR = 0.89 P = 0.25, OS; HR = 1.08 P = 0.64) and after PSM (RFS; HR = 0.93 P = 0.60, OS; HR = 1.07 P = 0.75). Subgroup analysis showed that the survival improvement effect of AR was observed in cases with a fucosylated fraction of alfa-fetoprotein (AFP-L3) > 10% and poorly differentiation (P for interaction <0.05). Moreover, the logistic regression analysis showed that preoperative AFP-L3 > 10% was an independent predictor for poorly differentiation (OR = 2.58, P = 0.03). CONCLUSION: The efficacy of AR for patients with primary HCC within Milan criteria was not shown. But it was suggested that AFP-L3 > 10% might be a preoperative indicator of AR for HCC within Milan criteria.

Usefulness of cell-penetrating peptides and penetration accelerating sequence for nose-to-brain delivery of glucagon-like peptide-2.

Neuropeptides are expected as therapeutic drug candidates for central nervous system (CNS) disorders. Intracerebroventricular (i.c.v.) administration of glucagon-like peptide-2 (GLP-2) has an antidepressant-like effect not only in depression model mice but also in treatment-resistant depression model mice. However, because i.c.v. administration is very invasive, research is progressing on brain delivery using intranasal administration as a non-invasive method. After intranasal administration of the drug, there are two routes to the brain. That of direct delivery from the paracellular route of olfactory epithelium to the brain via the olfactory bulb has been studied, and that of systemic absorption via the paracellular route of respiratory epithelium has been put to practical use. The high degree of vascularization and permeability of the nasal mucosa enables drug delivery via the paracellular route that leads to systemic delivery. Therefore, suppressing systemic absorption may increase drug delivery to brain, so we focused on the transcellular route. We created a GLP-2 derivative by adding cell-penetrating peptides (CPP) and penetration accelerating sequences (PAS), which are reported to provide efficient intracellular uptake, to GLP-2. However, to deliver GLP-2 by the transcellular route, GLP-2 must not only be taken up into cells but also move out of the cells. We investigated in vitro and in vivo function of PAS-CPP-GLP-2 to enable the translocation of GLP-2 directly from the nose to the brain. Derivatization of PAS-CPP-GLP-2 prevented its degradation. In the evaluation of intracellular dynamics, PAS-CPP-GLP-2 enhanced cellular uptake by macropinocytosis with CPP and promoted escape from endosomal vesicles by PAS. This study also showed that PAS-CPP-GLP-2 can move out of cells. Furthermore, only this PAS-CPP-GLP-2 showed an antidepression-like effect within 20 min of intranasal administration. Intranasal administered PAS-CPP-GLP-2 surprisingly showed the effect at the same dose with i.c.v. administration, but intravenous administered PAS-CPP-GLP-2 did not show the effect. These results suggested that PAS-CPP-GLP-2 can be efficiently delivered from the nose to the CNS and show a pharmacological effect, demonstrating the usefulness of PAS and CPP for nose-to-brain delivery of GLP-2.

Thoracic Reciprocal Change Can Be Predicted Before Surgery in Adult Spinal Deformity.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Analysis of postoperative sagittal alignment of the unfused spine is lacking in patients with adult spinal deformity (ASD). The present study aims to evaluate the efficacy of the whole spine full-flexion lateral radiograph to predict the reciprocal change of the unfused spine after correction surgery. We hypothesized that the novel parameter (T1-UIV angle: angle between the upper vertebral endplate of the T1 and the upper vertebral endplate of the upper instrumented vertebra) of the preoperative whole spine full-flexion lateral radiograph is similar to that of the postoperative lateral radiograph if the patient has the ideal sagittal alignment. METHODS: Twenty-six ASD patients who underwent correction surgery with a minimum 2-year follow-up were enrolled and separated into the Ideal and Non-Ideal groups according to the Scoliosis Research Society (SRS)-Schwab classification of the final follow-up radiograph. Radiographic parameters, including T1-UIV of the preoperative whole spine full-flexion lateral radiograph, were obtained. RESULTS: Thirteen patients were included in the Ideal group and 13 were in Non-Ideal group. Preoperative T1-UIV of the whole spine full-flexion lateral radiograph exhibited significant correlations with the T1-UIV angles of the postoperative and final follow-up radiographs (r = 0.64, P < .01, y = 0.800x + 8.012, and r = 0.69, P < .01, y = 0.857x + 2.960, respectively). Interestingly, this correlation was stronger for the Ideal group (r = 0.77, P < .01, y = 1.207x - 1.517, and r = 0.89, P < .01, y = 0.986x + 0.694, respectively). CONCLUSION: A novel radiographic strategy (T1-UIV of preoperative the whole spine full-flexion lateral radiograph) could estimate the postoperative alignment of the unfused spine correctly.

