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Pyrethroid insecticides are widely detected in aquatic ecosystems due to their extensive use in agriculture and horticulture, which could pose a potential risk to aquatic non-target organisms. While previous ecotoxicological studies have been conducted mainly with standard tests and local species under temperate conditions, scarce information is available on the effects of pyrethroid insecticides on communities and ecosystems under (sub-)tropical conditions. A single application of lambda-cyhalothrin at concentrations of 0, 9, 30, and 100 ng/L was evaluated in outdoor mesocosms under sub-tropical conditions. Lambda-cyhalothrin was found to dissipate rapidly in the water column, with only 11 % and 7 % of the remaining dose measured at 1 and 3 days after application, respectively. Lambda-cyhalothrin concentrations disappeared considerably faster from the water compartment compared to temperate conditions. Consistent decreases in abundance were observed for Lecane lunaris at the medium and higher treatments (NOEC = 9 ng/L) and at the highest treatment (NOEC = 30 ng/L) for Keratella tropica. On the contrary, two taxa belonging to Cladocera (i.e., Ceriodaphnia sp. and Diaphanosoma sp.) showed the most prominent increase in abundance related to the lambda-cyhalothrin treatments. At the community level, a consistent no observed effect concentrations (NOECs) of 9 ng/L could be calculated for the zooplankton community. A marginal significant overall treatment related effect was observed for the macroinvertebrate community. The results of species sensitivity distribution (SSD) analysis based on results of acute toxicity experiments conducted alongside the mesocosm experiment and obtained from the literature indicated that macroinvertebrates from temperate regions may be generally more sensitive than their counterparts in (sub-)tropical regions. Overall, these findings suggest that environmentally relevant concentrations of the pyrethroid insecticide lambda-cyhalothrin may lead to different ecological outcomes in freshwater ecosystems in the (sub-)tropics relative to temperate regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Psoriasis is a systemic immune-mediated chronic inflammatory skin disease; its systemic manifestations and periodic recurrence negatively affect a patient's quality of life. Inflammatory cytokines are known to have an important role in the onset and progression of psoriasis, however, data on the association between circulating inflammatory cytokines and psoriasis risk is inconclusive. Here, we explore the relevance of circulating proinflammatory factors to the pathogenesis of psoriasis using a meta-analysis., Objective: To explore the association between circulating levels of inflammatory factors and psoriasis to elucidate the mechanisms underlying psoriasis and improve clinical diagnosis and treatment., Methods: We systematically retrieved articles published in PubMed, EMBASE, the Cochrane Library and the Web of Science from the establishment of each database to January 2023. The standard mean difference (SMD) in cytokine levels of individuals with psoriasis and healthy controls was used to check for correlations between circulating inflammatory factor levels and psoriasis., Results: Fifty-seven studies, with data from 2838 patients, were retrieved and included in the meta-analysis. Eleven inflammatory factors were studied (circulating interleukin-2 (IL-2), IL-4, IL-12, IL-17, IL-18, IL-22, IL-23, IL-35, IL-36, transforming growth factor-beta (TGF-β) and gamma-interferon (IFN-γ)). Of these, IL-2 [SMD = 1.29 (95% CI: 0.61-1.97; P <0.001)], IL-17 [SMD = 0.71 (95% CI: 0.12-1.30; P = 0.018)], IL-18 [SMD = 1.27 (95% CI: 0.64-1.90; P <0.001)], and IFN-γ [SMD = 1.90 (95% CI: 1.27-2.52; P <0.001)] levels had significant correlations with psoriasis., Conclusion: Increased serum concentrations of the circulating inflammatory cytokines IL-2, IL-17, IL-18 and IFN-γ were significantly correlated with psoriasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Upper extremity (UE) microsurgical reconstruction relies upon proper wound healing for optimal outcomes. Cigarette smoking is associated with wound healing complications, yet conclusions vary regarding impact on microsurgical outcomes (replantation, revascularization, and free tissue transfer). We investigated how smoking impacted 30-day standardized postoperative outcomes following UE microsurgical reconstruction. Methods: Utilizing the National Surgical Quality Improvement Program, all patients who underwent (1) UE free flap transfer (n = 70) and (2) replantation/revascularization (n = 270) were identified. For each procedure, patients were stratified by recent smoking history (current smoker ≤1-year preoperatively). Baseline demographics and standardized 30-day complications, reoperations, and readmissions were compared between smokers and nonsmokers. Results: Replantation/revascularization patients had no differences in sex, race, or body mass index between smokers (n = 77) and nonsmokers. Smokers had a higher prevalence of congestive heart failure (5.2% vs 1.0%, P = .036) and nonsmokers were more often on hemodialysis (15.6% vs 10.4%, P = .030). Free flap transfer patients had no differences in age, sex, or race between smokers (n = 14) and nonsmokers. Smokers had a longer length of stay (6.6 vs 4.2 days, P = .001) and a greater prevalence of chronic obstructive pulmonary disorder (COPD; 7.1% vs 0%, P = .044). Recent smoking was not associated with increased odds of any 30-day minor and major standardized surgical complications, readmissions, or reoperations following UE microsurgical reconstruction via free flap transfer or replantation/revascularization. Baseline diagnosis of COPD was also not a predictor of adverse 30-day outcomes following free flap transfer. Conclusion: Recent smoking history was not associated with any 30-day adverse outcomes following UE microsurgical reconstruction via replantation/revascularization or free flap transfer. In light of these findings, further investigation is warranted, with particular focus on adverse events specific to free flaps and replantation/revascularization., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.M. Koehler discloses personal fees (consulting) from Integra LifeScience, unpaid consulting with TriMed, research support from Collagen Matrix, Inc., and board/committee membership with the American Association for Surgery of the Hand (ASSH). S.K. Mithani discloses personal fees (presenter or speaker) from Integra LifeScience., (© 2021 The Author(s).)

As a class of common emerging pollutants, per- and polyfluoroalkyl substances (PFASs) and their alternatives have been widely detected in various environmental matrices, exhibiting a great threat to the ecological environment and human health. Nevertheless, changes in biomolecular structure and function of duckweed caused by PFASs and their alternatives remain unknown thus far. Herein, the effects of four PFASs, including two common legacy PFASs (perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA)) and two PFASs alternatives (perfluorobutane sulfonic acid (PFBS) and 1H,1H,2H, 2H-perfluorooctane sulfonic acid (6:2 FTS)) on duckweed (Lemna minor) at biochemical level were investigated with Fourier transform infrared spectroscopy (FTIR). Although no obvious inhibitions were observed in the growth of L. minor with PFASs exposure at three levels of 1 μg L -1 , 100 μg L -1 , and 10 mg L -1 , significant structural and functional alterations were induced at the biochemical level. In response to PFASs exposure, lipid peroxidation, proteins aggregation and α-helix to β-sheet transformation of the protein conformation, as well as changes of DNA conformations were detected. Moreover, alterations in lipid, protein, and DNA were proved to be concentration-related and compound-specific. Compared to the two legacy PFASs (PFOS and PFOA), alternative ones exhibited greater effects on the biological macromolecules of L. minor. The findings of this study firstly reveal structural and functional alterations in L. minor induced by PFASs exposure, providing further understanding of their toxicity effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: There is limited research regarding the association between the mFI-5 and postoperative complications among adult spinal deformity (ASD) patients., Methods: Using the National Surgical Quality Improvement Project (NSQIP) database, patients with Current Procedural Terminology (CPT) codes for > 7-level fusion or < 7-level fusion with International Classification of Diseases, Ninth Revision (ICD-9) codes for ASD were identified between 2008 and 2016. Univariate analyses with post-hoc Bonferroni correction for demographics and preoperative factors were performed. Logistic regression assessed associations between mFI-5 scores and 30-day post-operative outcomes., Results: 2,120 patients met criteria. Patients with an mFI-5 score of 4 or 5 were excluded, given there were<20 patients with those scores. Patients with mFI-5 scores of 1 and 2 had increased 30-day rates of pneumonia (3.5 % and 4.3 % vs 1.6 %), unplanned postoperative ventilation for > 48 h (3.1 % and 4.3 % vs 0.9 %), and UTIs (4.4 % and 7.4 % vs 2.0 %) than patients with a score of 0 (all, p < 0.05). Logistic regression revealed that compared to an mFI-5 of 0, a score of 1 was an independent predictor of 30-day reoperations (OR = 1.4; 95 % CI 1.1-18). A score of 2 was an independent predictor of overall (OR = 2.4; 95 % CI 1.4-4.1) and related (OR = 2.2; 95 % CI 1.2-4.1) 30-day readmissions. A score of 3 was not predictive of any adverse outcome., Conclusion: The mFI-5 score predicted complications and postoperative events in the ASD population. The mFI-5 may effectively predict 30-day readmissions. Further research is needed to identify the benefits and predictive value of mFI-5 as a risk assessment tool., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The following authors have no conflicts of interest to report: NVS, DJK, NP, GAB, DAH, AJW, NK, DES, DM, PLZ, HME, CBP, BGD. PGP has received grant funding from CSRS, speaker and consultant honoraria from Globus Medical, Medicrea, SpineWave, and Zimmer, and other financial support from Allosource. FJS has received grant funding from DePuy, NuVasive, Allosource, K2M, Medtronic, and Si Bone, speaker and consultant honoraria from Globus Medical, Mainstay Medical, Medtronic, and ZimmerBiomet, royalties from Medicrea, Medtronic, and Zimmer, and serves on boards or committees for SRS, Spine Deformity, and ISSG. VL has received grant funding from DePuy, , NuVasive, Allosource, K2M, Medtronic, and Si-Bone, speaker and consultant honoraria from Globus Medical, DePuy, and Stryker, stock in VFT Solutions, and serves on boards or committees for ISSG and SRS. For the remaining authors none were declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: To develop and validate a nomogram for the prediction of stent dysfunction after transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatitis B cirrhosis., Materials and Methods: From 2012 to 2020, 355 patients with hepatitis B cirrhosis who underwent TIPS placements were enrolled in this study. A multivariable logistic regression analysis was applied to determine independent risk factors for the nomogram construction. Discrimination, calibration, and clinical usefulness of the prediction model were assessed by using receiver operating characteristic curves, calibration scatter plots, and a decision curve analysis (DCA)., Results: Independent factors for TIPS stent dysfunction included diabetes, previous splenectomy, the shunting branch of the portal vein, and stent position, which were used to construct the nomogram. The AUC values in the training and validation cohorts were 0.817 (95% CI: 0.731-0.903) and 0.804 (95% CI: 0.673-0.935), respectively, which suggested a good predictive ability. The calibration curves in both cohorts revealed good agreement between the predictions and actual observations. The DCA curve indicated that when the threshold probability ranged from 2% to 88%, the nomogram could provide clinical usefulness and a net benefit., Conclusion: The nomogram that we developed could be conveniently used to predict TIPS stent dysfunction in patients with hepatitis B cirrhosis., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Probing the orientation and oxygenation state of single molecules (SMs) is of great importance for understanding the advanced structure of individual molecules. Here, we manipulate molecules transporting through the hot spot of a sub-10 nm conical gold nanopore and acquire the multidimensional structural information of the SMs by surface enhanced Raman scattering (SERS) detection. The sub-10 nm size and conical shape of the plasmonic nanopore guarantee its high detection sensitivity. SERS spectra show a high correlation with the orientations of small-sized single rhodamine 6G (R6G) during transport. Meanwhile, SERS spectra of a single hemoglobin (Hb) reveal both the vertical/parallel orientations of the porphyrin ring and oxygenated/deoxygenated states of Hb. The present study provides a new strategy for bridging the primary sequence and the advanced structure of SMs.

