Single-center outcomes for percutaneous pedicle screw fixation in metastatic spinal lesions: can spontaneous facet fusion occur?

OBJECTIVE: Survival of cancer patients continues to improve with systemic treatment advancements, leading to an increase in cancer-related complications such as pathological spinal fractures. In this study, the authors aimed to evaluate the outcome of percutaneous stabilization with cement augmentation of the pedicle screws in the management of patients with metastatic cancer to the spine. METHODS: The authors reviewed a retrospective case series of 74 patients with symptomatic pathological spine fractures treated with cement-augmented pedicle screws implanted with a percutaneous technique. The mean imaging follow-up was 11.3 months. Data on demographics, clinical outcomes, and complications were collected. Cement extravasation, spinal hardware integrity, and fusion rates were assessed on CT scans. RESULTS: Among 50 patients with follow-up imaging, 23 patients (46%) showed facet joint fusion. The length of segmental stabilization was not a significant predictor of the occurrence of fusion. Pre- or postoperative radiation therapy, postoperative chemotherapy, and the location of spinal lesions did not have a statistically significant effect on the occurrence of fusion. Patients older than 60 years of age were more likely to have fusion across facet joints compared with younger patients. There was a significant difference in the mean visual analog scale pain score, with 6.28 preoperatively and 3.41 postoperatively, regardless of fusion status (p < 0.001). Cement extravasation was seen in 51% of the cohort, but in all instances, patients remained asymptomatic. Most importantly, the incidence of hardware failure was low (4%). CONCLUSIONS: Percutaneous fixation with cement-augmented pedicle screws in patients with pathological spine fractures provides an improvement in mechanical back pain, with a low incidence of failure, and in some patients, spontaneous facet fusion was observed. Further research is necessary with regard to both short-term benefits and long-term outcomes.

Failures of the Oxygen Supply.

Oxygen supply failures are potentially life-threatening and are often associated with death or brain damage. Knowledge of how oxygen is supplied is essential for understanding how failures are caused and their management. Even though safety mechanisms exist to reduce the likelihood of a supply failure, events still occur. Simulation studies have identified knowledge and performance gaps in management of supply failures. A straightforward approach to immediate management of these critical events is provided.

Surgical Airway in a Tactical Environment: A Case Report.

Surgical airway management should be regarded as one of many tools available to forward clinical Operators. The need for that intervention should be determined in a quick and decisive manner consistent with accepted protocols for combat care. The case presented discusses immediate surgical access to the airway required after the initial assessment of the patient and illustrates the clinical urgency of patients requiring surgical intervention in the field setting.

Carfentanil: A New and Often Unrecognized Threat.

Law enforcement officers, whether working the streets or on narcotic detail, and even those who operate in strike teams, face a new danger from an old drug: carfentanil. Drug dealers seeking to increase profits cut this cheap synthetic drug into expensive heroin, providing an extreme high. As a potent synthetic opioid narcotic, it is finding its way to the streets of the United States and can pose a threat to life for law enforcement, first responders, and medical examiners.

Association Between Perioperative Hyperglycemia and Survival in Patients With Glioblastoma.

BACKGROUND: Several studies have examined the association between hyperglycemia in the first 10 to 12 weeks following surgery and postoperative survival in glioblastoma multiforme (GBM) patients. We hypothesize that episodes of hyperglycemia before, during and/or following surgery for primary GBM are independent predictors of disease progression and mortality. MATERIALS AND METHODS: A total of 162 adult patients were included in the analysis. All patients received adjuvant temozolamide. The progression free survival (PFS) and overall survival (OS) rates at 1 and 5 years were analyzed using different glycemic cutoff values. Multivariate analyses were conducted to test the association between preoperative, intraoperative and postoperative hyperglycemia with PFS and OS. RESULTS: Kaplan-Meier curves revealed a trend toward increased PFS and OS with lower glucose concentrations with the exception of glucose concentrations >180 mg/dL in the intraoperative/postoperative day 0 time period. Univariate analysis of blood glucose levels did not demonstrate a statistically significant effect on PFS in any time period, however hyperglycemia was statistically significant for OS in the preoperative time period. Although, multivariate analysis showed no statistically significant association with hyperglycemia on PFS, a statistically significant decrease in OS was seen for plasma glucose concentrations >112 mg/dL (P=0.01) and >180 mg/dL (P=0.01) in the preoperative period. There was a decreasing effect on OS with blood glucose concentrations greater than the median in multiple time periods (P=0.02). CONCLUSIONS: Preoperative hyperglycemia is associated with poor OS after GBM surgery.

