bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Diagnostic and Prognostic Role of Interleukin 12B and Interleukin 6R Gene Polymorphism in Patients With Ankylosing Spondylitis
Authors: Ruan Wen-Feng , Xie Jiang-Tao , Jin Qi , Wang Wen-Da , Ping An-Song 
Published: December 2017

Objectives
Interleukin 23 (IL-23) pathway and IL-1 cluster genes play prominent role in the etiopathology of ankylosing spondylitis (AS). The aim of this study was to investigate the diagnostic and prognostic role of 5 single-nucleotide polymorphisms related to IL-23 pathway and IL-1 cluster genes in AS patients.

Methods
Four hundred thirty-one patients with AS and 206 age- and sex-matched healthy controls were recruited in this prospective cohort study. Five potential single-nucleotide polymorphisms (IL-23R [rs11209026], IL-12B [rs6871626], TYK2 [rs6511701], IL-6R [rs4129267], and IL-1R2 [rs2192752]) related to IL-23 pathway and IL-1 cluster genes by analyzing previous studies were genotyped. Among 431 total AS patients, 198 active cases were treated and followed up for 24 weeks.

Results
Frequencies of IL-12B AA (rs6871626) and IL-6R TT (rs4129267) genotypes were increased in AS patients compared with healthy controls (both P < 0.001), and IL-12B A (rs6871626) as well as IL-6R T (rs4129267) allele increased the risk of AS independently (both P < 0.001). The Bath Ankylosing Spondylitis Disease Activity Index score was found to be elevated in AS patients with IL-12B AA (rs6871626) compared with patients with the CA and CC genotypes (P = 0.002 and P < 0.001, respectively), and the Bath Ankylosing Spondylitis Functional Index score was also increased in AS patents with IL-12B AA (rs6871626) than in those with the CA and CC genotypes (P = 0.001 and P < 0.001). In addition, IL-6R T (rs4129267) allele could predict a worse ASAS-20 (Assessment of SpondyloArthritis international Society) response at week 24 as an independent factor by multivariate logistic regression analysis with additive model (P = 0.011).

Conclusions
Interleukin 12B (rs6871626) and IL-6R (rs4129267) gene polymorphisms could serve as promising biomarkers for diagnosis and prognosis in AS patients.
Large Artery Dysfunction in Primary Antiphospholipid Syndrome
Authors: Osmundo Gilmar S. , Carvalho Jozélio Freire , Bortolotto Luiz A. , Viana Vilma S.T. , Bonfá Eloisa 
Published: December 2017

Objective
The aim of this study was to assess the arterial distensibility of large vessels and changes in microvasculature in primary antiphospholipid syndrome.

Methods
Twenty-two antiphospholipid syndrome (APL) patients and 66 age-, sex-, height-, and blood pressure–matched controls were evaluated. Second derivative of the finger photoplethysmogram (SDPTG) was used as a noninvasive method to evaluate the pulse wave. The b/a and d/a indices, which reflect, respectively, large-vessel and small-vessel properties, were calculated from the SDPTG waveform components. Vascular age index was also determined.

Results
Arterial thrombosis occurred in 59.1% (13/22) of APL patients, with a predominance of stroke episodes (61.5%). Venous thromboembolism was observed in 36.4% (all deep venous thrombosis), and obstetric complications in 36.4%. Frequency of diabetes mellitus, smoking, and dyslipidemia was comparable in APL patients and control subjects (P > 0.05). Concerning plethysmography findings, b/a ratio was higher in patients than in control subjects (−0.44 ± 0.16 vs. −0.54 ± 0.18, P = 0.034), whereas d/a ratio (−0.30 ± 0.16 vs. −0.31 ± 0.18, P = 0.83) was comparable. Moreover, SDPTG (−0.16 ± 0.35 vs. −0.30 ± 0.38, P = 0.16) and vascular age index values (53.5 ± 11.6 vs. 51.8 ± 16.1, P = 0.65) were alike in both groups. Regarding disease-related factors, patients with arterial and venous thrombosis had similar b/a, d/a, and vascular age indices (P = 0.95; P = 0.06; P = 0.12, respectively).

