bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular imaging of patients with refractory Takayasu arteritis treated with tocilizumab: post hoc analysis of a randomized controlled trial
Authors: Nakaoka Yoshikazu , Yanagawa Masahiro , Hata Akinori , Yamashita Katsuhisa , Okada Norihiro , Yamakido Shinji , Hayashi Hiromitsu , Jayne David 
Published: September 2021

Abstract

Objectives
Tocilizumab, an anti-IL-6 receptor antibody, was investigated in patients with refractory Takayasu arteritis (TAK) in a phase 3 randomized controlled trial. In this post hoc analysis, we investigated whether tocilizumab treatment inhibited the progression of vascular lesions caused by TAK in these patients.

Methods
Included patients received at least one dose of tocilizumab and underwent CT at baseline and at week 48 after tocilizumab initiation. Three radiologists not involved in the original trial independently evaluated the CT images. Twenty-two arteries from each patient were assessed for change from baseline in wall thickness (primary endpoint), dilatation/aneurysm, stenosis/occlusion or wall enhancement for at least 96 weeks after tocilizumab initiation. Patient-level assessments were also conducted.

Results
In 28 patients, 86.7% of 22 arteries had improved or stable wall thickness at week 96. Proportions of patients with improved or stable, partially progressed or newly progressed lesions were 57.1%, 10.7% and 28.6%, respectively, for wall thickness; proportions with improved or stable lesions were 92.9% for dilatation/aneurysm, and 85.7% for stenosis/occlusion. Patients with newly progressed lesions, reflecting more refractory disease, were prescribed glucocorticoids at dosages that could not be reduced below 0.1 mg/kg/day at week 96.

Conclusions
Approximately 60% of patients with TAK did not experience progression in wall thickness within 96 weeks after initiation of tocilizumab treatment. Few patients experienced progressed dilatation/aneurysm, or stenosis/occlusion. Wall thickness progression likely resulted from refractory TAK. Patients who experience this should be monitored regularly by imaging, and additional glucocorticoid or immunosuppressive treatment should be considered to avoid vascular progression.

Trial registration
Japan Pharmaceutical Information Centre number, JapicCTI-142616.
Relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with systemic lupus erythematosus
Authors: Chia Yen Lin , Zhang Jianchun , Tummala Raj , Rouse Tomas , Furie Richard A , Morand Eric F 
Published: September 2021

Abstract

Objectives
To characterize the relationship of anifrolumab pharmacokinetics with efficacy and safety in patients with moderate to severe SLE despite standard therapy, using pooled data from two phase 3 trials.

Methods
TULIP-1 and TULIP-2 were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (every 4 weeks for 48 weeks). For the exposure–response analysis, BILAG-based Composite Lupus Assessment (BICLA) or SLE Responder Index [SRI(4)] response rates at week 52 in each quartile/tertile of average anifrolumab serum concentration (Cave) were compared for anifrolumab and placebo in all-comers, patients who completed treatment, and IFN gene signature (IFNGS)-high patients who completed treatment, using average marginal effect logistic regression. Relationships between exposure and key safety events were assessed graphically.

Results
Of patients in TULIP-1/TULIP-2 who received anifrolumab (150 mg, n = 91; 300 mg, n = 356) or placebo (n = 366), 574 completed treatment, of whom 470 were IFNGS high. In the exposure–efficacy analyses, BICLA and SRI(4) treatment differences favouring anifrolumab 300 mg vs placebo were observed across Cave subgroups and all analysis populations. Logistic regression identified Cave as a significant covariate for predicted BICLA response, as higher anifrolumab Cave predicted greater efficacy. There was no evidence of exposure-driven incidence of key safety events through week 52 in patients receiving anifrolumab 150 or 300 mg.

Conclusion
While higher Cave predicted greater efficacy, consistent positive benefit favouring anifrolumab 300 mg vs placebo was observed in BICLA and SRI(4) responses across Cave subgroups in the TULIP trials. There was no evidence of exposure-driven safety events.

