Fon Yih Tsuang

Calcitonin Inhibits SDCP-Induced Osteoclast Apoptosis and Increases Its Efficacy in a Rat Model of Osteoporosis

Introduction Treatment for osteoporosis commonly includes the use of bisphosphonates. Serious side effects of these drugs are caused by the inhibition of bone resorption as a result of osteoclast apoptosis. Treatment using calcitonin along with bisphosphonates overcomes these side-effects in some patients. Calcitonin is known to inhibit bone resorption without reducing the number of osteoclasts and is thought to prolong osteoclast survival through the inhibition of apoptosis. Further understanding of how calcitonin inhibits apoptosis could prove useful to the development of alternative treatment regimens for osteoporosis. This study aimed to analyze the mechanism by which calcitonin influences osteoclast apoptosis induced by a bisphosphate analog, sintered dicalcium pyrophosphate (SDCP), and to determine the effects of co-treatment with calcitonin and SDCP on apoptotic signaling in osteoclasts. Methods Isolated osteoclasts were treated with CT, SDCP or both for 48 h. Osteoclast apoptosis assays, pit formation assays, and tartrate-resistant acid phosphatase (TRAP) staining were performed. Using an osteoporosis rat model, ovariectomized (OVX) rats received calcitonin, SDCP, or calcitonin + SDCP. The microarchitecture of the fifth lumbar trabecular bone was investigated, and histomorphometric and biochemical analyses were performed. Results Calcitonin inhibited SDCP-induced apoptosis in primary osteoclast cultures, increased Bcl-2 and Erk activity, and decreased Mcl-1 activity. Calcitonin prevented decreased osteoclast survival but not resorption induced by SDCP. Histomorphometric analysis of the tibia revealed increased bone formation, and microcomputed tomography of the fifth lumbar vertebrate showed an additive effect of calcitonin and SDCP on bone volume. Finally, analysis of the serum bone markers CTX-I and P1NP suggests that the increased bone volume induced by co-treatment with calcitonin and SDCP may be due to decreased bone resorption and increased bone formation. Conclusions Calcitonin reduces SDCP-induced osteoclast apoptosis and increases its efficacy in an in vivo model of osteoporosis.

Risk profile of patients with poor-grade aneurysmal subarachnoid hemorrhage using early perfusion computed tomography.

OBJECTIVE To determine whether perfusion computed tomography (CT) is useful for identifying patients with poor-grade subarachnoid hemorrhage (SAH) with reversible etiologies and whether early obliteration in patients with poor-grade aneurysmal SAH leads to favorable outcomes. METHODS Patients with new-onset aneurysmal SAH in World Federation of Neurological Surgeons (WFNS) grade IV or V neurologic condition who had perfusion CT performed at admission were eligible for the study. The study retrospectively enrolled 38 patients seen between January 2007 and July 2009. The decision to perform an early obliteration was made by the family after a discussion with the neurosurgeons, neurointensivists, and interventional radiologists. The functional outcomes were correlated with the Glasgow Outcome Scale (GOS) at 6 months, and quantitative perfusion CT data were collected. RESULTS This study included 10 (26%) grade IV and 28 (74%) grade V patients. Favorable outcomes occurred in 19 (50%) patients, and 11 (29%) patients died. After a multivariate logistic regression analysis of the parameters, older age (odds ratio 1.104, P = 0.0317), bilateral prolonged mean transient time (MTT) at the thalami (odds ratio 4.155, P = 0.0362), and early obliteration (odds ratio 0.098, P = 0.003) were predictive of poor outcome. CONCLUSIONS Early bilateral prolonged MTT at the thalami and old age are associated with a poor outcome. Early obliteration benefits a significant portion of SAH patients.

