Application and Advantages of the Trans-Unco-Discal (TUD) Approach for Cervical Spondylotic Myelopathy and Radiculopathy: Classification and Modification of Surgical Technique Based on the Location of Spinal Cord and/or Nerve Root Compression.

Purpose: We assess the application and advantages of modifying the trans-unco-discal (TUD) approach which we underwent for cervical myelo-radiculopathy. We present the surgical techniques of the modified TUD approach. Materials and Methods: The material was 180 cases where anterior cervical decompression (ACD) was performed by the modified TUD approach. We classified the material into four groups based on the location of the nerve root and/or spinal cord compression: I, compression of the root at intervertebral foramen (IVF); II, compression of the posterior margin of the vertebral body; III, compression of the IVF and posterior margin of the vertebral body; IV, compression of the bilateral IVF and posterior margin of the vertebral body. We applied the modified TUD approach to these four types. We present the surgical procedures and techniques for the modified TUD approach. The Japanese orthopedic association (JOA) score and neuroradiological alignment were examined. Results: The improvement rate of the JOA score was 78.4% at 6 months post-surgery and 77.5% in the most recent examinations. By the modified TUD approach, compressive lesions of the spinal cord and/or nerve roots were removed, and good alignment was acquired and sustained. Conclusions: ACD by the modified TUD approach safely achieved appropriate decompression for the spinal cord and/or nerve roots, and the patients had a high improvement rate and good alignment. Complications were less common than with other surgical procedures. If the TUD approach and endoscopic approaches can be combined, their application to new area is anticipated.

Epidemiology and Comparative Analysis of Outcomes of Intramedullary Spinal Cord Tumor Between Pediatric and Adult Patients.

STUDY DESIGN: This was as clinical retrospective study. OBJECTIVES: We sought to evaluate the characteristics of Pediatric intramedullary spinal cord tumors (PISCTs) and to identify differences between pediatric and adult intramedullary spinal cord tumors. SUMMARY OF BACKGROUND DATA: PISCTs represent a rare clinical entity with limited evidence-base in the literature. METHODS: This study is a subanalysis of the retrospective multicenter observational study authorized by the Neurospinal Society of Japan, including consecutive patients with spinal intramedullary tumors treated surgically at 58 institutions between 2009 and 2020. Data on 1080 intramedullary spinal cord tumors were obtained, consisting of 91 pediatric and 939 adult patients. Survival was compared using Cox hazard regression while clinical differences were evaluated using multivariable logistic regression that controlled for confounders. RESULTS: Pediatric patients had a shorter overall, and progression-free, survival than adults. Pediatric patients with ISCTs were likely to have scoliosis [odds ratio (OR) = 6.49, 95% CI: 2.26-18.7], short preoperative symptom duration (OR = 0.99, 95% CI: 0.98-0.99), lower incidence of paresthesia (OR = 0.41, 95% CI: 0.22-0.77), higher incidence of paresis (OR = 2.10, 95% CI: 1.01-4.35), histopathology of astrocytoma (OR = 2.97, 95% CI: 1.19-7.43), and postoperative functional deterioration upon discharge (OR = 2.83, 95% CI: 1.43-5.58). Age was not a statistically significant prognostic factor of overall survival among the pediatric cohort. CONCLUSION: We found that the clinical characteristics of ISCTs differed between pediatric and adult patients. In terms of histopathological types, astrocytoma was most common in pediatric patients. ISCT occurring at an early age may not be an indicator for poor prognosis.

Nucleotide-binding oligomerization domain protein-1 is expressed and involved in the inflammatory response in human sebocytes.