Prognostic Impact of Coagulation Activity in Patients Undergoing Curative Resection for Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: The aim of this study was to elucidate the clinical impact of coagulation disorders on outcomes after curative resection of pancreatic ductal adenocarcinoma. PATIENTS AND METHODS: Preoperative coagulation activity in 135 patients, who had undergone curative resections for pancreatic ductal adenocarcinoma was retrospectively evaluated and the impact on survival outcomes analyzed. RESULTS: A prolonged prothrombin time-international normalized ratio (PT-INR) (≥1.1) was detected in 23/135 patients (17%). Univariate analysis that showed prolonged PT-INR was associated with worse relapse-free (hazard ratio=1.79, p=0.044) and overall (hazard ratio=2.18, p=0.004) survival. Multivariate analyses showed prolonged PT-INR, large tumor (>30 mm), and lymph node metastasis were independent predictors of poor overall survival. CONCLUSION: Prolonged PT-INR may be a predictor of poor prognosis in patients with pancreatic ductal adenocarcinoma who have undergone curative resection. Coagulation disorders may be a therapeutic target for improving outcomes of pancreatic ductal adenocarcinoma.

Controlled Fabrication of Optical Signal Input/Output Sites on Plasmonic Nanowires.

Silver nanowires have attracted considerable attention as subdiffraction limited diameter waveguides in a variety of applications including cell endoscopy and photonic integrated circuitry. Optical signal transport occurs by coupling light into propagating surface plasmons, which scatter back into light further along the wire. However, these interconversions only occur efficiently at wire ends, or at defects along the wire, which are not controlled during synthesis. Here, we overcome this limitation, demonstrating the visible laser light-induced fabrication of gold nanostructures at desired positions on silver nanowires, and their utility as efficient in/out coupling points for light. The gold nanostructures grow via plasmon-induced reduction of Au(III) and are shown to be excellent "hotspots" for surface-enhanced Raman scattering.

A Novel Method for the Prediction of the Pedicle Screw Stability: Regional Bone Mineral Density Around the Screw.

STUDY DESIGN: Prospective feasibility study on consecutive patients. OBJECTIVE: The aim of this study was to investigate the ability of regional BMD around the pedicle screw to predict the screw fixation. SUMMARY OF BACKGROUND DATA: Pedicle screw fixation is the gold standard technique for spinal fusion. Despite the advantage of biomechanical stability, screw loosening is a common complication. In previous studies, pullout strength and screw insertional torque were correlated, and most importantly, affected by bone mineral density (BMD). Although the density and structure of the vertebral body are not homogeneous, no study has yet evaluated the relationship between screw insertional torque and regional BMD around the pedicle screw in vivo. METHODS: Consecutive 50 patients, scheduled for transpedicular fixation, were evaluated preoperatively for BMD measured by dual-energy absorptiometry (DXA) and quantitative computed tomography (QCT). Regional volumetric BMD around the pedicle screw (PS-vBMD) using the novel QCT technique was also evaluated. Among all patients, 190 screws (diameter, 7.5 to 8.5 mm; length, 40 to 45 mm, inserted from L1 to L5) were eligible for this study and were analyzed to identify factors contributing to insertional torque. The following factors were investigated: age, body mass index, laboratory data, pedicle diameter, screw diameter, screw length, and 5 types of bone mineral density measures [DXA: spine-areal BMD (aBMD), total hip-aBMD, femoral neck-aBMD, QCT: central-vBMD, PS-vBMD]. RESULTS: Insertional torque was significantly correlated with each BMD measurement and strongest with PS-vBMD (r=0.61, P<0.001). Multiple regression analysis showed PS-vBMD was most strongly correlated with screw insertional torque (stdß=0.494; P<0.001). A model containing the following 5 predictors was significantly associated with screw insertional torque: age, pedicle diameter, screw diameter, screw length, and PS-vBMD. CONCLUSIONS: The preoperative measurement of PS-vBMD was technically feasible and reliably predictive of screw insertional torque during transpedicular fixation in a clinical setting.

