Opportunities and challenges of using augmented reality and heads-up display in orthopaedic surgery: A narrative review.

BACKGROUND & AIM: Utilization of augmented reality (AR) and heads-up displays (HUD) to aid orthopaedic surgery has the potential to benefit surgeons and patients alike through improved accuracy, safety, and educational benefits. With the COVID-19 pandemic, the opportunity for adoption of novel technology is more relevant. The aims are to assess the technology available, to understand the current evidence regarding the benefit and to consider challenges to implementation in clinical practice. METHODS & RESULTS: PRISMA guidelines were used to filter the literature. Of 1004 articles returned the following exclusion criteria were applied: 1) reviews/commentaries 2) unrelated to orthopaedic surgery 3) use of other AR wearables beyond visual aids leaving 42 papers for review.This review illustrates benefits including enhanced accuracy and reduced time of surgery, reduced radiation exposure and educational benefits. CONCLUSION: Whilst there are obstacles to overcome, there are already reports of technology being used. As with all novel technologies, a greater understanding of the learning curve is crucial, in addition to shielding our patients from this learning curve. Improvements in usability and implementing surgeons' specific needs should increase uptake.

Developing a Spinal CSF Leak Program in a Multihospital Network.

OBJECTIVE: Spontaneous spinal cerebrospinal fluid (CSF) leaks are rare and challenging to diagnose and treat. Patients may present to a variety of physicians, and many patients are often referred to a specialized center with a dedicated spinal CSF leak program and expertise in this condition. To our knowledge, there are no reported publications on how to create such a program. CONCLUSION: In this article, we describe the specific steps we took to develop a spinal CSF leak program, which we have implemented over a multihospital network.

Potential mechanisms for lumbar spinal stiffness change following spinal manipulative therapy: a scoping review.

INTRODUCTION: In individuals having low back pain, the application of spinal manipulative therapy (SMT) has been shown to reduce spinal stiffness in those who report improvements in post-SMT disability. The underlying mechanism for this rapid change in stiffness is not understood presently. As clinicians and patients may benefit from a better understanding of this mechanism in terms of optimizing care delivery, the objective of this scoping review of current literature was to identify if potential mechanisms that explain this clinical response have been previously described or could be elucidated from existing data. METHODS: Three literature databases were systematically searched (MEDLINE, CINAHL, and PubMed). Our search terms included subject headings and keywords relevant to SMT, spinal stiffness, lumbar spine, and mechanism. Inclusion criteria for candidate studies were publication in English, quantification of lumbar spinal stiffness before and after SMT, and publication between January 2000 and June 2019. RESULTS: The search identified 1931 articles. Of these studies, 10 were included following the application of the inclusion criteria. From these articles, 7 themes were identified with respect to potential mechanisms described or derived from data: 1) change in muscle activity; 2) increase in mobility; 3) decrease in pain; 4) increase in pressure pain threshold; 5) change in spinal tissue behavior; 6) change in the central nervous system or reflex pathways; and 7) correction of a vertebral dysfunction. CONCLUSIONS: This scoping review identified 7 themes put forward by authors to explain changes in spinal stiffness following SMT. Unfortunately, none of the studies provided data which would support the promotion of one theme over another. As a result, this review suggests a need to develop a theoretical framework to explain rapid biomechanical changes following SMT to guide and prioritize future investigations in this important clinical area.

NTG-101: A Novel Molecular Therapy that Halts the Progression of Degenerative Disc Disease.

The tremendous cost, pain and disability associated with degenerative disc disease (DDD) makes the development of a biological agent that can mitigate the course of DDD, a critical unmet need. We have identified and reported that a single injection of a combination of recombinant human (rh) Transforming growth factor beta 1 (TGF-ß1) and Connective tissue growth factor (CTGF) proteins into the injured intervertebral disc (IVD) nucleus pulposus (NP) can mediate DDD in a pre-clinical rodent model. In this study, we developed and evaluated the efficacy of a novel molecular therapy (NTG-101) containing rhTGF-ß1 and rhCTGF proteins suspended in an excipient solution using in vivo models of DDD including rat-tail and chondrodystrophic (CD) canines. Needle puncture injury in CD-canine NPs resulted in loss of hydration, disc height and showed radiographic evidence of DDD like humans. However, NTG-101-injected IVDs maintained disc height and demonstrated retention of viscoelastic properties as compared to IVDs injected with phosphate buffer saline (PBS, 1X, pH = 7.2). In addition, a single intra-discal injection of NTG-101 into the injured IVD-NPs resulted in sustained expression of healthy extra-cellular matrix (ECM) proteins (aggrecan, collagen 2A1) and reduced expression of inflammation associated proteins and molecules (IL-1ß, IL-6, IL-8, MMP-13, Cox-2 and PGE2) as compared to vehicle controls. In conclusion, we demonstrated that a single intra-discal injection of the novel formulation, NTG-101 confers a robust anti-inflammatory, anti-catabolic and pro-anabolic effects in pre-clinical models of DDD thereby restoring homeostasis. These findings suggest the therapeutic potential of NTG-101 for clinical use.