Growing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa&#95;circ&#95;0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B-miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

Objective: Our study aimed to evaluate the safety and efficacy of sequential interventional therapy for Budd-Chiari syndrome (BCS) caused by obstruction of the inferior vena cava (IVC) with fresh thrombus in the IVC., Methods: Full medical records were obtained for 20 patients with BCS associated with fresh IVC thrombus who received sequential interventional therapy from 2014 to 2019 at our hospital. All patients underwent small-diameter percutaneous transluminal angioplasty (PTA) balloon catheter predilation combined with sequential catheter-directed thrombolysis and large-diameter PTA balloon dilation. Ultrasound examinations were performed at 1 week, 1 month, 3 months, and every 6 months thereafter. Therapeutic effects and perioperative and postoperative adverse effects were recorded to assess the safety of the treatment., Results: All 20 patients were treated with small PTA balloon catheters (diameter, 10-14 mm) to predilate the occlusive segment of the IVC. Urokinase 400,000 to 600,000 (465,000 ± 93,000) units was administered to patients through the catheter for 6 to 20 (9.7 ± 4.2) consecutive days postoperatively. Ultrasound re-examination showed that the IVC thrombus disappeared completely in 14 patients (70.0%), and a small amount of the old thrombus remained in 6 patients (30.0%). After thrombolysis, all 20 patients received PTA balloon dilation (diameter, 26-30 mm) in the stenosed IVC segment, and blood flow recovered subsequently. No pulmonary embolism or death occurred in the perioperative course. The perioperative survival rate was 100.0%., Conclusions: Sequential interventional therapy for BCS associated with fresh IVC thrombus is safe and effective., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

The development of rapid, simple, and sensitive diagnostic methods for identification of avian infectious bronchitis virus (IBV) is crucial for the effective control of avian infectious bronchitis. In the present study, a tandemly arranged multiepitope peptide (named SEMN) was designed with four antigenic regions derived from four major structural proteins of IBV. Then, we performed codon optimization of SEMN gene by changing the codon-adaptation index from 0.45 to 0.94 and expressed the optimized gene in codon bias-adjusted Escherichia coli Rosetta (DE3), followed by determination of the immunoreactivity of the purified protein. Bioinformatics analysis of SEMN showed a high antigenicity, surface probability and hydrophilicity. The recombinant protein rSEMN was expressed both in soluble forms and as inclusion bodies, and the molecular weight of rSEMN was about 39 kDa. The preliminary diagnostic performance of rSEMN was confirmed by Western blotting analysis using chicken anti-IBV polyclonal antibodies. Further studies are needed to evaluate the immunogenicity in animal models and to give a final assessment of the diagnostic utility of this recombinant multi-epitope antigen., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2020.)

Objective: To assess the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with AngioJet mechanical thrombectomy for liver cirrhosis with extensive portal vein thrombosis. Methods: From March 2018 to April 2019, a total of 11 patients with liver cirrhosis and extensive portal vein thrombosis were treated by TIPS combined with AngioJet mechanical thrombectomy, including 6 males and 5 females, with the age of 37-71 (46±9) years old, 3 cases of Child-Pugh grade A, 8 cases of grade B and 0 cases of grade C. The intraoperative immediate thrombus clearance rate, perioperative complication rate, postoperative thrombus recurrence rate, rebleeding rate, the incidence of hepatic encephalopathy and the rate of stent patency of all cases were collected and analyzed. Results: All the patients were treated successfully. The immediate complete thrombus clearance (grade Ⅲ) rate of portal vein trunk was 9/11, and grade Ⅱ was 2/11, The average dose of urokinase was 30-60 (40±5) ten thousand U, slight puncture point bleeding occurred in 3 cases, and recurrence of PVT in portal vein trunk occurred in 1 case with Ⅱ grade clearance rate after operation, rebleeding occurred in 1 case, hepatic encephalopathy occurred in 2 cases, the primary patency rate of stents was 9 cases. Conclusion: TIPS combined with AngioJet mechanical thrombectomy can treat the liver cirrhosis with extensive portal vein thrombosis effectively and safely, and postoperative portal vein patency rate and intrahepatic shunt patency rate are high.

Objective: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) for the treatment of patients with cavernous transformation of portal vein (CTPV) with vareceal bleeding. Methods: From September 2016 to June 2018, a total of 21 patients suffered CTPV complicated with vareceal bleeding were admitted to First Affiliated Hospital of Zhengzhou University. TIPS were performed combined with percutaneous transhepatic portal vein assist. There were 13 males and 8 females, with an average age of 27-67 (48±11) years. Blood routine examination, liver function test, blood ammonia and ultrasound Doppler were conducted 1,3,6 months after operation, and every 6 months during follow-up. Abdominal enhanced CT and digital substraction angiography were followed every year. Results: TIPS were successfully performed in 19 cases (90.5%), esophageal and gastric varices were embolized in 17 cases; 2 cases failed to selective catheterized, then endoscopic therapy was performed.All bleeding stopped after operation. The pressure of portal vein decreased from 25.0-44.0 (33.7±5.4) mmHg (1 mmHg=0.133 kPa) to 17.0-30.0 (24.5±3.1) mmHg, portosystemic pressure gradient decreased from 16.0-32.0 (23.5±4.6) mmHg to 9.0-15.0 (11.4±1.9) mmHg after TIPS (all P< 0.05). During 3-24 months follow-up, 2 patients suffered from hepatic encephalopathy, 3 patients had recurrent upper gastrointestinal bleeding, including 1 duodenal ulcer and 2 esophageal varices. In-stent restenosis were found in 6 patients,in which 3 patients underwent shunt revision operation. At the end of the follow-up, the cumulative patency was 16/19. Conclusion: For patients with CTPV and vareceal bleeding, TIPS could reduce portal hypertension while embolizing varicose veins.It is a safe and effective treatment.

Surgical decompression using laminoplasty is commonly performed for multilevel stenosis with cervical spondylotic myelopathy. However, the long-term effects on the craniocervical range of motion (ROM) after surgery are not well understood. This study represents the first entry into the literature of photogrammetric analysis for clinical measurement of craniocervical ROM. All patients underwent a French-door laminoplasty from 1995 to 2016 and were evaluated radiologically and with postoperative photographs (photogrammetric analysis) to measure craniocervical ROM and axial rotation. Radiographic parameters were occiput to C2 angle, C1-2 angle, C2-7 angle/cervical lordosis (CL), T1-slope (T1S), and TS-CL were measured. Chin-brow vertical angle (CBVA) was utilized for flexion and extension, while nose-turn angle (NTA) was used to assess axial rotation. Forty-four patients (mean age: 65.7 years, 50% female) had a mean follow-up of 37.9 months. Mean values in neutral, flexion, and extension were occiput to C2 = 30°, 15°, and 43°; C1-C2 = -32°, -25°, -32°; and C2-C7 = -4°, 11°, -20°, respectively. Mean CL was within 1 SD of the established -17° (±13.86°). Mean T1S and TS-CL were 33° and 30° in the neutral position, respectively. Mean radiographic full range of motion from flexion to extension was 53°. NTA towards patients' left was 48° and the right side was 45°. Mean CBVA, was -4°, mean flexion 37°, and extension -45°; full range was 81°. Global craniocervical ROM has proven to be well preserved for many years following cervical laminoplasty. Photogrammetric analysis is a cost-effective and radiation-free method, accurate for quantitative assessment of craniocervical and cervical ROM., Competing Interests: Declaration of Competing Interest In compliance with the ICMJE uniform disclosure form, all authors assert the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have stated that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: To assess the feasibility and value of real-time image fusion technique guiding the procedure of transjugular intrahepatic portosystemic shunt(TIPS). Methods: From July 2017 to May 2018,a total of 48 consecutive patients complicated by portal venous hypertension due to cirrhosis who underwent TIPS were prospectively allocated into two groups that 27 cases underwent normal TIPS and 21 cases underwent image fusion guided TIPS. There were 25 males and 23 females with a mean age of 29-74(51±10) years. The differences of portal vein(PV) between image fusion angiographyand digital subtraction angiography(DSA), and the times of puncture PV, X-ray exposure dose and exposure time and contrast agent amount of all cases were collected and analyzed. Results: The longitudinal and traverse difference of PV between image fusion angiography and DSA were 1.7-2.5(2.1±0.2) mm and 0.9-1.8(1.4±0.3) mm, respectively.The times of puncture PV, X-ray exposure time and dose, and contrast agent amount between normal TIPS group and image fusion guided TIPS group were 1-7(3.8±0.6) times vs 1-3(2.0±0.6) times, 41-63(53±8)min vs 27-42(35±5) min, 513-787(644±96) mGy vs 357-524(423±59) mGy,102-196(151±23) ml vs 87-145(105±14) ml(all P< 0.05), respectively. Conclusions: There are minor differences between image fusion angiography of PV and DSA. Real-time image fusion guided TIPS is feasible and valuable to reduce intraprocedural X-ray exposure time and dose and contrast agent amount of TIPS.