Intranasal administration of neuromedin U derivatives containing cell-penetrating peptides and a penetration-accelerating sequence induced memory improvements in mice.

Neuromedin U (NMU) is a neuropeptide that is expressed and secreted in the brain and gut. We previously demonstrated that the intracerebroventricular (i.c.v.) administration of NMU inhibited inflammation-mediated memory impairment in mice. In order to utilize NMU as a clinical treatment tool for inflammation-mediated amnesia, we herein focused on non-invasive intranasal delivery because the i.c.v. administration route is invasive and impractical. In the present study, we prepared two NMU derivatives containing cell-penetrating peptides (CPPs), octaarginine (R8), and each penetration-accelerating sequence, namely FFLIPKG (PASR8-NMU) and FFFFG (F4R8-NMU), for intranasal (i.n.) administration. In the Y-maze test, the i.c.v. administration of lipopolysaccharide (LPS) (10µg/mouse) significantly decreased spontaneous alternation behavior, and this was prevented by the prior administration of PASR8-NMU or F4R8-NMU (5.6µg/mouse, i.n.). Moreover, the administration of PASR8-NMU or F4R8-NMU (5.6µg/mouse, i.n.) just before the Y-maze test also improved LPS-induced memory impairment. Indocyanine green (ICG)-labeled PASR8-NMU (i.n.) was significantly observed in the hippocampus and paraventricular hypothalamic nucleus 30min after its i.n. administration. PASR8-NMU, but not F4R8-NMU guaranteed the stability of the administration liquid for 24h. These results suggest that PASR8-NMU is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of inflammation-mediated amnesia.

Antidepressant-like effects exerted by the intranasal administration of a glucagon-like peptide-2 derivative containing cell-penetrating peptides and a penetration-accelerating sequence in mice.

The intracerebroventicular (i.c.v.) administration of glucagon-like peptide-2 (GLP-2) to rodents was shown to have antidepressant-like effects in imipramine-resistant depression-model mice. In order to utilize GLP-2 as a clinical treatment tool for depression, we herein focused on the intranasal delivery that is non-invasive approach, because the i.c.v. administration is invasive and impractical. In the present study, we prepared a GLP-2 derivative containing cell penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) (PAS-CPPs-GLP-2) for the intranasal (i.n.) administration. PAS-CPPs-GLP-2 (i.n.) exhibited antidepressant-like effects in the forced-swim test (FST) and tail suspension test (TST) in naïve mice as well as adrenocorticotropic hormone (ACTH) treated-mice. However, PAS-CPPs-GLP-2 (i.v.) and the GLP-2 derivative containing CPPs without a PAS (CPPs-GLP-2) (i.n.) did not affect the immobility time in the mouse FST. Moreover, fluorescein isothiocyanate (FITC)-labeled PAS-CPPs-GLP-2 (i.n.), but not FITC-labeled CPPs-GLP-2 (i.n.) was distributed through the mouse brain after the FST session. These results suggest that PAS-CPPs-GLP-2 is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of major depression.

Successful treatment of mixed yolk sac tumor and mature teratoma in the spinal cord: case report.

