bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Olfactory Outcome after Nasoseptal Flap Reconstructions in Midline Skull Base Surgery
Authors: Soyka Michael B. , Serra Carlo , Regli Luca , Meier Eva , Holzmann David 
Published: September 2017

Background The nasoseptal flap (NSF) is a universally used surgical technique to cover defects of the skull base after extended sinonasal surgery. Long-term follow-up of complications, sequelae, and smell function is largely unknown. Objective The main objective of this study was to investigate monorhinal olfaction after transsphenoidal skull base surgery. Methods Patients who underwent skull base surgery for midline lesions (craniopharyngioma and pituitary tumors) by using a NSF, also referred to as the Haddad flap, were assessed for their long-term outcome. Endoscopic examination was conducted and the bilateral “Sniffin’ Sticks” test was performed before surgery. Each side was tested separately in the postoperative follow-up consultation. Results Twenty patients were included in the study. No flap failures were observed. One anterior perforation and one small posterior septal perforation were found during long-term follow-up. None of the patients had nasal breathing impairment, whereas two patients had nose bleeds. A significant decrease in olfactory function was observed on the flap donor side in four patients (20%) compared with that observed in one patient (5%) on the opposite side. Conclusion NSF reconstructions for midline lesions were efficient and safe in the long term. Olfactory impairment on the donor side was frequently encountered. Although subclinical, these findings justified a monorhinal smell testing before surgery, which possibly prevented bilateral smell impairment in patient with preexisting single-sided olfactory loss.
Positive Nikolsky Sign and Pinpoint “Lakes of Pus”
Authors: Wong Christina Y , Billings Steven D , Warren Christine B 
Published: September 2017

A 54-year-old man with a past medical history of paraplegia, osteomyelitis, sacral decubitus ulcer, suprapubic catheter, and several reported drug eruptions was seen for evaluation of skin sloughing without any tenderness to palpation. He reported being on chronic oral antibiotics including amoxicillin/clavulanic acid and ciprofloxacin over the past two years for osteomyelitis. Two days prior to evaluation, he had been hospitalized for osteomyelitis of the left iliac bone and was treated with intravenous vancomycin and meropenem. Initial evaluation revealed widespread Nikolsky sign with extensive involvement of the back, abdomen, and extremities without any tenderness. Involving 30-40% body surface area were scattered deep red macules and patches. The histopathologic findings were consistent with the diagnosis of acute generalized exanthematous pustulosis (AGEP). Clinically, AGEP appears as diffuse erythema with several small, non-follicular pustules and possible peripheral neutrophilia or eosinophilia. A positive Nikolksy sign can be seen with AGEP, but is not specific, and has been referred to as a ‘pseudo-Nikolsky sign.’ Systemic involvement, such as renal insufficiency, has been reported in AGEP. There are few reports in the literature describing AGEP with TEN-like features. We present an interesting patient with AGEP and TEN-like features who improved after cessation of vancomycin and meropenem and a short course of systemic steroids.
OMERACT Endorsement of Patient-reported Outcome Instruments in Antineutrophil Cytoplasmic Antibody–associated Vasculitis
Authors: Robson Joanna C. , Tomasson Gunnar , Milman Nataliya , Ashdown Sue , Boonen Annelies , Casey George C. , Cronholm Peter F. , Cuthbertson David , Dawson Jill , Direskeneli Haner , Easley Ebony , Kermani Tanaz A. , Farrar John T. , Gebhart Don , Lanier Georgia , Luqmani Raashid A. , Mahr Alfred , McAlear Carol A. , Peck Jacqueline , Shea Beverley , Shea Judy A. , Sreih Antoine G. , Tugwell Peter S. , Merkel Peter A. 
Published: September 2017

Objective.The antineutrophil cytoplasmic antibody–associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016.Methods.A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented.Results.OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement).Conclusion.The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial.
Associations Between Knee Effusion-synovitis and Joint Structural Changes in Patients with Knee Osteoarthritis
Authors: Wang Xia , Jin Xingzhong , Blizzard Leigh , Antony Benny , Han Weiyu , Zhu Zhaohua , Cicuttini Flavia , Wluka Anita E. , Winzenberg Tania , Jones Graeme , Ding Changhai 
Published: September 2017

