Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model.

IMPORTANCE: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). OBJECTIVE: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. METHODS: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2 × 106 cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5 × 106 cells, group C with 3 × 106 cells, group D with 1 × 106 cells, group E with 1 × 106 cells injected twice with a one-day interval, group F with 2 × 106 cells in 100 µL of suspension, and group G with 2 × 106 cells in 300 µL of suspension. RESULTS: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). CONCLUSIONS AND RELEVANCE: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

A Beginner's Perspective on Biportal Endoscopic Spine Surgery in Single-Level Lumbar Decompression: A Comparative Study with a Microscopic Surgery.

Background: The application of biportal endoscopic spinal surgery (BESS) in spine surgery is increasing. However, the clinical results of related studies have been inconsistent. In this study, the perioperative and clinical outcomes of two techniques in single-level lumbar decompression surgery were compared using the perspective of a spine surgeon experienced in microscopic surgery but inexperienced in BESS. Methods: This is a retrospective study performed with prospectively collected data. From April 2019, 50 consecutive patients who underwent a single-level lumbar decompression surgery with BESS were evaluated. Additionally, the data of 150 consecutive patients who underwent the same microscopic surgery before April 2019 were collected. We performed 1 : 1 ratio propensity score matching for these two groups to adjust for baseline variables. The postoperative patient-reported outcome measures included the Oswestry Disability Index (ODI) and numeric rating scale for the back and leg preoperatively and at 6 months after surgery. The laboratory data (C-reactive protein [CRP, mg/L] and hemoglobin [Hb, g/dL]) were measured preoperatively and 3 times (1, 2, and 3 or 4 days) postoperatively. In these periods, the peak and lowest CRP and Hb concentrations were evaluated. The perioperative outcomes, operation time (from skin incision to dressing), length of hospital stay, drainage (for 24 hours after surgery), and surgery-related complications were also evaluated. Results: Forty-seven patients (27 men and 20 women) were included in each group. The postoperative 6-month ODI was significantly lower in the BESS group than in the microscope group (6.90 ± 5.98 vs. 11.54 ± 9.70). The peak CRP concentration (16.63 ± 19.41 vs. 42.40 ± 37.73, p < 0.001) and CRP increment (peak CRP minus preoperative CRP, 14.69 ± 19.47 vs. 40.71 ± 37.32, p < 0.001) were significantly higher in the microscope group. Operation time (83.72 ± 35.71 vs. 70.27 ± 23.24, p = 0.047) was significantly longer in the BESS group. Surgery-related complications were found in 6 and 3 cases in the BESS group (3 revisions, 2 dural tears, and 1 conversion to open surgery) and microscope group (2 revisions and 1 hematoma), respectively. Conclusions: BESS as a new technique resulted in satisfying short-term outcomes. It was a well-tolerated option for surgical treatment of single-level lumbar degenerative disease. The relatively high incidence of recurrence at the index level and incidental dural tears should be considered for surgeons new to BESS; however, these were manageable complications.

Postoperative Segmental Motion up to 1 Year Following Single-Level Anterior Cervical Discectomy and Fusion: Plate versus Non-plate.

STUDY DESIGN: Retrospective observational study. PURPOSE: This study aimed to investigate the impact of plating on postoperative serial segmental motion and its correlation with clinical outcomes in single-level anterior cervical discectomy and fusion (ACDF) for up to 1 year. OVERVIEW OF LITERATURE: The advantages and disadvantages of using cervical plating in ACDF have been well discussed; however, few studies compared the early serial segmental motions at the postoperative level between plating and non-plating. METHODS: In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM <1 mm. RESULTS: In both groups, ISM was the highest at 3 months and gradually decreased thereafter, and the plating group showed significantly lower serial ISM than the non-plating group at 12 months. The plating group had lower NRS and NDI scores than the nonplating group at 12 months, and the difference in the NRS scores was statistically significant, particularly at 3 and 6 months, although that of the NDI scores was not. In a multivariate analysis, plating was the most powerful predictor for fusion. CONCLUSIONS: Plating significantly decreases the serial ISM compared with non-plating in single-level ACDF, and such decreased motion is correlated with decreased neck pain until 12 months postoperatively, particularly at 3 and 6 months. Given that plating was the most predictive factor for fusion, we recommend plating even in single-level ACDF for better early clinical outcomes.