Conclusions
The higher b/a ratio in APL patients suggests decreased distensibility of large arteries and may be why APL patients are at higher risk for cardiovascular events. The d/a ratio, that is considered a marker of small vessel vascular resistance, was not different than controls. Further studies are needed to evaluate vascular factors that predispose APL patients to atherosclerotic events.
Sputum Anticitrullinated Protein Antibodies in Patients With Long-standing Rheumatoid Arthritis
Authors: Polachek Ari , Vree Egberts Wilma , Fireman Elizabeth , Druckman Ido , Stark Moshe , Paran Daphna , Kaufman Ilana , Wigler Irena , Levartovsky David , Caspi Dan , Pruijn Ger J.M. , Elkayam Ori 
Published: December 2017

Objective
The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA).

Methods
Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay.

Results
Patients with RA had the following characteristics: mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44, and Sharp–van der Heijde score of 57.5. Ten of the 19 RA patients showed high titers of ACPAs in their sera. Four of the seropositive (40%), none of the seronegative RA patients, and only 1 of the control subjects showed detectable levels of ACPAs in their sputum. The ratio between the reactivity with CitP and NorP peptides in the sputum was significantly higher in RA sputum than in control sputum (1.33 ± 1.2 vs. 0.64 ± 0.14, P = 0.02). A positive correlation was found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti-CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in the sputum. No significant correlation was found between sputum ACPAs and disease severity, history of smoking, lung function tests, or treatment for RA.

Conclusions
Anticitrullinated protein/peptide antibodies can be detected in the sputum of RA patients and are correlated with the presence in the serum.
Sonographic Findings of Hands and Wrists in Systemic Lupus Erythematosus Patients With Jaccoud Arthropathy
Authors: Lins Carolina Freitas , de Sá Ribeiro Daniel Lima , Santos Willer Gonçalves Dourado , Rosa Genevievi , Machicado Viviane , Pedreira Ana Luiza , da Fonseca Emanuela Pimenta , Souza Anna Paula Mota Duque , Silva Carla Baleeiro Rodrigues , Ferreira Luana Grazielle dos Santos , Galvão Verena , de Oliveira Isabela Silva , Atta Ajax Merces , Santiago Mittermayer Barreto 
Published: December 2017

Introduction
Jaccoud arthropathy (JA) is a deforming nonerosive arthropathy, characterized by the presence of “reversible” joint deformity. The study aims at describing the main musculoskeletal ultrasound (US) findings of a series of systemic lupus erythematosus (SLE) patients with JA.

Methods
Consecutive patients diagnosed as having JA and SLE were included in the study. All patients underwent a whole clinical evaluation and US of the hands and wrists. The US scan evaluated the presence of synovial hypertrophy, tenosynovitis, and bone erosions.

Results
Thirty-nine of 40 patients were female. The US examination was performed on 560 joints of the hands and wrists. At least 1 change was observed in the US examination of 20 patients (50.0%), but there was not a statistically significant association with disease activity (P = 0.33). Nineteen patients (47.5%) had synovial hypertrophy, 9 (22.5%) had tenosynovitis, and 7 (17.5%) had both. Isolated small bone erosions were identified in 2 patients (5.0%).

Conclusions
Ultrasound examination is a reliable and noninvasive imaging method for the evaluation of joint involvement in SLE. Half of the patients with JA have ultrasonographic signs of joint inflammation, and these abnormalities may be found even in the absence of disease activity.
Direct peritoneal resuscitation reduces intestinal permeability after brain death
Authors: Weaver Jessica L. , Matheson Paul J. , Matheson Amy , Graham Victoria , Harbrecht Brian G. , Downard Cynthia D. , Garrison R. Neal , Smith Jason W. 
Published: December 2017

Background
The profound inflammatory response associated with brain death is frequently cited as the reason organs procured from brain dead donors are associated with worse graft function. The intestine releases inflammatory mediators in other types of shock, but its role is brain death has not been well-studied. Direct peritoneal resuscitation (DPR) improves visceral organ blood flow and reduces inflammation after hemorrhagic shock. We hypothesized that use of DPR would maintain intestinal integrity and reduce circulating inflammatory mediators after brain death.