Use of optical motion capture for the analysis of normative upper body kinematics during functional upper limb tasks: A systematic review.

Quantifying three-dimensional upper body kinematics can be a valuable method for assessing upper limb function. Considering that kinematic model characteristics, performed tasks, and reported outcomes are not consistently standardized and exhibit significant variability across studies, the purpose of this review was to evaluate the literature investigating upper body kinematics in non-disabled individuals via optical motion capture. Specific objectives were to report on the kinematic model characteristics, performed functional tasks, and kinematic outcomes, and to assess whether kinematic protocols were assessed for validity and reliability. Five databases were searched. Studies using anatomical and/or cluster marker sets, along with optical motion capture, and presenting normative data on upper body kinematics were eligible for review. Information extracted included model characteristics, performed functional tasks, kinematic outcomes, and validity or reliability testing. 804 publication records were screened and 20 reviewed based on the selection criteria. Thirteen studies described their kinematic protocols adequately for reproducibility, and 8 studies followed International Society of Biomechanics standards for quantifying upper body kinematics. Six studies assessed their protocols for validity or reliability. While a substantial number of studies have adequately reported their protocols, more systematic work is needed to evaluate the validity and reliability of existing protocols.

Four-dimensional computed tomography scan utility in parathyroidectomy for primary hyperparathyroidism with low baseline intact parathyroid hormone.

OBJECTIVES/HYPOTHESIS: The prevalence of multiglandular disease (MGD) of the parathyroid has been reported to be higher in patients with primary hyperparathyroidism and low baseline intact parathyroid hormone (PTH) levels (<100 pg/mL). Low baseline PTH is associated with lower localization rate and positive predictive value with both preoperative sestamibi and ultrasound. This study sought to evaluate our experience with four-dimensional computed tomography (4D-CT) for the localization of abnormal parathyroid glands, including MGD, in patients with low baseline intact PTH (LBiPTH). STUDY DESIGN: A single institution case series. METHODS: A case series of patients with primary hyperparathyroidism with low baseline PTH or an inconclusive sestamibi, who underwent surgery with a single surgeon from April 2012 to June 2015 following 4D-CT to help with abnormal gland localization. RESULTS: We identified 14 patients who underwent a 4D-CT in the setting of primary hyperparathyroidism and LBiPTH. A sestamibi scan had been ordered in 71% and was inconclusive in all cases. No ultrasound was performed. In all patients, 4D-CT was 84.6% sensitive in localizing abnormal glands, yielding a positive predictive value of 91.7%. Overall, 42.9% of patients had evidence of MGD, and 4D-CT detected 83.3% of MGD cases. A focused unilateral exploration was performed in 28.6% of cases, and a four-gland exploration was performed in all remaining patients. CONCLUSIONS: In patients with hypercalcemia and LBiPTH, with higher likelihood of MGD and of inconclusive results on sestamibi, 4D-CT may be a superior modality for localizing smaller adenoma or multiple hypercellular glands. This may allow for improved interpretation of intraoperative PTH results, and in a minority of cases, a focused parathyroid exploration. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1476-1482, 2017.