Sebocytes express Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), which participate in the innate immune response of the skin. Although the roles of TLRs and NLR family pyrin domain-containing 3 (NLRP3) in inflammatory responses in sebocytes have been reported, the expression and functions of other NLR members, such as NOD protein-1 and -2 (NOD1 and NOD2, respectively), remain unclear. In this study, we showed that, in sebocytes, the expression of NOD1 is higher than that of NOD2, and that NOD1 is involved in inflammatory responses, such as the secretion of proinflammatory cytokines. A NOD1 agonist, L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP) induced the expression and secretion of interleukin-8 (IL-8) and activated the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. On the other hand, a NOD2 agonist, muramyl dipeptide, did not. Either inhibition with a NOD1 inhibitor, ML130, or knockdown of NOD1 expression abolished Tri-DAP-induced inflammatory responses, suggesting that NOD1 is involved in the immunogenic signaling system of sebocytes. Furthermore, Tri-DAP and an agonist of TLR2 or TLR4 additively increased IL-8 expression compared with each agonist alone. Our results reveal the role of NOD1 in the inflammatory responses of sebocytes and may provide a novel therapeutic target for sebaceous gland inflammatory diseases, such as acne vulgaris.

Impact of surgical treatment for intramedullary spinal cord metastasis on neurological function and survival: A multicenter retrospective study by the Neurospinal Society of Japan.

BACKGROUND: This retrospective multicenter study aimed to analyze the characteristics and surgical outcomes of intramedullary spinal cord metastasis (ISCM) and to discuss the controversy regarding its surgical indications. METHODS: This study included 29 ISCM patients who underwent surgery between 2009 and 2020. Biopsy cases were excluded from analysis. For functional and neurological functional assessments, Karnofsky Performance Status (KPS, %) and modified McCormick Scale (MMS, 5-grade scale) scores were determined before and after surgery. Patients were divided into two groups: a mild-to-moderate disability group with preoperative MMS grades 1 to 3, and a severe disability group with preoperative MMS grades 4 to 5. RESULTS: The mean preoperative KPS was 45.9, and the mean duration from symptom onset to surgical intervention was 1 month. The ISCM was located in the cervical spine in 10 cases and the thoracic spine in 19 cases. The access route (myelotomy) for ISCM removal was via the posterior median sulcus in 9 cases and via the posterior lateral sulcus in 11 cases, while others were not recorded. The degree of removal was gross total resection in 20 patients (69%), subtotal resection in 0 patients, and partial removal in 9 patients (31%). No significant complications related to the surgical procedures were recorded. Postoperative adjuvant therapy included radiotherapy in 17 patients (58.6%) and chemotherapy or molecular targeted therapy in 13 patients (44.8%). Pathological findings of ISCM showed that colorectal cancer was the most common in 9 cases, followed by lung cancer in 7, renal cell carcinoma in 5, and breast cancer in 2. Twenty-one of the 29 patients (72.4%) were confirmed to have survived 6 months after surgery: 8 of the 10 patients (80%) in the mild-to-moderate disability group and 13 of the 19 patients (68.4%) in the severe disability group. At 6 months after surgery, 3 of the 8 patients (38%) in the mild-to-moderate group were able to maintain or improve their function. Eleven of the 13 patients (85%) in the severe disability group maintained their function despite being severely disabled. CONCLUSIONS: This study suggests that surgical treatment can maintain or improve neurological function in a limited number of patients with ISCM, although it had minimal impact on improving the survival rate after surgery.

Predictors of Progression-Free Survival in Patients With Spinal Intramedullary Ependymoma: A Multicenter Retrospective Study by the Neurospinal Society of Japan.

BACKGROUND AND OBJECTIVES: Ependymoma is the most common spinal intramedullary tumor. Although clinical outcomes have been described in the literature, most of the reports were based on limited numbers of cases or been confined to institutional experience. The objective of this study was to analyze more detailed characteristics of spinal intramedullary ependymoma (SIE) and provide clinical factors associated with progression-free survival (PFS). METHODS: This retrospective observational multicenter study included consecutive patients with SIE in the cervical or thoracic spine treated surgically at a total of 58 institutions between 2009 and 2020. The results of pathological diagnosis at each institute were confirmed, and patients with myxopapillary ependymoma, subependymoma, or unverified histopathology were strictly excluded from this study. Outcome measures included surgical data, surgery-related complications, postoperative systemic adverse events, postoperative adjuvant treatment, postoperative functional condition, and presence of recurrence. RESULTS: This study included 324 cases of World Health Organization grade II (96.4%) and 12 cases of World Health Organization grade III (3.6%). Gross total resection (GTR) was achieved in 76.5% of cases. Radiation therapy (RT) was applied after surgery in 16 cases (4.8%), all of which received local RT and 5 of which underwent chemotherapy in combination. Functional outcomes were significantly affected by preoperative neurological symptoms, tumor location, extent of tumor resection, and recurrence. Multivariate regression analysis suggested that limited extent of tumor resection or recurrence resulted in poor functional outcomes. Multiple comparisons among the groups undergoing GTR, subtotal resection and biopsy, or partial resection of the tumor showed that the probability of PFS differed significantly between GTR and other extents of resection. CONCLUSION: When GTR can be safely obtained in the surgery for SIE, functional maintenance and longer PFS can be expected.

Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.

Many animal studies have shown that oral administration of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) prevents the reduction of NAD+ levels in organs and tissues, helping alleviate aging-related diseases. However, there are very few clinical reports of NMN supplementation in humans. Thus, this study aimed to investigate the influence of a 12-week NMN oral supplementation on biochemical and metabolic health parameters. A 12-week randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted. A total of 36 healthy middle-aged participants received one capsule of either 125 mg NMN or placebo twice a day. Among the NAD+ metabolites, the levels of nicotinamide in the serum were significantly higher in the NMN intake group than in the placebo group. Pulse wave velocity values indicating arterial stiffness tended to decrease in the NMN intake group. However, no significant difference was found between the two groups. Long-term NMN supplementation at 250 mg/day was well tolerated and did not cause adverse events. NMN safely and effectively elevated NAD+ metabolism in healthy middle-aged adults. Additionally, NMN supplementation showed potential in alleviating arterial stiffness.

The Symptomatic Calcification and Ossification of the Ligamentum Flavum in the Spine: Our Experience and Review of the Literature.

INTRODUCTION: We report our experience regarding the clinical features and pathological findings of the calcification of the ligamentum flavum (CLF) and ossification of the ligamentum flavum (OLF) in the spine. In addition, we reviewed the previous studies on CLF and OLF to enhance the understanding of these conditions. MATERIALS AND METHODS: We compared the clinical, radiological, and histopathological features of CLF and OLF. RESULTS: In CLF, a computed tomography (CT) scan showed egg-shaped or speck-like calcification in the ligamentum flavum. Magnetic resonance (MR) imaging demonstrated spinal cord compression due to a thickened ligamentum flavum, which appeared as a low-intensity mass. Pathological findings demonstrated fused islands of calcification resembling sand-like calcification. In OLF, CT showed beak-like ossification extending into the intervertebral foramen. MR imaging demonstrated spinal cord compression by a low-intensity mass. Pathological findings revealed laminar ossification of LF with chondrocytes near the calcification and laminar hyaline cartilage. CONCLUSIONS: CLF and OLF appear to be distinct entities based on their clinical, neuroradiological, histopathological, and pathogenetic features. We suggest that the causes of CLF include both metabolic and dystrophic factors, while the pathogenesis of OLF is characterized by enchondral ossification induced by a genetic cascade triggered by shearing/tension stress.

Porcine placental extract increase the cellular NAD levels in human epidermal keratinocytes.

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for numerous enzymes involved in energy metabolism. Because decreasing NAD levels is a common hallmark of the aging process in various tissues and organs, maintaining NAD levels has recently been of interest for the prevention of aging and age-related diseases. Although placental extract (PE) are known to possess several anti-aging effects, the NAD-boosting activity of PE remains unknown. In this study, we found that porcine PE (PPE) significantly increased intracellular NAD levels in normal human epidermal keratinocytes (NHEKs). PPE also attenuated the NAD depletion induced by FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Interestingly, only the fraction containing nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM) restored NAD content in NHEKs in the absence of NAMPT activity. These results suggest that PPE increases intracellular NAD by providing NAD precursors such as NMN, NR, and NAM. Finally, we showed that the application of PPE to the stratum corneum of the reconstructed human epidermis significantly ameliorated FK866-induced NAD depletion, suggesting that topical PPE may be helpful for increasing skin NAD levels. This is the first study to report the novel biological activity of PE as an NAD booster in human epidermal cells.

