Sevoflurane Exposure during the Critical Period Affects Synaptic Transmission and Mitochondrial Respiration but Not Long-term Behavior in Mice.

BACKGROUND: Anesthesia during the synaptogenic period induces dendritic spine formation, which may affect neurodevelopment. The authors, therefore, evaluated whether changes in synaptic transmission after dendritic spine formation induced by sevoflurane were associated with long-term behavioral changes. The effects of sevoflurane on mitochondrial function were also assessed to further understand the mechanism behind spinogenesis. METHODS: Postnatal day 16 to 17 mice were exposed to sevoflurane (2.5% for 2 h), and synaptic transmission was measured in the medial prefrontal cortex 6 h or 5 days later. The expression of postsynaptic proteins and mitochondrial function were measured after anesthesia. Long-term behavioral changes were assessed in adult mice. RESULTS: Sevoflurane increased the expression of excitatory postsynaptic proteins in male and female mice (n = 3 to 5 per group). Sevoflurane exposure in male mice transiently increased miniature excitatory postsynaptic current frequency (control: 8.53 ± 2.87; sevoflurane: 11.09 ± 2.58) but decreased miniature inhibitory postsynaptic current frequency (control: 10.18 ± 4.66; sevoflurane: 6.88 ± 2.15). Unexpectedly, sevoflurane increased miniature inhibitory postsynaptic current frequency (control: 1.81 ± 1.11; sevoflurane: 3.56 ± 1.74) in female mice (neurons, n = 10 to 21 per group). Sevoflurane also increased mitochondrial respiration in male mice (n = 5 to 8 per group). However, such changes from anesthesia during the critical period did not induce long-term behavioral consequences. Values are presented as mean ± SD. CONCLUSIONS: Sevoflurane exposure during the critical period induces mitochondrial hyperactivity and transient imbalance of excitatory/inhibitory synaptic transmission, without long-lasting behavioral consequences. Further studies are needed to confirm sexual differences and to define the role of mitochondrial activity during anesthesia-induced spine formation.

Single and multiple sevoflurane exposures during pregnancy and offspring behavior in mice.

BACKGROUND: The second trimester is a period of neurogenesis and neuronal migration, which can be affected by exposure to anesthetics. Studies also suggest that multiple exposures may have a greater impact on neurodevelopment. AIM: We investigated whether in utero single or multiple exposures to anesthetics caused long-term behavior changes. METHODS: Pregnant mice were randomly divided into four groups on gestational day 14 (GD 14). Mice in the Control × 1 group were exposed to 100% oxygen for 150 min. Mice in the Sevo × 1 group were also exposed to 100% oxygen for 150 min, except that 2.5% sevoflurane was added during the first 120 min. Mice in the Control × 3 and Sevo × 3 group were identically treated as Control × 1 and Sevo × 1 group for three consecutive days, respectively (GD 14-16). Behavioral tests were performed only with the male offspring at the age of 2-4 months. Synaptic plasticity was also compared by inducing long-term potentiation in acute hippocampal slices. RESULTS: Single or multiple sevoflurane exposures in pregnant mice during the second trimester did not cause long-lasting behavioral consequences or changes in long-term synaptic plasticity of their offspring. CONCLUSION: Our study suggests that neither single nor multiple exposures of mice to sevoflurane during the fetal developmental period induces long-term behavioral dysfunctions or affects long-term synaptic plasticity. Additional studies focusing on early stages of neurodevelopment are necessary to confirm the effects of sevoflurane exposure during pregnancy.

Efficacy of a 1 day Rifaximin and Metronidazole Regimen and Mechanical Bowel Preparation for Preventing Surgical Site Infection in Minimally Invasive Colorectal Cancer Surgery: A Prospective Observational Study.