Excessive plasma triglyceride (TG) and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism and is involved in the regulation of oxidative stress. Although inflammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE -/- ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE -/- mice. ApoE/Plin5 double knockout (ApoE -/- Plin5 -/- ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated TG, total cholesterol, and low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol contents. ApoE -/- Plin5 -/- exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IκBα/nuclear factor kappa B pathway was strongly activated in ApoE -/- Plin5 -/- . Notably, apoptosis was dramatically induced by ApoE -/- Plin5 -/- , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2. In addition, ApoE -/- Plin5 -/- contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinases pathways. In vitro, oxidized low-density lipoprotein (ox-LDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress, and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions., (© 2019 Wiley Periodicals, Inc.)

Background Context: Chin-Brow Vertical Angle (CBVA) is not routinely measured on radiographs even though it is a strong assessor of horizontal gaze., Study Design: Retrospective cohort study of patients with full-body stereoradiographs and a primary cervical diagnosis at the time of presentation., Purpose: Assess the utility of McGregor's Slope (McGS) and Slope of Line of Sight (SLS) as surrogate markers for the CBVA in cervical spine pathology., Methods: A retrospective review of patients with full-body stereoradiographs was performed. Patients were ≥18 years of age with a primary cervical diagnosis. Analysis of CBVA, McGS, and SLS was conducted as markers of horizontal gaze. Sagittal alignment was characterized by: pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), T1-pelvic angle (TPA), sagittal vertical axis (SVA), T2-T12 thoracic kyphosis, C2-C7 SVA (cSVA), C2-C7 Cervical lordosis, T1-Slope minus Cervical Lordosis (TS-CL), and C2-Slope (C2S). A subgroup analysis was performed in patients with cervical deformity. Independent sample t tests and paired t tests compared radiographic alignment. Pearson correlations characterized linear relationships. Linear regression analysis identified relationships between the parameters., Results: In all, 329 patients were identified with primary cervical spine diagnoses. Chin-Brow Vertical Angle was visible in 171 patients (52.0%), McGS in 281 (85.4%), and SLS in 259 (78.7%). Of the 171 patients with visible CBVA, the mean CBVA was 2.30±7.7, mean McGS was 5.02±8.1, and mean SLS was -1.588±2.03. Chin-Brow Vertical Angle strongly correlated with McGS (r=0.83) and SLS (r=0.89) with p<.001. McGregor's Slope positively correlated with SLS (r=0.89, p=.001)., Conclusions: This study demonstrates that McGS and SLS serve as strong, positive correlates for CBVA. The reported mean differences between these measurements provide a useful conversion, broadening CBVA's use as a radiographic assessment of horizontal gaze., (Copyright © 2019. Published by Elsevier Inc.)

Background: Regional and segmental changes of the lumbar spine have previously been described as patients transition from standing to sitting; however, alignment changes in the cervical and thoracic spine have yet to be investigated. So, the aim of this study was to assess cervical and thoracic regional and segmental changes in patients with thoracolumbar deformity versus a nondeformed thoracolumbar spine population., Methods: This study was a retrospective cohort study of a single center's database of full-body stereoradiographic imaging and clinical data. Patients were ≥ 18 years old with nondeformed spines (nondegenerative, nondeformity spinal pathologies) or thoracolumbar deformity (ASD: PI-LL > 10°). Patients were propensity-score matched for age and maximum hip osteoarthritis grade and were stratified by Scoliosis Research Society (SRS)-Schwab classification by PI-LL, SVA, and PT. Patients with lumbar transitional anatomy or fusions were excluded. Outcome measures included changes between standing and sitting in global alignment parameters: sagittal vertical axis (SVA), pelvic incidence minus lumbar lordosis (PI-LL), pelivc tilt (PT), thoracic kyphosis, cervical alignment, cervical SVA, C2-C7 lordosis (CL), T1 slop minus CL (TS-CL), and segmental alignment from C2 to T12. Another analysis was performed using patients with cervical and thoracic segmental measurements., Results: A total of 338 patients were included (202 nondeformity, 136 ASD). After propensity-score matching, 162 patients were included (81 nondeformity, 81 ASD). When categorized by SRS-Schwab classification, all nondeformity patients were nonpathologically grouped for PI-LL, SVA, and PT, whereas ASD patients had mix of moderately and markedly deformed modifiers. There were significant differences in pelvic and global spinal alignment changes from standing to sitting between nondeformity and ASD patients, particularly for SVA (nondeformed: 49.5 mm versus ASD: 27.4 mm; P &thinsp ; < .001) and PI-LL (20.12° versus 13.01°, P  < .001). With application of the Schwab classification system upon the cohort, PI-LL ( P  = .040) and SVA ( P  = .007) for severely classified deformity patients had significantly less positional alignment change. In an additional analysis of patients with segmental measurements from C2 to T12, nondeformity patients showed significant mobility of T2-T3 (-0.99° to -0.54°, P  = .023), T6-T7 (-3.39° to -2.89°, P  = .032), T7-T8 (-2.68° to -2.23°, P  = .048), and T10-T11 (0.31° to 0.097°, P  = .006) segments from standing to sitting. ASD patients showed mobility of the C6-C7 (1.76° to 3.45°, P  < .001) and T11-T12 (0.98° to 0.54°, P  = 0.014) from standing to sitting. The degree of mobility between nondeformity and ASD patients was significantly different in C6-C7 (-0.18° versus 1.69°, P  = .003), T2-T3 (0.45° versus -0.27°, P  = .034), and T10-T11 (0.45° versus -0.30°, P  = .001) segments. With application of the Schwab modifier system upon the cohort, mobility was significant in the C6-C7 (nondeformed: 0.18° versus moderately deformed: 2.12° versus markedly deformed: 0.92°, P  = .039), T2-T3 (0.45° versus -0.08° versus -0.63°, P  = .020), T6-T7 (0.48° versus 0.36° versus -1.85°, P  = .007), and T10-T11 (0.45° versus -0.21° versus -0.23°, P  = .009) segments., Conclusions: Nondeformity patients and ASD patients have significant differences in mobility of global spinopelvic parameters as well as segmental regions in the cervical and thoracic spine between sitting and standing. This study aids in our understanding of flexibility and compensatory mechanisms in deformity patients, as well as the possible impact on unfused segments when considering deformity corrective surgery., Competing Interests: Disclosures and COI: No funding was received in relation to the creation of this work. Each institution obtained approval from their local Institutional Review Board to enroll patients in the prospective database and informed consent was obtained from each patient. Peter G. Passias, MD, reports personal consulting fees for Spinewave, Zimmer Biomet, and Medicrea outside the submitted work. Virginie Lafage, PhD, reports Depuy Synthes paid lectures, Nuvasive paid lectures, K2M paid lectures, Medtronic paid lectures, and Nemaris board member and shareholder.

Background: Klippel-Feil syndrome (KFS) includes craniocervical anomalies, low posterior hairline, and brevicollis, with limited cervical range of motion; however, there remains no consensus on inheritance pattern. This study defines incidence, characterizes concurrent diagnoses, and examines trends in the presentation and management of KFS., Methods: This was a retrospective review of the Kid's Inpatient Database (KID) for KFSpatients aged 0-20 years from 2003 to 2012. Incidence was established using KID-supplied year and hospital-trend weights. Demographics and secondary diagnoses associated with KFS were evaluated. Comorbidities, anomalies, and procedure type trends from 2003 to 2012 were assessed for likelihood to increase among the years studied using ANOVA tests., Results: Eight hundred and fifty-eight KFS diagnoses (age: 9.49 years; 51.1% females) and 475 patients with congenital fusion (CF) (age: 8.33 years; 50.3% females) were analyzed. We identified an incidence rate of 1/21,587 discharges. Only 6.36% of KFS patients were diagnosed with Sprengel's deformity; 1.44% with congenital fusion. About 19.1% of KFS patients presented with another spinal abnormality and 34.0% presented with another neuromuscular anomaly. About 36.51% of KFS patients were diagnosed with a nonspinal or nonmusculoskeletal anomaly, with the most prevalent anomalies being of cardiac origin (12.95%). About 7.34% of KFS patients underwent anterior fusions, whereas 6.64% of KFS patients underwent posterior fusions. The average number of levels operated on was 4.99 with 8.28% receiving decompressions. Interbody devices were used in 2.45% of cases. The rate of fusions with <3 levels (7.46%) was comparable to that of 3 levels or greater (7.81%)., Conclusions: KFS patients were more likely to have other spinal abnormalities (19.1%) and nonnervous system abnormalities (13.63%). Compared to congenital fusions, KFS patients were more likely to have congenital abnormalities such as Sprengel's deformity. KFS patients are increasingly being treated with spinal fusion., Level of Evidence: III., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Craniovertebral Junction and Spine.)

Background: The study aimed to characterize trends in incidence, etiology, fracture types, surgical procedures, complications, and concurrent injuries associated with traumatic pediatric cervical fracture using a nationwide database., Methods: The Kids' Inpatient Database (KID) was queried. Trauma cases from 2003 to 2012 were identified, and cervical fracture patients were isolated. Demographics, etiologies, fracture levels, procedures, complications, and concurrent injuries were assessed. The t -tests elucidated significance for continuous variables, and χ 2 for categoric values. Logistic regressions identified predictors of spinal cord injury (SCI), surgery, any complication, and mortality. Level of significance was P < .05., Results: A total of 11 196 fracture patients were isolated (age, 16.63 years; male, 65.7%; white, 65.4%; adolescent, 55.4%). Incidence significantly increased since 2003 (2003 vs 2012, 2.39% vs 3.12%, respectively), as did Charlson Comorbidity Index (CCI; 2003 vs 2012, 0.2012 vs 0.4408, respectively). Most common etiology was motor vehicle accidents (50.5%). Infants and children frequently fractured at C2 (closed: 43.1%, 32.9%); adolescents and young adults frequently fractured at C7 (closed: 23.9%, 26.5%). Upper cervical SCI was less common (5.8%) than lower cervical SCI (10.9%). Lower cervical unspecified-SCI, anterior cord syndrome, and other specified SCIs significantly decreased since 2003. Complications were common (acute respiratory distress syndrome, 7.8%; anemia, 6.7%; shock, 3.0%; and mortality, 4.2%), with bowel complications, cauda equina, anemia, and shock rates significantly increasing since 2003. Concurrent injuries were common (15.2% ribs; 14.4% skull; 7.1% pelvis) and have significantly increased since 2003. Predictors of SCI included sports injury and CCI. Predictors of surgery included falls, sports injuries, CCI, length of stay, and SCI. CCI, SCIs, and concurrent injuries were predictors of any complication and mortality, all ( P < .001)., Conclusions: Since 2003, incidence, complications, concurrent injuries, and fusions have increased. CCI, SCI, falls, and sports injuries were significant predictors of surgical intervention. Decreased mortality and SCI rates may indicate improving emergency medical services and management guidelines., Level of Evidence: III., Clinical Relevance: Clinicians should be aware of increased case complexity in the onset of added perioperative complications and concurrent injuries. Cervical fractures resultant of sports injuries should be scrutinized for concurrent SCIs., Competing Interests: Disclosures and COI: Dr Gerling received personal consulting fees for Paradigm Spine and speaking/teaching fees for Stryker Spine. Dr Passias received personal consulting fees for Spinewave and Medicrea. The other authors received no funding for this study and report no conflicts of interest.