ClinicalTrial.gov numbers
NCT02446912, NCT02446899
Sudanese Refugees and the “Syrian Refugee Response” in Lebanon: Racialised Hierarchies, Processes of Invisibilisation, and Resistance
Authors: Janmyr Maja 
Published: September 2021

Abstract
By focusing on Sudanese refugees and asylum-seekers in Lebanon, who in 2018 constituted 4 per cent of all persons of concern to United Nations High Commissioner for Refugees (UNHCR) in that country, this article explores how the UNHCR protects and assists refugees not encompassed by the mainstream humanitarian response. The article finds that in terms of refugee recognition, resettlement, and overall protection, Sudanese refugees receive differential treatment when compared with the more dominant refugee groups. More precisely, it argues that the humanitarian practices contribute to structural processes of invisibilisation of the particularities of the protection concerns and circumstances of Sudanese refugees. It spotlights how, while racism and racial discrimination remain major protection concerns for the Sudanese community in Lebanon, humanitarian vulnerability assessments are altogether blind to these categories of harm. In examining how Sudanese refugees respond to and resist such processes of invisibilisation, the article also examines two key collective action approaches through which Sudanese refugees seek to access better protection and assistance: the establishment of representative refugee committees, on the one hand, and refugee protest, on the other. It finds that refugee protest was an important means of countering humanitarian processes of invisibilisation.
Intra-host evolution during SARS-CoV-2 prolonged infection
Authors: Voloch Carolina M , da Silva Francisco Jr Ronaldo , de Almeida Luiz G P , Brustolini Otavio J , Cardoso Cynthia C , Gerber Alexandra L , Guimarães Ana Paula de C , Leitão Isabela de Carvalho , Mariani Diana , Ota Victor Akira , Lima Cristiano X , Teixeira Mauro M , Dias Ana Carolina F , Galliez Rafael Mello , Faffe Débora Souza , Pôrto Luís Cristóvão , Aguiar Renato S , Castiñeira Terezinha M P P , Ferreira Orlando C , Tanuri Amilcar , R de Vasconcelos Ana Tereza 
Published: September 2021

Abstract
Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing A→U and decreasing G→A signatures. G→A mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host’s innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.
Intraoperative Use of Robotics With Navigation for Pedicle Screw Placement in Treatment of Pediatric High-grade Spondylolisthesis: A Preliminary Report
Authors: Linden Gabriel S. , Birch Craig M. , Hresko M. Timothy , Cook Danielle , Hedequist Daniel J. 
Published: September 2021

Background:
Accurate pedicle screw placement is critical to surgically correct pediatric high-grade spondylolisthesis (HGS). The recent advent of robotics coupled with computer-assisted navigation (RAN) may represent a novel option to improve surgical outcomes of HGS, secondary to enhanced pedicle screw placement safety. This series presents the HGS-RAN technique adopted by our site, describing its surgical outcomes and feasibility.

Methods:
Consecutive patients with a diagnosis of HGS (Meyerding grade III to V), operated on using RAN from 2019 to 2020 at a single-center were reviewed. Demographics, screw accuracy, sagittal L5-S1 parameters, complications, and perioperative outcomes were described. All patients were treated with instrumentation, decompression, posterior lumbar interbody fusion, and reduction. Robotic time included anatomic registration to end of screw placement. Screw accuracy—defined as a screw placed safely within the planned intrapedicular trajectory—was characterized by the Gertzbein-Robbins system for patients with additional 3-dimensional imaging.