Surgical Causes of Significant Intraoperative Neuromonitoring Signal Changes in Three-Column Spinal Surgery.

STUDY DESIGN: Retrospective case series. PURPOSE: To evaluate the risks and causes of neurologic complications in three-column spinal surgery by analyzing intraoperative neurophysiological monitoring (IONM) data. OVERVIEW OF LITERATURE: Three-column spinal surgery, which may be required to correct complex spinal deformities or resection of spinal tumors, is known to carry a high risk of neurologic complications. However, few studies reported a specific surgical procedure related to a significant IONM signal change during surgery. METHODS: Multimodality IONM data, including somatosensory-evoked potentials (SSEP) and motor-evoked potentials (MEP), were reviewed in 64 patients who underwent three-column spinal surgery from 2011 to 2015. Surgical procedures included posterior vertebral column resection, pedicle subtraction osteotomy, total en bloc spondylectomy, piecemeal spondylectomy, and corpectomy with laminectomy (n=27) in three cervical, 34 thoracic, and 31 lumbar procedures. RESULTS: Significant IONM signal changes occurred in 11 of 64 (17.1%) patients. SSEP and MEP were changed in 11 patients. Postoperative neurologic deterioration occurred in 54.5% (6 of 11) of the patients, and two of them were permanent. There was no postoperative neurologic deterioration in patients without significant signal change. Suspected causes of IONM data changes are as follows: adhesion/tethering, translation, contusion, and perfusion. CONCLUSIONS: Based on the results of this study, to enhance neurologic safety in three-column spinal surgery, surgeons should pay attention to protect the spinal cord from mechanical insult, especially when the spinal column was totally destabilized during surgery, and not to compromise perfusion to the spinal cord in close cooperation with a neurologist and anesthesiologist.

Anterior Bridging Bone in a Newly Designed Cage for Lumbar Interbody Fusion: Radiographic and Finite Element Analysis.

OBJECTIVE: To evaluate the distribution of multiple anterior bridging bone (ABB) patterns using a newly designed interbody cage with 4 anterior holes that enable communication between the inside and outside of the cage and to estimate its mechanical effect by finite element analysis (FEA). METHODS: Patients underwent single-level lumbar interbody fusion using ABB cages. Two raters evaluated the distribution patterns of ABB on computed tomography scans 1 year after surgery. We defined the term H-fusion as the presence of complete anterior extracage and intracage bone bridging, with ≥1 ABBs between them. We performed finite element analysis to investigate the effect of ABB on maximal stiffness. RESULTS: The study enrolled 98 patients. ABB was most frequently observed in the medial hole of the cages (73.7%). The mean number of ABBs was 3.65, and H-fusion was observed at 135 levels (34%). Postoperative improvement in the Oswestry Disability Index was significantly higher in patients who achieved interbody fusion and H-fusion than in patients who did not. As ABB was added, the increment in the relative maximal stiffness was most affected under flexion and extension forces. CONCLUSIONS: We observed an average of 3.65 complete ABBs. Finite element analysis demonstrated that ABB could increase the stability in fused segments, especially under flexion and extension stress. Our results suggest that the ABB cage, which allows communicating cross-bridging between inside and outside of the cage, may facilitate a more stable fusion process than a conventionally designed cage.

Ginseng Gintonin Contains Ligands for GPR40 and GPR55.