Objective.To describe the associations between effusion-synovitis and joint structural abnormalities in patients with knee osteoarthritis (OA) over 24 months.Methods.A posthoc analysis using data from a randomized controlled trial in 413 patients with symptomatic OA (aged 63 ± 7 yrs, 208 women). Knee effusion-synovitis volume and score, cartilage defects, cartilage volume, and bone marrow lesions (BML) were assessed using magnetic resonance imaging. Joint space narrowing (JSN) and osteophytes were assessed using radiograph. Least significant change criterion was used to define change in effusion-synovitis volume. Knee symptoms were assessed by Western Ontario and McMaster University OA Index. Multivariable linear/logistic regression and multilevel generalized mixed-effects models were used in longitudinal analyses.Results.Total effusion-synovitis volume increased modestly from baseline (8.0 ± 8.5 ml) to followup (9.0 ± 10.5 ml). Baseline BML, cartilage defect, JSN, and osteophyte scores were positively associated with change in effusion-synovitis volume (p < 0.05). Baseline cartilage defects and JSN were also associated with change in effusion-synovitis score (p < 0.05). However, neither baseline effusion-synovitis score nor volume consistently predicted change in the above structures except cartilage volume. In the mixed-effects models, knee effusion-synovitis was positively associated with BML (volume: β = 1.19 ml/grade; score: OR = 1.75/grade) and cartilage defects (volume: β = 1.87 ml/grade; score: OR = 2.22/grade), while negatively associated with cartilage volume loss. Change in effusion-synovitis volume was positively correlated with changes in knee pain and stiffness scores (p < 0.05).Conclusion.Knee cartilage and subchondral bone abnormalities predicted change in effusion-synovitis, but effusion-synovitis did not predict knee structural changes. These findings suggest that synovial inflammation is likely the result of joint structural abnormalities in established OA. ClinicalTrials.gov identifier: NCT01176344. Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.
Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of “Non-criteria” Antiphospholipid Antibodies
Authors: Zohoury Navid , Bertolaccini Maria Laura , Rodriguez-Garcia Jose Luis , Shums Zakera , Ateka–Barrutia Oier , Sorice Maurizio , Norman Gary L. , Khamashta Munther 
Published: September 2017

Objective.Most clinicians use the 2006 Sydney classification criteria to evaluate patients suspected of having antiphospholipid syndrome (APS). Although sensitive and specific for APS, many patients fulfilling clinical criteria for the syndrome are persistently negative for the specific serological tests (“laboratory criteria”). These “seronegative APS” (SN-APS) patients can go undiagnosed and untreated until they experience serious clinical events. This study’s objective was to describe antibody profiles of SN-APS patients using non-criteria markers, assess the clinical utility of these markers separately and in combination, and suggest incorporation into guidelines for patients suspected of APS.Methods.We categorized 175 consecutive patients suspected of APS into 2 subgroups: 107 fulfilling Sydney APS classification for seropositive APS (SP-APS) and 68 with clinical manifestations suggestive of APS but having negative serology, on 2 occasions, for criteria markers (SN-APS). On study inclusion, samples were retested for criteria and 11 non-criteria markers, including antiphosphatidylserine/prothrombin antibodies.Results.Using 4 of 11 non-criteria tests, a cumulative 30.9% of SN-APS patients were detected. Combining results of all 11 non-criteria tests, 25 SN-APS (36.8%) and 89 SP-APS (83.2%) were positive for 1 or more non-criteria antibodies.Conclusion.Failure to diagnose APS can result in severe clinical consequences. Patients displaying clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. In our cohort, around one-third of SN-APS patients showed reactivity to 1 or more non-criteria markers. An update to the current classification criteria incorporating new serological markers should be considered to identify and stratify patients with APS for more effective treatment and management.
Trends in Treatment, Outcomes, and Incidence of Orthopedic Surgery in Patients with Rheumatoid Arthritis: An Observational Cohort Study Using the Japanese National Database of Rheumatic Diseases
Authors: Matsumoto Takumi , Nishino Jinju , Izawa Naohiro , Naito Masashi , Hirose Jun , Tanaka Sakae , Yasui Testuro , Saisho Koichiro , Tohma Shigeto 
Published: September 2017