Results:
Ten HGS patients, with an average age of 13.7 years old, were included in the series. All 62 screws were placed without neurological deficit or complication. Seven patients had additional 3-dimensional imaging to assess screw accuracy (42 of 62 screws). One hundred percent of screws were placed safely with no pedicle breaches (Gertzbein-Robbins—grade A). Thirty screws (48%) were placed through separate incisions that were percutaneous/transmuscular and 32 screws (52%) were inserted through the main incision. There were statistically significant improvements in L5 slippage (P=0.002) and lumbosacral angle (P=0.002), reflecting successful HGS correction. The total median operative time was 324 minutes with the robotic usage time consuming a median of 72 minutes. Median estimated blood loss was 150 mL, and length-of-stay was a median 3 days.

Conclusions:
This case-series demonstrates that RAN represents a viable option for HGS repair, indicated by high screw placement accuracy, safety, and L5-S1 slippage correction. Surgeons looking to adopt an emerging technique to enhance safety and correction of pediatric HGS should consider the RAN platform.

Level of Evidence:
Level IV—therapeutic study.
Functional Outcomes of Arthroscopic Os Trigonum Excision in Adolescents
Authors: Chun Liane , Bastrom Tracey P. , Carroll Alyssa N. , Edmonds Eric W. 
Published: September 2021

Background:
Outcomes of symptomatic os trigonum excision have been well described as a successful treatment in adults; however, the literature lacks information on standardized longer term functional outcomes in the pediatric population. This study intends to report functional outcomes of arthroscopic os trigonum excision in adolescents who failed conservative management, with the hypothesis that these younger patients would have similar, successful outcomes of adult patients.

Methods:
A retrospective study was performed on adolescents who underwent arthroscopic os trigonum excision at a single institution between 2011 and 2017. Patient demographic, clinical history, radiographic, and operative data were documented. Outcome measures included the Foot and Ankle Ability Measure (FAAM) score comprised of the Activities of Daily Living (ADL) and Sports subscales, Single Assessment Numeric Evaluation (SANE) score, ability to return to the same level of sport, and any additional foot/ankle surgery.

Results:
Ten patients (12 ankles) met criteria with a mean age at surgery of 15.4 years (range, 12 to 18 y) and a mean follow-up of 6.5 years (range, 2.8 to 9.1 y). Mean FAAM ADL subscale, Sports subscale, and SANE scores were 91.0±15.5, 76.3±29.1, and 88.6±15.1, respectively. A chronic duration of symptoms before surgery was associated with a lower FAAM Sports current level of function score (P=0.032). Four patients (40%) discontinued their sport due to continued ankle issues and reported significantly lower FAAM ADL subscale (P=0.01), Sports subscale (P<0.001), and SANE scores (P=0.002).

Conclusions:
Os trigonum syndrome in the adolescent population may not have the same rate of success as that seen in adult athletes over the long-term. However, if proven to be refractory to conservative measures and surgical intervention is indicated, patients and their families should be counseled about the risk for persistent ankle symptoms and the possibility that they may not be able to return to their previous level of sport.

Level of Evidence:
Level IV—case series.
Parents' Concerns Are Associated with Early Intervention Evaluation and Eligibility Outcomes
Authors: Solgi Mohadeseh , Feryn Alicia , Chavez Alison E. , Wilson Laura , King Margaret , Scholz Julie , Fombonne Eric , Zuckerman Katharine E. 
Published: September 2021

ABSTRACT:

Objective:
To test the association of parents' concerns with early intervention (EI) developmental services outcomes including evaluation, eligibility, and enrollment in services.

Method:
We collected survey data on parents' concerns and EI service use data from a sample of 428 children referred to EI from 2016 to 2018 in 6 Oregon primary care clinics serving lower-income families as part of a developmental and autism spectrum disorder screening intervention. We assessed EI service use trajectories and associations of the presence of parent concern, age of child at the time of parents' concerns, number of concerns, and type of provider concern, with EI evaluation, EI eligibility, and enrollment in EI services, using bivariate testing and multivariable logistic regression.