Gintonin, a novel ginseng-derived glycolipoprotein complex, has an exogenous ligand for lysophosphatidic acid (LPA) receptors. However, recent lipid analysis of gintonin has shown that gintonin also contains other bioactive lipids besides LPAs, including linoleic acid and lysophosphatidylinositol (LPI). Linoleic acid, a free fatty acid, and LPI are known as ligands for the G-protein coupled receptors (GPCR), GPR40, and GPR55, respectively. We, herein, investigated whether gintonin could serve as a ligand for GPR40 and GPR55, using the insulin-secreting beta cell-derived cell line INS-1 and the human prostate cancer cell line PC-3, respectively. Gintonin dose-dependently enhanced insulin secretion from INS-1 cells. Gintonin-stimulated insulin secretion was partially inhibited by a GPR40 receptor antagonist but not an LPA1/3 receptor antagonist and was down-regulated by small interfering RNA (siRNA) against GPR40. Gintonin dose-dependently induced [Ca2+]i transients and Ca2+-dependent cell migration in PC-3 cells. Gintonin actions in PC-3 cells were attenuated by pretreatment with a GPR55 antagonist and an LPA1/3 receptor antagonist or by down-regulating GPR55 with siRNA. Taken together, these results demonstrated that gintonin-mediated insulin secretion by INS-1 cells and PC-3 cell migration were regulated by the respective activation of GPR40 and GPR55 receptors. These findings indicated that gintonin could function as a ligand for both receptors. Finally, we demonstrated that gintonin contained two more GPCR ligands, in addition to that for LPA receptors. Gintonin, with its multiple GPCR ligands, might provide the molecular basis for the multiple pharmacological actions of ginseng.

Does Surgical-site Multimodal Drug Injection After Palmar Plating of Distal Radius Fractures Improve Pain Scores?

BACKGROUND: Although palmar locked plating is a stable fixation method frequently used to treat unstable distal radius fractures (DRFs), surgical treatment may be painful, and so interventions to decrease that pain might improve our patients' experiences with surgery. Some surgeons use local multimodal drug injections to decrease postoperative pain after lower-extremity arthroplasty, but little is known about the effectiveness of a local multimodal drug injection in patients who undergo palmar plating for DRFs. QUESTIONS/PURPOSES: (1) Do patients who receive a local multimodal drug injection after palmar plating for unstable DRFs have better pain scores at 4, 8, 24, and 48 hours after surgery than patients who have not received such an injection? (2) Do patients who receive a local multimodal drug injection have lower fentanyl consumption and administration of anti-emetic drugs within the first 48 hours after surgery than patients who have not received such an injection? METHODS: A randomized controlled study was performed between August 2018 and August 2019 at a single tertiary care referral center. Patients who underwent palmar plating for DRFs under general anesthesia were eligible for inclusion. Patients were allocated into two groups: Those who received a local multimodal drug injection, and those who did not receive an injection. During the study period, 101 patients treated with palmar plating for DRFs met the inclusion criteria and were enrolled and randomized. Fifty-two patients were allocated to the multimodal injection group and 49 were allocated to the control group. Three patients (two in the multimodal injection group and one in the control group) were excluded after randomization because their pain level was not registered at any timepoint and so they could not be analyzed; our analysis was by intention to treat, and there was no crossover. After palmar plating, patients in the multimodal injection group received an injection of ropivacaine (10 mL), morphine (5 mL), ceftezole (5 mL) as well as normal saline (5 mL) to the periosteal area, pronator quadratus muscle, subcutaneous area, and skin. There were no differences between the groups in terms of age (62 years ± 13 years in the multimodal injection group versus 62 years ± 11 years in the control group; p = 0.93), gender (84% [42 of 50] women in the multimodal injection group versus 77% [37 of 48] women in the control group; p = 0.39), hand dominance (70% [35 of 50] dominant wrist in the multimodal injection group versus 60% [29 of 48] dominant wrist in the control group; p = 0.32) and AO/Orthopaedic Trauma Association (AO/OTA) classification (p = 0.57). All patients underwent treatment with the same perioperative protocol, and 25 µg of fentanyl was injected intravenously when a patient complained of pain and asked for additional pain control after surgery. In addition, when a patient complained of nausea or vomiting associated with fentanyl use, an anti-emetic drug was also injected. All nursing staff who administered the analgesics and anti-emetic drugs were blinded to treatment allocation. These two groups were compared regarding their pain level using a 100-mm VAS at 4, 8, 24, and 48 hours postoperatively. The minimum clinically important difference (MCID) for the VAS score was set to 20 mm. VAS scores were also collected by nursing staff who remained blinded to the treatment allocation. The total amount of fentanyl use and the number of patients who received anti-emetic drugs associated with administration of fentanyl within the first 48 hours were also recorded. RESULTS: With an MCID of 20 points, we found no clinically important reduction in VAS scores among patients who received a local multimodal injection compared with those who did not receive an injection at 4 hours (34 ± 15 versus 41 ± 20, mean difference -7.079 [95% CI -13.986 to -0.173]; p = 0.045), 8 hours (27 ± 16 versus 40 ± 19, mean difference -12.263 [95% CI -19.174 to -5.353]; p = 0.001), 24 hours (18 ± 12 versus 29 ± 20, mean difference -11.042 [95% CI -17.664 to -4.419]; p = 0.001), and 48 hours (9 ± 8 versus 10 ± 6, mean difference -1.318 [95% CI -4.000 to 1.365]; p = 0.33). Within the first 48 hours after surgery, fentanyl consumption was lower in patients receiving a local multimodal injection than in control patients (25 µg [range 0-100 µg] versus 37.5 µg [range 0-125 µg], difference of medians -12.5; p = 0.01). There was also a difference between the study groups in terms of the proportion of patients who received anti-emetic medications (16% [8 of 50] in the multimodal injection group versus 35% [17 of 48] in the control group, odds ratio = 2.879 [95% CI 1.102 to 7.519]; p = 0.03). CONCLUSIONS: Our data suggest that patients who received a surgical-site multimodal analgesic injection after palmar plating for a distal radius fracture had no clinically important reduction in pain scores, but they did consume lower doses of opioid analgesics and fewer of these patients received anti-emetic drugs within 2 days of surgery. The high-potency opioids or other analgesia usually used for postoperative pain management have many side effects. Thus, reducing additional analgesia is as important as postoperative pain management and a surgical-site multimodal analgesic injection is one of the methods to achieve this a goal. LEVEL OF EVIDENCE: Level I, therapeutic study.