Utilization of laser interstitial thermotherapy guided by real-time thermal MRI as an alternative to separation surgery in the management of spinal metastasis.

OBJECT: High-grade malignant spinal cord compression is commonly managed with a combination of surgery aimed at removing the epidural tumor, followed by spinal stereotactic radiosurgery (SSRS) aimed at local tumor control. The authors here introduce the use of spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery prior to SSRS. METHODS: Patients with a high degree of epidural malignant compression due to radioresistant tumors were selected for study. Visual analog scale (VAS) scores for pain and quality of life were obtained before and within 30 and 60 days after treatment. A laser probe was percutaneously placed in the epidural space. Real-time thermal MRI was used to monitor tissue damage in the region of interest. All patients received postoperative SSRS. The maximum thickness of the epidural tumor was measured, and the degree of epidural spinal cord compression (ESCC) was scored in pre- and postprocedure MRI. RESULTS: In the 11 patients eligible for study, the mean VAS score for pain decreased from 6.18 in the preoperative period to 4.27 within 30 days and 2.8 within 60 days after the procedure. A similar VAS interrogating the percentage of quality of life demonstrated improvement from 60% preoperatively to 70% within both 30 and 60 days after treatment. Imaging follow-up 2 months after the procedure demonstrated a significant reduction in the mean thickness of the epidural tumor from 8.82 mm (95% CI 7.38-10.25) before treatment to 6.36 mm (95% CI 4.65-8.07) after SLITT and SSRS (p = 0.0001). The median preoperative ESCC Grade 2 was scored as 4, which was significantly higher than the score of 2 for Grade 1b (p = 0.04) on imaging follow-up 2 months after the procedure. CONCLUTIONS: The authors present the first report on an innovative minimally invasive alternative to surgery in the management of spinal metastasis. In their early experience, SLITT has provided local control with low morbidity and improvement in both pain and the quality of life of patients.

Transmembrane domain of surface-exposed outer membrane lipoprotein RcsF is threaded through the lumen of ß-barrel proteins.

RcsF (regulator of capsule synthesis) is an outer membrane (OM) lipoprotein that functions to sense defects such as changes in LPS. However, LPS is found in the outer leaflet, and RcsF was thought to be tethered to the inner leaflet by its lipidated N terminus, raising the question of how it monitors LPS. We show that RcsF has a transmembrane topology with the lipidated N terminus on the cell surface and the C-terminal signaling domain in the periplasm. Strikingly, the short, unstructured, charged transmembrane domain is threaded through the lumen of ß-barrel OM proteins where it is protected from the hydrophobic membrane interior. We present evidence that these unusual complexes, which contain one protein inside another, are formed by the Bam complex that assembles all ß-barrel proteins in the OM. The ability of the Bam complex to expose lipoproteins at the cell surface underscores the mechanistic versatility of the ß-barrel assembly machine.

Awake craniotomy for gliomas in a high-field intraoperative magnetic resonance imaging suite: analysis of 42 cases.

