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Failure of lumbopelvic fixation after long construct fusions in patients with adult spinal deformity: clinical and radiographic risk factors: clinical article.
No full textObjectLumbopelvic fixation provides biomechanical support to the base of the long constructs used for adult spinal deformity. However, the failure rate of the lumbopelvic fixation and its risk factors are not well known. The authors' objective was to report the failure rate and risk factors for lumbopelvic fixation in long instrumented spinal fusion constructs performed for adult spinal deformity.MethodsThis retrospective review included 190 patients with adult spinal deformity who had long construct instrumentation (> 6 levels) with iliac screws. Patients' clinical and radiographic data were analyzed. The patients were divided into 2 groups: a failure group and a nonfailure group. A minimum 2-year follow-up was required for inclusion in the nonfailure group. In the failure group, all patients were included in the study regardless of whether the failure occurred before or after 2 years. In both groups, the patients who needed a revision for causes other than lumbopelvic fixation (for example, proximal junctional kyphosis) were also excluded. Failures were defined as major and minor. Major failures included rod breakage between L-4 and S-1, failure of S-1 screws (breakage, halo formation, or pullout), and prominent iliac screws requiring removal. Minor failures included rod breakage between S-1 and iliac screws and failure of iliac screws. Minor failures did not require revision surgery. Multiple clinical and radiographic values were compared between major failures and nonfailures.ResultsOf 190 patients, 67 patients met inclusion criteria and were enrolled in the study. The overall failure rate was 34.3%; 8 patients had major failure (11.9%) and 15 had minor failure (22.4%). Major failure occurred at a statistically significant greater rate in patients who had undergone previous lumbar surgery, had greater pelvic incidence, and had poor restoration of lumbar lordosis and/or sagittal balance (that is, undercorrection). Patients with a greater number of comorbidities and preoperative coronal imbalance showed trends toward an increase in major failures, although these trends did not reach statistical significance. Age, sex, body mass index, smoking history, number of fusion segments, fusion grade, and several other radiographic values were not shown to be associated with an increased risk of major failure. Seventy percent of patients in the major failure group had anterior column support (anterior lumbar interbody fusion or transforaminal lumbar interbody fusion) while 80% of the nonfailure group had anterior column support.ConclusionsThe incidence of overall failure was 34.3%, and the incidence of clinically significant major failure of lumbopelvic fixation after long construct fusion for adult spinal deformity was 11.9%. Risk factors for major failures are a large pelvic incidence, revision surgery, and failure to restore lumbar lordosis and sagittal balance. Surgeons treating adult spinal deformity who use lumbopelvic fixation should pay special attention to restoring optimal sagittal alignment to prevent lumbopelvic fixation failure
Evaluation of the impact of a novel denoising algorithm on image quality in dual-energy abdominal CT of obese patients.
No full textObjectivesEvaluate a novel algorithm for noise reduction in obese patients using dual-source dual-energy (DE) CT imaging.MethodsSeventy-nine patients with contrast-enhanced abdominal imaging (54 women; age: 58 ± 14 years; BMI: 39 ± 5 kg/m2, range: 35-62 kg/m2) from seven DECT (SOMATOM Flash or Force) were retrospectively included (01/2019-12/2020). Image domain data were reconstructed with the standard clinical algorithm (ADMIRE/SAFIRE 2), and denoised with a comparison (ME-NLM) and a test algorithm (rank-sparse kernel regression). Contrast-to-noise ratio (CNR) was calculated. Four blinded readers evaluated the same original and denoised images (0 (worst)-100 (best)) in randomized order for perceived image noise, quality, and their comfort making a diagnosis from a table of 80 options. Comparisons between algorithms were performed using paired t-tests and mixed-effects linear modeling.ResultsAverage CNR was 5.0 ± 1.9 (original), 31.1 ± 10.3 (comparison; p ConclusionsThe test algorithm produces quantitatively higher image quality than current standard and existing denoising algorithms in obese patients imaged with DECT and readers show a preference for it.Clinical relevance statementAccurate diagnosis on CT imaging of obese patients is challenging and denoising algorithms can increase the diagnostic comfort and quantitative image quality. This could lead to better clinical reads.Key points• Improving image quality in DECT imaging of obese patients is important for accurate and confident clinical reads, which may be aided by novel denoising algorithms using image domain data. • Accurate diagnosis on CT imaging of obese patients is especially challenging and denoising algorithms can increase quantitative and qualitative image quality. • Image domain algorithms can generalize well and can be implemented at other institutions
Integrating Large-Scale Planning into Environmental Markets and Related Programs: Status and Trends