Objective.In this study, we investigated the changes in clinical outcome, treatment, and incidence of orthopedic surgery in patients with rheumatoid arthritis (RA) from 2004 to 2014.Methods.Data were studied from the Japanese nationwide cohort database, NinJa (National Database of Rheumatic Diseases by iR-net in Japan), from 2004 to 2014. The time trends in the incidence of orthopedic procedures were analyzed using linear regression analysis. The cross-sectional annual data were compared between 2004 and 2014 to analyze the changes in clinical outcome and treatment.Results.The incidence of orthopedic surgeries in patients with RA consistently decreased from 72.2 procedures per 1000 patients in 2004 to 51.5 procedures per 1000 patients in 2014 (regression coefficient = −0.0028, 95% CI −0.0038 to −0.0019, p < 0.001). The greatest reduction was found in total knee arthroplasty and total hip arthroplasty. Disease activity and functional disability improved significantly over this decade. The proportions of patients receiving methotrexate and biologic disease-modifying antirheumatic drugs significantly increased from 39.6% and 1.7% in 2004 to 63.8% and 27.4% in 2014, respectively.Conclusion.The overall incidence of orthopedic surgeries in patients with RA significantly decreased, accompanied by improved clinical outcomes because of the expanded use of effective drugs; however, the declining trend differed between procedures or locations. The results from the present study suggest that there might be a change in supply and demand for orthopedic surgeries.
Risk of Retinal Toxicity in Longterm Users of Hydroxychloroquine
Authors: Kim Ji-Won , Kim Yoon Young , Lee Hwajeong , Park Sung-Hoon , Kim Seong-Kyu , Choe Jung-Yoon 
Published: September 2017

Objective.Several studies have reported risk factors for hydroxychloroquine (HCQ) retinal toxicity, but data are limited for patients of Asian ancestry. The aim of this study was to investigate the rate of and factors for HCQ retinal toxicity in the Korean population.Methods.There were 123 patients enrolled in this study who were using or had used HCQ. Retinal toxicity was detected using spectral domain optical coherence tomography, fundus autofluorescence, multifocal electroretinography, and automated visual field testing. Binary logistic regression analysis was performed to identify factors associated with HCQ retinal toxicity.Results.Mean duration of HCQ use and mean HCQ dose in study participants was 10.1 years and 6.4 mg/kg, respectively. We found 17 patients (13.8%) with HCQ retinal toxicity among 123 patients. Patients with retinal toxicity took HCQ ranging from 6.7–21.9 years and daily dosage ranging from 4.9–9.1 mg/kg. Only 1 patient had retinal toxicity among patients with daily dose < 5.0 mg/kg. These factors increased the risk of HCQ retinal toxicity: longer duration of HCQ use [adjusted OR (aOR) = 4.71, 95% CI 2.18–10.15 for duration of HCQ use in 5-yr increments], higher daily HCQ dose (aOR = 3.34, 95% CI 1.03–10.80 for daily HCQ dose in 100-mg increments), and the presence of kidney disease (aOR = 8.56, 95% CI 1.15–64.00).Conclusion.HCQ retinal toxicity is associated with duration of HCQ use, daily HCQ dose, and presence of kidney disease. Proper dosing of maximum 5 mg/kg and regular screening according to risk factors are important in HCQ use.
Phenotypic Features and Longterm Outcomes of Pediatric Inflammatory Bowel Disease Patients with Arthritis and Arthralgia
Authors: Nir Osnat , Rinawi Firas , Amarilyo Gil , Harel Liora , Shamir Raanan , Assa Amit 
Published: September 2017