OBJECTIVES: The object of this study was to describe the experience of combining awake craniotomy techniques with high-field (1.5 T) intraoperative MRI (iMRI) for tumors adjacent to eloquent cortex. METHODS: From a prospective database the authors obtained and evaluated the records of all patients who had undergone awake craniotomy procedures with cortical and subcortical mapping in the iMRI suite. The integration of these two modalities was assessed with respect to safety, operative times, workflow, extent of resection (EOR), and neurological outcome. RESULTS: Between February 2010 and December 2011, 42 awake craniotomy procedures using iMRI were performed in 41 patients for the removal of intraaxial tumors. There were 31 left-sided and 11 right-sided tumors. In half of the cases (21 [50%] of 42), the patient was kept awake for both motor and speech mapping. The mean duration of surgery overall was 7.3 hours (range 4.0-13.9 hours). The median EOR overall was 90%, and gross-total resection (EOR ≥ 95%) was achieved in 17 cases (40.5%). After viewing the first MR images after initial resection, further resection was performed in 17 cases (40.5%); the mean EOR in these cases increased from 56% to 67% after further resection. No deficits were observed preoperatively in 33 cases (78.5%), and worsening neurological deficits were noted immediately after surgery in 11 cases (26.2%). At 1 month after surgery, however, worsened neurological function was observed in only 1 case (2.3%). CONCLUSIONS: There was a learning curve with regard to patient positioning and setup times, although it did not adversely affect patient outcomes. Awake craniotomy can be safely performed in a high-field (1.5 T) iMRI suite to maximize tumor resection in eloquent brain areas with an acceptable morbidity profile at 1 month.

The entomopathogenic bacterial endosymbionts Xenorhabdus and Photorhabdus: convergent lifestyles from divergent genomes.

Members of the genus Xenorhabdus are entomopathogenic bacteria that associate with nematodes. The nematode-bacteria pair infects and kills insects, with both partners contributing to insect pathogenesis and the bacteria providing nutrition to the nematode from available insect-derived nutrients. The nematode provides the bacteria with protection from predators, access to nutrients, and a mechanism of dispersal. Members of the bacterial genus Photorhabdus also associate with nematodes to kill insects, and both genera of bacteria provide similar services to their different nematode hosts through unique physiological and metabolic mechanisms. We posited that these differences would be reflected in their respective genomes. To test this, we sequenced to completion the genomes of Xenorhabdus nematophila ATCC 19061 and Xenorhabdus bovienii SS-2004. As expected, both Xenorhabdus genomes encode many anti-insecticidal compounds, commensurate with their entomopathogenic lifestyle. Despite the similarities in lifestyle between Xenorhabdus and Photorhabdus bacteria, a comparative analysis of the Xenorhabdus, Photorhabdus luminescens, and P. asymbiotica genomes suggests genomic divergence. These findings indicate that evolutionary changes shaped by symbiotic interactions can follow different routes to achieve similar end points.

The free and bound forms of Lpp occupy distinct subcellular locations in Escherichia coli.

The lipoprotein Lpp is the most numerically abundant protein in Escherichia coli, has been investigated for over 40 years, and has served as the paradigmatic bacterial lipoprotein since its initial discovery. It exists in two distinct forms: a 'bound-form', which is covalently bound to the cell's peptidoglycan layer, and a 'free-form', which is not. Although it is known that the carboxyl-terminus of bound-form Lpp is located in the periplasm, the precise location of free-form Lpp has never been determined. For decades, it has been widely assumed that free-form Lpp is associated with bound-form. In this work, we show that the free and bound forms of Lpp are not largely associated with each other, but are found in distinct subcellular locations. Our results indicate that free-form Lpp spans the outer membrane and is surface-exposed, whereas bound-form Lpp resides in the periplasm. Thus, Lpp represents a novel example of a single lipoprotein that is able to occupy distinct subcellular locations, and challenges models in which the free and bound forms of Lpp are assumed to be associated with each other.

The Xenorhabdus nematophila nilABC genes confer the ability of Xenorhabdus spp. to colonize Steinernema carpocapsae nematodes.