Primary spinal germ cell tumors are rare, and spinal nongerminomatous germ cell tumors represent an even rarer subset for which no standard therapy has been established. The authors report the case of a 24-year-old woman with multifocal primary spinal germ cell tumors scattered from T-12 to L-5 that consisted of yolk sac tumor and mature teratoma. After diagnostic partial resection, the patient was treated with 30 Gy of craniospinal irradiation and 30 Gy of local spinal irradiation, followed by 8 courses of chemotherapy based on ifosfamide, cisplatin, and etoposide (ICE). Salvage surgery was also performed for residual mature teratoma components after the third course of ICE chemotherapy. Chemotherapy was continued after the operation, but ifosfamide was entirely eliminated from the ICE regimen because severe myelosuppression was observed after previous courses. The patient remains recurrence free as of more than 5 years after the completion of chemotherapy. This case suggests that this treatment strategy is an effective option for primary spinal yolk sac tumor.

LARETH-25 and ß-CD improve central transitivity and central pharmacological effect of the GLP-2 peptide.

Depression is a common mental disorder. More than 350 million people of all ages suffer from depression worldwide. Although a number of antidepressants are available, >20% of patients with major depressive disorder suffer from treatment-resistant depression. Therefore, development of novel therapeutics to overcome this condition is required. We reported that intracerebroventricular administration of glucagon-like peptide-2 (GLP-2) exerts antidepressant-like effects treated with or without adrenocorticotropic hormone. In the present study, we developed a nasal formulation of GLP-2 containing 5% polyoxyethylene (25) lauryl ether and 1% ß-cyclodextrin that enhanced the resistance of GLP-2 to inactivation by dipeptidyl peptidase-4. Intranasal administration of this formulation (60µg/kg) increased the delivery of GLP-2 to the brain and had antidepressant-like effects on rats. These results suggest the potential of the GLP-2 nasal formulation for use as a novel antidepressant.

Effectiveness of brace treatment for adolescent idiopathic scoliosis.

OBJECTIVES: Effectiveness of brace treatment for adolescent idiopathic scoliosis (AIS) was demonstrated by the BrAIST study in 2013. Objectives of this study were to confirm its effectiveness by analyzing our results and to clarify the factors affecting the results of the treatment. MATERIALS AND METHODS: According to the Scoliosis Research Society AIS brace studies standardization criteria, patients with age 10 years or older, Risser 0 to II, less than 1 year post-menarche, curve magnitude 25 to 40 degrees before brace treatment and who received no prior treatment were included in the study. At skeletal maturity, the rate of the patients whose curve was stabilized, exceeded 45 degrees, and who were recommended or underwent surgery were investigated. Additionally, initial correction rate by the brace and factors affecting the results were investigated. RESULTS: A total of 33 patients (27 females and 6 males) could be followed-up until their skeletal maturity and included in the analysis. An average age was 11.9 years, average Cobb angle was 30.8°, and Risser sign was 0 in 13 patients, I in 5, and II in 15 patients before treatment. There were 13 thoracic curves, 14 thoracolumbar or lumbar curves, and 6 double curves. Initial correction rate by the brace was 53.8% for the total curves. In terms of curve pattern, 34.4% for thoracic curve, 73.9% for thoracolumbar or lumbar curve, and 48.8% for double curve. After an average follow-up period of 33 months, 8 patients improved in more than 6 degrees, change of 17 patients were within 6 degrees, and 8 progressed in more than 6 degrees. Therefore, totally, 76% (25/33) of the curves were stabilized by the treatment. Four curves (12%) exceeded 45 degrees and one patient (3%) underwent surgery. Our results were better than the reported natural history. Factors that affected the results were hump degree before treatment and initial correction rate by the brace. CONCLUSIONS: 76% of the curve with AIS could be stabilized by brace treatment. Brace treatment was effective for treatment of AIS. Factors affecting the results were hump degrees and initial correction rate.

Milwaukee brace.