False-negative Interpretations of Cranial Computed Tomography in Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Prior studies examining the sensitivity of cranial computed tomography (CT) for the detection of subarachnoid hemorrhage (SAH) have used the final radiology report as the reference standard. However, optimal sensitivity may have been underestimated due to misinterpretation of reportedly normal cranial CTs. This study aims to estimate the incidence of missed CT evidence of SAH among a cohort of patients with aneurysmal SAH (aSAH). METHODS: We performed a retrospective chart review of emergency department (ED) encounters within an integrated health delivery system between January 2007 and June 2013 to identify patients diagnosed with aSAH. All initial noncontrast CTs from aSAH cases diagnosed by lumbar puncture (LP) and angiography following a reportedly normal noncontrast cranial CT (CT-negative aSAH) were then reviewed in a blinded, independent fashion by two board-certified neuroradiologists to assess for missed evidence of SAH. Reviewers rated the CT studies as having definite evidence of SAH, probable evidence of SAH, or no evidence of SAH. Control patients who underwent a negative evaluation for aSAH based on cranial CT and LP results were also included at random in the imaging review cohort. RESULTS: A total of 452 cases of aSAH were identified; 18 (4%) were cases of CT-negative aSAH. Of these, seven (39%) underwent cranial CT within 6 hours of headache onset, and two (11%) had their initial CTs formally interpreted by board-certified neuroradiologists. Blinded independent CT review revealed concordant agreement for either definite or probable evidence of SAH in nine of 18 (50%) cases overall and in five of the seven (71%) CTs performed within 6 hours of headache onset. Inter-rater agreement was 83% for definite SAH and 72% for either probable or definite SAH. CONCLUSIONS: CT evidence of SAH was frequently present but unrecognized according to the final radiology report in cases of presumed CT-negative aSAH. This finding may help explain some of the discordance between prior studies examining the sensitivity of cranial CT for SAH.

Invasive facial fungal infections: Orofacial soft-tissue infiltration in immunocompromised patients.

Invasive facial fungal infections affect the orofacial soft tissues in immunocompromised patients and can cause significant morbidity and mortality. Primary infection occurs from direct inoculation of the skin surface, while secondary infection occurs from extension from an adjacent sinonasal process. The imaging features of secondary infection are similar to acute fulminant invasive fungal sinusitis with infiltration of the orofacial soft tissues in combination with sinonasal disease. However, primary infection can occur in the absence of sinonasal disease, making diagnosis challenging. We present two cases, one of primary and one of secondary invasive facial fungal infection. Careful scrutiny of the orofacial soft tissues in immunocompromised patients is necessary to detect invasive facial fungal infections so that appropriate surgical and medical therapies can maximize patient outcomes.

Utility of MRI in spinal arteriovenous fistula.

OBJECTIVE AND BACKGROUND: Spinal arteriovenous fistula (SAVF) is a rare but treatable cause of myelopathy. The diagnostic accuracy of MRI for detecting SAVF is unknown. Our objective was to determine the sensitivity and specificity of MRI in the diagnosis SAVF and characterize its radiographic features. METHODS: We conducted a retrospective case-control study of all SAVF treated at our institution from 1995 to 2010, including patients who presented with myelopathy, had MRIs available for review, and underwent either spinal angiogram or had another diagnosis confirming test. Two blinded board-certified radiologists reviewed a series of MRIs and listed the most likely diagnoses, radiologic findings, and recommended follow-up. Sensitivities and specificities of MRI compared to spinal angiogram were calculated. We additionally conducted a literature review of cases describing MRI findings in spinal dural and perimedullary arteriovenous fistula. RESULTS: We identified 36 cases of SAVF (median age 56, 67% male) and 32 controls (median age 54, 44% male). MRI was sensitive in identifying SAVF as the primary diagnosis in 94% (radiologist A, 95% confidence interval [CI] 0.87-1.02) and 89% (radiologist B, 95% CI 0.79-0.99) of cases. The sensitivity of spinal cord T2 hyperintensity or flow voids was 100% and the specificity of T2 hyperintensity and flow voids was 97%. CONCLUSIONS: Among patients with myelopathy, spinal angiography is mandatory in the presence of both T2 hyperintensity and flow voids but may be unnecessary if both of these findings are absent.

Epigenetic silencing of the kinase tumor suppressor WNK2 is tumor-type and tumor-grade specific.