Impact of Preoperative Diagnosis on Clinical Outcomes of Oblique Lateral Interbody Fusion for Lumbar Degenerative Disease in a Single-institution Prospective Cohort.

OBJECTIVES: Oblique lateral interbody fusion is considered a useful surgical option for various lumbar degenerative diseases with favorable clinical results and few complications. However, clinical outcomes following oblique lateral interbody fusion stratified according to the preoperative diagnosis have not been fully evaluated in a large cohort. The purpose of the present study was to evaluate the clinical outcomes following oblique lateral interbody fusion for lumbar degenerative disease and to identify differences in outcomes when stratified according to preoperative diagnosis. METHODS: All patients receiving oblique lateral interbody fusion for lumbar degenerative diseases were included in the current study and were stratified into four diagnostic groups: (i) degenerative spondylolisthesis; (ii) spondylolytic spondylolisthesis; (iii) spinal stenosis without spondylolisthesis and instability; and (iv) deformity. Clinical outcomes were assessed using multiple patient-reported questionnaires. Radiologic outcomes, including cage subsidence and completion of fusion, were also evaluated. RESULTS: Overall, 169 patients with 262 operative levels were included in the study. All clinical scoring items showed significant improvement at 1 year postoperatively for all diagnostic groups. Net and percent improvement, and a proportion of patients reaching a threshold for substantial clinical benefit were not significantly different between the diagnostic groups in all scoring items, except for lower extremity radiating pain of the deformity group. Although the deformity group had the highest overall complication rate, neurologic complications were more frequent in the spondylolytic spondylolisthesis group. The rate of complete fusion and cage subsidence for individual levels at 1 year postoperatively was 62.7% and 32.6% respectively, with no significant difference between the diagnostic groups. CONCLUSIONS: The large single-institution prospective cohort of the present study showed favorable clinical outcomes following oblique lateral interbody fusion for lumbar degenerative disease, even in spinal stenosis without spondylolisthesis and instability.