Study Design: Retrospective review of KID Inpatient Database (KID) from 2003, 2006, 2009, and 2012., Objectives: The aim of this study was to evaluate the impact of advances in spinal surgery on patient outcomes in the treatment of Scheuermann kyphosis (SK)., Summary of Background Data: SK is one of the most common causes of back pain in adolescents. Trends in diagnoses and surgical treatment and approach to SK have not been well described., Methods: SK patients aged 0-20 years in KID were identified by ICD-9 code 732.0. KID-supplied year- and hospital-trend weights were used to establish prevalence. Patient demographics, surgical details, and outcomes were analyzed with analysis of variance., Results: A total of 1,070 SK patients were identified (33.2% female), with increasing incidence of SK diagnosed from 2003 to 2012 (3.6-7.5 per 100,000, p < .001). The average age of operative patients was 16.1±2.0 years and did not change (16.27-16.06 years, p = .905). The surgical rate has not changed over time (72.8%-72.8%, p = .909). Overall, 96.3% of operative patients underwent fusion, with 82.2% of cases spanning ≥4 levels; in addition, 8.6% underwent an anterior-only surgery, 74.6% posterior-only, and 13.6% combined approach. From 2003 to 2012, rates of posterior-only surgeries increased (62.4%-84.4%, p < .001) whereas the rate of combined-approach surgeries decreased (37.6%-8.8%, p < .001). Overall complication rates for SK surgeries have decreased (2003: 20.9%; 2012: 11.9%, p = .029). Concurrently, the rate of ≥4-level fusions has increased (43.5%-89.6%, p < .001), as well as the use of Smith-Peterson (7.8%-23.6%, p < .001) and three-column osteotomies (0.0%-2.7%, p = .011). In subanalysis comparing posterior to combined approaches, complication rates were significantly different (posterior: 9.88%, combined: 19.46%, p = .005). Patients undergoing a combined approach have a longer length of stay (LOS) than patients undergoing a posterior-only approach (7.8 vs. 5.6 days, p < .001)., Conclusions: Despite unchanged demographics and operative rates in SK, there has been a shift from combined to isolated posterior approaches, with a concurrent increase in levels treated. A combined approach was associated with increased complication rates, LOS, and total charges compared to isolated approaches. Awareness of these inherent differences is important for surgical decision making and patient education., Levels of Evidence: Level III., (Copyright © 2018 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Introduction: This study assessed the incidence and risk factors for pseudarthrosis among primary spine fusion patients., Methods: Retrospective review of ACS-NSQIP (2005-2013). Differences in comorbidities between spine fusion patients with and without pseudarthrosis (Pseud, N-Pseud) were assessed using chi-squared tests and Independent Samples t -tests. Binary logistic regression assessed patient-related and procedure-related predictors for pseudarthrosis., Results: 52,402 patients (57yrs, 53%F, 0.4% w/pseudarthrosis). Alcohol consumption (OR:2.6[1.2-5.7]) and prior history of surgical revision (OR:1.6[1.4-1.8]) were risk factors for pseudarthrosis operation. Pseud patients at higher risk for deep incisional SSI (at 30-days:OR:6.6[2.0-21.8]). Pseud patients had more perioperative complications (avg:0.24 ± 0.43v0.18 ± 0.39, p =0.026)., Conclusions: Alcoholism and surgical revision are major risk factors for pseudarthrosis in patients undergoing spine fusion.

Study Design: A cross-sectional study., Objective: The goal of this study is to investigate how surgeons differ in collar and narcotic use, as well as return to driving recommendations following cervical spine surgeries and the associated medico-legal ramifications of these conditions., Summary of Background Data: Restoration of quality of life is one of the main goals of cervical spine surgery. Patients frequently inquire when they may safely resume driving after cervical spine surgery. There is no consensus regarding postoperative driving restrictions. This study addresses how surgeons differ in their recommendations concerning cervical immobilization, narcotic analgesia, and suggested timeline of return to driving following cervical spine surgery., Methods: Surgeons at the Cervical Spine Research Society annual meeting completed anonymous surveys assessing postoperative patient management following fusion and nonfusion cervical spine surgeries., Results: Seventy percent of surgeons returned completed surveys (n = 71). About 80.3% were orthopedic surgeons and 94.2% completed a spine fellowship. Experienced surgeons (>15 years in practice) were more likely to let patients return to driving within 2 weeks than less experienced surgeons (47.1% vs. 24.3%, P = 0.013) for multilevel anterior discectomy and fusion (ACDF) and laminectomy with fusion procedures. There were no differences between surgeons practicing inside and outside the USA for prescribing collars or return to driving time. Cervical collars were used more for fusions than nonfusions (57.7% vs. 31.0%, P = 0.001). Surgeons reported 75.3% of patients ask when they may resume driving. For cervical fusions, 31.4% of surgeons allowed their patients to resume driving while restricting them with collars for longer durations. Furthermore, 27.5% of surgeons allowed their patients to resume driving while taking narcotics postoperatively., Conclusion: This survey-based study highlights the lack of consensus regarding patient "fitness to drive" following cervical spine surgery. The importance of establishing evidence-based guidelines is critical, as recommendations for driving in the postoperative period may have significant medical, legal, and financial implications., Level of Evidence: 5.

Background: Informed patient selection and counseling is key in improving surgical outcomes. Understanding the impact that certain baseline variables can have on postoperative outcomes is essential in optimizing treatment for certain symptoms, such as radiculopathy from cervical spine pathologies. The aim was to identify baseline characteristics that were related to improved or worsened postoperative outcomes for patients undergoing surgery for cervical spine radiculopathic pain., Methods: Retrospective review of prospectively collected data. Patient Sample: Surgical cervical spine patients with a diagnosis classification of "degenerative." Diagnoses included in the "degenerative" category were those that caused radiculopathy: cervical disc herniation, cervical stenosis, and cervical spondylosis without myelopathy. Baseline variables considered as predictors were: (1) age, (2) body mass index (BMI), (3) gender, (4) history of cervical spine surgery, (5) baseline Neck Disability Index (NDI) score, (6) baseline SF-36 Physical Component Summary (PCS) scores, (7) baseline SF-36 Mental Component Summary (MCS) scores, (8) Visual Analog Scale (VAS) Arm score, and (9) VAS Neck. Outcome Measures: Improvement in NDI (≥50%), VAS Arm/Neck (≥50%), SF-36 PCS/MCS (≥10%) scores at 2-years postoperative. An arm-to-neck ratio (ANR) was also generated from baseline VAS scores. Univariate and multivariate analyses evaluated predictors for 2-year postoperative outcome improvements, controlling for surgical complications and technique., Results: Three hundred ninety-eight patients were included. Patients with ANR ≤ 1 (n = 214) were less likely to reach improvements in 2-year NDI (30.0% vs 39.2%, P = .050) and SF-36 PCS (42.4% vs 53.5%, P = .025). Multivariate analysis for neck disability revealed higher baseline SF-36 PCS (odds ratio [OR] 1.053) and MCS (OR 1.028) were associated with over 50% improvements. Higher baseline NDI were reduced odds of postoperative neck pain improvement (OR 0.958). Arm pain greater than neck pain at baseline was associated with both increased odds of postoperative arm pain improvement (OR 1.707) and SF36 PCS improvement (OR 1.495)., Conclusions: This study identified specific symptom locations and health-related quality of life (HRQL) scores, which were associated with postoperative pain and disability improvement. In particular, baseline arm pain greater than neck pain was determined to have the greatest impact on whether patients met at least 50% improvement in their upper body pain score. These findings are important for clinicians to optimize patient outcomes through effective preoperative counseling., Competing Interests: Disclosures and COI: Dr. Passias reports consultancy for Medicrea and SpineWave, speaking/teaching arrangements from Zimmer-Biomet, and grant from CSRS, all outside the submitted work. All other authors have no conflicts of interest to report. Institutional Review Board (IRB) approval was obtained from each contributing center prior to study initiation.

Purpose: Sagittal spinal deformity (SSD) patients utilize pelvic tilt (PT) and their lower extremities in order to compensate for malalignment. This study examines the effect of hip osteoarthritis (OA) on compensatory mechanisms in SSD patients., Methods: Patients ≥ 18 years with SSD were included for analysis. Spinopelvic, lower extremity, and cervical alignment were assessed on standing full-body stereoradiographs. Hip OA severity was graded by Kellgren-Lawrence scale (0-4). Patients were categorized as limited osteoarthritis (LOA: grade 0-2) and severe osteoarthritis (SOA: grade 3-4). Patients were matched for age and T1-pelvic angle (TPA). Spinopelvic [sagittal vertical axis (SVA), T1-pelvic angle, thoracic kyphosis (TK), pelvic tilt (PT), lumbar lordosis (LL), pelvic incidence minus lumbar lordosis (PI-LL), T1-spinopelvic inclination (T1SPi)] and lower extremity parameters [sacrofemoral angle, knee angle, ankle angle, posterior pelvic shift (P. Shift), global sagittal axis (GSA)] were compared between groups using independent sample t test., Results: 136 patients (LOA = 68, SOA = 68) were included in the study. SOA had less pelvic tilt (p = 0.011), thoracic kyphosis (p = 0.007), and higher SVA and T1Spi (p < 0.001) than LOA. SOA had lower sacrofemoral angle (p < 0.001) and ankle angle (p = 0.043), increased P. Shift (p < 0.001) and increased GSA (p < 0.001) compared to LOA. There were no differences in PI-LL, LL, knee angle, or cervical alignment (p > 0.05)., Conclusions: Patients with coexisting spinal malalignment and SOA compensate by pelvic shift and thoracic hypokyphosis rather than PT, likely as a result of limited hip extension secondary to SOA. As a result, SOA had worse global sagittal alignment than their LOA counterparts. These slides can be retrieved under Electronic Supplementary Material.