Methods
Brain death was induced in male Sprague-Dawley rats by inserting a 4F Fogarty catheter into the epidural space and slowly inflating it. After herniation, rats were resuscitated with normal saline to maintain a mean arterial pressure of 80 mm Hg and killed with tissue collected immediately (time 0), or 2 hours, 4 hours, or 6 hours after brain death. Randomly selected animals received DPR via an intraperitoneal injection of 30-mL commercial peritoneal dialysis solution.

Results
Levels of proinflammatory cytokines, including IL-1β and IL-6, as well as high-mobility group box 1 protein and heat shock protein 70, were all increased after brain death and decreased with DPR. Fatty acid binding protein and lipopolysaccharide, both markers of intestinal injury, were increased in the serum after brain death and decreased with DPR. Immunohistochemistry staining for zona occludin-1 showed decreased intestinal tight junction integrity after brain death, which improved with DPR.

Conclusions
Intestinal permeability increases after brain death, and this contributes to the increased inflammation seen throughout the body. Using DPR prevents intestinal ischemia and helps preserve intestinal integrity. This suggests that using this novel therapy as an adjunct to the resuscitation of brain dead donors has the potential to reduce inflammation and potentially improve the quality of transplanted organs.
Gut epithelial cell-derived exosomes trigger posttrauma immune dysfunction
Authors: Kojima Mitsuaki , Costantini Todd W. , Eliceiri Brian P. , Chan Theresa W. , Baird Andrew , Coimbra Raul 
Published: December 2017

BACKGROUND
Exosomes are extracellular vesicles that act as endogenous mediators of the immune response. We have previously shown that exosomes released into mesenteric lymph (ML) following trauma (T)/hemorrhagic shock (HS) induce proinflammatory cytokine production in macrophages and are involved in the pathogenesis of postshock acute lung injury. However, the cellular origin of ML exosomes and their role in the posttrauma immune response remains unclear. We hypothesized that exosomes released from damaged-intestinal epithelial cells contribute to posttrauma immune dysfunction by altering the function of dendritic cells (DCs), key regulators of the adaptive immunity.

METHODS
Male rats underwent cannulation of the femoral artery, jugular vein and ML duct. T/HS was induced by laparotomy and 60 minutes of hemorrhagic shock followed by resuscitation. The ML was collected before (preshock) and after T/HS (post-T/HS) for isolation of exosomes. Surface epitopes of exosomes isolated from ML were assessed by flow cytometry to determine their cellular origin and phenotypic changes. The immunomodulatory effects of ML exosomes on DCs were assessed by Annexin V apoptosis assay, expression of costimulatory molecules, and antigen-presenting capacity to lymphocytes.

RESULTS
Exosomes isolated from ML highly expressed CD63 (exosome marker) and epithelial cell-specific marker, suggesting their derivation from intestinal epithelial cells. The expression of immunomodulatory molecules, such as major histocompatibility complex class II and Fas ligand on ML exosomes, was significantly increased after T/HS. Coincubation of DCs with exosomes isolated from ML after T/HS increased DC apoptosis twofold compared with preshock ML exosomes. Furthermore, post-T/HS ML exosomes significantly suppressed lipopolysaccharide-mediated expression of CD80 and CD86 on DCs as well as decreased their antigen-presenting capacity to induce lymphocytes proliferation.

CONCLUSION
Gut epithelial cells release immunomodulatory exosomes into the ML after T/HS and resuscitation. Mesenteric lymph exosomes may be critical mediators of posttraumatic immunosuppression causing depletion and dysfunction of DCs.
Tubastatin A prevents hemorrhage-induced endothelial barrier dysfunction
Authors: Bruhn Peter J. , Nikolian Vahagn C. , Halaweish Ihab , Chang Zhigang , Sillesen Martin , Liu Baoling , Li Yongqing , Alam Hasan B. 
Published: December 2017

Background
Microvascular hyperpermeability resulting from endothelial barrier dysfunction (EBD) is associated with worse clinical outcomes in trauma-induced hemorrhagic shock. We have previously shown that treatment with Tubastatin A (TubA), a histone deacetylase 6 inhibitor, improves outcomes in animal models of shock. In this study, we investigate whether TubA treatment may prevent trauma-related EBD.