Results:
Only 22.9% of children referred to EI were enrolled in services 6 months later. Children whose parents had developmental and/or behavioral concerns were more likely to receive an EI evaluation and were also more likely to be eligible for services, compared with children whose parents had no concerns. There was no association between age, number of concerns, and type of concern with EI evaluation, eligibility, or services enrollment.

Conclusion:
Although only a minority of children referred to EI enrolled in services, the presence of parent concern is strongly associated with EI services evaluation and eligibility outcomes. Study results suggest that providers should assess the presence of parent concern when deciding on EI referrals and provide more support to parents who are not concerned at all.
Clinical Profiles of Glaucomatous Patients With High-tension and Low-tension Optic Disc Hemorrhages: A Comparative Study
Authors: Almeida Izabela N.F. , Dias Diego T. , Alhadeff Paula A. , Lopes Flavio S.S. , Paranhos Augusto , Ritch Robert , Gracitelli Carolina P.B. , Prata Tiago S. 
Published: September 2021

Précis:
Patients with low-tension optic disc hemorrhages (DHs) are more frequently women, have a diagnosis of normal-tension glaucoma (NTG) diagnosis and greater visual field (VF) loss. Symptoms of vascular dysregulation and Asian race also seem to be more prevalent in this clinical subtype.

Purpose:
Optic DH is an important glaucoma risk factor, and occurs in a wide intraocular pressure (IOP) range. We sought to characterize distinct clinical subtypes of patients with high-tension disc hemorrhage (HTDH) and low-tension disc hemorrhage (LTDH).

Patients and Methods:
In this cross-sectional study, treated glaucomatous patients with DHs from 2 glaucoma services were consecutively enrolled. Disc photographs were evaluated for the presence of DH by 2 glaucoma specialists. After inclusion, patients were classified on HTDH (IOP≥16 mm Hg) and LTDH (IOP<16 mm Hg; median split). Clinical and ocular data from the time of DH detection were compared between groups.

Results:
One hundred thirty-three DH patients were included (LTDH=66 eyes; HTDH=67 eyes). Patients with LTDH were more often women than those with HTDH (77% vs. 42%; P=0.030). There was also a trend for a higher prevalence of Asian descendants (24% vs. 9%; P=0.058) and symptoms suggestive of vascular dysregulation (34% vs. 14%; P=0.057) in LTDH patients. Eyes with LTDH also had worse VF mean deviation index (P=0.037), higher prevalence of NTG diagnosis (46% vs. 17%; P<0.001), and tended to have thinner central corneas (P=0.066).

Conclusions:
Patients developing DHs with treated IOPs in the low teens seem to more frequently fit in a profile represented by women, NTG diagnosis and greater VF loss. The presence of symptoms suggestive of vascular dysregulation and race also seem to differ between these 2 clinical subtypes. A closer optic disc surveillance is recommended for patients with the LTDH subtype, as they may develop DHs despite seemingly well-controlled IOP.
Influenza-associated Neurologic Complications in Hospitalized Pediatric Patients
Authors: Choi Gwang-Jun , Park Ji Young , Choi Joon-Sik , Choi Sae Rom , Kim Dongsub , Lee Jun Hwa , Woo Young-Jong , Lee Jeehun , Kim Yae-Jean 
Published: September 2021

Background:
The rates of influenza-associated neurologic complications are variable among studies, and a difference has been observed between the Western and Asian countries. The study aims to evaluate the frequency and characteristics of influenza-associated neurologic complications.

Methods:
We performed a retrospective review of hospitalized cases of influenza infection from October 2010 to April 2017 from 3 referral hospitals.