Study Design: Retrospective radiographic review., Objectives: To understand the effect of variability in sacral endplate selection in transitional lumbosacral vertebrae (TLSV) and its impact on pelvic, regional, and global spinal alignment parameters., Background: TLSV can have the characteristics of both lumbar and sacral vertebrae. Difficulties in identification of the S1 endplate may come from nomenclature, number of lumbar vertebrae, sacra, and morphology and may influence the interpretation and consistency of spinal alignment parameters., Methods: Patients with TLSV were identified and radiographic measurements including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), sagittal vertical axis (SVA), T1-pelvic angle (TPA), pelvic incidence-lumbar lordosis (PI-LL) mismatch, thoracic kyphosis (TK), and spinal inclination (T1SPi) were obtained. Radiographic measurements were performed twice with the sacral endplate at the cephalad and caudal options. Paired t tests assessed the difference between different selection groups., Results: Of 1,869 patients, 70 (3.7%) were found to have TLSV on radiographic imaging. Fifty-eight (82.9%) had lumbarized sacral segments whereas 12 (17.1%) had sacralized lumbar segments. T1-SPi (mean: -1.77°) and TK (mean: 34.86°) did not vary from altering sacral endplate selection. Selection of the caudal TLSV as the sacral endplate resulted in an increase in all pelvic parameters (PI: 66.8° vs. 44.3°, PT: 25.1° vs. 12.7°, and SS: 41.6° vs. 31.6°), regional lumbar parameters (LL: -54.1° vs. 44.0°, PI-LL: 12.7° vs. 0.3°), and global parameters (SVA: 46.1 mm vs. 28.3 mm, TPA: 23.3° vs. 10.8°) as compared to selecting the cephalad TLSV. All mean differences between radiographic parameters were found to be statistically significant (p < .001)., Conclusions: Variation in sacral endplate selection in TLSV significantly affects spinal alignment parameter measurements. A standardized method for measuring TLSV is needed to reduce measurement error and ultimately allow more accurate understanding of alignment targets in patients with TLSV., Level of Evidence: Level III., (Copyright © 2018 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Early Onset and Adolescent Idiopathic Scoliosis, relatively common diagnoses (∼3% general population), have been associated with developmental dysplasia of the hip (DDH); a more rare spectrum of anomalies related to the abnormal development of acetabulum, proximal femur, and hip joint. To the best of our knowledge, no high powered investigations have been performed in an attempt to assess incidence and associated risks of DDH in scoliosis patients., Methods: The KID database was queried for ICD-9 codes from 2003 to 2012 pertaining to EOS (Congenital and Idiopathic <10y/o) and AIS patients. Descriptive analysis assessed patient demographics and yearly trends in hip dysplasia rates. EOS and AIS patients with hip dysplasia were isolated, and incidence of hospital admissions for associated anomalies (osteonecrosis, osteoarthritis, recurrent hip dislocation, hip ankylosis) and hip arthroplasty (total + partial) were investigated. Univariate analysis of hip pathology determined significant predictors of hip arthroplasty. Binary logistic regression analysis was used to determine the relationship between these predictors., Results: 111,827 scoliosis patients (EOS: 25,747; AIS: 77,183) were included. AIS patients were older (15.2 vs 4.3), more female (64.2% vs 52.1%), had a higher CCI (0.84 vs 0.64), and less racially diverse (all p < 0.001). The incidence of hip dysplasia was 1.4% for AIS patients and 3.9% for EOS patients (p < 0.001). Of the AIS (n = 1073) and EOS (n = 1005) patients with hip dysplasia, 0.3% (p > 0.05 between groups) developed hip osteonecrosis, 0% of patients were coded as having a hip labral tear, hip ankylosis, and 0.6% (EOS: 0.2%; AIS: 0.9%, p = 0.025) developed hip osteoarthritis. AIS patients were more likely to have recurrent hip dislocations (35.4% vs 17.0%, p < 0.001), and both groups had similar primary hip arthroplasty rates (6.7% vs 5.4%, p = 0.118) and revision hip arthroplasty rates (0% vs 0.4%, p = 0.053). Hip osteoarthritis (OR: 13.43[5.21-34.66], p=<0.001) and older age (OR: 1.039[1.007-1.073], p = 0.017) were the only significant predictors of hip arthroplasty (p=<.001)., Conclusions: The incidence of hip dysplasia in EOS and AIS populations is higher than that of the general population. The rate of DDH was 3.9% and 1.8% for EOS and AIS, respectively. While the incidence of DDH is higher, associated anomalies of osteoarthritis, osteonecrosis, labral tears, and ankylosis appear to be a minimal risk for AIS and EOS patients with Hip Dysplasia.

Background: Risk of death is important in counseling patients and improving quality of care. Incidence of death in cervical surgery is not firmly established due to its rarity and limited sample sizes, particularly in the context of different surgeries, demographics, and risk factors. Particularly, different patient risk profiles may have varying degrees of risk in terms of surgeries, comorbidities, and demographics. This study aims to use a large patient cohort available on a national database to study the prevalence of death associated with cervical spine surgery., Methods: This study was a retrospective review of the Nationwide Inpatient Sample (NIS) years 2003-2012. A total of 342 477 patients were identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes undergoing spinal fusion or decompression for disc degeneration, stenosis, spondylosis, myelopathy, postlaminectomy syndrome, scoliosis, or neck pain associated with the cervical region. Patients with malignancy were excluded from analysis. Incidence of mortality was assessed by χ 2 tests across different patient demographics and comorbidities, procedures performed, and concurrent in-hospital complications. Binary logistic regression identified significant increases or decreases in risk of death while controlling for comorbidities, race, sex, and Mirza invasiveness. Significance was defined as P < .05 differences relative to overall cohort., Results: The study analyzed 342 477 patients with an overall mortality rate of 0.32%. A total of 231 977 simple fusions (single approach and <3 levels) experienced a mortality rate of 0.256%; 49 594 complex fusions (combined approach or ≥3 levels) had a mortality rate of 0.534%; and 61 285 decompression-only procedures reported a 0.424% mortality rate, all P < .001 from overall rate. In reporting rates across different demographics, male patients experienced a significantly higher risk for mortality (odds ratio [OR], 2.16; 95% CI, 1.87-4.49), as did black patients (OR, 1.58; CI, 1.32-1.90) and patients over age 75 (OR, 7.55; 95% CI, 6.58-8.65), all P < .001. Patients with liver disease reported 6.40% mortality. Similarly, patients with congestive heart failure (3.91%), cerebrovascular disease (3.41%), and paraplegia (3.79%) experienced high mortality rates, all in cohorts of over 2000 patients, all P < .001. Concurrent in-hospital complications with the highest risk of mortality were shock (OR, 51.41; 95% CI, 24.08-109.76), pulmonary embolism (OR, 25.01; 95% CI, 14.70-42.56), and adult respiratory distress disorder (OR, 14.94; 95% CI, 12.75-17.52), all P < .001., Conclusion: In 342 477 cervical spine surgery patients an overall mortality rate of 0.32% was reported. The rate was 3.91% in a cohort of 5933 patients with congestive heart failure and 3.79% in a cohort of 6947 patients with paraplegia. These findings are consistent with previous estimates and may help counsel patients and improve in-hospital safety., Level of Evidence: 3., Competing Interests: Disclosures and COI: Gregory Wyatt Poorman, John Y. Moon, Samantha R. Horn, Cyrus Jalai, Peter L. Zhou, and Olivia Bono all report no conflict of interest. Peter G. Passias, the corresponding author, reports consulting with Medicrea and Zimmer, unrelated to and outside of the current work. Given the deidentified nature of the data reported from this study, it is exempt from IRB approval.

Background: Cardiac anomalies are prevalent in patients with bony spinal anomalies. Prior studies evaluating incidences of bony congenital anomalies of the spine are limited. The Kids' Inpatient Database (KID) yields national discharge estimates of rare pediatric conditions like congenital disorders. This study utilized cluster analysis to study patterns of concurrent vertebral anomalies, anal atresia, cardiac malformations, trachea-esophageal fistula, renal dysplasia, and limb anomalies (VACTERL anomalies) co-occurring in patients with spinal congenital anomalies., Methods: Retrospective review of KID 2003-2012. KID-supplied hospital- and year-adjusted weights allowed for incidence assessment of bony spinal anomalies and cardiac, gastrointestinal, urinary anomalies of VACTERL. K-means clustering assessed relationships between most frequent anomalies within bony spinal anomaly discharges; k set to n - 1(n = first incidence of significant drop/little gain in sum of square errors within clusters)., Results: There were 12,039,432 KID patients 0-20 years. Incidence per 100,000 discharges: 2.5 congenital fusion of spine, 10.4 hemivertebra, 7.0 missing vertebra. The most common anomalies co-occurring with bony vertebral malformations were atrial septal defect (ASD 12.3%), large intestinal atresia (LIA 11.8%), and patent ductus arteriosus (PDA 10.4%). Top congenital cardiac anomalies in vertebral anomaly patients were ASD, PDA, and ventricular septal defect (VSD); all three anomalies co-occur at 6.6% rate in this vertebral anomaly population. Cluster analysis revealed that of bony anomaly discharges, 55.9% of those with PDA had ASD, 34.2% with VSD had PDA, 22.9% with LIA had ASD, 37.2% with ureter obstruction had LIA, and 35.5% with renal dysplasia had LIA., Conclusions: In vertebral anomaly patients, the most common co-occurring congenital anomalies were cardiac, renal, and gastrointestinal. Top congenital cardiac anomalies in vertebral anomaly patients were ASD, PDA, and VSD. VACTERL patients with vertebral anomalies commonly presented alongside cardiac and renal anomalies.

