Inhibitory Effect of Insulin Treatment on Apoptosis of Intervertebral Disc Cells in a Streptozotocin-Induced Diabetic Rat Model

Methods@#Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs). @*Results@#Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group. @*Conclusions@#The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

Diagnosing Polypoidal Choroidal Vasculopathy Using Color Fundus Photography, Optical Coherence Tomography, and Optical Coherence Tomography Angiography

Purpose@#To compare the diagnostic accuracy of differentiating polypoidal choroidal vasculopathy (PCV) from exudative age-related macular degeneration (AMD), using color fundus photography (CFP), optical coherence tomography (OCT), and swept-source OCT angiography (SS-OCTA) without using indocyanine green angiography (ICGA). @*Methods@#Treatment-naive eyes with exudative AMD that underwent CFP, OCT, SS-OCTA, and ICGA imaging before treatment were identified. Images of each patient were categorized into two sets (set A, CFP + OCT; set B, CFP + SS-OCTA). In set B, both the en face and cross-sectional B scans were analyzed. Each set was reviewed by two graders, and it was determined whether the presumed diagnosis was PCV. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for the diagnosis of PCV were assessed for each set by comparing diagnoses that included ICGA. The number of polypoidal lesions in each set was calculated and compared to ICGA. @*Results@#A total of 94 eyes from 94 patients with AMD were included in the study, of which 66.0% were male, and the mean age was 71.8 ± 9.0 years. The PCV diagnosis rate using ICGA was 45.7%. The sensitivity was 0.88 for set A and 0.93 for set B, while the specificity was 0.94 for set A and 0.96 for set B. The AUC was 0.90 (95% confidence interval [CI], 0.83–0.97) for set A and 0.96 (95% CI, 0.90–1.00) for set B. Set A detected 1.28 ± 0.91 polypoidal lesions, while set B detected 1.47 ± 1.01; ICGA showed 1.51 ± 0.86. @*Conclusions@#This study highlights that, without using ICGA, both CFP combined with OCT and CFP combined with SS-OCTA demonstrate high sensitivity, specificity, and AUC in diagnosing PCV. It is evident that SS-OCTA contributes to enhancing sensitivity, specificity, and AUC for PCV diagnosis.

Lumbar Interbody Fusion and Osteobiologics for Lumbar Fusion

Lumbar interbody fusion (LIF) is an excellent treatment option for a number of lumbar diseases. LIF can be performed through posterior, transforaminal, anterior, and lateral or oblique approaches. Each technique has its own pearls and pitfalls. Through LIF, segmental stabilization, neural decompression, and deformity correction can be achieved. Minimally invasive surgery has recently gained popularity and each LIF procedure can be performed using minimally invasive techniques to reduce surgery-related complications and improve early postoperative recovery. Despite advances in surgical technology, surgery-related complications after LIF, such as pseudoarthrosis, have not yet been overcome. Although autogenous iliac crest bone graft is the gold standard for spinal fusion, other bone substitutes are available to enhance fusion rate and reduce complications associated with bone harvest. This article reviews the surgical procedures and characteristics of each LIF and the osteobiologics utilized in LIF based on the available evidence.

Proximal Junctional Kyphosis in Adult Spinal Deformity: Definition, Classification, Risk Factors, and Prevention Strategies

Proximal junctional problems are among the potential complications of surgery for adult spinal deformity (ASD) and are associated with higher morbidity and increased rates of revision surgery. The diverse manifestations of proximal junctional problems range from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). Although there is no universally accepted definition for PJK, the most common is a proximal junctional angle greater than 10° that is at least 10° greater than the preoperative measurement. PJF represents a progression from PJK and is characterized by pain, gait disturbances, and neurological deficits. The risk factors for PJK can be classified according to patient-related, radiological, and surgical factors. Based on an understanding of the modifiable factors that contribute to reducing the risk of PJK, prevention strategies are critical for patients with ASD.