Early parenchymal contrast extravasation predicts subsequent hemorrhage progression, Clinical deterioration, and need for surgery in patients with traumatic cerebral contusion

BACKGROUND This study aimed to identify early radiologic signs that are predictive of hemorrhage progression and clinical deterioration in patients with traumatic cerebral contusion. We hypothesized that contrast extravasation (CE) and blood-brain barrier disruption might be associated with hemorrhage progression, brain edema, and clinical deterioration in these patients. METHODS Twenty-two patients with traumatic cerebral contusion (diagnosed on initial noncontrast head computed tomography [CT]) who initially did not require surgical intervention were enrolled in this study. Contrast-enhanced and perfusion CT scans were performed within 6 hours of injury, and follow-up noncontrast CT scans were performed at 24 hours and 72 hours. RESULTS In each noncontrast CT scan, the volumes of the contusion hemorrhage and edema were calculated using computerized planimetric techniques. The initial Glasgow Coma Scale, hemorrhage progression, clinical deterioration, and the need for subsequent surgery were recorded. The early radiologic findings were compared with these parameters and functional outcome at 6 months to identify predictive radiologic signs. CE was present in 9 of 22 patients (41%) and was highly associated with hemorrhage progression (p < 0.05), clinical deterioration (p < 0.01), and need for subsequent surgery (p < 0.01). In addition, patients with CE had a greater volume of edema at 24 hours (p < 0.01) and 72 hours (p < 0.01) than those who did not have CE. However, CE was not found to be associated with poor outcome. CONCLUSIONS Early parenchymal CE is associated with hemorrhage progression, cerebral edema, clinical deterioration, and need for subsequent surgery. These patients should be monitored closely, and early surgery may be needed if deterioration occurs. Further elucidation of the pathophysiology is needed to formulate effective treatment for these high-risk patients.

Hyperacute cerebral aneurysm rerupture during CT angiography

OBJECT The object of this study was to identify the clinical features and outcomes of a subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) who had active contrast extravasation from a ruptured aneurysm during initial cerebral CT angiography (CTA). METHODS The authors performed a retrospective study of spontaneous SAH cases involving patients treated at their institute. They identified 9 cases in which active contrast extravasation was evident on the initial CT angiogram. Another 12 similar cases were also identified in a literature review and data was gathered from these cases to evaluate the outcomes. RESULTS Analysis of all 21 cases revealed that the overall outcomes in cases characterized by active aneurysmal bleeding during CTA were poor. Seventy-six percent of patients had unfavorable results. Patients who showed poor neurological status at presentation died no matter what kind of treatment they received. In contrast, patients who presented with good neurological status initially had a chance of favorable outcome. Among the patients with good initial neurological status, most demonstrated rapid deterioration of their condition during the CTA examination; only those who received immediate and effective decompressive surgery and aneurysm obliteration had good results. CONCLUSIONS Active aneurysmal rebleeding during CTA is an uncommon but devastating event. Though the mortality of this distinct group of patients remains high, a clinical subgroup may benefit from immediate surgery. Patients with good initial neurological status who show rapid neurological deterioration may still have a favorable outcome if they undergo timely and successful decompressive surgery and proper aneurysm obliteration. Patients who present with poor neurological status do badly, and there is no effective treatment for such patients.

The protective effects of coumestrol against amyloid-beta peptide- and lipopolysaccharide-induced toxicity on mice astrocytes

Abstract Objectives: Estrogen replacement therapy can decrease the risk of developing Alzheimer’s disease. Phytoestrogens have been proposed as potential alternatives to estrogen replacement therapy. The purpose of this study was to evaluate the in vitro protective effects of coumestrol on mice astrocytes. Methods: Different concentrations of coumestrol were tested for their protective efficacy against two toxic insults, lipopolysaccharide (LPS) and amyloid-beta peptide, on astrocytes. The mitochondrial activity of astrocytes was determined, and the protective efficacy and pathway were examined by their specific gene expression and protein change. Results: The results showed that coumestrol induced a modest but significant increase in viability of astrocytes, while the viability of astrocytes was reduced following exposure to LPS and amyloid-beta peptide. The addition of coumestrol could reverse the toxic effect induced by LPS and amyloid-beta peptide. Both the LPS and amyloid-beta peptide enhanced interleukin 1, interleukin 6, and tumor necrosis factor-alpha synthesis and these effects were inhibited by 10−9M coumestrol. This effect was more obvious on the LPS-induced inflammation. The estrogen receptor expression was upregulated by coumestrol, while the effect was more obvious on estrogen receptor-beta (ER-beta). These effects can be inhibited by extracellular signal-regulated kinase and c-Jun N-terminal kinase inhibitors but not p38 inhibitor. Discussion: The current data support a possible role for astrocytes in the mediation of neuroprotection by coumestrol. An indirect extracellular signal-regulated kinase/c-Jun N-terminal kinase signaling pathway to downregulate the expression of interleukin 1, interleukin 6, and the tumor necrosis factor-alpha cytotoxic effect may act in concert with the proposed direct ER-beta biosynethsis pathway to achieve a widespread, global protection of ER-beta positive neurons.