Influence of pain sensitivity on surgical outcomes after lumbar spine surgery in patients with lumbar spinal stenosis.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To assess the influence of pain sensitivity on surgical outcomes after lumbar spine surgery in patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: No previous study has investigated the relationship between the surgical outcomes for LSS and pain sensitivity questionnaire (PSQ) scores. METHODS: The study included 171 patients who were scheduled to undergo spine surgery for LSS. On the basis of their PSQ scores, patients were assigned to either a low (PSQ score<6.5, n=87) or high PSQ group (PSQ score≥6.5, n=84). The primary outcome was the Oswestry Disability Index (ODI) at 12 months after surgery. RESULTS: The ODI at 12 months after surgery was significantly lower in the low PSQ group than in the high PSQ group. Twelve months after surgery, the mean ODI scores (95% confidence interval) in the low and high PSQ groups were 21.1 (16.8-25.5) and 29.6 (25.0-34.1), respectively. The difference (95% confidence interval) in the ODI between the 2 groups was 3.2 (-14.7 to -2.2) (P=0.009). There were significant differences in the secondary endpoints, including the ODI and visual analogue scale (VAS) scores for back and leg pain, in the follow-up assessments during a 12-month period after surgery, between the 2 groups (PSQ group; P<0.001 for the ODI, VAS score for back pain, and VAS score for leg pain). However, the patterns of changes of the ODI and VAS scores for back pain and leg pain in the follow-up assessments during a 12-month period were not significantly different (interaction between the PSQ group and follow-up assessment time; P=0.757, 0.126, and 0.950, respectively). CONCLUSION: Patients with high pain sensitivity may display less improvement in back pain, leg pain, and disability after surgery for LSS compared with patients with low pain sensitivity. Furthermore, the PSQ can be used to predict surgical outcomes after spine surgery for LSS. LEVEL OF EVIDENCE: 2.

Flexible and transparent gas molecule sensor integrated with sensing and heating graphene layers.

Graphene leading to high surface-to-volume ratio and outstanding conductivity is applied for gas molecule sensing with fully utilizing its unique transparent and flexible functionalities which cannot be expected from solid-state gas sensors. In order to attain a fast response and rapid recovering time, the flexible sensors also require integrated flexible and transparent heaters. Here, large-scale flexible and transparent gas molecule sensor devices, integrated with a graphene sensing channel and a graphene transparent heater for fast recovering operation, are demonstrated. This combined all-graphene device structure enables an overall device optical transmittance that exceeds 90% and reliable sensing performance with a bending strain of less than 1.4%. In particular, it is possible to classify the fast (≈14 s) and slow (≈95 s) response due to sp(2) -carbon bonding and disorders on graphene and the self-integrated graphene heater leads to the rapid recovery (≈11 s) of a 2 cm × 2 cm sized sensor with reproducible sensing cycles, including full recovery steps without significant signal degradation under exposure to NO2 gas.

A physicochemical mechanism of chemical gas sensors using an AC analysis.

Electrical modeling of the chemical gas sensors was successfully applied to TiO2 nanofiber gas sensors by developing an equivalent circuit model where the junction capacitance as well as the resistance can be separated from the comparable stray capacitance. The Schottky junction impedance exhibited a characteristic skewed arc described by a Cole-Davidson function, and the variation of the fit and derived parameters with temperature, bias, and NO2 gas concentration indicated definitely a physicochemical sensing mechanism based on the Pt|TiO2 Schottky junctions against the conventional supposition of the enhanced sensitivity in nanostructured gas sensors with high grain boundary/surface area. Analysis on a model Pt|TiO2|Pt structure also confirmed the characteristic impedance response of TiO2 nanofiber sensors.