Both genetic and epigenetic mechanisms contribute to meningioma development by altering gene expression and protein function. To determine the relative contribution of each mechanism to meningioma development, we used an integrative approach measuring copy number and DNA methylation changes genomewide. We found that genetic alterations affected 1.9%, 7.4%, and 13.3% of the 691 loci studied, whereas epigenetic mechanisms affected 5.4%, 9.9%, and 10.3% of these loci in grade I, II, and III meningiomas, respectively. Genetic and epigenetic mechanisms rarely involved the same locus in any given tumor. The predilection for epigenetic rather than genetic silencing was exemplified at the 5' CpG island of WNK2, a serine-threonine kinase gene on chromosome 9q22.31. WNK2 is known to negatively regulate epidermal growth factor receptor signaling via inhibition of MEK1 (mitogen-activated protein kinase kinase 1), and point mutations have been reported in WNK1, WNK2, WNK3, and WNK4. In meningiomas, WNK2 was aberrantly methylated in 83% and 71% of grade II and III meningiomas, respectively, but rarely in a total of 209 tumors from 13 other tumor types. Aberrant methylation of the CpG island was associated with decreased expression in primary tumors. WNK2 could be reactivated with a methylation inhibitor in IOMM-Lee, a meningioma cell line with a densely methylated WNK2 CpG island and lack of WNK2 expression. Expression of exogenous WNK2 inhibited colony formation, implicating it as a potential cell growth suppressor. These findings indicate that epigenetic mechanisms are common across meningiomas of all grades and that for specific genes such as WNK2, epigenetic alteration may be the dominant, grade-specific mechanism of gene inactivation.

Molecular signatures define two main classes of meningiomas.

BACKGROUND: Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant) and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis. RESULTS: We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH) to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs) compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups. CONCLUSION: Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.

Epigenome scans and cancer genome sequencing converge on WNK2, a kinase-independent suppressor of cell growth.

Human cancer genome and epigenome projects aim to identify new cancer genes and targets for therapy that have been overlooked by conventional approaches. Here we integrated large-scale genomics and epigenomics of 31 human infiltrative gliomas and identified low-frequency deletion and highly recurrent epigenetic silencing of WNK2, encoding a putative serine/threonine kinase. Prior cancer genome sequencing projects also identified point mutations in WNK1-4, suggesting that WNK family genes may have a role in cancers. We observed consistent gene silencing in tumors with dense aberrant methylation across 1.3 kb of the CpG island but more variable expression when the 5'-most region remained unmethylated. This primary tumor data fit well with WNK2 promoter analysis, which showed strong promoter activity in the 5'-most region, equivalent to the simian virus 40 promoter, but no activity in the 3' region. WT WNK2 exhibited autophosphorylation and protein kinase activity that was enhanced in cells exposed to hypertonic conditions, similar to WNK1. WNK2 inhibited up to 78% of colony formation by glioma cells but in an unexpectedly kinase-independent manner. The WNK2 silencing by epigenetic mechanisms was significantly associated (P < 0.01) with a known genetic signature of chemosensitive oligodendroglial tumors, 1p and 19q deletion, in two small but independent tumor sets. Taken together, the epigenetic silencing, occasional deletion and point mutation, and functional assessment suggest that aberrations of WNK2 may contribute to unregulated tumor cell growth. Thus, our integrated genetic and epigenetic approach might be useful to identify genes that are widely relevant to cancer, even when genetic alterations of the locus are infrequent.

The supratonsillar approach to the inferior cerebellar peduncle: anatomy, surgical technique, and clinical application to cavernous malformations.

OBJECTIVE: To introduce the supratonsillar approach, an approach that traverses the tonsillobiventral fissure in a trajectory over the cerebellar tonsil to the inferior cerebellar peduncle, and to demonstrate the utility of this approach for resecting peduncular cavernous malformations. METHODS: Anatomy of the cerebellar tonsil and surrounding fissures, arteries, and veins are reviewed using cadaveric brain specimens. The surgical approach uses the three-quarter prone position, a suboccipital craniotomy, and wide splitting of the tonsillobiventral fissure. RESULTS: Of our experience with 171 patients with cavernous malformations, six patients had lesions in the inferior cerebellar peduncle that were resected using the supratonsillar approach. All cavernous malformations were removed completely and no patients experienced surgical complications or new deficits. CONCLUSION: The supratonsillar approach differs from the transvermian and telovelar approaches to the fourth ventricle, with a more superolateral trajectory that leads instead to the inferior cerebellar peduncle. By splitting the tonsillobiventral fissure and mobilizing the tonsil inferomedially, the point of access to the lesion is deepened and transgression of normal cerebellar tissue is minimized. This elegant approach is ideally suited to the removal of cavernous malformations.