BACKGROUND: A combination of oral antibiotics and mechanical bowel preparation is recommended for patients scheduled to undergo elective colorectal surgery on the basis of recent large trials that have reported the superiority of this approach in preventing surgical site infections (SSIs). However, there are no standard recommendations for this approach. Therefore, in this study, we evaluated the efficacy of rifaximin and metronidazole and mechanical bowel preparation for preventing SSIs in cases of minimally invasive surgery for colorectal cancer. METHODS: This single-arm prospective observational study included 256 individuals. The primary end point was the rate of SSI. Rifaximin 400 mg and metronidazole 500 mg were administered twice daily (10 am and 10 pm), and mechanical bowel preparation was administered the day before the operation. RESULTS: After excluding 15 patients, 241 were enrolled. No adverse event occurred following the administration of oral antibiotics and mechanical bowel preparation; there was 100% compliance. The total SSI rate was 2.9%; the rates of incisional and organ/space SSIs were 1.2% and 1.7%, respectively. All patients were treated conservatively. Univariate analyses revealed preoperative anemia, hypoalbuminemia, and transfusion and postoperative transfusion were significantly associated with SSIs. DISCUSSION: A 1 day rifaximin and metronidazole regimen with mechanical bowel preparation for elective minimally invasive surgery for colorectal cancer was associated with a favorable SSI rate of 2.9%, safety, and high compliance. This approach is appropriate for inclusion in the current guidelines for perioperative management of patients scheduled to undergo minimally invasive surgery for colorectal cancer.

Feasibility of using the homologous parietal peritoneum as a vascular substitute for venous reconstruction during abdominal surgery: An animal model.

BACKGROUND: The interest in vascular substitutes has recently increased. We evaluated the feasibility of using a homologous parietal peritoneum as a vascular substitute for venous reconstruction during abdominal surgery. METHODS: The inferior vena cava was replaced with a homologous parietal peritoneum after cross-linking with glutaraldehyde in 36 rabbits. At 7, 14, and 28 days, the patency rate, outer and inner graft diameters, histology, and immunohistochemistry were evaluated. RESULTS: Both the 7- and 14-day groups maintained vascular patency. Vascular patency was maintained in 3 rabbits in the 28-day group. The inner diameters of the anastomotic sites were 6.23 ± 0.18, 5.64 ± 0.16, and 2.34 ± 0.21 mm in the 7-day, 14-day, and 28-day groups, respectively. The midpoint inner diameters of the homologous parietal peritoneum grafts were 624 ± 0.46, 5.74 ± 0.26, and 2.14 ± 0.28 mm in each group, respectively. Endothelial cell proliferation on the homologous parietal peritoneum graft surfaces in all groups was based on the histological findings from the first group. Multiple neovascularizations of the homologous parietal peritoneum graft were found in the 14- and 28-day groups, indicating neo-media formation. Acute inflammation appeared to progress to the entire layer of the homologous parietal peritoneum graft without an intraluminal thrombus, but the graft was patent in the 14-day group. In the 28-day group, 6 rabbits showed near-total occlusion and a thrombus formed in the homologous parietal peritoneum graft at the anastomosis site with severe stricture; however, the rabbits were alive and had collateral vessel formation. CONCLUSION: Using homologous parietal peritoneum is feasible for venous reconstruction in abdominal surgery.

Influence of Osteoporosis Following Spine Surgery on Reoperation, Readmission, and Economic Costs: An 8-Year Nationwide Population-Based Study in Korea.

OBJECTIVE: To evaluate the relationship between prevalence of osteoporosis and risk factors, medical costs, reoperation, and readmission in patients after spine surgery. METHODS: Patients >50 years old with thoracic or lumbar spine diseases who underwent spine surgery between 2005 and 2008 were selected from the Korean National Health Insurance Service databases for analysis. There were 147,676 patients selected, who were divided into 2 groups (osteoporosis and non-osteoporosis) and followed for 8 years. Multiple logistic regressions were performed to examine the effect of osteoporosis following spine surgery. RESULTS: Patients with osteoporosis showed significant increases in readmission rates (odds ratio = 1.26, P < 0.001). Osteoporosis was found to be significantly associated with longer hospital stays and increased medical costs regardless of the cause of spine disease. For readmission, there was a 62-day difference in hospitalization time and U.S. dollars $2040 difference in medical costs between the osteoporosis group and non-osteoporosis group. Total medical costs of the osteoporosis group were about U.S. dollars $310 million more than total medical costs of the non-osteoporosis group. Osteoporosis increased the risk of reoperation in fusion surgery, particularly in the first 3 months postoperatively (odds ratio = 1.34, P < 0.001). CONCLUSIONS: Osteoporosis was significantly associated with higher readmission rates, longer hospitalization, and greater medical costs during the 8-year follow-up. It also increased the risk of reoperation in fusion surgery. Proper management of osteoporosis is essential before spine surgery, particularly fusion surgery, to help reduce patients' socioeconomic burden and produce more satisfactory surgical outcomes.