Methods
Wistar-Kyoto rats subjected to 40% hemorrhage were treated with TubA or vehicle control. Acute lung injury (ALI) was assessed histologically from tissues harvested 6 hours posthemorrhage. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured in EGM BulletKit medium. Medium was exchanged for glucose-free Dulbecco’s Modified Eagle Medium (0.5% fetal bovine serum) with or without TubA, and cells were placed in an anoxic chamber (5% CO2, 95% N2, 20–48 hours). Expression of acetylated tubulin and hypoxia-inducible factor 1α was measured by Western blot. Soluble Intercellular Adhesion Molecule-1 concentration within the medium, a marker of endothelial integrity, was determined using enzyme-linked immunosorbent assay. Monolayers were assessed for permeability via transwell assays using fluorescein isothiocyanate-labeled albumin.

Results
Rats treated with TubA had significantly reduced ALI relative to vehicle control. In vitro, TubA significantly attenuated anoxia-induced hyperpermeability, hypoxia-inducible factor 1α expression, and glycocalyx shedding.

Conclusions
Our findings demonstrate that TubA prevents hemorrhage-induced ALI in rats. Additionally, we have shown that TubA prevents anoxia-induced EBD in vitro. Taken together, these results suggest that TubA could attenuate microvascular hyperpermeability related to hemorrhagic shock.
Preliminary results of a novel hay-hole fall prevention initiative
Authors: Batra Erich K. , Gross Brian W. , Jammula Shreya , Bradburn Eric H. , Baier Ronald D. , Reihart Michael J. , Murphy Dennis , Moyer Kay , Hess Joseph , Lackmann Susan , Miller Jo Ann , Rogers Frederick B. 
Published: December 2017

BACKGROUND
Hay-hole falls are a prevalent source of trauma among Anabaptists—particularly Anabaptist youth. We sought to decrease hay-hole falls in South Central Pennsylvania through the development and distribution of all-weather hay-hole covers to members of the at-risk Anabaptist community.

METHODS
Following the creation of a rural trauma prevention syndicate, hay-hole cover prototypes co-designed and endorsed by the Pennsylvania Amish Safety Committee were developed and distributed throughout South Central Pennsylvania. Preintervention and postintervention surveys were distributed to recipients to gain an understanding of the hay-hole fall problem in this population, to provide insight into the acceptance of the cover within the community, and to determine the efficacy of the cover in preventing falls.

RESULTS
A total of 231 hay-hole covers were distributed throughout eight rural trauma-prone counties in Pennsylvania. According to preintervention survey data, 52% of cover recipients reported at least one hay-hole fall on their property, with 46% reporting multiple falls (median fall rate, 1.00 [1.00–2.00] hay-hole falls per respondent). The median self-reported distance from hay-hole to ground floor was 10.0 (8.00–12.0) feet, and the median number of hay-holes present on-property was 3.00 (2.00–4.00) per respondent. Postintervention survey data found 98% compliance with hay-hole cover installation and no subsequent reported hay-hole falls.

CONCLUSION
With the support of the Pennsylvania Amish Safety Committee, we developed a well-received hay-hole cover which could effectively reduce fall trauma across other rural communities in the United States.

LEVEL OF EVIDENCE
Epidemiological study, Level III.
Variations in outcomes of emergency general surgery patients across hospitals: A call to establish emergency general surgery quality improvement program
Authors: Ogola Gerald O. , Crandall Marie L. , Shafi Shahid 
Published: December 2017

BACKGROUND
National Surgical Quality Improvement Program and Trauma Quality Improvement Program have shown variations in risk-adjusted outcomes across hospitals. Our study hypothesis was that there would be similar variation in risk-adjusted outcomes of emergency general surgery (EGS) patients.