Analyses of Corneal Morphology of Patients with Obstructive Sleep Apnea

Purpose@#To analyze the relationship between corneal morphological factors and polysomnographic factors in patients with obstructive sleep apnea (OSA). @*Methods@#In all, 22 eyes of 22 patients with OSA were analyzed retrospectively under specular microscopy. The central corneal thickness (CCT), endothelial cell density (ECD), hexagonal cell percentage, and cell variation coefficient were measured using specular microscopy, and polysomnographic factors including the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index, and lowest O2 saturation were compared and analyzed between the OSA group and a control group consisting of 32 subjects. Additionally, we examined the statistical correlation between retinal nerve fiber layer (RNFL) thickness and the polysomnographic factors for the 12 OSA patients in which the RNFL thickness was measured. @*Results@#The mean CCT and mean ECD were significantly lower in the OSA group than in controls (p = 0.033, p = 0.021, respectively). As the severity of OSA worsened, a significant negative correlation developed, such that the CCT decreased as the AHI and RDI increased (r = -0.519, p = 0.013 and r = -0.542, p = 0.009, respectively); in addition, the ECD decreased as the RDI increased (r = -0.454, p = 0.034). As OSA progressed, the nasal RNFL thickness decreased with the lowest O2 saturation (r = 0.703, p = 0.011). @*Conclusions@#CCT and ECD were significantly lower in OSA patients than in controls and there was a significant correlation between corneal morphological factors and polysomnographic factors. Due to the possibility of hypoxia and various ophthalmic clinical diseases associated with OSA, close observation of ophthalmic abnormalities in OSA patients is required.

Analyses of Corneal Morphology of Patients with Obstructive Sleep Apnea

Purpose@#To analyze the relationship between corneal morphological factors and polysomnographic factors in patients with obstructive sleep apnea (OSA). @*Methods@#In all, 22 eyes of 22 patients with OSA were analyzed retrospectively under specular microscopy. The central corneal thickness (CCT), endothelial cell density (ECD), hexagonal cell percentage, and cell variation coefficient were measured using specular microscopy, and polysomnographic factors including the apnea-hypopnea index (AHI), respiratory disturbance index (RDI), oxygen desaturation index, and lowest O2 saturation were compared and analyzed between the OSA group and a control group consisting of 32 subjects. Additionally, we examined the statistical correlation between retinal nerve fiber layer (RNFL) thickness and the polysomnographic factors for the 12 OSA patients in which the RNFL thickness was measured. @*Results@#The mean CCT and mean ECD were significantly lower in the OSA group than in controls (p = 0.033, p = 0.021, respectively). As the severity of OSA worsened, a significant negative correlation developed, such that the CCT decreased as the AHI and RDI increased (r = -0.519, p = 0.013 and r = -0.542, p = 0.009, respectively); in addition, the ECD decreased as the RDI increased (r = -0.454, p = 0.034). As OSA progressed, the nasal RNFL thickness decreased with the lowest O2 saturation (r = 0.703, p = 0.011). @*Conclusions@#CCT and ECD were significantly lower in OSA patients than in controls and there was a significant correlation between corneal morphological factors and polysomnographic factors. Due to the possibility of hypoxia and various ophthalmic clinical diseases associated with OSA, close observation of ophthalmic abnormalities in OSA patients is required.

Xeroderma Pigmentosum in a Pediatric Patient with a Progressive Pterygium-like Lesion

Purpose@#We report a case of xeroderma pigmentosum in a pediatric patient with a progressive pterygium-like lesion.Case summary: A 2-year-old girl with photophobia and localized, scattered, small, round brownish macules on skin areas exposed to the sun visited hospital. During follow-up, at the age of 7, she was diagnosed with xeroderma pigmentosum in Japan, and pigmented freckles on the upper and lower eyelids of both eyes were observed. At the age of 11, a possible medial limbal pingueculum and lower lid telangiectasis of the right eye were observed via slit-lamp examination, and one year later, a pterygium-like lesion and gradual fibrovascular tissue growth were found in the same location of the right eye. At the last visit, the progressive pterygium-like lesion and, lower lid telangiectasis of the right eye, and lid pigmentations of both eyes (xeroderma pigmentosum) were observed. The size of pterygium-like lesion continues to increase, but the patient remains under observation because the lesion was too small to remove. @*Conclusions@#We report the first case of xeroderma pigmentosum in a pediatric patient with a progressive pterygium-like lesion that showed age-related degeneration. We suggest that the pterygium-like lesion may reflect the photosensitivity to ultraviolet radiation characteristic of xeroderma pigmentosum.