A Comparison of fixed-hole and slotted-hole dynamic plates for anterior cervical discectomy and fusion.

STUDY DESIGN: A retrospective review of clinical data at 1 institution was performed. OBJECTIVES: To compare the clinical and radiologic outcomes between fixed-hole and slotted-hole dynamic cervical plates. SUMMARY OF BACKGROUND DATA: Anterior cervical plating is commonly used to increase stability and promote spinal fusion. Two techniques, fixed-hole dynamic plating that uses variable angled screws and slotted-hole dynamic plating that permits sliding, are viable options, but there have been no clinical studies comparing their effectiveness. METHODS: Fifty-six patients at 1 institution having anterior cervical discectomy and fusion for degenerative disease over a 5-year period were entered into this study. Surgeries were performed with 1 of the dynamic plates for 1 to 3 levels. For the slotted-hole dynamic plate group, a slotted-hole plate was used (ABC, Aesculap, Tuttlingen, Germany or C-tek, Biomet, Parssipany, NJ) and for the fixed-hole dynamic plated group, a variable angled screw was used (C-tek, Biomet, Parssipany, NJ). Radiographic measurements included were graft subsidence, lordotic angle change from each end plate of fusion construct, and implant translation from end plates after a minimum of 12 months follow-up. Fusion state and clinical outcome using Odom's criteria were also evaluated. RESULTS: Demographics were not different among patient populations. The average age of the patients was 51.0 years (range: 27 to 77 y). Mean follow-up period was 20.6 months (range: 12 to 41 mo). Slotted-hole dynamic plates were used for 29 patients (ABC plate, 17; C-tek plate, 12) and fixed-hole dynamic plates for 27 patients. Clinical outcomes and pseudoarthrosis rates were similar for both types of plates. Radiographic measurements showed a statistically significant increased incidence of graft subsidence and implant translation with the slotted-hole dynamic plates. Loss of lordosis was also greater in the slotted-hole dynamic plated group, although the difference was not statistically significant. CONCLUSIONS: The use of a fixed-hole dynamic plate is more favorable in regards to graft subsidence and implant translation in the follow-up period, although clinical outcome and fusion rates are similar in patients with either the fixed-hole or slotted-hole dynamic plates.

The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury.

Objective: To identify that the combined G-CSF and treadmill exercise is more effective in functional recovery after spinal cord injury (SCI).Design: Rats were divided into 4 groups: a SCI group treated with G-CSF (G-CSF group, n = 6), a SCI group treated with treadmill exercise plus G-CSF (G-CSF/exercise group, n = 6), a SCI group with treadmill exercise (exercise group, n = 6), and a SCI group without treatments (control group, n = 6). We performed laminectomy at the T8-10 spinal levels with compression injury of the spinal cord in all rats. G-CSF (20 µg/ml) was administered intraperitoneally for 5 consecutive days after SCI in G-CSF and G-CSF/exercise groups. From one week after surgery, animals in G-CSF/exercise and exercise groups received 30 min of exercise 5 days per week for 4 weeks. Functional recoveries were assessed using the Basso, Beattie, and Bresnahan (BBB) scale and the inclined plane test. Five weeks after SCI, hematoxylin and eosin staining for cavity size and immunohistochemistry for glial scar formation and neuro-regeneration factor expression were conducted.Setting: Inha University School of medicine, Incheon, KoreaResults: Rats in G-CSF/exercise group showed the most effective functional recovery in the BBB scale and the inclined plane test, and spinal cord cavity size by injury were the smallest, and immunohistochemistry revealed expression of higher BDNF (brain-derived neurotrophic factor) and VEGF (vascular endothelial growth factor) and lower GFAP (glial fibrillary acidic protein) than others.Conclusion: Combined treatment provided more effective neuroplasty and functional recovery than individual treatments.

Is Adjacent Segment Disease More Frequent in Proximal Levels in Comparison with Distal Levels? Based on Radiological Data of at Least 2 Years Follow Up with More than 2 Level Thoracolumbar Fusions.