METHODS
We undertook a retrospective analysis of the National Inpatient Sample database for 2010. Patients with EGS diseases were identified using American Association for the Surgery of Trauma definitions. A hierarchical logistic regression model was used to model in-hospital mortality, accounting for patient characteristics, including age, sex, race, ethnicity, insurance type, and comorbidities. Predicted-to-expected mortality ratios with 90% confidence intervals were used to identify hospitals as low mortality (ratio significantly lower than 1), high mortality (ratio significantly higher than 1), or average mortality (ratio overlapping 1).

RESULTS
Nationwide, 2,640,725 patients with EGS diseases were treated at 943 hospitals in 2010. About one-sixth of the hospitals (139, 15%) were low mortality, a quarter were high mortality (221, 23%), and the rest were average mortality. Mortality ratio at low mortality hospitals was almost four times lower than that of high mortality hospitals (0.57 vs. 2.03, p < 0.0001). If high and average mortality hospitals performed at the same level as low mortality hospitals, we estimate 16,812 (55%) more deaths than expected.

CONCLUSION
There are significant variations in risk-adjusted outcomes of EGS patients across hospitals, with several thousand higher than expected number of deaths nationwide. Based on the success of National Surgical Quality Improvement Program and Trauma Quality Improvement Program, we recommend establishing EGS quality improvement program for risk-adjusted benchmarking of hospitals for EGS patients.

LEVEL OF EVIDENCE
Care management, level III.
One-Year Retention Study of Adjunctive Perampanel Treatment in Epilepsy Patients
Authors: Kim Dong Wook , Oh Jeeyoung 
Published: December 2017

ObjectivesPerampanel is a recently introduced antiepileptic drug (AED) with a unique action mechanism of noncompetitive and selective α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist. Because of delayed approval of perampanel in most Asian countries, there is limited information on the clinical usefulness of perampanel in the Asian population. We performed a retrospective analysis of retention rate, seizure outcome, and adverse events for perampanel treatment in South Korea.MethodsThis was a retrospective, single-center, 1-year observational study. A total of 137 epilepsy patients (86 men, 51 women; age, 17–86 years) who were treated with perampanel as an adjunctive treatment were included. Perampanel was administered at a starting dose of 2 mg/d, and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed during a 1-year follow-up.ResultsThe overall retention rate was 71.3% at the 6-month follow-up and 61.0% at the 1-year follow-up. Retention rates were similar between patients with 1 concomitant AED and those taking 2 or more concomitant AEDs. The most common adverse event was somnolence, followed by dullness and psychiatric reactions, and the presence of psychiatric comorbidity was significantly associated with the development of psychiatric adverse reactions.ConclusionsWe showed that the retention rate and adverse events for adjunctive perampanel treatment in the Korean population were comparable with those in Western countries. Our study also suggests that adjuvant perampanel treatment may be effective in patients taking a higher number of concomitant AEDs and that psychiatric comorbidity may be a risk factor for perampanel-induced psychiatric reactions.
Anger Assessment in Patients Treated With Brivaracetam
Authors: Ortega Gemma , Abraira Laura , Martí Glòria , Quintana Manuel , Mazuela Gonzalo , Santamarina Estevo , Salas-Puig Xavier , Toledo Manuel 
Published: December 2017

Objectives
To assess state and trait anger, adjusted by epilepsy type, seizure control, anxiety-depression status and quality of life, in patients treated with brivaracetam (BRV) from an open study.

Methods
We evaluated prospectively consecutive patients with partial onset seizures in an open-label study. Patients had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic drugs. They were treated with BRV and compared with a control group selected from outpatients attending our epilepsy unit who met the following criteria: age ≥16 years and diagnosis of epilepsy with focal-onset seizures at least 1 year before inclusion in the study. The following tests were assessed: State-Trait Anger with the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of Life in Epilepsy Inventory.

Results
We recruited 39 patients, 17 treated with BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was 47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100% BRV vs 68.2% control group). Demographic and clinical characteristics, as well as Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale scores were similar in both groups. When compared with the subgroup of LEV groups did not differ significantly on their Hospital Anxiety and Depression Scale scores.

Conclusions
This small, open study suggests that BRV increases anger measures less than LEV in epilepsy patients. However, larger, blinded control studies are required to establish whether this apparent difference can be confirmed.