Cervical Lift-up Basket Laminoplasty after Resection of Spinal Intramedullary Tumors: A Finite Element Analysis and Clinical Image Evaluation.

Although reconstructive laminoplasty is commonly performed after resection of spinal intramedullary tumors of the cervical spine, its biomechanical rigidity of laminoplasty framework remains unclear. The objective of this study was to examine the structural reliability of our unique method of cervical lift-up basket laminoplasty by using computed tomography (CT)-based finite element analysis (FEA) and clinical radiological evaluation. A finite element model of cervical laminoplasty was created based on CT images using FEA software. Cervical lift-up basket laminoplasty (Basket) was compared with the standard style of open-door basket laminoplasty (Open-door). Clinical subjects for radiological evaluation comprised 33 patients who underwent cervical lift-up basket laminoplasty after resection of spinal intramedullary tumors. An FEA-equivalent stress histogram showed that stress was moderately dispersed around the basket. Virtual displacement of the spinous process of the Basket model was equivalent to that of the Open-door model in any direction of posterior-to-anterior, right-to-left, or top-to-bottom force. In the clinical analysis, radiological data with a minimum postoperative period of 6 months were obtained in a total of 28 out of 33 patients. No patients underwent revision surgery because of implant-related complications. No significant differences in C2-C7 angle or cervical tilt angle were observed between pre- and postoperatively. The structural rigidity of cervical lift-up basket laminoplasty was equivalent to the open-door style on the FEA. Clinical radiological evaluation suggested that there were no serious adverse events associated with cervical laminoplasty, although the longer postoperative follow-up is mandatory.

Anatomical Limitation of Posterior Spinal Myelotomy for Intramedullary Hemorrhage Associated with Ependymoma or Cavernous Malformation of the High Cervical Spine.

Spinal intramedullary tumors such as ependymoma or vascular lesions such as cavernous malformation are often at risk of intramedullary hemorrhage. Surgical procedures involving the high cervical spinal cord are often challenging. This technical note included four patients who presented with acute, subacute, or gradual onset of spinal cord dysfunction associated with intramedullary hemorrhage at the C1 or C1/2 level of the high cervical spine. The mean age was 46.3 years (16-74 years). All patients underwent posterior spinal cord myelotomy of the posterior median sulcus or posterolateral sulcus. It was not to exceed the caudal opening of the fourth ventricle (foramen of Magendie) and was assumed to be as high as the caudal medulla oblongata. Total removal of the intramedullary ependymoma or cavernous malformation occurred in three of four cases, and the remaining case had subtotal removal of the ependymoma. None of the patients showed postoperative deterioration of the neurological condition. Pathological examination of all cases revealed intramedullary hemorrhage was associated with ependymoma or cavernous malformation. Posterior spinal myelotomy should be limited to the caudal opening of the fourth ventricle (foramen of Magendie), that is the caudal medulla oblongata, to avoid the significant deterioration after surgery.

Rhamnazin suppresses melanosome transport by promoting the ubiquitin-mediated proteasomal degradation of melanophilin.

BACKGROUND: Melanosomes are intracellularly transported from the perinuclear region to the cell periphery and then to neighboring keratinocytes. We recently reported that the flavonoid rhamnazin suppresses melanosomal transport within pigment cells, yet the action mechanism remained unclear. OBJECTIVE: Our aim was to elucidate how rhamnazin influences the intracellular transport of melanosomes. METHODS: A melanosome distribution assay and immunostaining were performed using B16F10 mouse melanoma cells and normal human epidermal melanocytes, respectively. Expression levels of melanosome transport-related proteins, including melanophilin (MLPH), RAB27A, and myosin VA (MYO5A), were analyzed by immunoblotting. Ubiquitinated MLPH was detected using a commercial ubiquitin detection kit. To investigate the interaction between rhamnazin and MLPH, we prepared rhamnazin conjugated with magnetic FG beads. RESULTS: Immunoblotting analysis revealed that rhamnazin specifically reduces the expression of MLPH but not RAB27A or MYO5A proteins. The ubiquitin detection assay, which made use of a proteasome inhibitor, showed that MLPH accumulated as a polyubiquitinated protein after treatment with rhamnazin. We speculated that the affinity of rhamnazin for the components of the melanosome transport-related tripartite complex may alter the stability of the formation of the tripartite assembly. By using affinity-based techniques with B16F10 whole cell lysates or recombinant MLPH and RAB27A proteins, we revealed the interaction of rhamnazin with the components of the tripartite complex. CONCLUSION: We found that rhamnazin inhibits intracellular transport of melanosomes through proteasomal degradation of MLPH. Our results suggest that topical application of rhamnazin may provide a new approach for treating skin pigmentation disorders.