OBJECTIVE: The purpose of this retrospective study was to determine which of the proximal adjacent segment disease (ASD) and distal ASD was more prevalent and what parameters is more related to ASD in proximal levels and distal levels after more than 2 levels fusions. METHODS: The medical records were reviewed retrospectively for 856 cases. A total of 66 cases of ASD were enrolled. On preop magnetic resonance imaging, disc degeneration was measured at the upper and lower parts of surgically treated levels and confirmed by the commonly used Pfirrmann grade. Segmental flexibility in sagittal plane was embodied in segment range of motion (ROM) obtained through flexion and extension X-ray before surgery. Coronal angle was recorded as methods Cobb's angle including fusion levels preoperatively. For the comparison of categorical variables between two independent groups, the chi-square test and Fisher exact test were performed. RESULTS: Proximal ASD and distal ASD were 37/856 (4.32%) and 29/856 (3.39%), respectively. The incidence of proximal ASD was relatively high but insignificant differences. In comparison between ASD group and non ASD group, proximal Pfirmman was higher in proximal ASD and distal Pfirmman was higher in distal ASD group (p=0.005, p<0.008, respectively). However, in the ROM, proximal ROM was higher in proximal ASD, but distal ROM was not different between the two groups (p<0.0001, p=0.995, respectively). Coronal angle was not quite different in both groups (p=0.846). CONCLUSION: In spite of higher frequency in ASD in proximal level in spinal fusion, it is not clear that incidence of ASD in proximal level is not higher than that of distal ASD group in more than 2 level thoracolumbar fusions. Not only Pfirrmann grade but also proximal segmental ROM is risk factor for predicting the occurrence of ASD in patients more than 2 level of thoracolumbar spine fusion operation excluding L5S1.

Prospective Observational Cohort Study of Health-related Quality of Life: Marked Adult Sagittal Deformity (ASD) in Comparison With Mild to Moderate ASD.

STUDY DESIGN: Retrospective analysis of prospective observational cohort OBJECTIVE.: This study assessed the difference in health-related quality of life (HRQOL) between participants with a mild to moderate adult sagittal deformity (ASD) (sagittal vertical axis [SVA] ≤9.5 cm) and those with a marked deformity (SVA >9.5 cm). We also evaluated predisposing factors for a marked deformity. SUMMARY OF BACKGROUND DATA: Sagittal imbalance is closely associated with HRQOL for the patient. However, how the effect changes depending on the degree of imbalance has not been fully evaluated. The understanding of the predisposing factor associated with marked deformity also lacks. METHODS: A total of 124 elderly persons with a stooping posture were enrolled. Questionnaires related to HRQOL were administered. Sagittal alignment parameters and pelvic parameters were measured with a whole spine x-ray. Lumbar spine magnetic resonance imaging was used to assess the presence of pathologic conditions, muscle quality and quantity. Multivariate logistic regression analysis was conducted to analyze potential risk factors. RESULTS: Marked ASD was associated with female sex, lower height and weight, and osteoporosis (P < 0.05). Back pain (assessed by a visual analogue scale) and the Oswestry Disability Index were significantly higher in the marked deformity group (P = 0.012, 0.002, respectively). Multivariate logistic regression analysis showed significant relationships between the following parameters and marked deformity: preexisting compression fracture (odds ratio [OR] = 7.793; 95% confidence interval [CI], 1.527-39.768), severe L5/S1 Pfirrmann disc degeneration grade (OR = 1.916; 95% CI, 1.086-3.382), and lower quantities of multifidus and psoas muscles (OR = 0.994, 0.997; 95% CI, 0.991-0.998, 0.994-0.999, respectively). CONCLUSION: Participants with a marked ASD showed different features from those with a mild to moderate ASD. This study also implies that anatomical factors, including the vertebrae, intervertebral discs, and paraspinal muscles, synergistically contribute to progression into marked deformity. LEVEL OF EVIDENCE: 3.

A porcine model of intervertebral disc degeneration induced by annular injury characterized with magnetic resonance imaging and histopathological findings. Laboratory investigation.