The Milwaukee brace had been a standard of nonsurgical treatment for scoliosis since 1954. Milwaukee brace 23-hours wearing protocol was most effective for the treatment of adolescent idiopathic scoliosis. However, Milwaukee brace 23-hours wearing showed an impact on psychosocial functioning of the patients. Moreover, even with thoraco-lumbo-sacral orthosis, 23-hours wearing protocol affects patients' psychosocial function. To maintain the effectiveness of the Milwaukee brace and at the same time to reduce physical and psychological burden of the patients, we adopted part-time wearing of Milwaukee brace. Our part-time wearing treatment was effective and did not affect the quality of life of the patients with idiopathic scoliosis.

Aorta movement in patients with scoliosis after posterior surgery.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To evaluate movement of the aorta in patients with scoliosis who have undergone the posterior correction and fusion. SUMMARY OF BACKGROUND DATA: Surgeons check preoperative imaging for pedicle screw placement, but past analyses indicated that the aorta shifts after scoliosis surgery. Few studies, however, evaluated the aorta movement in detail. METHODS: A total of 22 patients with a right thoracic curve underwent posterior instrumentation and fusion. The average age at surgery was 17.2 years. The average of the preoperative Cobb angle was 65.2° which decreased to 20.0°.Computed-tomographic data were analyzed by multiplanar reconstruction. In our coordinate system, the middle of the base of the left superior facet was set as the origin and a line connecting the middle points of both bases of the superior facets was defined as the X-axis. We defined the angle and the distance to describe the aorta position and analyzed the movement of the aorta relative to the spine. Deformity parameters were examined to determine their correlation with the aorta parameters.We simulated variable pedicle screw placement and defined a warning pedicle when the aorta enters the expected area of the screw and examined them in 24 scenarios. RESULTS: The aorta moved 4.7 ± 3.0 mm on an average. The aorta had a tendency to migrate in the anteromedial direction and this movement correlated with preoperative apical vertebral translation, preoperative sagittal alignment, and change of sagittal alignment. The ratio of warning pedicles at the middle thoracic level (T7-T9) increased after deformity correction. CONCLUSION: The aorta moved anteromedially relative to the spine after the posterior correction and the risk of the aorta by a pedicle screw increased by correction of the deformity at the middle thoracic spine. Surgeons are recommended to anticipate the aorta movement in the surgical planning.

New parameters to represent the position of the aorta relative to the spine for pedicle screw placement.

Parameters of the position of the aorta in previous reports were determined for anterior surgery. This study evaluated the relative position of the aorta to the spine by new parameters, which could enhance the safety of pedicle screw placement. Three parameters were defined in a new Cartesian coordinate system. We selected an entry point of a left pedicle screw as the origin. The transverse plane was determined to include both the bases of the superior facet and to be parallel to the upper endplate of the vertebral body. A line connecting the entry points of both sides was defined as the X-axis. The angle formed by the Y-axis and a line connecting the origin and the center of the aorta was defined as the left pedicle-aorta angle. The length of a line connecting the origin and the aorta edge was defined as the left pedicle-aorta distance. Distance from the edge of the aorta to the X-axis was defined as the pedicular line-aorta distance. These parameters were measured preoperatively in 293 vertebral bodies of 24 patients with a right thoracic curve. We simulated the placement of the pedicle screw with variable length and with some direction error. We defined a warning pedicle as that when the aorta enters the expected area of the screw. Sensitivity analysis was performed to find the warning pedicle ratio in 12 scenarios. The left pedicle-aorta angle averaged 29.7 degrees at the thoracic spine and -16.3 degrees at the lumbar spine; the left pedicle-aorta distance averaged 23.7 and 55.2 mm; the pedicular line-aorta distance averaged 18.3 and 51.0 mm, respectively. The ratio of warning pedicles was consistently high at T4-5 and T10-12. When a left pedicle screw perforates an anterior/lateral wall of the vertebral body, the aorta may be at risk. These new parameters enable surgeons to intuitively understand the position of the aorta in surgical planning or in placement of a pedicle screw.