Background: Previous studies have built a foundation for understanding compensation in patients with adult spinal deformity (ASD) by using full-body stereographic assessments. These mechanisms, in relation to age-adjusted alignment targets, have yet to be studied fully. The aim of this study was to assess lower-limb compensatory mechanisms of patients failing to meet age-adjusted alignment goals., Methods: Patients with ASD ≥40 years with full body baseline and follow-up radiographs were included. Patients were stratified by age (40-65 years, >65 years) and spinopelvic correction. Lower-limb compensation parameters (pelvic shift, hip extension, knee flexion [KA], ankle flexion [AA], and global sagittal angle [GSA]) for patients who matched and failed to match age-adjusted alignment targets were compared with analysis of variance and t-test analysis., Results: In total, 108 patients were included. At 1 year, AA increased with age in the "match" pelvic tilt (PT) and spinopelvic mismatch (PI-LL) cohorts (PT: AA, 5.6-7.8, P = 0.041; PI-LL: 4.9-8.8, P = 0.026). KA, AA, and GSA increased with age in the "match" sagittal vertical axis (SVA) cohort (KA: 3.8-13.1, P = 0.002; AA: 5.8-10.2, P = 0.008; GSA: 3.9-7.8, P < 0.001), as did KA and GSA in the "match" T1 pelvic angle group (KA: 1.8-8.7, P = 0.020; GSA: 2.6-5.7, P = 0.004)., Conclusions: Greater compensation captured by KA and GSA was associated with age progression in the "match" SVA and T1 pelvic angle cohorts. In addition, older SVA, PT, and PI-LL "match" cohorts used increased AA, suggesting that ideal postoperative alignment of aged individuals with ASD involves increased compensation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: This study aims to describe properties of adult spinal deformity (ASD) revisions relative to primary surgeries and determine clinical variables that can predict revision. ASD is a common pathology that can lead to decreased quality of life, pain, physical limitations, and dissatisfaction with self-image. Durability of interventions for deformity treatment is of paramount concern to surgeons, as revision rates remain high., Methods: Patients undergoing thoracolumbar fusion, five or more levels, for scoliosis (primary diagnosis ICD-9 737.x) were identified on a state-wide database. Primary and revision (returning for re-fusion procedure) surgeries were compared based on demographic, hospital stay, and clinical characteristics. Differences between primary and revision surgeries, and predictors of primary surgeries requiring revision, utilized binary logistic regression controlling for age, comorbidity burden, and levels fused., Results: A total of 1,063 patients (average 7.4 levels fused, mean age: 47.6 years, 69.0% female) undergoing operative treatment for ASD were identified, of which 123 (average 7.1 levels fused, 11.6%, mean age 61.43, 80.5% female) had surgical revision. Primary surgeries were ~0.3 levels longer (P=0.013), used interbody ~11% more frequently (P=0.020), and used BMP ~12% less frequently (P=0.008). Revisions occurred 176.4 days after the primary on average. The most frequent causes of revisions were: 43.09% implant failure, 24.39% acquired kyphosis, and 14.63% enduring scoliosis. After controlling for age, comorbidities, and levels fused older, more comorbid, female, and white-race patients were more likely to be revised. Upon multivariate regression, after controlling for age and levels fused, overall complications remained non-different (OR: 0.8, 95% CI: 0.6-1.2). However, revision remained an independent predictor for infection (OR: 5.5, 95% CI: 2.8-10.5)., Conclusions: In a statewide database with individual patient follow up of up to 4 years 10% of ASD patients undergoing scoliosis correction required revision. Revision surgeries had higher infection incidence., Competing Interests: Conflicts of Interest: Dr. PG Passias discloses consulting agreements with Medicrea, Zimmer Biomet, and Spinewave, as well as scientific advisory board membership with Allosource. The other authors have no conflicts of interest to declare.

Study Design: Retrospective cohort study., Objectives: The purpose of this study was to report incidence of cardiopulmonary complications in elective spine surgery, demographic and surgical predictors, and outcomes. Understanding the risks and predictors of these sentinel events is important for risk evaluation, allocation of hospital resources, and counseling patients., Methods: A retrospective review of the National Surgical Quality Improvement Program (NSQIP) was performed on 60 964 patients undergoing elective spine surgery (any region; laminectomy, arthrodesis, discectomy, or laminoplasty) between 2011 and 2013. Incidence of myocardial infarction, cardiac arrest, unplanned reintubation, on ventilator >48 hours, perioperative pneumonia, and pulmonary embolism was measured. Demographic and surgical predictors of cardiopulmonary complications and associated outcomes (length of stay, discharge disposition, and mortality) were measured using binary logistic regression controlling for confounders., Results: Incidence rates per 1000 elective spine patients were 2.1 myocardial infarctions, 1.3 cardiac arrests, 4.3 unplanned intubations, 3.5 on ventilator >48 hours, 6.1 perioperative pneumonia, and 3.7 pulmonary embolisms. In analysis of procedure, diagnosis, and approach risk factors, thoracic cavity (odds ratio = 2.47; confidence interval = 1.95-3.12), scoliosis diagnosis, and combined approach (odds ratio = 1.51; confidence interval = 1.15-1.96) independently added the most risk for cardiopulmonary complication. Cardiac arrest had the highest mortality rate (34.57%). Being on ventilator greater than 48 hours resulted in the greatest increase to length of stay (17.58 days)., Conclusions: Expected risk factors seen in the Revised Cardiac Risk Index were applicable in the context of spine surgery. Surgical planning should take into account patients who are at higher risk for cardiopulmonary complications and the implications they have on patient outcome., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chiari malformations type 1 (CM-1), a developmental anomaly of the posterior fossa, usually presents in adolescence or early adulthood. There are few studies on the national incidence of CM-1, taking into account outcomes based on concurrent diagnoses. To quantify trends in treatment and associated diagnoses, as retrospective review of the Kid's Inpatient Database (KID) from 2003-2012 was conducted., Methods: Patients aged 0-20 with primary diagnosis of CM-1 in the KID database were identified. Demographics and concurrent diagnoses were analyzed using chi-squared and t -tests for categorical and numerical variables, respectively. Trends in diagnosis, treatments, and outcomes were analyzed using analysis of variance (ANOVA)., Results: Five thousand four hundred and thirty-eight patients were identified in the KID database with a primary diagnosis of CM-1 (10.5 years, 55% female). CM-1 primary diagnoses have increased over time (45 to 96 per 100,000). CM-1 patients had the following concurrent diagnoses: 23.8% syringomyelia/syringobulbia, 11.5% scoliosis, 5.9% hydrocephalus, 2.2% tethered cord syndrome. Eighty-three point four percent of CM-1 patients underwent surgical treatment, and rate of surgical treatment for CM-1 increased from 2003-2012 (66% to 72%, P<0.001) though complication rate decreased (7% to 3%, P<0.001) and mortality rates remained constant. Seventy percent of surgeries involved decompression-only, which increased neurologic complications compared to fusions (P=0.039). Cranial decompressions decreased from 2003-2012 (42.2-30.5%) while spinal decompressions increased (73.1-77.4%). Fusion rates have increased over time (0.45% to 1.8%) and are associated with higher complications than decompression-only (11.9% vs. 4.7%). Seven point four percent of patients experienced at least one peri-operative complication (nervous system, dysphagia, respiratory most common). Patients with concurrent hydrocephalus had increased; nervous system, respiratory and urinary complications (P<0.006) and syringomyelia increased the rate of respiratory complications (P=0.037)., Conclusions: CM-1 diagnoses have increased in the last decade. Despite the decrease in overall complication rates, fusions are becoming more common and are associated with higher peri-operative complication rates. Commonly associated diagnoses including syringomyelia and hydrocephalus, can dramatically increase complication rates., Competing Interests: Conflicts of Interest: Dr. PG Passias reports personal consulting fees for Spinewave, Zimmer Biomet, and Medicrea, grants to the institution from the Cervical Spine Research Society. The other authors have no conflicts of interest to declare.

Objective: The causes and epidemiology of traumatic cervical spine fracture have not been described with sufficient power or recency. Our goal is to describe demographics, incidence, cause, spinal cord injuries (SCIs), concurrent injuries, treatments, and complications of traumatic cervical spine fractures., Methods: A retrospective review was carried out of the Nationwide Inpatient Sample. International Classification of Disease, Ninth Revision E-codes identified trauma cases from 2005 to 2013. Patients with cervical fracture were isolated. Demographics, incidence, cause, fracture levels, concurrent injuries, surgical procedures, and complications were analyzed. t tests elucidated significance for continuous variables and χ 2 for categorical variables. Level of significance was P < 0.05., Results: A total of 488,262 patients were isolated (age, 55.96 years; male, 60.0%; white, 77.5%). Incidence (2005, 4.1% vs. 2013, 5.4%), Charlson Comorbidity Index (2005, 0.6150 vs. 2013, 1.1178), and total charges (2005, $71,228.60 vs. 2013, $108,119.29) have increased since 2005, whereas length of stay decreased (2005, 9.22 vs. 2013, 7.86) (all P < 0.05). The most common causes were motor vehicle accident (29.3%), falls (23.7%), and pedestrian accidents (15.7%). The most frequent fracture types were closed at C2 (32.0%) and C7 (20.9%). Concurrent injury rates have significantly increased since 2005 (2005, 62.3% vs. 2013, 67.6%). Common concurrent injuries included fractures to the rib/sternum/larynx/trachea (19.6%). Overall fusion rates have increased since 2005 (2005, 15.7% vs. 2013, 18.0%), whereas decompressions and halo insertion rates have decreased (all P < 0.05). SCIs have significantly decreased since 2005, except for upper cervical central cord syndrome. Complication rates have significantly increased since 2005 (2005, 31.6% vs. 2013, 36.2%). Common complications included anemia (7.7%), mortality (6.6%), and acute respiratory distress syndrome (6.6%)., Conclusions: Incidence, complications, concurrent injuries, and fusions have increased since 2005. Length of stay, SCIs, decompressions, and halo insertions have decreased. Indicated trends should guide future research in management guidelines., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Excessive plasma triglyceride and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism, and is involved in the regulation of oxidative stress. Although, in?ammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE -/- ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE -/- mice. ApoE/Plin5 double knockout (ApoE -/- Plin5 -/- ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and reduced high-density lipoprotein cholesterol (HDLC) contents. ApoE -/- Plin5 -/- exhibited higher number of inflammatory monocytes and neutrophils, as well as over-expression of cytokines and chemokines linked with inflammatory response. Consistently, IκBα/nuclear factor kappa B (NF-κB) pathway was strongly activated in ApoE -/- Plin5 -/- . Notably, apoptosis was dramatically induced by ApoE -/- Plin5 -/- , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2 (PARP-2). In addition, ApoE -/- Plin5 -/- contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) pathways. In vitro, oxidized low-density lipoprotein (oxLDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Purpose To identify the characteristics and evaluate the long-term outcomes of endovascular treatment of Budd-Chiari syndrome with upper gastrointestinal hemorrhage. Methods Forty-seven consecutive Budd-Chiari syndrome patients with upper gastrointestinal hemorrhage were referred for the treatment with percutaneous transluminal balloon angioplasty, and subsequently underwent follow-up. Data were retrospectively collected and follow-up observations were performed at 1, 2, 2-5, and 5-8 years postoperatively. Results Cirrhosis was presented in 16 patients, and splenoportography reviewed obvious varices in 18 patients. Percutaneous transluminal balloon angioplasty was technically successful in all patients. Major procedure-related complications occurred in 3 of the 47 patients (6.38%). The cumulative 1, 2, 2-5, and 5-8 year primary patency rates were 100% (46/46), 93.2% (41/44), 90.9% (40/44), and 86.4% (19/22), respectively. The cumulative 1, 2, 2-5, and 5-8 year secondary patency rates were 100% (47/47), 100% (44/44), 100% (44/44), and 95.5% (21/22), respectively. Mean and median duration of primary patency was 65.17 ± 3.78 and 69.0 ± 5.69 months, respectively. No upper gastrointestinal hemorrhage recurred during follow-ups. The mean survival time was 66.97 ± 3.61 months and the median survival time was 69.0 ± 4.10 months. Conclusion PTBA was an effective treatment that can prevent recurrence of the life-threatening complications and ensured long-term satisfactory clinical outcomes for Budd-Chiari syndrome patients with upper gastrointestinal hemorrhage. Percutaneous transhepatic variceal embolization was not recommended for all Budd-Chiari syndrome patients with upper gastrointestinal hemorrhage.