[Key of Classification and Diagnosis of Spinal Arteriovenous Malformation].

Spinal arteriovenous malformation(AVM)is a rare disease in which blood is received from the spinal feeding arteries. Owing to its rarity, there is limited experience regarding its diagnosis and treatment. In addition, the various classifications that have been proposed historically make it more difficult for the young neurosurgeons to understand this disease. Because delayed initial diagnosis leads to irreversible damage of the spinal cord, neurosurgeons should always consider spinal AVM as one of the differential diagnoses. In order to understand the pathological condition of spinal AVM, it is important to learn basic classification. Spinal AVM is classified as intradural, dural, and epidural. Spinal digital subtraction angiography(DSA)is the gold-standard for the diagnosis of spinal AVM and is indispensable toolfor treatment planning. The purpose of this paper is to summarize a basic classification and diagnosis of spinal AVM.

1,25-Dihydroxyvitamin D3 attenuates IL-1ß secretion by suppressing NLRP1 inflammasome activation by upregulating the NRF2-HO-1 pathway in epidermal keratinocytes.

The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein (NLRP) inflammasome is a key inflammatory signaling pathway activated via a two-step signaling process consisting of priming and activation steps. Several studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3) inhibits the priming step required for NLRP3 inflammasome activation in immune cells. However, as activating the NLRP1 inflammasome in keratinocytes does not necessarily require a priming step, whether 1,25(OH)2VD3 inhibits NLRP1 activation in unprimed keratinocytes is currently unknown. In this study, we showed that 1,25(OH)2VD3 inhibits nigericin-induced NLRP1 inflammasome activation in unprimed keratinocytes. 1,25(OH)2VD3 suppressed nigericin-induced interleukin-1ß (IL-1ß) secretion and caspase-1 activation in human primary keratinocytes. In addition, 1,25(OH)2VD3 significantly inhibited the formation of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomers and specks, but not caspase-1 enzymatic activity, suggesting that 1,25(OH)2VD3 prevents NLRP1-ASC complex assembly in keratinocytes. Vitamin D receptor (VDR)-knockdown abolished the inhibitory effects of 1,25(OH)2VD3 on nigericin-induced ASC oligomerization and IL-1ß secretion, suggesting that 1,25(OH)2VD3 suppresses inflammasome activation via VDR signaling. Furthermore, nigericin induced K+ efflux and cellular reactive oxygen species (ROS) production, and 1,25(OH)2VD3 pretreatment suppressed nigericin-induced ROS production. 1,25(OH)2VD3 increased the expression of both nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1), whereas HO-1 inhibition or NRF2 and HO-1 knockdown abrogated the inhibitory effects of 1,25(OH)2VD3 on IL-1ß secretion. Our results indicate that 1,25(OH)2VD3 inhibits nigericin-induced activation step of NLRP1 inflammasome activation in unprimed keratinocytes. Our findings reveal the mechanism underlying the inhibitory effect of 1,25(OH)2VD3, which involves NRF2-HO-1 pathway activation through the VDR, providing further insight into the potential function of 1,25(OH)2VD3 as a therapeutic agent for inflammasome-related skin diseases.

Low-molecular-weight whey proteins promote collagen production in dermal fibroblasts via the TGF-ß receptor/Smad pathway.