Adult Spinal Deformity: Current Concepts and Decision-Making Strategies for Management

Adult spinal deformity (ASD) is characterized by three-dimensional abnormalities of the thoracic or thoracolumbar spine that exerts significant impacts on the health-related quality of life (HRQoL). With the important effects that deformity of the sagittal plane exerts on the HRQoL, there have been paradigm shifts in ASD evaluation and management. Loss of lumbar lordosis is recognized as a key driver of ASD followed by reducing kyphosis, pelvic retroversion, and knee flexion. The Scoliosis Research Society (SRS)– Schwab classification reflects the sagittal spinopelvic parameters that correlate pain and disability in ASD patients. Although the SRS–Schwab classification provides a realignment target framework for surgeons, a structured patient-specific systemic approach is crucial for the process of decision-making. ASD management should be focused on restoring age-specific harmonious alignment and should consider the comorbidities and risk factors of each patient to prevent catastrophic complications and enhance the HRQoL.

Adult Spinal Deformity: Current Concepts and Decision-Making Strategies for Management

Adult spinal deformity (ASD) is characterized by three-dimensional abnormalities of the thoracic or thoracolumbar spine that exerts significant impacts on the health-related quality of life (HRQoL). With the important effects that deformity of the sagittal plane exerts on the HRQoL, there have been paradigm shifts in ASD evaluation and management. Loss of lumbar lordosis is recognized as a key driver of ASD followed by reducing kyphosis, pelvic retroversion, and knee flexion. The Scoliosis Research Society (SRS)– Schwab classification reflects the sagittal spinopelvic parameters that correlate pain and disability in ASD patients. Although the SRS–Schwab classification provides a realignment target framework for surgeons, a structured patient-specific systemic approach is crucial for the process of decision-making. ASD management should be focused on restoring age-specific harmonious alignment and should consider the comorbidities and risk factors of each patient to prevent catastrophic complications and enhance the HRQoL.

Esophageal Perforation after Anterior Cervical Spine Surgery

STUDY DESIGN: Retrospective case analyses.PURPOSE: To investigate the causes, diagnosis, and management of esophageal perforation, depending on the time of diagnosis.OVERVIEW OF LITERATURE: To date, few studies have addressed these issues.METHODS: A total of seven patients were included in this study. The patients were classified into three groups based on esophageal perforation diagnosis time: intraoperative (diagnosed during surgery), perioperative (diagnosed within 30 days postoperatively), and delayed (diagnosed >30 days postoperatively) groups.RESULTS: In the intraoperative group (N=2), infectious spondylitis was the main cause of esophageal perforation. Anterior plate and screw removal, followed by posterior instrumentation, was performed. The injured esophagus was managed by omentum flap repair in one patient and primary repair in one patient. In the perioperative group (N=2), revision surgery for infection and metal failure were the main causes of esophageal perforation. In both cases, food residue was drained on the third postoperative day. The injured esophagus was managed conservatively. In the delayed group (N=3), chronic irritation caused by metal failure was the main cause of esophageal perforation. In all patients, there was no associated infection. The anterior instrumentation was removed, and the two patients were treated by primary repair, and one patient was treated using sternocleidomastoid muscle flap. One patient in intraoperative group died of sepsis.CONCLUSIONS: The main cause of intraoperative esophageal perforation was esophageal adhesions because of infectious spondylitis. However, perioperative and delayed esophageal perforations were caused by chronic irritation because of metal failure. Anterior plate and screw removal was necessary, and posterior instrumentation and fusion may be considered, depending on the fusion status.

Influence of Atlantoaxial Fusion on Sagittal Alignment of the Occipitocervical and Subaxial spines in Os Odontoideum with Atlantoaxial Instability

STUDY DESIGN: Retrospective case analysis. PURPOSE: We hypothesized that larger the C1–C2 fusion angle, greater the severity of the sagittal malalignment of C0–C1 and C2–C7. OVERVIEW OF LITERATURE: In our experience, instances of sagittal malalignment occur at C0–C1 and C2–C7 following atlantoaxial fusion in patients with Os odontoideum (OO). METHODS: We assessed 21 patients who achieved solid atlantoaxial fusion for reducible atlantoaxial instability secondary to OO. The mean patient age at the time of the operation was 42.8 years, and the mean follow-up duration was 4.9 years. Radiographic parameters were preoperatively measured and at the final follow-up. The patients were divided into two groups (A and B) depending on the C1–C2 fusion angle. In group A (n=11), the C1–C2 fusion angle was ≥22°, whereas in group B, it was <22°. The differences in the radiographic parameters of the two groups were evaluated. RESULTS: At the final follow-up, the C1–C2 angle was increased. However, this increase was not statistically significant (18° vs. 22°, p=0.924). The C0–C1 angle (10° vs. 5°, p<0.05) and C2–C7 angle (22° vs. 13°, p<0.05) significantly decreased. The final C1–C2 angle was negatively correlated with the final C0–C1 and C2–C7 angles. The final C0–C1 angle (4° vs. 6°, p<0.05) and C2–C7 angle (8° vs. 20°, p<0.05) were smaller in group A than in group B. After atlantoaxial fusion, the C0–C1 range of motion (ROM; 17° vs. 9°, p<0.05) and the C2–C7 ROM (39° vs. 31°, p<0.05) were significantly decreased. CONCLUSIONS: We found a negative association between the sagittal alignment of C0–C1 and C2–C7 after atlantoaxial fusion and the C1–C2 fusion angle along with decreased ROM. Therefore, overcorrection of C1–C2 kyphosis should be avoided to maintain good physiologic cervical sagittal alignment.