Results:
A total of 1988 influenza cases were identified. Influenza-associated neurologic complications were 161 cases (8.1%); influenza virus A was detected in 113 (70.2%) cases, B in 47 (29.2%) cases and both A and B in 1 case (0.6%). Twenty-four patients (15%) had underlying neurologic diseases. The most common diagnosis was a simple febrile convulsion (44%), followed by complex febrile convulsion (29%), fever-provoked seizure under pre-existing neurologic disease or afebrile seizure (14%), encephalopathy/encephalitis (8%) and meningitis (5%). Most of the patients fully recovered (96%). Three patients (1.9%) died of myocarditis (n = 1), encephalopathy (n = 1), and simultaneous encephalitis and myocarditis (n = 1). Pre-existing neurologic disease, age groups of 6 months to 6 years and 6–12 years were a risk factor of influenza-associated neurologic complications with an adjusted odds ratio of 5.41 (95% confidence interval [CI] 3.23–9.06, P < 0.001), 12.99 (95% CI 1.77–95.19, P = 0.01) and 8.54 (95% CI 1.14–64.79, P = 0.04), respectively. There was no association between neuropsychiatric adverse events and oseltamivir prescription (P = 0.17).

Conclusions:
Influenza-associated neurologic complications are not uncommon, and most patients fully recovered. The frequency of influenza-associated neurologic complications in Korean children was not significantly different from that of children in Western countries.
Cytomegalovirus Colitis in Immunocompetent and Immunocompromised Children
Authors: Bayrak Nevzat Aykut , Polat Esra , Erdogan Furkan 
Published: September 2021

Background:
Data about cytomegalovirus (CMV) colitis in children are scarce. We aimed to describe the characteristics of childhood CMV colitis in terms of risk factors, clinical symptoms, diagnosis, therapeutic approaches, and outcomes.

Methods:
Inflammatory bowel disease (IBD) and non-IBD patients with CMV colitis diagnosed by histology and tissue CMV PCR at 2 tertiary centers between January 2017 and November 2019 were studied. Clinical and laboratory data were retrieved from medical records. Underlying conditions, immune status, response to therapy and outcomes were described and followed up to 6 months after diagnosis.

Results:
A total of 16 children (8 non-IBD, 7 ulcerative colitis and 1 Crohn’s disease) with CMV colitis were included. All patients had persistent diarrhea (bloody in 13 cases). There was a significant age difference between IBD and non-IBD children (P < 0.05). The final diagnosis in 1 patient was immunodeficiency with a mutation in JAK1 gene. Three children were categorized as apparently immunocompromised and 4 children as apparently immunocompetent. Ulcer was not visible in 2 children from the non-IBD group. The mean fecal calprotectin level of IBD children was significantly higher than that of non-IBD children (376.12 ± 231.21 µg/g vs. 160.96 ± 69.94 µg/g, P < 0.05). After follow-up, 1 patient died because of another reason. Ganciclovir was used in 14 of 16 children for 3 weeks and the treatment was continued with valganciclovir in selected 6 children.

Conclusions:
CMV colitis is a rare but overlooked cause of prolonged diarrhea in immunocompetent and immunocompromised children. CMV colitis might present without any ulcer formation at colonoscopy in infants.
Break-even Analysis of Respirable Crystalline Silica (RCS) Exposure Interventions in the Construction Sector
Authors: Tompa Emile , Mofidi Amirabbas , Song Chaojie , Arrandale Victoria , Jardine Katherine J. , Davies Hugh , Tenkate Thomas , Demers Paul A. 
Published: September 2021

Objective:
We investigated long-term economic impacts of respirable crystalline silica (RCS) removal interventions in the construction at the societal level.

Methods:
We estimated costs and benefits of two RCS exposure interventions, use of “respirators” and “wet method,” over a 30-year time period. We identified economic impacts of the interventions under four different scenarios.

Results:
Under current practices, we estimated that approximately 125 lung cancer cases attributable to RCS exposure would arise in 2060. Under the full exposure removal scenario, we estimated there would be 53 new cases. Over the 30-year time period, the estimated cumulative averted cases are 787 and 482 for respirators and wet method, respectively, which amount to net benefits of $422.13 and $394.92 million.

Conclusions:
Findings provide important information for policymakers seeking to reduce the economic burden of occupational lung cancer in society.