OBJECT: Appropriate animal models of disc degeneration are critical for the study of proposed interventions as well as to further delineate the degenerative process. The purpose of this study was to characterize a porcine model for disc degeneration confirmed on magnetic resonance (MR) imaging studies and histological analysis. METHODS: Twelve miniature pigs were used (weight 48-65 kg) to study degeneration in the lumbar spine. Under fluoroscopic guidance, the disc was percutaneously punctured with a 3.2-mm-diameter trephine to a 5-mm depth into the annulus fibrosus. Control and experimental levels were randomized among 6 levels in the lumbar spine. The unlesioned spinal levels were used as controls and were compared with lesioned levels. Magnetic resonance imaging grading and disc height were serially recorded preoperatively, and at 5, 8, 19, 32, and 39 weeks postoperatively. The animals were killed in groups of 3 at 7, 18, 32, and 41 weeks postinjury, and the discs were examined histopathologically. RESULTS: Consistent, sequential, and progressive degeneration of the annular injury was observed on MR imaging and histopathological studies from the time of injury to the final time point. The disc height and the disc height index also sequentially decreased from the time of the injury in a consistent manner. The uninjured control levels did not show any progressive degeneration and maintained their normal state. CONCLUSIONS: Based on MR imaging and histopathological findings, the authors demonstrated and characterized a reliable model of sequential disc degeneration in miniature pigs with percutaneous injury to the annulus fibrosus. In the early stages, as soon as 5 weeks after injury, significant disc degeneration was seen on MR imaging grading with decreases in disc height. This degeneration did not improve by the final time point of 39 weeks.

Multiple exposures of sevoflurane during pregnancy induces memory impairment in young female offspring mice.

BACKGROUND: Earlier studies have reported conflicting results regarding long-term behavioral consequences after anesthesia during the fetal period. Previous studies also suggest several factors that may explain such conflicting data. Thus, we examined the influence of age and sex on long-term behavioral consequences after multiple sevoflurane exposures during the fetal period. METHODS: C57BL/6J pregnant mice received oxygen with or without sevoflurane for 2 hours at gestational day (GD) 14-16. Offspring mice were subjected to behavioral assays for general activity (open field test), learning, and memory (fear chamber test) at postnatal day 30-35. RESULTS: Multiple sevoflurane exposures at GD 14-16 caused significant changes during the fear chamber test in young female offspring mice. Such changes did not occur in young male offspring mice. However, general activity was not affected in both male and female mice. CONCLUSIONS: Multiple sevoflurane exposures in the second trimester of pregnancy affects learning and memory only in young female mice. Further studies focusing on diverse cognitive functions in an age-, sex-dependent manner may provide valuable insights regarding anesthesia-induced neurotoxicity.

Time-related changes in detrusor overactivity in awake rats with spinal cord injury observed by simultaneous registrations of intravesical and intraabdominal pressures.

PURPOSE: To compare the physical characteristics of detrusor overactivity (DO) induced by intravesical infusion of saline in awake, sham rats and rats with chronic spinal cord injury (SCI), by simultaneous registrations of intravesical and intraabdominal pressures. METHODS: Male Sprague-Dawley rats, normal or with a spinal vascular clip at the level of Th9, were investigated cystometrically 1 and 4 weeks after SCI. Intravesical pressure (IVP) and intraabdominal pressure (IAP) were recorded simultaneously to evaluate true DO. During the filling phase, the event of IVP rises, defined as increments that exceeded 2 cmH(2)O from baseline, were determined as DO according to the absence of simultaneous changes in IAP. RESULTS: All SCI rats exhibited DO during the filling phase, which was not shown in sham rats. The frequency and pressure of DO had a tendency to decrease with time. The DO frequency of SCI rats after 4 weeks (0.9±0.2 min(-1)) was decreased compared with that after 1 week (2.1±0.4 min(-1); P<0.05). The DO pressure of SCI rats after 4 weeks (8.4±1.9 cmH(2)O) was decreased compared with that after 1 week (11.6±2.9 cmH(2)O; P>0.05). CONCLUSIONS: Cystometric studies in awake male SCI rats showed some significant changes in bladder function after SCI. All SCI rats exhibited DO during the filling phase, and showed different physical characteristics of DO over the course of time. The neurological basis of these time-related changes remains poorly understood, but may provide important prognostic information about long-term urological management in SCI patients.