Posterior Sublaminar Wiring and/or Transarticular Screw Fixation for Reducible Atlantoaxial Instability Secondary to Symptomatic Os Odontoideum: A Neglected Technique?

STUDY DESIGN: Retrospective case analysis. PURPOSE: We retrospectively evaluated the clinical and radiological outcomes of posterior sublaminar wiring (PSLW) and/or transarticular screw fixation (TASF) for reducible atlantoaxial instability (AAI) secondary to os odontoideum. OVERVIEW OF LITERATURE: Limited information is available about the surgical outcomes of symptomatic os odontoideum with AAI. METHODS: We examined 23 patients (12 women and 11 men) with os odontoideum and reducible AAI. The average age of the patients at the time of the operation was 44.2 years. The average follow-up duration was 4.5 years. Thirteen patients with anterior AAI underwent PSLW alone, while 10 patients with combined (anterior+posterior) AAI underwent PSLW and TASF. An autogenous iliac bone graft was used for all patients. Nine patients complained of neck or suboccipital pain, and 14 complained of myelopathy. RESULTS: Angulational instability (preoperative 18.7°±8.9° vs. postoperative 2.1°±4.6°, p<0.001), translational instability (16.3±4.9 mm vs. 1.8±2.2 mm, p<0.001), and segmental angle of the C1–C2 joint (23.7°±7.2° vs. 28.4°±3.8°, p<0.05) showed significant improvement postoperatively. Neck Visual Analog Scale score (6.2±2.4 vs. 2.5±1.8, p<0.05) and the modified Japanese Orthopedic Association (9.1±3.1 vs. 13.2±2.6, p<0.05) score also improved, with a recovery rate of 51.8%. Among the three patients who developed nonunion and/or wire breakage, one underwent revision surgery with repeat PSLW and was finally able to achieve fusion. The final fusion rate was 91.3%. CONCLUSIONS: PSLW and/or TASF provided satisfactory clinical and radiological outcomes in reducible AAI secondary to os odontoideum without significant neurological complications. Our results suggest that PSLW and/or TASF can be considered a viable surgical option over segmental fixation in highly selected cases of os odontoideum with reducible AAI.

Small Interfering RNA–Mediated Suppression of Fas Modulate Apoptosis and Proliferation in Rat Intervertebral Disc Cells

STUDY DESIGN: In vitro cell culture model. PURPOSE: To investigate the effect of small interfering RNA (siRNA) on Fas expression, apoptosis, and proliferation in serum-deprived rat disc cells. OVERVIEW OF LITERATURE: Synthetic siRNA can trigger an RNA interference (RNAi) response in mammalian cells and precipitate the inhibition of specific gene expression. However, the potential utility of siRNA technology in downregulation of specific genes associated with disc cell apoptosis remains unclear. METHODS: Rat disc cells were isolated and cultured in the presence of either 10% fetal bovine serum (FBS) (normal control) or 0% FBS (serum deprivation to induce apoptosis) for 48 hours. Fas expression, apoptosis, and proliferation were determined. Additionally, siRNA oligonucleotides against Fas (Fas siRNA) were transfected into rat disc cells to suppress Fas expression. Changes in Fas expression were assessed by reverse transcription-polymerase chain reaction and semiquantitatively analyzed using densitometry. The effect of Fas siRNA on apoptosis and proliferation of rat disc cells were also determined. Negative siRNA and transfection agent alone (Mock) were used as controls. RESULTS: Serum deprivation increased apoptosis by 40.3% (p<0.001), decreased proliferation by 45.3% (p<0.001), and upregulated Fas expression. Additionally, Fas siRNA suppressed Fas expression in serum-deprived cultures, with 68.5% reduction at the mRNA level compared to the control cultures (p<0.001). Finally, Fas siRNA–mediated suppression of Fas expression significantly inhibited apoptosis by 9.3% and increased proliferation by 21% in serum-deprived cultures (p<0.05 for both). CONCLUSIONS: The observed dual positive effect of Fas siRNA might be a powerful therapeutic approach for disc degeneration by suppression of harmful gene expression.