Accuracy over space and time of computer-assisted fluoroscopic navigation in the lumbar spine in vivo.

OBJECTIVE: The integration of digital image-guided surgical navigation with C-arm fluoroscopy, known as virtual fluoroscopy (VF), has been shown to enhance the safety of spine surgery in vitro. Few clinical studies have assessed the accuracy of VF during actual spinal surgery, and no studies have investigated variations in accuracy over the course of a series of measurements obtained during operative cases. We sought to study the intraoperative accuracy of VF over time and space during lumbar pedicle screw placement in human patients. METHODS: Fluoroscopic images of the lumbar spine were obtained, calibrated, and saved to the Stealth Station (FluoroNav) on seven patients undergoing lumbar fusion surgery. The tracking arc was attached to an exposed lumbar spinous process, which was designated the index level. With use of anatomic surface irregularities in the laminae and spinous processes, several points were identified and registered on three different vertebrae directly adjacent to the index level vertebra. Every 15 minutes, throughout the operative case, the probe was brought to each point and the apparent distance from the original location recorded (as measured by the FluoroNav system). Measurements were collected from three vertebral levels adjacent to the index level over a time course of 120 minutes during the operation. RESULTS: At the index, index +1, index +2, and index +3 levels, 89%, 81%, 92%, and 64% of measurements were within <2 mm, whereas 97%, 96%, 97%, and 91% were within <3 mm, respectively. At 15, 30, 45, 60, 75, 90, 105, and 120 minutes, 96%, 89%, 85%, 61%, 85%, 90%, 93%, and 50% of measurements were within <2 mm, whereas 100%, 93%, 100%, 83%, 100%, 90%, 100%, and 100% of measurements were within <3 mm, respectively. The error in millimeters tended to increase as the distance from the index level increased (R = 0.19, P < 0.05) and as operative time increased (R = 0.26, P < 0.01). Calibration studies of intraoperative VF (IoVF) in the lumbar spine documented a reasonable degree of accuracy. The majority of sequential measurements obtained during IoVF in the lumbar spine were within an error range of <3 mm. CONCLUSIONS: Our results suggest that the use of VF is a reliable method of verifying the use of anatomic and/or radiographic landmarks for guidance during lumbar pedicle screw placement.

Airbag deployment and improperly restrained children: a lethal combination.

BACKGROUND: Airbag deployment is an acknowledged mechanism of serious trauma in children involved in motor vehicle crashes. From a review of national databases, we determined the number and types of fatal and nonfatal injuries to children caused by airbag deployment and child restraint system use. We also reviewed the relevant literature and provide information useful for caregivers and health care professionals in hopes of reducing future injuries. METHODS: We retrospectively reviewed 263 reported cases in which airbag deployment caused fatal or nonfatal injuries in children from reports released by the National Highway and Transportation Safety Administration and the National Pediatric Trauma Registry. Data were collected from January 1993 to December 2002 and imported into a database program for analysis. RESULTS: Of the 263 pediatric injuries caused by airbag deployment, 159 were fatal, and 104 were nonfatal. The peak incidence occurred in 1998, when 58 children were reported injured. Head injuries were most frequent, involving 170 children (64.6%), followed by spinal injuries, involving 100 children (38.0%). For children in their first year of life, head injuries were the sole mechanism of fatality. Of all children studied, only six (2.3%) were properly restrained. CONCLUSION: Airbag deployment in motor vehicle crashes is a well-recognized mechanism of morbidity and mortality in the pediatric population. Most injuries include trauma to the head and spine, which can have significant long-term consequences. Although the reported incidence of such injuries is decreasing, many children are improperly restrained. In our study, only 2.3% of children were properly restrained, suggesting that proper child restraint and seating position could have prevented most injuries.

Meningioma transcript profiles reveal deregulated Notch signaling pathway.

Meningiomas constitute the second most common central nervous system tumor, and yet relatively little is known about the molecular events that are important for the pathogenesis and malignant progression of these tumors. We have used serial analysis of gene expression to compare the transcriptomes of nonneoplastic meninges and meningiomas of all malignancy grades. A novel finding from this screen is the induction of three components of the Notch signaling pathway: the transcription factor, hairy and enhancer of Split1 (HES1) and two members of the Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3. TLE corepressors interact and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. We have shown that the transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the Jagged1 ligand are induced in meningiomas of all grades, whereas induction of TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell lines express components of the Notch signaling pathway and an inhibitor of this pathway suppresses meningioma cell survival. These results suggest that deregulated expression of the Notch pathway is a critical event in meningioma pathogenesis and that modulation of this and potentially other signaling pathways by TLE corepressors leads to a more malignant phenotype.

Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3.

CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.

Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of the growth suppressor SLC5A8.

Tumors arise in part from the deleterious effects of genetic and epigenetic mechanisms on gene expression. In several mouse models of human tumors, the tumorigenic phenotype is reversible, suggesting that epigenetic mechanisms also contribute significantly to tumorigenesis in mice. It is not known whether these are the same epigenetic mechanisms in human and mouse tumors or whether they affect homologous genes. Using an integrated approach for genome-wide methylation and copy number analyses, we identified SLC5A8 on chromosome 12q23.1 that was affected frequently by aberrant methylation in human astrocytomas and oligodendrogliomas. SLC5A8 encodes a sodium monocarboxylate cotransporter that was highly expressed in normal brain but was significant down-regulated in primary gliomas. Bisulfite sequencing analysis showed that the CpG island was unmethylated in normal brain but frequently localized methylated in brain tumors, consistent with the tumor-specific loss of gene expression. In glioma cell lines, SLC5A8 expression was also suppressed but could be reactivated with a methylation inhibitor. Expression of exogenous SLC5A8 in LN229 and LN443 glioma cells inhibited colony formation, suggesting that it may function as a growth suppressor in normal brain cells. Remarkably, 9 of 10 murine oligodendroglial tumors (from p53+/- or ink4a/arf+/- animals transgenic for S100beta-v-erbB) showed a similar tumor-specific down-regulation of mSLC5A8, the highly conserved mouse homologue. Taken together, these data suggest that SLC5A8 functions as a growth suppressor gene in vitro and that it is silenced frequently by epigenetic mechanisms in primary gliomas. The shared epigenetic inactivation of mSLC5A8 in mouse gliomas indicates an additional degree of commonality in the origin and/or pathway to tumorigenesis between primary human tumors and these mouse models of gliomas.

The sonographic features of papillary thyroid carcinomas: pictorial essay.

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy in children and adults, with an incidence of 22,000 cases per year in the United States. Differentiating PTC from more frequently occurring benign thyroid nodules has proved challenging as there may be significant overlap in their clinical presentation and sonographic appearance. That said, high-resolution ultrasound provides a safe and affordable way of identifying and characterizing thyroid nodules and guiding percutaneous biopsies. Although no single sonographic feature is pathognomonic for PTC, certain features should raise suspicion and the combination of several features may be even more suggestive. In this pictorial essay, we describe the high-resolution sonographic features of pathologically proven PTCs. The nodule number, echo texture, internal architecture, calcifications, margins, contours, vascularity, and lymph nodes are considered. While the classic sonographic description of PTC is a solitary, hypoechoic solid nodule with microcalcifications and intrinsic vascularity, in practice, PTC may manifest with a myriad of sonographic appearances making biopsy necessary for a definitive diagnosis.

General principles in the medical and surgical management of spinal infections: a multidisciplinary approach.

OBJECT: Infections along the spinal axis are characterized by an insidious onset, and the resulting delays in diagnosis are associated with serious neurological consequences and even death. Infections of the spine can affect the vertebral bodies, intervertebral discs, spinal canal, and surrounding soft tissues. Neurological dysfunction occurs when the spinal cord becomes compressed, edematous, or ischemic due to compression by abscess or vascular compromise. The aim of this paper was to detail general diagnostic and management principles for this disease. METHODS: Recent progress in medical technologies, including the development of potent antimicrobial drugs, advanced imaging, and improved surgical methods, have dramatically reduced morbidity and mortality rates for spinal infections; however, debate still exists on the proper management of this disease. In this paper, the authors review the current management protocols for spinal infections at their institution, focusing on medical and surgical treatments for vertebral osteomyelitis, intervertebral disc space infections, and spinal canal and soft-tissue abscesses. CONCLUSIONS: Technological advances in imaging modalities, pharmaceutics, and surgery have resulted in excellent outcomes and have greatly reduced the morbidity and mortality rates associated with spinal infections. Currently, treatment of spinal infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons. The key to successful management of spinal infections is early detection.