Whey proteins (WPs) reportedly enhance cutaneous tissue regeneration in in vivo studies. However, the underlying mechanisms of such regenerative processes are poorly understood. In this study, we show that low-molecular-weight WPs (LMWPs; 1-30 kDa) accelerate the dermal collagen production via the transforming growth factor ß receptor (TßR)/Smad pathway. We showed that LMWPs increased type I and III collagen expression in normal human dermal fibroblasts. Moreover, LMWPs rapidly induced Smad protein phosphorylation and nuclear translocation. Notably, type I TßR/Smad signaling inhibitor treatment or type II TßR siRNA knockdown blocked the LMWP-induced type I collagen expression. To identify the active components, we fractionated LMWPs and identified ß-lactoglobulin and α-lactalbumin as potential TßR/Smad signaling inducers. Our findings unravel novel biological functions of WPs, involving the TßR/Smad-dependent induction of dermal collagen synthesis, highlighting the therapeutic potential of LMWPs in wound healing.

Spinal cord astroblastoma with EWSR1-BEND2 fusion classified as HGNET-MN1 by methylation classification: a case report.

The most recurrent fusion of central nervous system high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) is MN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showing Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3-5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. Histological examinations demonstrated solid growth of epithelioid tumor cells showing high cellularity, a pseudopapillary structure, intervening hyalinized fibrous stroma, and some mitoses. Astroblastoma was diagnosed, classified as HGNET-MN1 by the German Cancer Research Center methylation classifier. MN1 alteration was not detected by fluorescence in situ hybridization (FISH), but EWSR1-BEND2 fusion was detected by FISH and RNA sequencing. Previously, a child with EWSR1-BEND2 fusion-positive spinal astroblastoma classified as HGNET-MN1 was reported. In conjunction with that, the present case provides evidence that EWSR1-BEND2 fusion is identified in the entity of HGNET-MN1. Taken together, the BEND2 alteration rather than MN1 may determine the biology of a subset of the central nervous system HGNET-MN1 subclass.

Restoring NAD+ by NAMPT is essential for the SIRT1/p53-mediated survival of UVA- and UVB-irradiated epidermal keratinocytes.

Nicotinamide adenine dinucleotide (NAD+) is a crucial coenzyme in energy production. The imbalance of NAD+ synthesis has been found to trigger age-related diseases, such as metabolic disorders, cancer, and neurodegenerative diseases. Also, UV irradiation induces NAD+ depletion in the skin. In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway and essential for NAD+ homeostasis. However, but few studies have focused on the role of NAMPT in response to UV irradiation. Here, we show that NAMPT prevents NAD+ depletion in epidermal keratinocytes to protect against the mild-dose UVA and UVB (UVA/B)-induced proliferation defects. We showed that poly(ADP-ribose) polymerase (PARP) inhibitor rescued the NAD+ depletion in UVA/B-irradiated human keratinocytes, confirming that PAPR transiently exhausts cellular NAD+ to repair DNA damage. Notably, the treatment with a NAMPT inhibitor exacerbated the UVA/B-induced loss of energy production and cell viability. Moreover, the NAMPT inhibitor abrogated the sirtuin-1 (SIRT1)-mediated deacetylation of p53 and significantly inhibited the proliferation of UVA/B-irradiated cells, suggesting that the NAMPT-NAD+-SIRT1 axis regulates p53 functions upon UVA/B stress. The supplementation with NAD+ intermediates, nicotinamide mononucleotide and nicotinamide riboside, rescued the UVA/B-induced phenotypes in the absence of NAMPT activity. Therefore, NAD+ homeostasis is likely essential for the protection of keratinocytes from UV stress in mild doses. Since the skin is continuously exposed to UVA/B irradiation, understanding the protective role of NAMPT in UV stress will help prevent and treat skin photoaging.

Combination of p53 and Ki67 as a Promising Predictor of Postoperative Recurrence of Meningioma.

BACKGROUND: Meningioma is a common intracranial tumor originating from arachnoid cap cells. Meningiomas are generally benign tumors curable by one-time resection. However, some meningiomas regrow and invade into the dura mater, and thus frequently require additional treatment. A useful marker to predict the regrowth of meningioma is desired. This study aimed to clarify the significance of p53 and Ki67 for postoperative recurrence of meningioma. MATERIALS AND METHODS: The expression of p53 and Ki67 in 215 intracranial or intraspinal meningiomas was investigated by immunohistochemistry. RESULTS: Of the 215 meningiomas, 35 cases (16.3%) were p53-positive and 49 cases (22.8%) were Ki67-positive. Multivariate analysis revealed Ki67 and p53 status as being significantly correlated with recurrence. Positivity for either Ki67- or p53 was significantly associated with poor recurrence-free survival. CONCLUSION: Combined p53 and Ki67 status might represent a useful independent predictive marker for recurrence of meningioma.

Microsurgical or endovascular strategy for complete obliteration of spinal arteriovenous shunts in a single-institute 10-year retrospective study.

The objective of this retrospective study is to more fully understand the optimal strategy to manage spinal arteriovenous (AV) shunts. This study included a cohort of 35 patients with a diagnosis of spinal AV shunts who were treated over the past 10 years at a single institute. Angiographic diagnosis of intramedullary AV malformations (IM-AVM), perimedullary AV fistulas (PM-AVF), dural AV fistulas (D-AVF), or epidural AV fistulas (ED-AVF) was carefully made, and the microsurgical or endovascular strategy for them was determined at the interdisciplinary meeting consisting of neurospinal surgeons and endovascular specialists. Endovascular surgery was first considered whenever safely possible. Microscopic direct surgery using intraoperative image guidance was considered for cases in which endovascular access was challenging or not safely possible. Combined treatment was another option. The clinical condition was assessed using the modified Rankin scale (mRS). Seventeen of 35 cases were treated with microscopic direct surgery, 13 cases with endovascular surgery, and the remaining five cases with the combination. Complete angiographic obliteration was achieved in 30 of 35 cases (85.7%). Although residual AV shunts was recognized in 3 cases of IM-AVM, 1 case of PM-AVF and 1 case of ED-AVF, no angiographic recurrence was present with an average postoperative follow-up period of 44 months. The average mRS before surgery was 2.37 and significantly improved to 1.94 at the most recent follow-up. Interdisciplinary collaboration between neurospinal surgeons and endovascular specialists should be standard to achieve safe and successful outcomes in treating such rare and difficult spinal disorders.

Posterior Direct Reduction of Lateral Atlantoaxial Joints for Rigid Pediatric Atlantoaxial Subluxation: A Fulcrum Lever Technique.

STUDY DESIGN: Clinical case series. OBJECTIVE: To present a surgical technique and results of posterior direct reduction of lateral atlantoaxial joints for rigid pediatric atlantoaxial subluxation (AAS) using a fulcrum lever technique. SUMMARY OF BACKGROUND DATA: The surgical treatment of pediatric rigid AAS is still technically challenging. Several factors contribute to the surgical difficulty, such as small vertebrae, incomplete bone formation, dysplasia, the difficulty of reduction and external fixation are considered as a surgical daunting challenge. Herein, the surgical technique of posterior direct reduction of lateral atlantoaxial joints for rigid pediatric AAS using a fulcrum lever technique is presented. METHODS: This retrospective study included 10 pediatric patients with rigid AAS who underwent posterior direct reduction of bilateral C1/2 facet joints via a fulcrum lever technique. The indication for surgery was the presence of neurological symptoms and spinal cord atrophy with an intramedullary high signal at the C1 level on T2-weighted magnetic resonance (MR) images. The surgical procedure consisted of three steps: (1) opening and distraction of the C1/2 facet joints and placement of tricortical bone as a spacer and fulcrum; (2) placement of C1 and C2 screws; and finally, (3) compression between the C1 posterior arch and C2 lamina and constructing C1/2 fusion. All patients underwent the neurological and radiological evaluations before and after surgery. RESULTS: Eight of 10 patients demonstrated genetic disorders, either Down syndrome or chondrodysplasia punctate. Besides, all cases documented congenital anomaly of the odontoid process. Bilateral C1 lateral mass screws were successfully placed in all cases. No evidence of postoperative neurovascular complications. Radiological evaluation showed the corrections and bony fusions of C1/2 facet joint in all cases. CONCLUSION: The fulcrum lever technique for rigid pediatric AAS can be one of the effective surgical solutions to this challenging pediatric spinal disorder. LEVEL OF EVIDENCE: 4.