OBJECTIVE It is becoming increasingly necessary for surgeons to provide evidence supporting cost-effectiveness of surgical treatment for cervical spine pathology. Anticipating surgical risk is critical in accurately evaluating the risk/benefit balance of such treatment. Determining the risk and cost-effectiveness of surgery, complications, revision procedures, and mortality rates are the most significant limitations. The purpose of this study was to determine independent risk factors for medical complications (MCs), surgical complications (SCs), revisions, and mortality rates following surgery for patients with cervical spine pathology. The most relevant risk factors were used to structure an index that will help quantify risk and anticipate failure for such procedures. METHODS The authors of this study performed a retrospective review of the National Inpatient Sample (NIS) database for patients treated surgically for cervical spine pathology between 2001 and 2010. Multivariate models were performed to calculate the odds ratio (OR) of the independent risk factors that led to MCs and repeated for SCs, revisions, and mortality. The models controlled for age (< and > 65 years old), sex, race, revision status (except for revision analysis), surgical approach, number of levels fused/re-fused (2-3, 4-8, ≥ 9), and osteotomy utilization. ORs were weighted based on their predictive category: 2 times for revision surgery predictors and 4 times for mortality predictors. Fifty points were distributed among the predictors based on their cumulative OR to establish a risk index. RESULTS Discharges for 362,989 patients with cervical spine pathology were identified. The mean age was 52.65 years, and 49.47% of patients were women. Independent risk factors included medical comorbidities, surgical parameters, and demographic factors. Medical comorbidities included the following: pulmonary circulation disorder, coagulopathy, metastatic cancer, renal failure, congestive heart failure, alcohol abuse, neurological disorder, nonmetastatic cancer, liver disease, rheumatoid arthritis/collagen vascular diseases, and chronic blood loss/anemia. Surgical parameters included posterior approach to fusion/re-fusion, ≥ 9 levels fused/re-fused, corpectomy, 4-8 levels fused/re-fused, and osteotomy; demographic variables included age ≥ 65 years. These factors increased the risk of at least 1 of MC, SC, revision, or mortality (risk of death). A total of 50 points were distributed among the factors based on the cumulative risk ratio of every factor in proportion to the total risk ratios. CONCLUSIONS This study proposed an index to quantify the potential risk of morbidity and mortality prior to surgical intervention for patients with cervical spine pathology. This index may be useful for surgeons in patient counseling efforts as well as for health insurance companies and future socioeconomics studies in assessing surgical risks and benefits for patients undergoing surgical treatment of the cervical spine.

We describe the case of a patient with Budd-Chiari syndrome who presented with an unusual membranous obstruction of the inferior vena cava complicated by massive portal vein thrombosis (PVT). The patient underwent percutaneous transluminal balloon angioplasty through the right groin and was prescribed oral warfarin for 6 months. Treatment resulted in the complete disappearance of the PVT. This therapeutic strategy should be considered in the management of other cases of this rare, complex disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Opioid analgesics remain the first choice for the treatment of moderate to severe pain, but they are also notorious for their respiratory depression and addictive effects. This study focused on the pharmacology of a novel opioid receptor mixed agonist DPI-125 and attempted to elucidate the relationship between the δ-, μ- and κ-receptor potency ratio and respiratory depression and abuse liability. Five diarylmethylpiperazine compounds (DPI-125, DPI-3290, DPI-130, KUST202 and KUST13T02) were selected for this study. PKA fluorescence redistribution assays in CHO cells individually expressing δ-, μ- or κ-receptors were used to measure the agonist potency. The respiratory safety profiles were estimated in rats by the ratio of ED 50 (pCO 2 increase)/ED 50 (antinociception). The abuse liability of DPI-125 was evaluated with a self-administration model in rhesus monkeys. The observed agonist potencies of DPI-125 for δ-, μ- and κ-opioid receptors were 4.29±0.36, 11.10±3.04, and 16.57±4.14 nmol/L, respectively. The other four compounds were also mixed agonists with varying potencies. DPI-125 exhibited a high respiratory safety profile, clearly related to its high δ-receptor potency. The ratio of the EC 50 potencies for the μ- and δ-receptors was found to be positively correlated with the respiratory safety ratio. DPI-125 has similar potencies for μ- and κ-receptors, which is likely the reason for its reduced abuse potential. Our results demonstrate that the opioid receptor mixed agonist DPI-125 is safer and less addictive than traditional μ-agonist analgesics. These findings suggest that the development of δ>μ∼κ opioid receptor mixed agonists is feasible, and such compounds could represent a promising class of potent analgesics with wider therapeutic windows.

Purpose: To compare the results of computed tomography venography (CTV) with a fixed and a flexible delayed scan time for Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction., Material and Methods: A total of 209 consecutive BCS patients with IVC obstruction underwent either a CTV with a fixed delayed scan time of 180s (n=87) or a flexible delayed scan time for good image quality according to IVC blood flow in color Doppler ultrasonography (n=122). The IVC blood flow velocity was measured using a color Doppler ultrasound prior to CT scan. Image quality was classified as either good, moderate, or poor. Image quality, surrounding structures and the morphology of the IVC obstruction were compared between the two groups using a χ 2 -test or paired or unpaired t-tests as appropriate. Inter-observer agreement was assessed using Kappa statistics., Results: There was no significant difference in IVC blood flow velocity between the two groups. Overall image quality, surrounding structures and IVC obstruction morphology delineation on the flexible delayed scan time of CTV images were rated better relative to those obtained by fixed delayed scan time of CTV images (p<0.001). Evaluation of CTV data sets was significantly facilitated with flexible delayed scan time of CTV. There were no significant differences in Kappa statistics between Group A and Group B., Conclusion: The flexible delayed scan time of CTV was associated with better detection and more reliable characterization of BCS with IVC obstruction compared to a fixed delayed scan time., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To prospectively determine the value of blood flow velocity in the inferior vena cava (IVC) on color Doppler ultrasonography for the optimization of the delay in scanning time after contrast injection during computed tomography (CT) venography in patients with Budd-Chiari syndrome (BCS) with IVC obstruction., Methods: We enrolled 122 consecutive BCS patients with IVC obstruction. All patients underwent color Doppler ultrasonography, CT venography, and digital subtraction angiography (DSA) in that order prior to treatment. The delay in scanning time during CT venography was set at 120, 180, 240, and 300 s after contrast injection. The correlation between delay in CT scanning and IVC blood flow velocity on color Doppler ultrasonography was explored. Image quality was classified as good, moderate, or poor. Patients with good CT image quality were considered to have an optimal delay in scanning time., Results: Delays in scanning time of 120, 180, 240, and 300 s yielded good-quality images in 2, 7, 49, and 64 patients, respectively. The corresponding IVC blood flow velocities in these patients were 16.10 ± 0.42 cm/s (range 15.8-16.4 cm/s), 12.90 ± 1.58 cm/s (range, 11-15 cm/s), 7.53 ± 1.35 cm/s (range 5-10 cm/s), and 1.95 ± 1.75 cm/s (range 0-5.5 cm/s)., Conclusion: IVC blood flow velocity on color Doppler ultrasonography could serve as a useful tool for the optimization of the delay in scanning time during CT venography to ensure good-quality images for the diagnosis of BCS with IVC obstruction.

Introduction: Posterior C1-C2 fusion is a highly successful treatment for atlantoaxial instability and other pathologies of the cervical spine, with fusion rates approaching 95%-100%. However, poor visualization of the lateral masses of C1 secondary to the course of the C2 nerve root along with blood loss from the venous plexus and compression of the C2 nerve from lateral mass screws are technical obstacles that can arise during surgery. Thus, sacrifice of the C2 nerve root has long since been debated in fusions involving the C1 and C2 vertebral bodies., Methods: Cadaveric dissections on four adult specimens were performed. Both intradural and extradural courses of C2 were studied in detail. The tentative site of C2 nerve root compression during placement of C1 lateral mass screws was studied in detail. Both the indication as well as the ease of C2 neurectomy were studied in relation to postoperative compression and entrapment., Results: Four-six dorsal rootlets of C2 nerve were observed while studying the intradural course. The extradural course was studied with respect to the lateral mass of C1. The greater occipital nerve (GON) course was fairly consistent in all specimens. Transection of C2 around its ganglion would allow for proper C1 lateral mass screw placement as the course of C2 nerve interferes with proper placement of instrumentation., Conclusion: C2 nerve root transection is associated with occipital numbness but this often has no effect on health-related quality of life (HRQOL). The C2 nerve root preservation is often associated with entrapment neuropathy or occipital neuralgia, which greatly affects HRQOL. The C2 nerve root transection helps in better visualization, aids in optimal placement of C1 lateral mass screws, minimizes estimated blood loss and improves surgical outcome with successful fusion., Competing Interests: The authors have declared that no competing interests exist.

Background: Many preventive methodologies seek to reduce the risk of surgical site infections after total knee arthroplasty (TKA), including the use of preoperative chlorhexidine baths and cloths. Although we have demonstrated in previous studies that this may be an efficacious method for infection prevention, our study was underpowered and we therefore set out to evaluate this with a larger sample size., Questions/purposes: (1) Does a preadmission chlorhexidine cloth skin preparation protocol decrease the risk of surgical site infection in patients undergoing TKA? (2) When stratified using the National Healthcare Safety Network (NHSN) risk categories, which categories are associated with risk reduction from the preadmission chlorhexidine preparation protocol?, Methods: In our study, all patients (3717 total) who had undergone primary or revision TKA at a single institution between January 1, 2007, and December 31, 2013, were identified, of whom 991 patients used the chlorhexidine cloths before surgery and 2726 patients did not. All patients were provided cloths with instructions before surgery; however, as a result of a lack of compliance, we were able to substratify patients into treatment and control cohorts. Additionally, we substratified patients by NHSN risk category to determine differences in infection between the two cohorts (cloth versus no cloth). Patient medical records and an infection-tracking database were reviewed to determine the development of periprosthetic infection (patients who had superficial infections were excluded from our study) in both groups after 1 year surveillance. We then calculated relative risk reductions with use of chlorhexidine gluconate and stratified results based on NHSN risk category., Results: Use of a preoperative chlorhexidine cloth skin preparation protocol is associated with reduced relative risk of periprosthetic infection after TKA (infections with protocol: three of 991 [0.3%]; infections in control: 52 of 2726 [1.9%]; relative risk [RR]: 6.3 [95% confidence interval [CI], 1.9-20.1]; p = 0.002). When stratified by NHSN risk category, periprosthetic infection risk reduction was seen in the medium-risk category (protocol: one of 402 [0.3%]; control: 25 of 1218 [2.0%]; RR, 8.3 [CI, 1.1-60.7]; p = 0.038), but no significant difference was detected in the low- and medium-risk groups (RR, 2.1 [CI, 0.5-9.6; p = 0.33] and RR, 11.3 [CI, 0.7-186.7; p = 0.09])., Conclusions: A prehospital chlorhexidine gluconate wipe protocol appears to reduce the risk of periprosthetic infections after TKA, primarily in those patients with medium and high risk. Although future multicenter randomized trials will need to confirm these preliminary findings, the intervention is inexpensive and is unlikely to be risky and therefore might be considered on the basis of this retrospective, comparative study., Level of Evidence: Level III, therapeutic study.

Background: Nowadays, flat detector (FD) equipped angiographic C-arm computed tomography (CACT) systems can be used to acquire CT-like cross-sectional images directly within the interventional suite. The CACT systems offer real time visualization of transthoracic needle biopsy (TNB) procedure and more flexibility in the orientation of the detector system around the patient compared to traditional CT systems., Purpose: To evaluate the value of a flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy (PTNB) for small (≤3 cm) pulmonary lesions in clinical practice., Material and Methods: A total of 60 patients with solid lung lesions were retrospectively enrolled to undergo PTNB procedures. The mean diameter of lesions was 2.3 ± 0.6 cm (range, 0.6-3 cm). The needle path was carefully planned and calculated on the C-arm CT system, which acquired three-dimensional CT-like cross-sectional images. The PTNB procedures were performed under needle guidance with fluoroscopic feedbacks., Results: Histopathologic tissue was successfully obtained from 59 patients with a puncture success rate of 98.3% (59/60). The diagnostic accuracy rate was found to be 91.5% (54/59). There were only two cases of pneumothorax (3.3%) requiring therapy. The rates of pneumothorax and hemoptysis were low (15.0% [9/60] and 8.3% [5/60], respectively). The overall procedural time was in the range of 12-18 min, resulting in a mean exposure dose of 224.4 ± 4.8 mGy., Conclusion: Our study shows that C-arm CT-based needle guidance enables reliable and efficient needle positioning and progression by providing real-time intraoperative guidance for small (≤3 cm) pulmonary lesions in clinical practice., (© The Foundation Acta Radiologica 2015.)

Individual differences in cognitive aging exist in humans and in rodent populations, yet the underlying mechanisms remain largely unclear. Activity-dependent delivery of GluR1-containing AMPA receptor (AMPARs) plays an essential role in hippocampal synaptic plasticity, learning and memory. We hypothesize that alterations of surface GluR1 expression in the hippocampus might correlate with age-related cognitive decline. To test this hypothesis, the present study evaluated the cognitive function of young adult and aged rats using Morris water maze. After the behavioral test, the surface expression of GluR1 protein in hippocampal CA1 region of rats was determined using Western blotting. The results showed that the surface expression of GluR1 in the hippocampus of aged rats that are cognitively impaired was much lower than that of young adults and aged rats with preserved cognitive abilities. The phosphorylation levels of GluR1 at Ser845 and Ser831 sites, which promote the synaptic delivery of GluR1, were also selectively decreased in the hippocampus of aged-impaired rats. Correlation analysis reveals that greater decrease in surface GluR1 expression was associated with worse behavioral performance. These results suggest that reduced surface GluR1 expression may contribute to cognitive decline that occurs in normal aging, and different pattern of surface GluR1 expression might be responsible for the individual differences in cognitive aging., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Budd-Chiari syndrome (BCS) caused by hepatic venous outflow obstruction may result in portal hypertension and the development of intrahepatic collaterals that bypass the obstruction. Spontaneous intrahepatic portosystemic venous shunt (SIPSVS) is uncommon and may be associated with portal hypertension. SIPSVS is extremely rare in patients with BCS and has not been well documented. We report a case of SIPSVS in a 42-year-old woman with BCS caused by membranous obstruction and chronic thrombosis in the inferior vena cava (IVC). A direct vascular communication between the left portal vein and IVC was confirmed by sonography and a computed tomography angiography scan. The patient underwent successful percutaneous balloon angioplasty of the IVC. Surgical or endovascular treatment for SIPSVS was not carried out because the patient was asymptomatic and remained asymptomatic in terms of encephalopathy at a 1-year follow-up., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Mas-related G protein-coupled receptor D (MrgD) is expressed almost exclusively in nociceptive primary sensory neurons and the neurons located in stratum granulosum of skin. More and more evidence suggest that MrgD plays an important role in pain sensation and/or transduction. Recent studies have demonstrated that the receptor is also involved in itch sensation in both mouse and human. In the present study, we identified a robust inward current in MrgD-expressing Xenopus oocytes by using β-alanine, a putative ligand of MrgD. The currents were sensitive to inhibitor of Ca(2+)-activated chloride channels (CaCCs) and intracellular Ca(2+) chelator, suggesting they were produced by endogenous CaCCs. Furthermore, it was demonstrated that upon the application of phospholipase C (PLC) inhibitor, or antisense oligonucleotides of inositol trisphosphate receptor (IP3R), the β-alanine-induced currents were dramatically depressed. However, protein kinase C inhibitor did not display any visible effect on CaCC currents. In summary, our data suggest that the activation of MrgD promotes the open of endogenous CaCCs via G(q)-PLC-IP3-Ca(2+) pathway. The current findings reveal the functional coupling between MrgD and CaCCs in Xenopus oocytes and also provide a facile model to assay the activity of MrgD.

Aims: It is considered that a long-acting therapy would be advantageous in the treatment of addiction. In a search for novel buprenorphine analogues, thienorphine was demonstrated to be an extremely long-acting orally active partial opioid agonist. This study explored the mechanisms underlying the long-lasting effects of thienorphine., Methods: The binding kinetics of [(3) H]thienorphine were measured in membrane preparations expressing cloned rat opioid receptors. Flow cytometric analysis was used to determine the effect of thienorphine on the surface opioid receptor number. The long-lasting effects of thienorphine were also confirmed at the tissue level and in vivo., Results: At 37°C, [(3) H]thienorphine showed rapid association with μ- and κ-opioid receptors, while its dissociation was sluggish and biphasic (K-1 = 0.21 min(-1) , K-2 = 0.0078 min(-1) for the μ-receptor; K-1 = 0.17 min(-1) , K-2 = 0.0042 min(-1) for the κ-receptor). Treatment with thienorphine for 24, 48, and 72 h downregulated surface μ-receptor in a dose- and time-dependent manner. The inhibitory effect of thienorphine on guinea pig ileum persisted for more than 120 min after prolonged washing. In vivo, thienorphine exhibited significant antagonism of morphine-induced antinociception for more than 7 days., Conclusions: These results indicate that multiple factors, including persistent receptor occupation and enhanced receptor downregulation, may contribute to the long-lasting effects of thienorphine that would be beneficial for its application in addiction treatment., (© 2013 John Wiley & Sons Ltd.)

We describe an elderly woman who presented with an unusual primary arterioportal fistula and cavernous transformation of the portal vein caused by portal thrombosis, which were subsequently managed with endovascular coil embolization and transjugular intrahepatic portosystemic shunt using 2 stents after balloon remodeling. This case shows a rarely seen condition in the elderly and a novel management strategy that should be considered in the management of this complex disease., (Published by Elsevier Inc.)

Purpose: This study was done to evaluate the clinical implications and results of a prospective protocol using 64-row computed tomographic angiography (CTA) for diagnosis and pre-treatment planning in pulmonary sequestration (PS)., Materials and Methods: Forty-five patients with suspected PS were referred for CTA examination. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of measures used to detect PS were determined by patient-based and aberrant systemic artery-based evaluations. The location, the size and the number of aberrant systemic arteries, and the feasibility of endovascular treatment were analysed. The capability of CTA to provide a working view and the accuracy of measurements in choosing a coil were also assessed., Results: Digital subtraction angiography and/or surgery revealed PS in 38 patients, and 7 patients had no PS. The patient-based evaluation yielded an accuracy of 97.8 %, sensitivity of 97.4 %, specificity of 100 %, PPV of 100 % and NPV of 87.5 %, in the detection of PS. CTA clearly depicted the PS in all 38 patients, and the aberrant systemic artery was accurately demonstrated in 37 out of 38 patients where endovascular treatment was possible. Working views for endovascular treatment were found in all patients with PS, and the choice of coil was correct in 37 out of 38 patients using CTA., Conclusions: 64-row CTA appears to be effective in terms of supporting accurate diagnosis and pre-treatment planning in PS. CTA is not only able to provide clear visualisation of aberrant systemic arteries but also provides detailed images of abnormal lung parenchyma and the airways.