Effect of RNA Interference-Mediated Suppression of p75 on the Viability of Rat Notochordal Cells

STUDY DESIGN: In vitro cell culture model. PURPOSE: To investigate the effects of RNA interference (RNAi) on p75 expression and viability of rat notochordal cells treated with serum deprivation. OVERVIEW OF LITERATURE: RNAi enables the inhibition of specific genes by sequence-specific gene silencing using a double-stranded RNA. METHODS: Notochordal cells were isolated, cultured, and placed in 10% (control) or 0% (apoptosis-promoting) fetal bovine serum (FBS) for 48 hours. The expression of p75, apoptosis, and cell proliferation were determined. To suppress p75 expression, a small interfering RNA (siRNA) was synthesized against p75 (p75 siRNA) and transfected into cells. The suppression of p75 mRNA expression was investigated using the reverse transcription-polymerase chain reaction. The degree of p75 suppression was semiquantitatively analyzed using densitometry. The effect of p75 siRNA on apoptosis and proliferation of cells was determined. Solutions of an unrelated siRNA and transfection agent alone served as controls. RESULTS: Serum deprivation significantly increased apoptosis by 40.3%, decreased proliferation of notochordal cells by 45.3% (both, p<0.001), and upregulated p75 expression. The p75 siRNA suppressed p75 expression in cells cultured in 0% FBS. The rate of suppression by p75 siRNA of p75 mRNA was 72.9% (p<0.001). Suppression of p75 expression by p75 siRNA inhibited apoptosis by 7% and increased proliferation by 14% in cells cultured in 0% FBS (both, p<0.05). CONCLUSIONS: siRNA-mediated suppression of p75 inhibited apoptosis and increased proliferation of notochordal cells under conditions of serum deprivation, suggesting that RNAi might serve as a novel therapeutic approach for disc degeneration caused by insufficient viability of disc cells through the suppression of the expression of harmful genes.

Adjacent Segment Pathology after Anterior Cervical Fusion

Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion.

Agreement on the Level Selection in Laminoplasty among Experienced Surgeons: A Survey-Based Study

STUDY DESIGN: Survey based study. PURPOSE: To assess the degree of agreement in level selection of laminoplasty (LP) for the selected cervical myeloradiculopathy cases between experienced spine surgeons. OVERVIEW OF LITERATURE: Although, cervical LP is a widely used surgical technique for multi-level spinal cord compression, until now there is no consensus about how many segments or which segments should be opened to achieve a satisfactory decompression. METHODS: Thorough clinical and radiographic data (plain X-ray, computed tomography, and magnetic resonance imaging) of 30 patients who had cervical myelopathy were prepared. The data were provided to three independent spine surgeons with over 10 years experience in operation of their own practices. They were questioned about the most preferable surgical method and suitable decompression levels. The second survey was carried out after 6 months with the same cases. If the level difference between respondents was a half level or below, agreement was considered acceptable. The intraobserver and interobserver agreements in level selection were assessed by kappa statistics. RESULTS: Three respondents selected LP as an option for 6, 8, and 22 cases in the first survey and 10, 21, and 24 cases in the second survey. The reasons for selection of LP were levels of ossification of the posterior longitudinal ligament (p=0.004), segmental kyphotic deformity (p=0.036) and mean compression score (p=0.041). Intraobserver agreement showed variable results. Interobserver agreement was poor to fair by perfect matching (kappa=0.111–0.304) and fair to moderate by acceptable matching (kappa=0.308–0.625). CONCLUSIONS: The degree of agreement for level selection of LP was not high even though experienced surgeons would choose the opening segments on the basis of same criteria. These results suggest that more specific guidelines in determination of levels for LP should be required to decrease unnecessary wide decompression according to individual variance.