Occipitocervical malformation with atlas duplication

A 55-year-old man presented to our institution with tetraparesis after a ground-level fall. The presence of hyper-reflexia in four limbs led to suspicion of cervical myelopathy. Initial cervical spine plain x-ray films showed spinal canal stenosis at C1/C2, os odontoideum and two atlas-like vertebrae. Duplication of the atlas in humans …

Removal of fixation construct could mitigate adjacent segment stress after lumbosacral fusion: A finite element analysis

Background data: Combined usage of posterior lumbar interbody fusion and transpedicular fixation has been extensively used to treat the various lumbar degenerative disc diseases. The transpedicular fixator aims to increase stability and enhance the fusion rate. However, how the fused disc and bridged vertebrae respectively affect adjacent‐segment diseases progression is not yet clear. Methods: Using a validated lumbosacral finite‐element model, three variations at the L4–L5 segment were analyzed: 1) moderate disc degeneration, 2) instrumented with a stand‐alone cage and pedicle screw fixators, and 3) with the cage only after fusion. The intersegmental angles, disc stresses, and facet loads were examined. Four motion tests, flexion, extension, bending, and twisting, were also simulated. Findings: The adjacent‐segment disease was more severe at the cephalic segment than the caudal segment. After solid fusion and fixation, the increase in intersegmental angles, disc stresses and facet loads of the adjacent segments were about 57.6%, 47.3%, and 59.6%, respectively. However, these changes were reduced to 30.1%, 22.7%, and 27.0% after removal of the fixators. This was attributed to the differences between the biomechanical characteristics of the fusion and fixation mechanisms. Interpretation: Fixation superimposes a stiffer constraint on the mobility of the bridged segment than fusion. The current study suggested that the removal of spinal fixators after complete fusion could decrease the stress at adjacent segments. Through a minimally invasive procedure, we could reduce secondary damage to the paraspinal structures while removing the fixators, which is of utmost concern to surgeons. HighlightsThe rigidity‐raising effect in instrumented segment induces adjacent segmental degeneration.The intersegmental angles, disc stress, and facet loads are higher in caudal segments.The compensations at adjacent segments could be decreased after removal of spinal fixators.Remove spinal fixators after fusion might mitigate the progression of adjacent segment disease.

Percutaneous pedicle screw placement under single dimensional fluoroscopy with a designed pedicle finder—a technical note and case series

BACKGROUND CONTEXT Minimally invasive spine surgery has become increasingly popular in clinical practice, and it offers patients the potential benefits of reduced blood loss, wound pain, and infection risk, and it also diminishes the loss of working time and length of hospital stay. However, surgeons require more intraoperative fluoroscopy and ionizing radiation exposure during minimally invasive spine surgery for localization, especially for guidance in instrumentation placement. In addition, computer navigation is not accessible in some facility-limited institutions. PURPOSE This study aimed to demonstrate a method for percutaneous screws placement using only the anterior-posterior (AP) trajectory of intraoperative fluoroscopy. STUDY DESIGN A technical report (a retrospective and prospective case series) was carried out. PATIENT SAMPLE Patients who received posterior fixation with percutaneous pedicle screws for thoracolumbar degenerative disease or trauma comprised the patient sample. METHOD We retrospectively reviewed the charts of consecutive 670 patients who received 4,072 pedicle screws between December 2010 and August 2015. Another case series study was conducted prospectively in three additional hospitals, and 88 consecutive patients with 413 pedicle screws were enrolled from February 2014 to July 2016. The fluoroscopy shot number and radiation dose were recorded. In the prospective study, 78 patients with 371 screws received computed tomography at 3 months postoperatively to evaluate the fusion condition and screw positions. RESULTS In the retrospective series, the placement of a percutaneous screw required 5.1 shots (2-14, standard deviation [SD]=2.366) of AP fluoroscopy. One screw was revised because of a medialwall breach of the pedicle. In the prospective series, 5.8 shots (2-16, SD=2.669) were required forone percutaneous pedicle screw placement. There were two screws with a Grade 1 breach (8.6%), both at the lateral wall of the pedicle, out of 23 screws placed at the thoracic spine at T9-T12. Forthe lumbar and sacral areas, there were 15 Grade 1 breaches (4.3%), 1 Grade 2 breach (0.3%), and 1 Grade 3 breach (0.3%). No revision surgery was necessary. CONCLUSION This method avoids lateral shots of fluoroscopy during screw placement and thus decreases the operation time and exposes surgeons to less radiation. At the same time, compared with the computer-navigated procedure, it is less facility-demanding, and provides satisfactory reliability and accuracy.