Objective.The natural history of pediatric inflammatory bowel disease (IBD) patients with joint involvement has not been clearly described. Thus, we aimed to investigate phenotypic features and clinical outcomes of this distinct association.Methods.The medical records of patients with pediatric IBD diagnosed from 2000 to 2016 were reviewed retrospectively. Main outcome measures included time to first flare, hospitalization, surgery, and biologic therapy.Results.Of 301 patients with Crohn disease (median age 14.2 yrs), 37 (12.3%) had arthritis while 44 (14.6%) had arthralgia at diagnosis. Arthritis and arthralgia were more common in women (p = 0.028). Patients with arthritis and arthralgia demonstrated lower rates of perianal disease (2.7% and 4.5% vs 16.9%, p = 0.013), whereas patients with arthritis were more likely to be treated with biologic therapy (HR 2.05, 95% CI 1.27–3.33, p = 0.009). Of 129 patients with ulcerative colitis (UC; median age 13.7 yrs), 3 (2.3%) had arthritis and 16 (12.4%) had arthralgia at diagnosis. Patients with arthralgia were treated more often with corticosteroids (p = 0.03) or immunomodulator therapies (p = 0.003) compared with those without joint involvement. The likelihood to undergo colectomy was significantly higher in patients with arthralgia (HR 2.9, 95% CI 1.1–7.4, p = 0.04). During followup (median 9.0 yrs), 13 patients developed arthritis (3.3%). Arthralgia at diagnosis was a significant predictor for the development of arthritis during followup (HR 9.0, 95% CI 2.86–28.5, p < 0.001).Conclusion.Pediatric IBD patients with arthritis have distinct phenotypic features. Arthralgia at diagnosis is a predictor for colectomy in UC and a risk factor for the development of arthritis during followup.
IL-17 Signaling Triggers Degradation of the Constitutive NF-κB Inhibitor ABIN-1
Authors: Cruz J Agustin , Childs Erin E , Amatya Nilesh , Garg Abhishek V , Beyaert Rudi , Kane Lawrence P , Aneskievich Brian J , Ma Averil , Gaffen Sarah L 
Published: September 2017

Abstract
IL-17 activates NF-κB and induces expression of proinflammatory genes. IL-17 drives disease in autoimmune conditions, and anti–IL-17 Abs have shown impressive success in the clinic. Although produced by lymphocytes, IL-17 predominantly signals in fibroblasts and epithelial cells. IL-17–driven inflammation is kept in check by negative feedback signaling molecules, including the ubiquitin editing enzyme A20, whose gene TNFAIP3 is linked to autoimmune disease susceptibility. The A20 binding inhibitor of NF-κB activation 1 (ABIN-1) is an A20-binding protein encoded by the TNIP1 gene, which is also linked to autoimmune disease susceptibility including psoriasis. Accordingly, we hypothesized that ABIN-1 might play a role in negatively regulating IL-17 signaling activity. Indeed, ABIN-1 enhanced both tonic and IL-17–dependent NF-κB signaling in IL-17–responsive fibroblast cells. Interestingly, the inhibitory activities of ABIN-1 on IL-17 signaling were independent of A20. ABIN-1 is a known NF-κB target gene, and we found that IL-17–induced activation of NF-κB led to enhanced ABIN-1 mRNA expression and promoter activity. Surprisingly, however, the ABIN-1 protein was inducibly degraded following IL-17 signaling in a proteasome-dependent manner. Thus, ABIN-1, acting independently of A20, restricts both baseline and IL-17–induced inflammatory gene expression. We conclude that IL-17–induced signals lead to degradation of ABIN-1, thereby releasing a constitutive cellular brake on NF-κB activation.
Peripheral Deletion of CD8 T Cells Requires p38 MAPK in Cross-Presenting Dendritic Cells
Authors: Smith Trevor , Lin Xiaotian , Mello Marielle , Marquardt Kristi , Cheung Jocelyn , Lu Binfeng , Sherman Linda A. , Verdeil Grégory 
Published: September 2017

Abstract
Peripheral tolerance mechanisms exist to prevent autoimmune destruction by self-reactive T cells that escape thymic deletion. Dominant tolerance imposed by CD4+Foxp3+ T regulatory cells can actively control autoaggressive T cell responses. Tolerance mechanisms that act endogenous to the T cell also exist. These mechanisms include T cell inactivation (anergy) and deletion. A major difference between anergic T cells and T cells undergoing peripheral deletion is the capacity of the latter to still signal through MAPKs upon TCR stimulation, suggesting these signals may be required for T deletion. In this study, we used several different models of CD8 T cell deletion to investigate the contribution of MAPK activation. Using chemical inhibitors, we established that inhibition of p38, but not ERK or JNK, rescue T cells from undergoing peripheral deletion both in vitro and in vivo. Using T cell–specific murine lines genetically altered in expression of p38α, and mice in which p38α was deleted only in CD11c-expressing cells, we surprisingly found that CD8 T cell–intrinsic p38α activation was not responsible for increased survival, but rather that inhibition of p38α in the Ag-presenting dendritic cells prevented CD8 T cell deletion.
Monitoring C5aR2 Expression Using a Floxed tdTomato-C5aR2 Knock-In Mouse
Authors: Karsten Christian M. , Wiese Anna V. , Mey Fabian , Figge Julia , Woodruff Trent M. , Reuter Tom , Scurtu Olga , Kordowski Anna , Almeida Larissa N. , Briukhovetska Daria , Quell Katharina M. , Sun Jing , Ender Fanny , Schmudde Inken , Vollbrandt Tillman , Laumonnier Yves , Köhl Jörg 
Published: September 2017

Abstract
The biological significance of C5a receptor [(C5aR)2/C5L2], a seven-transmembrane receptor binding C5a and C5adesArg, remains ill-defined. Specific ligation of C5aR2 inhibits C5a-induced ERK1/2 activation, strengthening the view that C5aR2 regulates C5aR1-mediated effector functions. Although C5aR2 and C5aR1 are often coexpressed, a detailed picture of C5aR2 expression in murine cells and tissues is still lacking. To close this gap, we generated a floxed tandem dye (td)Tomato–C5aR2 knock-in mouse that we used to track C5aR2 expression in tissue-residing and circulating immune cells. We found the strongest C5aR2 expression in the brain, bone marrow, and airways. All myeloid-derived cells expressed C5aR2, although with different intensities. C5aR2 expression in blood and tissue neutrophils was strong and homogeneous. Specific ligation of C5aR2 in neutrophils from tdTomato–C5aR2 mice blocked C5a-driven ERK1/2 phosphorylation, demonstrating functionality of C5aR2 in the reporter mice. In contrast to neutrophils, we found tissue-specific differences in C5aR2 expression in eosinophils, macrophages, and dendritic cell subsets. Naive and activated T cells stained negative for C5aR2, whereas B cells from different tissues homogeneously expressed C5aR2. Also, NK cell subsets in blood and spleen strongly expressed C5aR2. Activation of C5aR2 in NK cells suppressed IL-12/IL-18–induced IFN-γ production. Intratracheal IL-33 challenge resulted in decreased C5aR2 expression in pulmonary eosinophils and monocyte-derived dendritic cells. In summary, we provide a detailed map of murine C5aR2 immune cell expression in different tissues under steady-state conditions and upon pulmonary inflammation. The C5aR2 knock-in mouse will help to reliably track and conditionally delete C5aR2 expression in experimental models of inflammation.
HVEM Imprints Memory Potential on Effector CD8 T Cells Required for Protective Mucosal Immunity
Authors: Desai Pritesh , Abboud Georges , Stanfield Jessica , Thomas Paul G. , Song Jianxun , Ware Carl F. , Croft Michael , Salek-Ardakani Shahram 
Published: September 2017

Abstract
Mucosal immunity to reinfection with a highly virulent virus requires the accumulation and persistence of memory CD8 T cells at the site of primary infection. These cells may derive from memory precursor effector cells (MPECs), which are distinct from short-lived effector cells that provide acute protection but are often destined to die. Using respiratory virus infection, we show that herpes virus entry mediator (HVEM; TNFRSF14), a member of the TNF receptor superfamily, provides key signals for MPEC persistence. HVEM-deficient CD8 T cells expanded normally but were skewed away from MPECs with resultant poor development of circulating and lung-resident memory cells. HVEM was selectively expressed on MPECs whereas MPECs deficient in HVEM failed to survive in adoptive transfer recipients. As a consequence, HVEM-deficient recipients failed to afford protection against respiratory reinfection with influenza virus. HVEM therefore represents a critical signal for MPECs and development of protective mucosal CD8 T cell memory.