No full textBuilding on earlier efforts, guidance from the federal government on mitigation for environmental impacts recommends the use of large-scale plans, preferably carried out in advance of impacts, to steer both development and mitigation. The idea is that advanced planning can improve site selection for proposed projects and increase the return on investment for mitigation while helping to provide greater predictability for project proponents, increase the efficiencies of project review, reduce permitting times, and support better environmental results. This paper explores progress in integrating large-scale, spatially explicit planning into environmental markets and programs in the United States. Through interviews with experts and review of the gray literature and government documents, it identifies examples of large-scale planning in these programs. It describes how the planning is guiding decisions about impact avoidance and compensatory mitigation, whether the planning is required or optional, and if the planning incorporates co-benefits or other regulatory-driven priorities. The assessed programs cover wetlands and streams, at-risk species, water quality, stormwater, greenhouse gases, and natural resource damages. They range from somewhat centrally planned programs in which spatially explicit planning is more common to distributed, market-based approaches in which such planning is less common. Large-scale planning appears to face few barriers to development and use, but its uptake may be limited by other factors like cost and time, uncertainty in the required spatial models, or insufficient proof of value. There has been little study of such planning’s investment return, environmental outcomes, or permitting time
Loss of ephrin B2 receptor (EPHB2) sets lipid rheostat by regulating proteins DGAT1 and ATGL inducing lipid droplet storage in prostate cancer cells.
No full textLipid droplet (LD) accumulation in cancer results from aberrant metabolic reprograming due to increased lipid uptake, diminished lipolysis and/or de novo lipid synthesis. Initially implicated in storage and lipid trafficking in adipocytes, LDs are more recently recognized to fuel key functions associated with carcinogenesis and progression of several cancers, including prostate cancer (PCa). However, the mechanisms controlling LD accumulation in cancer are largely unknown. EPHB2, a tyrosine kinase (TKR) ephrin receptor has been proposed to have tumor suppressor functions in PCa, although the mechanisms responsible for these effects are unclear. Given that dysregulation in TRK signaling can result in glutaminolysis we postulated that EPHB2 might have potential effects on lipid metabolism. Knockdown strategies for EPHB2 were performed in prostate cancer cells to analyze the impact on the net lipid balance, proliferation, triacylglycerol-regulating proteins, effect on LD biogenesis, and intracellular localization of LDs. We found that EPHB2 protein expression in a panel of human-derived prostate cancer cell lines was inversely associated with in vivo cell aggressiveness. EPHB2 silencing increased the proliferation of prostate cancer cells and concurrently induced de novo LD accumulation in both cytoplasmic and nuclear compartments as well as a "shift" on LD size distribution in newly formed lipid-rich organelles. Lipid challenge using oleic acid exacerbated the effects on the LD phenotype. Loss of EPHB2 directly regulated key proteins involved in maintaining lipid homeostasis including, increasing lipogenic DGAT1, DGAT2 and PLIN2 and decreasing lipolytic ATGL and PEDF. A DGAT1-specific inhibitor abrogated LD accumulation and proliferative effects induced by EPHB2 loss. In conclusion, we highlight a new anti-tumor function of EPHB2 in lipid metabolism through regulation of DGAT1 and ATGL in prostate cancer. Blockade of DGAT1 in EPHB2-deficient tumors appears to be effective in restoring the lipid balance and reducing tumor growth
Sustained Virologic Response in People Who Inject Drugs and/or Who Are on Opioid Agonist Therapy: Is 90% Enough?
No full textKnowledge and Conversion in the Making of Western History, a Philosophical Investigation
No full textIn academia in general, and in the humanistic social sciences in particular, there is a problem. The "cruel optimism" of concepts is a problem faced by every specialization, and every discipline (Berlant 2011). In the social sciences, and history especially, cruel optimism takes the form of an endless quest to prove that our concepts today are superior to the concepts of yesterday, that if we work hard enough and get our methods just right, we will finally find pure, objective, true concepts to express historical reality. I use this dissertation in order to reconfigure our relationship with our concepts, to try to grapple with and ultimately subdue the cruel optimism of concepts. I employ discourse analysis, a method of analyzing knowledge as the imprint of dynamic relations of force and friction between institutions and human beings. Rather than seeing our social scientific concepts as the result of methodical research applied to a critical mass of archival documents, I see them as the result of power relations that are used to control reality as much as they purport to describe it. My materials are documentary sources—published social science scholarship and declassified intelligence reports using social scientific analysis. My conclusion is that we can use our concepts in a way that releases us from the dread of cruel optimism, so long as we see them as "snapshots of processes" (Levins 2006) rather than things in themselves. </p
Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.