Members of the Steinernema genus of nematodes are colonized mutualistically by members of the Xenorhabdus genus of bacteria. In nature, Steinernema carpocapsae nematodes are always found in association with Xenorhabdus nematophila bacteria. Thus, this interaction, like many microbe-host associations, appears to be species specific. X. nematophila requires the nilA, nilB, and nilC genes to colonize S. carpocapsae. In this work, we showed that of all the Xenorhabdus species examined, only X. nematophila has the nilA, nilB, and nilC genes. By exposing S. carpocapsae to other Xenorhabdus spp., we established that only X. nematophila is able to colonize S. carpocapsae; therefore, the S. carpocapsae-X. nematophila interaction is species specific. Further, we showed that introduction of the nilA, nilB, and nilC genes into other Xenorhabdus species enables them to colonize the same S. carpocapsae host tissue that is normally colonized by X. nematophila. Finally, sequence analysis supported the idea that the nil genes were horizontally acquired. Our findings indicate that a single genetic locus determines host specificity in this bacteria-animal mutualism and that host range expansion can occur through the acquisition of a small genetic element.

The global regulator Lrp contributes to mutualism, pathogenesis and phenotypic variation in the bacterium Xenorhabdus nematophila.

Xenorhabdus nematophila is a Gram-negative bacterium that leads both pathogenic and mutualistic lifestyles. In this study, we examine the role of Lrp, the leucine-responsive regulatory protein, in regulating both of these lifestyles. lrp mutants have attenuated virulence towards Manduca sexta insects and are defective in suppression of both cellular and humoral insect immunity. In addition, an lrp mutant is deficient in initiating colonization of and growth within mutualistic host nematodes. Furthermore, nematodes reared on lrp mutant lawns exhibit decreased overall numbers of nematode progeny. To our knowledge, this is the first demonstration of virulence attenuation associated with an lrp mutation in any bacterium, as well as the first report of a factor involved in both X. nematophila symbioses. Protein profiles of wild-type and mutant cells indicate that Lrp is a global regulator of expression in X. nematophila, affecting approximately 65% of 290 proteins. We show that Lrp binds to the promoter regions of genes known to be involved in basic metabolism, mutualism and pathogenesis, demonstrating that the regulation of at least some host interaction factors is likely direct. Finally, we demonstrate that Lrp influences aspects of X. nematophila phenotypic variation, a spontaneous process that occurs during prolonged growth in stationary phase.

Clonal variation in Xenorhabdus nematophila virulence and suppression of Manduca sexta immunity.

Virulence of the insect pathogen Xenorhabdus nematophila is attributed in part to its ability to suppress immunity. For example, X. nematophila suppresses transcripts encoding several antimicrobial proteins, even in the presence of Salmonella enterica, an inducer of these transcripts. We show here that virulence and immune suppression phenotypes can be lost in a subpopulation of X. nematophila. Cells that have undergone 'virulence modulation' (vmo) have attenuated virulence and fail to suppress antimicrobial transcript levels, haemocyte aggregation and nodulation in Manduca sexta insects. When plated on certain media, vmo cells have a higher proportion of translucent (versus opaque) colonies compared with non-vmo cells. Like vmo strains, translucent colony isolates are defective in virulence and immune suppression. The X. nematophila genome encodes two 'opacity' genes with similarity to the Ail/PagC/Rck family of outer membrane proteins involved in adherence, invasion and serum resistance. Quantitative polymerase chain reaction analysis shows that RNA levels of one of these opacity genes, opaB, are higher in opaque relative to translucent colonies. We propose that in X. nematophila opaB may be one of several factors involved in immune suppression during infection, and expression of these factors can be co-ordinately eliminated in a subpopulation, possibly through a phase variation mechanism.

nilR is necessary for co-ordinate repression of Xenorhabdus nematophila mutualism genes.

The bacterial mutualist Xenorhabdus nematophila colonizes a specific region of its nematode host Steinernema carpocapsae. We previously reported the identification of a chromosomal locus encoding three X. nematophila genes of unknown function, nilA, B and C, that are each necessary for colonization. Subsequent work indicated the global regulator Lrp is a repressor of nilC: nilC transcription is elevated in an lrp mutant and Lrp interacts directly with the nilC promoter. In this manuscript, we report the identification of an additional gene, nilR, required for repression of nilC transcription. We show that nilR and lrp mutants also have elevated expression of nilA and nilB, demonstrating that nilA, B and C are co-ordinately regulated. nil gene expression is derepressed most strongly when both nilR and lrp are lacking, suggesting NilR and Lrp synergistically repress nil transcription. NilR contains a helix-turn-helix-type DNA binding domain and likely acts directly at promoters. A comparison of the wild type and nilR proteomes indicates that NilR, unlike Lrp, regulates a small number of genes. Finally, X. nematophila carrying an ectopic copy of nilR colonizes at approximately 60-fold lower levels than the control strain, suggesting that derepression of nil gene expression is necessary for nematode colonization.

Characterization of a lipoprotein, NilC, required by Xenorhabdus nematophila for mutualism with its nematode host.

Xenorhabdus nematophila is a gamma-proteobacterial mutualist of an insect-pathogenic nematode, Steinernema carpocapsae. X. nematophila requires nilC, a gene predicted to encode an outer membrane lipoprotein of unknown function, for colonization of its nematode host. Characterization of NilC, described here, demonstrated it is a 28 kDa lipoprotein directed to the periplasm by an N-terminal signal sequence. Lipidation and processing of NilC occurs by a mechanism that is conserved in proteobacteria. This work also showed NilC is membrane associated and oriented towards the periplasm of X. nematophila and is produced as an outer membrane-associated protein when expressed in Escherichia coli. Expression analyses revealed that nilC transcription is directly or indirectly repressed by Lrp, and this regulatory link may explain the nematode mutualism defect of a previously identified lrp::Tn5 mutant. An lrp::Tn5 mutant produces an additional nilC transcript, not observed in wild-type cells growing in vitro, and produces approximately 75-fold more nilC than wild-type cells in late stationary phase. These fundamental characterizations of nilC expression and nilC localization and processing events have provided firm bases for understanding the role of this colonization factor in the X. nematophila/S. carpocapsae microbe-host interaction.

Identification of Xenorhabdus nematophila genes required for mutualistic colonization of Steinernema carpocapsae nematodes.

One stage in the symbiotic interaction between the bacterium Xenorhabdus nematophila and its nematode host, Steinernema carpocapsae, involves the species-specific colonization of the nematode intestinal vesicle by the bacterium. To characterize the bacterial molecular determinants that are essential for vesicle colonization, we adapted and applied a signature-tagged mutagenesis (STM) screen to this system. We identified 15 out of 3000 transposon mutants of X. nematophila with at least a 15-fold reduction in average vesicle colonization. These 15 mutants harbour disruptions in nine separate loci. Three of these loci have predicted open reading frames (ORFs) with similarity to genes (rpoS, rpoE, lrp) encoding regulatory proteins; two have predicted ORFs with similarity to genes (aroA, serC) encoding amino acid biosynthetic enzymes; one, designated nilB (nematode intestine localization), has an ORF with similarity to a gene encoding a putative outer membrane protein (OmpU) in Neisseria; and three, nilA, nilC and nilD, have no apparent homologues in the public database. nilA, nilB and nilC are linked on a single 4 kb locus. nilB and nilC are > 104-fold reduced in their ability to colonize the nematode vesicle and are predicted to encode membrane-localized proteins. The nilD locus contains an extensive repeat region and several small putative ORFs. Other than reduced colonization, the nilB, nilC and nilD mutants did not display alterations in any other phenotype tested, suggesting a specific role for these genes in allowing X. nematophila to associate with the nematode host.