Pretreatment serum lactate level as a prognostic biomarker in patients undergoing supratentorial primary brain tumor resection

Introduction Malignant primary brain tumors are one of the most aggressive cancers. Pretreatment serum nonneuronal biomarkers closely associated with postoperative outcomes are of high clinical relevance. The present study aimed to identify potential pretreatment serum biomarkers that may influence oncological outcomes in patients with primary brain tumors. Methods A total of 74 patients undergoing supratentorial primary brain tumor resection were enrolled. Before tumor resection, serum neuronal biomarkers, namely neuron-specific enolase (NSE), S100β, and glial fibrillary acidic protein (GFAP), and serum nonneuronal biomarkers, namely neutrophil gelatinase-associated lipocalin (NGAL), lactate dehydrogenase (LDH), and lactate, were measured and associated postoperative oncological outcomes, including brain tumor grading, progression-free survival (PFS), and overall survival (OS), were compared. Results Patients with high-grade brain tumors had significantly higher pretreatment serum lactate levels (p = 0.011). By contrast, other biomarkers were comparable between patients with high-grade and low-grade brain tumors. Receiver operating characteristic curve analysis of serum lactate levels yielded an area under the curve of 0.71 for differentiating between high-grade and low-grade brain tumors. Kaplan–Meier survival analysis revealed patients with high serum lactate levels (≧2.0 mmol/L) had shorter PFS and OS (p = 0.021 and p = 0.093, respectively). In a multiple regression model, only elevated serum lactate levels were associated with poor PFS and OS (p = 0.021 and p = 0.048, respectively). Conclusions An elevated pretreatment serum lactate level is a prognostic biomarker of high-grade primary brain tumors and is significantly associated with poor PFS in patients with supratentorial brain tumors undergoing tumor resection. By contrast, other serum biomarkers are not significantly associated with oncological outcomes.

Assessment of the suitability of biodegradable rods for use in posterior lumbar fusion: An in-vitro biomechanical evaluation and finite element analysis

Interbody fusion with posterior instrumentation is a common method for treating lumbar degenerative disc diseases. However, the high rigidity of the fusion construct may produce abnormal stresses at the adjacent segment and lead to adjacent segment degeneration (ASD). As such, biodegradable implants are becoming more popular for use in orthopaedic surgery. These implants offer sufficient stability for fusion but at a reduced stiffness. Tailored to degrade over a specific timeframe, biodegradable implants could potentially mitigate the drawbacks of conventional stiff constructs and reduce the loading on adjacent segments. Six finite element models were developed in this study to simulate a spine with and without fixators. The spinal fixators used both titanium rods and biodegradable rods. The models were subjected to axial loading and pure moments. The range of motion (ROM), disc stresses, and contact forces of facet joints at adjacent segments were recorded. A 3-point bending test was performed on the biodegradable rods and a dynamic bending test was performed on the spinal fixators according to ASTM F1717-11a. The finite element simulation showed that lumbar spinal fusion using biodegradable implants had a similar ROM at the fusion level as at adjacent levels. As the rods degraded over time, this produced a decrease in the contact force at adjacent facet joints, less stress in the adjacent disc and greater loading on the anterior bone graft region. The mechanical tests showed the initial average fatigue strength of the biodegradable rods was 145 N, but this decreased to 115N and 55N after 6 months and 12 months of soaking in solution. Also, both the spinal fixator with biodegradable rods and with titanium rods was strong enough to withstand 5,000,000 dynamic compression cycles under a 145 N axial load. The results of this study demonstrated that biodegradable rods may present more favourable clinical outcomes for lumbar fusion. These polymer rods could not only provide sufficient initial stability, but the loss in rigidity of the fixation construct over time gradually transfers loading to adjacent segments.