No full textBackground & aimsNonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSCs) and liver fibrogenesis in mice. However, it is unclear how changes in HSC glutamine metabolism contribute to net changes in hepatic glutaminolytic activity during fibrosis progression, or whether this could be used to track fibrogenic activity in NASH. We postulated that increased HSC glutaminolysis marks active scarring in NASH.MethodsGlutaminolysis was assessed in mouse NASH fibrosis models and in NASH patients. Serum and liver levels of glutamine and glutamate and hepatic expression of glutamine transporter/metabolic enzymes were correlated with each other and with fibrosis severity. Glutaminolysis was disrupted in HSCs to examine if this directly influenced fibrogenesis. 18F-fluoroglutamine positron emission tomography was used to determine how liver glutamine assimilation tracked with hepatic fibrogenic activity in situ.ResultsThe serum glutamate/glutamine ratio increased and correlated with its hepatic ratio, myofibroblast content, and fibrosis severity. Healthy livers almost exclusively expressed liver-type glutaminase (Gls2); Gls2 protein localized in zone 1 hepatocytes, whereas glutamine synthase was restricted to zone 3 hepatocytes. In fibrotic livers, Gls2 levels reduced and glutamine synthase zonality was lost, but both Slc1a5 (glutamine transporter) and kidney-type Gls1 were up-regulated; Gls1 protein was restricted to stromal cells and accumulated in fibrotic septa. Hepatocytes did not compensate for decreased Gls2 by inducing Gls1. Limiting glutamine or directly inhibiting GLS1 inhibited growth and fibrogenic activity in cultured human HSCs. Compared with healthy livers, fibrotic livers were 18F-fluoroglutamine-avid by positron emission tomography, suggesting that glutamine-addicted myofibroblasts drive increased hepatic utilization of glutamine as fibrosis progresses.ConclusionsGlutaminolysis is a potential diagnostic marker and therapeutic target during NASH fibrosis progression
Development of a Modified Cervical Deformity Frailty Index: A Streamlined Clinical Tool for Preoperative Risk Stratification.
No full textStudy designRetrospective review.ObjectiveDevelop a simplified frailty index for cervical deformity (CD) patients.Summary of background dataTo improve preoperative risk stratification for surgical CD patients, a CD frailty index (CD-FI) incorporating 40 health deficits was developed. While novel, the CD-FI is clinically impractical due to the large number of factors needed for its calculation. To increase clinical utility, a simpler, modified CD-FI (mCD-FI) is necessary.MethodsCD patients (C2-C7 Cobb>10°, CL>10°, cSVA>4 cm, or CBVA>25°) >18 year with preoperative CD-FI component factors. Pearson bivariate correlation assessed relationships between component deficits of the CD-FI and overall CD-FI score. Top deficits contributing to CD-FI score were included in multiple stepwise regression models. Deficits from model with largest R were dichotomized, and the mean score of all deficits calculated, resulting in mCD-FI score from 0 to 1. Patients were stratified by mCD-FI: Not Frail (NF, 0.5). Means comparison tests established correlations between frailty category and clinical outcomes.ResultsIncluded: 121 CD patients (61 ± 11 yr, 60%F). Multiple stepwise regression models identified 15 deficits as responsible for 86% of the variation in CD-FI; these factors were used to construct the mCD-FI. Overall, mean mCD-FI was 0.31 ± 0.14. Breakdown of patients by mCD-FI category: NF: 47.9%, Frail: 46.3%, SF: 5.8%. Compared with NF and Frail, SF patients had the longest inpatient hospital stays (P = 0.042), as well as greater baseline neck pain (P = 0.033), inferior Neck Disability Index scores (PConclusionIncreased frailty, assessed by mCD-FI, correlated with increased length of stay, neck pain, and decreased health-related quality of life. Frail patients were at greater risk for infection, and severely frail patients had greater odds of mortality. This relationship between frailty and clinical outcomes suggests that mCD-FI offers clinical utility as a preoperative risk stratification tool.Level of evidence3