Prognostic Factors for Postsurgical Recovery of Deltoid Palsy due to Cervical Disc Herniations

STUDY DESIGN: Retrospective multicenter study. PURPOSE: We aimed to investigate prognostic factors affecting postsurgical recovery of deltoid palsy due to cervical disc herniation (CDH). OVERVIEW OF LITERATURE: Little information is available about prognostic factors affecting postsurgical recovery of deltoid palsy due to CDH. METHODS: Sixty-one patients with CDH causing deltoid palsy (less than grade 3) were included in this study: 35 soft discs and 26 hard discs. Average duration of preoperative deltoid palsy was 11.9 weeks. Thirty-two patients underwent single-level surgery, 22 two-level, four three-level, and three four-level. Patients with accompanying myelopathy, shoulder diseases, or peripheral neuropathy were excluded from the study. RESULTS: Deltoid palsy (2.4 grades vs. 4.5 grades, p<0.001) and radiculopathy (6.4 points vs. 2.1 points, p<0.001) significantly improved after surgery. Thirty-six of 61 patients (59%) achieved full recovery (grade 5) of deltoid palsy, with an average time of 8.4 weeks. Longer duration of preoperative deltoid palsy and more severe radiculopathy negatively affected the degree of improvement in deltoid palsy. Age, gender, number of surgery level, and disc type did not affect the degree of improvement of deltoid palsy. Contrary to our expectations, severity of preoperative deltoid palsy did not affect the degree of improvement. Due to the shorter duration of preoperative deltoid palsy, in the context of rapid referral, early surgical decompression resulted in significant recovery of more severe grades (grade 0 or 1) of deltoid palsy compared to grade 2 or 3 deltoid palsy. CONCLUSIONS: Early surgical decompression significantly improved deltoid palsy caused by CDH, irrespective of age, gender, number of surgery level, and disc type. However, longer duration of deltoid palsy and more severe intensity of preoperative radiating pain were associated with less improvement of deltoid palsy postoperatively.

Effect of High Glucose on Stress-Induced Senescence of Nucleus Pulposus Cells of Adult Rats

STUDY DESIGN: In vitro cell culture model. PURPOSE: We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells. OVERVIEW OF LITERATURE: DM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells. METHODS: Adult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-beta-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways. RESULTS: The mean SA-beta-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations. CONCLUSIONS: The current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM.

Rat Notochordal Cells Undergo Premature Stress-Induced Senescence by High Glucose

STUDY DESIGN: In vitro cell culture. PURPOSE: The purpose of the study was to investigate the effect of high glucose on premature stress-induced senescence of rat notochordal cells. OVERVIEW OF LITERATURE: Glucose-mediated increase of oxidative stress is a major causative factor for the development of diseases associated with diabetes mellitus such as senescence. However, no information is available for the effect of high glucose on premature stress-induced senescence of rat notochordal cells. METHODS: Notochordal cells were isolated from 4-week-old rats, cultured and placed in either 10% fetal bovine serum (FBS, normal control) or 10% FBS plus two high glucose concentrations (0.1 M and 0.2 M, experimental conditions) for 1 and 3 days. We identified and quantified the mitochondrial damage (mitochondrial transmembrane potential), reactive oxygen species (ROS) and antioxidants, such as manganese superoxide dismutase (MnSOD) and catalase, for each condition. We also identified and quantified senescence and telomerase activity. Finally, we determined the expression of proteins related to replicative senescence (p53-p21-pRB) and stress-induced senescence (p16-pRB) pathways. RESULTS: Two high glucose concentrations enhanced the disruption of mitochondrial transmembrane potential and excessive generation of ROS in notochordal cells for 1 and 3 days, respectively. The expressions of MnSOD and catalase were increased in notochordal cells treated with both high glucose concentrations at 1 and 3 days. The telomerase activity declined at 1 and 3 days. Two high glucose concentrations increased the occurrence of stress-induced senescence of notochordal cells by p16-pRB pathways at 1 and 3 days. CONCLUSIONS: Despite compensatory expression of antioxidants, high glucose-induced oxidative stress accelerates stress-induced senescence in rat notochordal cells. This may result in dysfunction of notochordal cells, leading to accelerated premature disc degeneration. The prevention of excessive generation of oxidative stress by strict blood glucose control is important to prevent or to delay premature disc degeneration in young patients with diabetes mellitus.

High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

STUDY DESIGN: In vitro cell culture. PURPOSE: The purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells. OVERVIEW OF LITERATURE: Diabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells. METHODS: Nucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified. RESULTS: Two high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner. CONCLUSIONS: The results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus.