Endoscopic transorbital decompression for traumatic superior orbital fissure syndrome: from cadaveric study to clinical application.

PURPOSE: The endoscopic endonasal approach (EEA) is a minimally invasive and promising modality for treating traumatic superior orbital fissure (SOF) syndrome (tSOFS). Recently, the endoscopic transorbital approach (ETOA) has been considered an alternative method for reaching the anterolateral skull base. This study accessed the practicality of using the ETOA to treat SOF decompression using both cadaveric dissection and clinical application. METHODS: Bilateral anatomic dissections were performed on four adult cadaveric heads using the ETOA and EEA to address SOF decompression. The ETOA procedure for SOF decompression is described, and the extent of SOF decompression was compared between the ETOA and EEA. The clinical feasibility of the ETOA for treating SOF decompression was performed in two patients diagnosed with tSOFS. RESULTS: ETOA allowed for decompression over the lateral aspect of the SOF, from the meningo-orbital band superolaterally to the maxillary strut inferomedially. By contrast, the EEA allowed for decompression over the medial aspect of the SOF, from the lateral opticocarotid recess superiorly to the maxillary strut inferiorly. In both patients treated using the ETOA and SOF decompression, the severity of ophthalmoplegia got obvious improvement. CONCLUSIONS: Based on the cadaveric findings, ETOA provided a feasible access pathway for SOF decompression with reliable outcomes, and our patients confirmed the clinical efficacy of the ETOA for managing tSOFS.

TOM40 mediates the effect of TSPO on postpartum depression partially through regulating calcium homeostasis in microglia.

AIMS: To assess the effect of the translocator protein 18 kDa (TSPO) on postpartum depression and explore its mechanism. METHODS: Postpartum depression (PPD) mouse model was established, and flow cytometry, immunofluorescence, Western blot analysis, real-time quantitative PCR, adeno-associated virus (AAV), co-immunoprecipitation-mass spectrometry and immunofluorescence co-staining were used to detect the effect of TSPO ligand ZBD-2 on PPD mice. RESULTS: ZBD-2 inhibits the overactivation of microglia in the hippocampus and amygdala of PPD model mice. ZBD-2 not only inhibited the inflammation but also repressed the burst of reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Meanwhile, ZBD-2 protects mitochondria from LPS-induced damages through inhibiting the influx of calcium. ZBD-2 modulated the calcium influx by increasing the level of translocase of the outer mitochondrial membrane 40 (TOM40) and reducing the interaction of TSPO and TOM40. In addition, the effect of ZBD-2 was partially dependent on anti-oxidative process. Knockdown of TOM40 by adeno-associated virus (AAV) in the hippocampus or amygdala dramatically reduced the effect of ZBD-2 on PPD, indicating that TOM40 mediates the effect of ZBD-2 on PPD. CONCLUSIONS: TOM40 is required for the effect of ZBD-2 on treating anxiety and depression in PPD mice. This study reveals the role of microglia TSPO in PPD development and provides the new therapeutic strategy for PPD.

Transorbital transposition of the temporoparietal fascia flap to reconstruct the skull base defects: A preclinical study with comparison to the transpterygoid transposition.

BACKGROUND: Transpterygoid transposition of the temporoparietal fascia flap (TPFF) is a feasible selection for ventral skull base defect (VSBD) reconstruction, but not anterior skull base defect (ASBD) reconstruction, after expanded endoscopic endonasal approach (EEEA). The goal of this study is to introduce the transorbital transposition of the TPFF for skull base defects reconstruction after EEEA, and make quantitative comparison between the transpterygoid transposition and transorbital transposition. METHODS: Cadaveric dissections were performed in five adult cadaveric heads with creating three transporting corridors bilaterally, encompassing superior transorbital corridor, inferior transorbital corridor, and transpterygoid corridor. For each transporting corridor, the minimum necessary length of the TPFF for skull base defects reconstruction was measured. RESULTS: The areas of ASBD and VSBD were 1019.63 ± 176.32 mm2 and 572.99 ± 126.21 mm2 . The length of the harvested TPFF was 149.38 ± 6.21 mm. In contrast to the transpterygoid transposition with incomplete coverage, transorbital transposition of the TPFF allowed full coverage of ASBD with a minimum necessary length of 109.75 ± 8.31 mm. For VSBD reconstruction, transorbital transposition of the TPFF needs shorter minimum necessary length (123.88 ± 4.49 mm) than transpterygoid transposition (138.00 ± 6.28 mm). CONCLUSIONS: Transorbital corridor is a novel pathway for transporting the TPFF into the sinonasal cavity for skull base defects reconstruction after EEEA. In comparison with transpterygoid transposition, transorbital transposition provides wider coverage of skull base defects with a fixed length of the TPFF.

Endoscopically assisted presigmoid retrolabyrinthine approach to the lateral mesencephalic sulcus: a cadaveric study with comparison to the variant supracerebellar infratentorial approaches.

The supracerebellar infratentorial (SCIT) approach is commonly used to gain access to the lateral mesencephalic sulcus (LMS), which has been established as a safe entry point into the posterolateral midbrain. This study describes a lateral variant of the SCIT approach, the supreme-lateral SCIT approach, for accessing the LMS through the presigmoid retrolabyrinthine craniectomy and quantitatively compares this approach with the paramedian and extreme-lateral SCIT approaches. Anatomical dissections were performed in four cadaveric heads. In each head, the supreme-lateral SCIT approach was established on one side, following a detailed description of each step, whereas the paramedian and supreme-lateral SCIT approaches were established on the other side. Quantitative measurements of the exposed posterolateral midbrain, the angles of LMS entry, and the depth of surgical corridors were recorded and compared between the three SCIT approach variants. The supreme-lateral (67.70 ± 23.14 mm2) and extreme-lateral (70.83 ± 24.99 mm2) SCIT approaches resulted in larger areas of exposure anterior to the LMS than the paramedian SCIT approach (38.61 ± 9.84 mm2); the supreme-lateral SCIT approach resulted in a significantly smaller area of exposure posterior to the LMS (65.24 ± 6.81 mm2) than the other two variants (paramedian = 162.75 ± 31.98 mm2; extreme-lateral = 143.10 ± 23.26 mm2; both P < .001). Moreover, the supreme-lateral SCIT approach resulted in a surgical corridor with a shallower depth and a smaller angle relative to the horizontal plane than the other two variants. The supreme-lateral SCIT approach is a more lateral approach than the extreme-lateral SCIT approach, providing a subtemporal approach with direct LMS visualization. The supreme-lateral SCIT offers the benefits of both subtemporal and SCIT approaches and represents a suitable option for the management of selected midbrain pathologies.

Endoscopic transcanal transpetrosal approach to the petroclival region: a cadaveric study with comparison to the Kawase approach.

This study introduces expanded application of the endoscopic transcanal approach with anterior petrosectomy (ETAP) in reaching the petroclival region, which was compared through a quantitative analysis to the middle fossa transpetrosal-transtentorial approach (Kawase approach). Anatomical dissections were performed in five cadaveric heads. For each head, the ETAP was performed on one side with a detailed description of each step, while the Kawase approach was performed on the contralateral side. Quantitative measurements of the exposed area over the ventrolateral surface of the brainstem, and of the angles of attack to the posterior margin of the trigeminal nerve root entry zone (CN V-REZ) and porus acusticus internus (PAI) were obtained for statistical comparison. The ETAP provided significantly larger exposure over the ventrolateral surface of the pons (93.03 ± 21.87 mm2) than did the Kawase approach (34.57 ± 11.78 mm2). In contrast to the ETAP, the Kawase approach afforded greater angles of attack to the CN V-REZ and PAI in the vertical and horizontal planes. The ETAP is a feasible and minimally invasive procedure for accessing the petroclival region. In comparison to the Kawase approach, the ETAP allows for fully anterior petrosectomy and larger exposure over the ventrolateral surface of the brainstem without passing through the cranial nerves or requiring traction of the temporal lobe.

Quantitative comparison of endoscopically assisted endonasal, sublabial and transorbital transmaxillary approaches to the anterolateral skull base.

OBJECTIVES: The aim of this anatomical study is to make quantitative comparison among three endoscopic approaches, encompassing contralateral endonasal transseptal transmaxillary transpterygoid approach (contralateral EEA), endoscopic sublabial transmaxillary transalisphenoid (Caldwell-Luc) approach and endoscopic transorbital transmaxillary approach through inferior orbital fissure (ETOA), to the anterolateral skull base for assisting preoperative planning. DESIGN & PARTICIPANTS: Anatomical dissections were performed in four adult cadaveric heads bilaterally using three endoscopic transmaxillary approaches described above. SETTING: Skull Base Laboratory at the National Defense Medical Center. MAIN OUTCOME MEASURES: The area of exposure, angles of attack and depth of surgical corridor of each approach were measured and obtained for statistical comparison. RESULTS: The ETOA had significantly larger exposure over middle cranial fossa (731.40 ± 80.08 mm2 ) than contralateral EEA (266.60 ± 46.74 mm2 ) and Caldwell-Luc approach (468.40 ± 59.67 mm2 ). In comparison with contralateral EEA and Caldwell-Luc approach, the ETOA offered significantly greater angles of attack and shorter depth of surgical corridor (P < .05 for all comparisons). CONCLUSIONS: The ETOA is the superior choice for target lesion occupying multiple compartments with its epicentre located in the middle cranial fossa or superior portion of infratemporal fossa.

Association of early vertebroplasty with risk of hip replacement: A nationwide population-based cohort study in Taiwan.

Studies show that vertebral fractures could predict the risk of hip fractures. We aimed to evaluate the potential benefits of whether the timing of vertebroplasty (VP) for vertebral fracture associated with the risk of hip fracture for hip replacement.We identified 142,782 patients from the Taiwan National Health Insurance Database with thoracolumbar vertebral fracture (International Classification of Diseases, Ninth Revision, Clinical Modification:805.2-805.9) who were followed up from 2000 to 2013. These patients were divided into those who underwent VP (VP group) (International Classification of Diseases, Ninth Revision, Clinical Modification : 78.49) within 3 months and those who did not (non-VP group). After adjusting for the confounding factors, the Cox proportional hazards analysis was used to estimate the effect of early VP on reducing the risk of hip fracture. The difference in the risk of hip replacement, between the VP group and non-VP group was estimated using the Kaplan-Meier method with the log-rank test.In the 14-year follow-up, the cumulative incidence rate of hip replacement in the VP group was lower than that in the non-VP group (0.362% and 0.533%, respectively, long-rank P < .001). There was a significant difference between the 2 groups since the first-year follow-up.Our study showed that early VP performed to avoid progression of the kyphotic changes following thoracolumbar vertebral fracture may reduce the risk of hip fracture. These results, obtained from retrospective data, indicate that a prospective study is warranted.

Endoscopic transorbital approach to anterolateral skull base through inferior orbital fissure: a cadaveric study.

BACKGROUND: Endoscopic transorbital approach (eTOA) has been announced as an alternative minimally invasive surgery to skull base. Owing to the inferior orbital fissure (IOF) connecting the orbit with surrounding pterygopalatine fossa (PPF), infratemporal fossa (ITF), and temporal fossa, the idea of eTOA to anterolateral skull base through IOF is postulated. The aim of this study is to access its practical feasibility. METHODS: Anatomical dissections were performed in five human cadaveric heads (10 sides) using 0-degree and 30-degree endoscopes. A stepwise description of eTOA to anterolateral skull base through IOF was documented. The anterosuperior corner of the maxillary sinus in the horizontal plane of the upper edge of zygomatic arch was defined as reference point (RP). The distances between the RP to the foramen rotundum (FR), foramen ovale (FO), and Gasserian ganglion (GG) were measured. The exposed area of anterolateral skull base in the coronal plane of the posterior wall of the maxillary sinus was quantified. RESULTS: The surgical procedure consisted of six steps: (1) lateral canthotomy with cantholysis and preseptal lower eyelid approach with periorbita dissection; (2) drilling of the ocular surface of greater sphenoid wing and lateral orbital rim osteotomy; (3) entry into the maxillary sinus and exposure of PPF and ITF; (4) mobilization of infraorbital nerve with drilling of the infratemporal surface of the greater sphenoid wing and pterygoid process; (5) exposure of middle cranial fossa, Meckel's cave, and lateral wall of cavernous sinus; and (6) reconstruction of orbital floor and lateral orbital rim. The distances measured were as follows: RP-FR = 45.0 ± 1.9 mm, RP-FO = 55.7 ± 0.5 mm, and RP-GG = 61.0 ± 1.6 mm. In comparison with the horizontal portion of greater sphenoid wing, the superior and inferior axes of the exposed area were 22.3 ± 2.1 mm and 20.5 ± 1.8 mm, respectively. With reference to the FR, the medial and lateral axes of the exposed area were 11.6 ± 1.1 mm and 15.8 ± 1.6 mm, respectively. CONCLUSIONS: The eTOA through IOF can be used as a minimally invasive surgery to access whole anterolateral skull base. It provides a possible resolution to target lesion involving multiple compartments of anterolateral skull base.

Endoscopic transorbital transtentorial approach to middle incisural space: preclinical cadaveric study.

BACKGROUND: Endoscopic transorbital approach is a novel development of minimally invasive skull base surgery. Recently, anatomical studies have started to discuss the expanded utilization of endoscopic transorbital route for intracranial intradural lesions. The goal of this cadaveric study is to assess the feasibility of endoscopic transorbital transtentorial approach for exposure of middle incisural space. METHODS: Anatomical dissections were performed in four human cadaveric heads (8 sides) using 0- and 30-degree endoscopes. A stepwise description of endoscopic transorbital transtentorial approach to middle incisural space and related anatomy was provided. RESULTS: Orbital manipulation following superior eyelid crease incision with lateral canthotomy and cantholysis established space for bone drilling. Extradural stage consisted of extensive drilling of orbital roof of frontal bone, lessor, and greater wings of sphenoid bone. Intradural stage was composed of dissection of sphenoidal compartment of Sylvian fissure, lateral mobilization of mesial temporal lobe, and penetration of tentorium. A cross-shaped incision of tentorium provided direct visualization of crural cistern with anterolateral aspect of cerebral peduncle and upper pons. Interpeduncular cistern, prepontine cistern, and anterior portions of ambient and cerebellopontine cisterns were exposed by 30-degree endoscope. CONCLUSION: The endoscopic transorbital transtentorial approach can be used as a minimally invasive surgery for exposure of middle incisural space. Extensive drilling of sphenoid wing and lateral mobilization of mesial temporal lobe are the main determinants of successful dissection. Further studies are needed to confirm the clinical feasibility of this novel approach.

Impact of global spine balance and cervical regional alignment on determination of postoperative cervical alignment after laminoplasty.

The aim of this study is to analyze the combined impact of preoperative T1 slope (T1S) and C2-C7 sagittal vertical axis (C2-C7 SVA) on determination of cervical alignment after laminoplasty.Forty patients undergoing laminoplasty for cervical spondylotic myelopathy (CSM) with more than 2 years follow-up were enrolled. Three parameters, including cervical lordosis, T1S, and C2-C7 SVA, were measured by preoperative and postoperative radiographs. Receiver operating characteristics (ROC) curve analysis was used to determine the optimal cut-off values of preoperative T1S and C2-C7 SVA for predicting postoperative loss of cervical lordosis. Patients were classified into 4 categories based on cut-off values of preoperative T1S and C2-C7 SVA. The primary outcome was postoperative C2-C7 SVA. Change in radiographic parameters between 4 groups were compared and analyzed.Optimal cut-off values for predicting loss of cervical lordosis were T1S of 20 degrees and C2-C7 SVA of 22 mm. Patients with small C2-C7 SVA, no matter what the value of T1S, got slight loss of cervical lordosis and increase in C2-C7 SVA. Patients with low T1S and large SVA (T1 ≤20° and SVA >22 mm) got postoperative correction of kyphosis and decrease of C2-C7 SVA. However, patients with high T1S and large SVA (T1 >20° and SVA >22 mm) got mean postoperative C2-C7 SVA value of 37.06 mm, close to the threshold value of 40 mm.Determination of cervical alignment after laminoplasty relies on the equilibrium between destruction of cervical structure, kyphotic force, and adaptive compensation of whole spine, lordotic force. Lower T1S means bigger compensatory ability to adjust different severity of cervical sagittal malalignment, and vice versa.

Preoperative grading of intracranial meningioma by magnetic resonance spectroscopy (1H-MRS).

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery.

The Efficacy of Therapeutic Plasma Exchange in Antiphospholipid Antibody-positive Patients With Spontaneous Intracerebral Hemorrhage and High D-dimer Levels.

OBJECTIVE: We investigated the efficacy of plasma exchange (PE) in antiphospholipid antibody (aPL)-positive patients with a spontaneous intracerebral hemorrhage (ICH) and high D-dimer levels. MATERIALS AND METHODS: From May 2013 to May 2016, we evaluated 32 patients who were below the age of 50 and presented with spontaneous ICH. Five patients were positive for aPL antibody and 3 had a higher level of D-dimer. These 3 patients underwent 5 sessions of PE using fresh frozen plasma as replacement fluid. We analyzed the days postadmission until PE-start, the days of intensive care unit (ICU) hospitalization, D-dimer series, Glasgow Coma Scale (GCS) scores, and modified Rankin scale (mRS) scores. D-dimer levels and GCS scores were recorded at both pre-PE and post-PE stages. The mRS scores were recorded at pre-PE stage and 3 months post-PE. RESULTS: The mean postadmission period until PE-start was 8.33 days. The mean ICU hospitalization was 17.33 days. The D-dimer level pre-PE ranged from 2.34 to 5.44 mg/L fibrinogen equivalent unit (FEU). The D-dimer level post-PE ranged from 1.05 to 3.30 mg/L FEU. The amount of decline of the D-dimer level between pre-PE and post-PE ranged from 0.65 to 2.14 mg/L FEU. The GCS score pre-PE was between 7 and 8. The highest post-PE GCS score was 14. The improved GCS scores post-PE ranged from 3 to 6. The improved mRS scores of 3 months post-PE ranged from 3 to 4. CONCLUSIONS: The concurrent presence of positive aPL and a higher D-dimer level may worsen the neurological outcome of patients with a spontaneous ICH. Aggressive PE is effective for the treatment of such patients, decreasing the extent of the ICU hospitalization.

Decreased antimicrobial resistance and defined daily doses after implementation of a clinical culture-guided antimicrobial stewardship program in a local hospital.

BACKGROUND: We aimed to report the implementation of an antimicrobial stewardship program (ASP) guided by clinically significant cultures in a hospital to assess its pharmaceutical, microbiological, financial, and outcome effects. METHODS: A 3-year cohort study of an antimicrobial restriction policy implementation was performed. The ASP with culture-guided de-escalation of antibiotics was instituted in a local hospital since January 1, 2012. The cost of antimicrobials, defined daily dose (DDD), susceptibility to antimicrobials, and outcome of all admitted patients were calculated and evaluated before and after the ASP implementation. RESULTS: Average monthly length of stay of admitted patients decreased from 7.8 ± 0.5 days in 2011 to 6.9 ± 0.3 days in 2013 (p < 0.001). The average monthly cost of antimicrobials decreased 46.9% from US$30,146.8 in 2011 to US$16,021.3 in 2013 (p < 0.001). Total intravenous antimicrobial DDDs per 100 bed-days of the inpatients were 66.9, 54.1 and 48.4 in 2011, 2012 and 2013, respectively. A total of 18.6 DDDs per 100 bed-days of inpatients (27.7%) decreased from 2011 to 2013. By comparing data in 2013 to those in 2011, the ASP reduced antimicrobial resistance of Gram-positive bacteria (p = 0.013), Gram-negative bacteria (p < 0.001), and predominant species (all p < 0.05). The yearly mortality also decreased from 1.3% in 2011 to 1.1% in 2012 and 1.0% in 2013. CONCLUSIONS: The ASP with a culture-guided de-escalation of antibiotics successfully reduced length of stay, mortality, the cost of antimicrobials, DDDs, and antimicrobial resistance rate, and that is highly recommended for local hospitals.

Quantitative analysis of anatomical relationship between cavernous segment internal carotid artery and pituitary macroadenoma.

Cavernous segment internal carotid artery (CSICA) injury during endoscopic transsphenoidal surgery for pituitary tumor is rare but fatal. The aim of this study is to investigate anatomical relationship between pituitary macroadenoma and corresponding CSICA using quantitative means with a sense to improve safety of surgery.In this retrospective study, a total of 98 patients with nonfunctioning pituitary macroadenomas undergoing endoscopic transsphenoidal surgeries were enrolled from 2005 to 2014. Intercarotid distances between bilateral CSICAs were measured in the 4 coronal levels, namely optic strut, convexity of carotid prominence, median sella turcica, and dorsum sellae. Parasellar extension was graded and recorded by Knosp-Steiner classification.Our findings indicated a linear relationship between size of pituitary macroadenoma and intercarotid distance over CSICA. The correlation was absent in pituitary macroadenoma with Knosp-Steiner grade 4 parasellar extension.Bigger pituitary macroadenoma makes more lateral deviation of CSICA. While facing larger tumor, sufficient bony graft is indicated for increasing surgical field, working area and operative safety.

A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management in Moderate and Severe Traumatic Brain Injury Patients.

The purpose of this study was to compare the effect of PbtO2-guided therapy with traditional intracranial pressure- (ICP-) guided treatment on the management of cerebral variables, therapeutic interventions, survival rates, and neurological outcomes of moderate and severe traumatic brain injury (TBI) patients. From 2009 to 2010, TBI patients with a Glasgow coma scale <12 were recruited from 6 collaborative hospitals in northern Taiwan, excluding patients with severe systemic injuries, fixed and dilated pupils, and other major diseases. In total, 23 patients were treated with PbtO2-guided management (PbtO2 > 20 mmHg), and 27 patients were treated with ICP-guided therapy (ICP < 20 mmHg and CPP > 60 mmHg) in the neurosurgical intensive care unit (NICU); demographic characteristics were similar across groups. The survival rate in the PbtO2-guided group was also significantly increased at 3 and 6 months after injury. Moreover, there was a significant correlation between the PbtO2 signal and Glasgow outcome scale-extended in patients from 1 to 6 months after injury. This finding demonstrates that therapy directed by PbtO2 monitoring is valuable for the treatment of patients with moderate and severe TBI and that increasing PaO2 to 150 mmHg may be efficacious for preventing cerebral hypoxic events after brain trauma.

Image analysis of open-door laminoplasty for cervical spondylotic myelopathy: comparing the influence of cord morphology and spine alignment.

OBJECTIVES: Previous studies have identified the factors affecting the surgical outcome of cervical spondylotic myelopathy (CSM) following laminoplasty. Nonetheless, the effect of these factors remains controversial. It is unknown about the association between pre-operative cervical spinal cord morphology and post-operative imaging result following laminoplasty. The goal of this study is to analyze the impact of pre-operative cervical spinal cord morphology on post-operative imaging in patients with CSM. METHODS: Twenty-six patients with CSM undergoing open-door laminoplasty were classified according to pre-operative cervical spine bony alignment and cervical spinal cord morphology, and the results were evaluated in terms of post-operative spinal cord posterior drift, and post-operative expansion of the antero-posterior dura diameter. RESULTS: By the result of study, pre-operative spinal cord morphology was an effective classification in predicting surgical outcome - patients with anterior convexity type, description of cervical spinal cord morphology, had more spinal cord posterior migration than those with neutral or posterior convexity type after open-door laminoplasty. Otherwise, the interesting finding was that cervical spine Cobb's angle had an impact on post-operative spinal cord posterior drift in patients with neutral or posterior convexity type spinal cord morphology - the degree of kyphosis was inversely proportional to the distance of post-operative spinal cord posterior drift, but not in the anterior convexity type. CONCLUSIONS: These findings supported that pre-operative cervical spinal cord morphology may be used as screening for patients undergoing laminoplasty. Patients having neutral or posterior convexity type spinal cord morphology accompanied with kyphotic deformity were not suitable candidates for laminoplasty.

Notch prevents transforming growth factor-beta-assisted epithelial-mesenchymal transition in cultured limbal progenitor cells through the induction of Smad7.

PURPOSE: Continuous culture of limbal epithelial stem cells (LSCs) slows down proliferation, which inevitably results in differentiation. Transforming growth factor-beta (TGFß)-assisted epithelial-mesenchymal transition (EMT) is often found in the late stage of LSC culture. Thus, EMT is proposed to be part of the mechanism responsible for the loss of LSCs in culture. To explore the regulation mechanism of EMT, we investigated the early stage culture for factor(s) that may potentially prevent EMT. METHODS: LSCs from the corneal limbus region of rabbits were isolated and expanded to confluence in culture (P0), and then serial passage of these LSCs (P1 to P3) was performed. EMT in LSCs was induced with TGFß1, and the corresponding EMT signaling was confirmed with Smad2/3 phosphorylation. The expression of mesenchymal markers, including alpha-smooth muscle actin (α-SMA) and vimentin, was determined with western blot analysis. Proteins extracted from different passaged cells were also subjected to western blot analysis of TGFß signaling components, including TGFß1, TGFß receptor I/II, and Smad2/3 as well as Smad7, the main negative regulator of TGFß signaling. The mitogenic response was measured with the bromodeoxyuridine (BrdU) labeling index and real-time PCR using primers for Ki67. N-(N-[3,5-difluorophenacetyl]-l-alanyl)-S-phenylglycine t-butyl ester (DAPT), a gamma-secretase inhibitor, and Jagged-1 Notch ligand were used to block and activate Notch signaling, respectively, and their efficacy was evaluated by determining the expression of Hes1, a Notch signaling target. RESULTS: Mesenchymal marker induction and growth arrest were found in the TGFß1-treated P1 cells, and the changes were less significant in the TGFß1-treated P0 cells. Western blot analysis confirmed that the expressed levels of TGFß signaling components, including TGFß1, TGFß receptor I/II, and Smad2/3, were relatively stable with passages. In contrast, the expression of Hes1 and Smad7 markedly decreased after the first passage, and with each passage, the levels diminished even further. Hes1 and Smad7 were expressed only in the limbal epithelium and not in the corneal epithelium. DAPT effectively blocked the expression of Hes1. DAPT also dose-dependently suppressed Smad7 expression in P0 cells, which was associated with the susceptibility of P0 cells to TGFß1-induced Smad2/3 phosphorylation, EMT formation, and growth arrest. Reciprocally, Jagged-1 upregulated Smad7 expression in LSCs against TGFß signaling. CONCLUSIONS: These findings indicate that Smad7 plays a crucial role in antagonizing EMT induced by TGFß signaling and support our proposition that Smad7 is a Notch signaling target in LSCs, and may mediate the Notch function in preventing the occurrence of EMT.

Pigment epithelium-derived factor 34-mer peptide prevents liver fibrosis and hepatic stellate cell activation through down-regulation of the PDGF receptor.

Pigment epithelium-derived factor (PEDF) has been shown previously to prevent liver fibrosis and hepatic stellate cell (HSC) activation. By investigating the functional domains in PEDF, we identified a 34-mer peptide (residues Asp44-Asn77) that harbors the same function as the full-length PEDF protein. Not only did the 34-mer suppress the development of fibrosis in carbon tetrachloride (CCl4)-treated mouse liver but it also upregulated peroxisome proliferator-activated receptor-gamma (PPARγ) expression in HSCs in vivo. Platelet-derived growth factor (PDGF) plays a crucial role on the process of HSC activation in response to liver damage. The 34-mer suppressed PDGF-induced cell proliferation and expression of myofibroblastic marker proteins in primary rat HSC culture, increased the levels of PPARγ mRNA and protein in a dose-dependent manner and markedly reduced the level of active ß-catenin protein, an HSC activating factor, in HSC-T6 cells. Similarly, IWR-1, an inhibitor of the Wnt response, displayed the same effect as the 34-mer in preventing HSC-T6 activation. The Wnt signaling-mediated PPARγ suppression was abolished by both the IWR-1 inhibitor and a small interfering RNA (siRNA) targeting ß-catenin and the Wnt coreceptor, LRP6. Both PEDF and the 34-mer down-regulated PDGF receptor-α/ß expression and blocked the PDGF-induced phosphorylation of Akt and ERK. Moreover, the inhibitory effect on PDGF receptor expression was abolished by PPARγ antagonists and PPARγ siRNA. Our observations indicate that the PEDF-derived 34-mer peptide can mimic PEDF in attenuating HSC activation. Investigation of this 34-mer peptide led to the identification of a signaling mechanism involving PPARγ induction, suppression of Wnt/ß-catenin signaling and down-regulation of the PDGF receptor-α/ß.

Temozolomide-related acute lymphoblastic leukemia with translocation (4;11)(q21;q23) in a glioblastoma patient.

Temozolomide (TMZ), an alkylating agent, is widely used for treating high-grade gliomas. TMZ has been reported to cause secondary myelodysplastic syndrome and acute myeloid leukemia. However, TMZ-related acute lymphoblastic leukemia is rare. Here we describe a 54-year-old woman with glioblastoma multiforme, who developed precursor-B acute lymphoblastic leukemia with translocation (4;11)(q21;q23) after 15 months of TMZ treatment.