bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum trough levels of infliximab are not associated with peripheral arthralgia activity in patients with inflammatory bowel disease
Authors: Sekhri Shaina , Rao Bharat , Mohananey Akanksha , Beniwal-Patel Poonam , Bruss Alexandra , Stein Daniel J , Yarur Andres J 
Published: November 2021

BackgroundInfliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined.ObjectiveWe aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease.DesignIn this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia.ResultsOut of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively).ConclusionsThis study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn’s disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease.
Frequency Responses of Molar Electrochemical Peltier Heat and Entropy Changes Analyzed as Thermometric Transfer Functions
Authors: Sanchez-Amaya M. , Bárcena-Soto M. , Antaño-López R. , Rodríguez-López A. , Gutierrez-Becerra A. , Larios-Durán E. R. 
Published: November 2021

In honor of Prof. Dr. Fritz Scholz in his recent retirement.
This work proposes a theoretical framework to obtain the frequency response of molar electrochemical Peltier heat and entropy changes induced by a modulated electrical signal. This is based on an internal energy balance developed for a working electrode thermistor in ac regime. Then, from an analysis that correlates the electrochemical impedance and the interfacial temperature variation, two new transfer functions that depend on the frequency

ω
,

named as entropy changes

Δ
S

ω

,

and molar electrochemical Peltier heat,

Π

ω

are obtained. This strategy is tested in two electrochemical systems: the ferrocyanide/ferricyanide couple and the copper ions in an acid sulphate-chloride medium. Both systems are analyzed by dc thermometric measurements, electrochemical impedance spectroscopy and ac-thermometric experiments namely variation of interfacial temperature. As a result,

Δ
S

ω

and

Π

ω

,

are obtained and their values are correlated to the relaxation processes involved in the electrochemical reaction. Additionally, a brief discussion is included concerning the differences between the classical dc thermoelectrochemical methodology and the proposed approach here.
Elevated Serum Neuropeptide FF Levels Are Associated with Cognitive Decline in Patients with Spinal Cord Injury
Authors: Sun Shifei , Sun Shilong , Meng Yan , Shi Bin , Chen Yuanzhen 
Published: November 2021

Background. Spinal cord injury (SCI) has high incidence globally and is frequently accompanied by subsequent cognitive decline. Accurate early risk-categorization of SCI patients for cognitive decline using biomarkers can enable the timely application of appropriate neuroprotective measures and the development of new agents for the management of SCI-associated cognitive decline. Neuropeptide FF is an endogenous neuropeptide with a multitude of functions and is associated with neuroinflammatory processes. This prospective study investigated the predictive value of serum neuropeptide FF levels measured after acute SCI for subsequent cognitive decline. Methods. 88 patients presenting with acute SCI without preexisting neurological injury, brain trauma, or severe systemic illness and 60 healthy controls were recruited. Serum neuropeptide FF levels, clinical, and routine laboratory variables including low-density lipoprotein, high-density lipoprotein, fasting blood glucose, total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) levels collected from all subjects were assessed. Montreal cognitive assessment (MoCA) was performed 3 months after enrollment. SCI patients were grouped according to quartile of serum neuropeptide FF level and MoCA scores were compared using ANOVA. Additionally, multivariate linear regression with clinical and laboratory variables was performed to predict MoCA scores. Results. SCI patients displayed significantly higher baseline serum neuropeptide FF levels than healthy controls (

38.5
±
4.1

versus

23.4
±
2.0

pg
/
ml

,

p
<

0.001

∗

∗

). SCI patients in higher quartiles of baseline serum neuropeptide FF displayed significantly lower MoCA scores at 3 months. Linear regression analysis indicated serum neuropeptide FF levels as a significant independent predictor of worse MoCA scores after SCI (

r
=
0.331

,

p
=

0.034

∗

). Conclusion. Early serum neuropeptide FF levels significantly and independently predicted cognitive decline after acute SCI among patients without preexisting neurological disorders.
Adjuvant Pembrolizumab versus IFNα2b or Ipilimumab in Resected High-Risk Melanoma
Authors: Grossmann Kenneth F. , Othus Megan , Patel Sapna P. , Tarhini Ahmad A. , Sondak Vernon K. , Knopp Michael V. , Petrella Teresa M. , Truong Thach-Giao , Khushalani Nikhil I. , Cohen Justine V. , Buchbinder Elizabeth I. , Kendra Kari , Funchain Pauline , Lewis Karl D. , Conry Robert M. , Chmielowski Bartosz , Kudchadkar Ragini R. , Johnson Douglas B. , Li Hongli , Moon James , Eroglu Zeynep , Gastman Brian , Kovacsovics-Bankowski Magdalena , Gunturu Krishna S. , Ebbinghaus Scot W. , Ahsan Sama , Ibrahim Nageatte , Sharon Elad , Korde Larissa A. , Kirkwood John M. , Ribas Antoni 
Published: November 2021

Abstract

We conducted a randomized phase III trial to evaluate whether adjuvant pembrolizumab for one year (647 patients) improved recurrence-free survival (RFS) or overall survival (OS) in comparison with high-dose IFNα-2b for one year or ipilimumab for up to three years (654 patients), the approved standard-of-care adjuvant immunotherapies at the time of enrollment for patients with high-risk resected melanoma. At a median follow-up of 47.5 months, pembrolizumab was associated with significantly longer RFS than prior standard-of-care adjuvant immunotherapies [HR, 0.77; 99.62% confidence interval (CI), 0.59–0.99; P = 0.002]. There was no statistically significant association with OS among all patients (HR, 0.82; 96.3% CI, 0.61–1.09; P = 0.15). Proportions of treatment-related adverse events of grades 3 to 5 were 19.5% with pembrolizumab, 71.2% with IFNα-2b, and 49.2% with ipilimumab. Therefore, adjuvant pembrolizumab significantly improved RFS but not OS compared with the prior standard-of-care immunotherapies for patients with high-risk resected melanoma.

Significance:
Adjuvant PD-1 blockade therapy decreases the rates of recurrence, but not survival, in patients with surgically resectable melanoma, substituting the prior standard-of-care immunotherapies for this cancer.
See related commentary by Smithy and Shoushtari, p. 599.
This article is highlighted in the In This Issue feature, p. 587
Systems Approach to Integrating Preclinical Apolipoprotein E-Knockout Investigations Reveals Novel Etiologic Pathways and Master Atherosclerosis Network in Humans
Authors: Shuey Megan M. , Xiang Rachel R. , Moss M. Elizabeth , Carvajal Brigett V. , Wang Yihua , Camarda Nicholas , Fabbri Daniel , Rahman Protiva , Ramsey Jacob , Stepanian Alec , Sebastiani Paola , Wells Quinn S. , Beckman Joshua A. , Jaffe Iris Z. 
Published: November 2021

Objective:
Animal models of atherosclerosis are used extensively to interrogate molecular mechanisms in serial fashion. We tested whether a novel systems biology approach to integration of preclinical data identifies novel pathways and regulators in human disease.

Approach and Results:

Of 716 articles published in
ATVB
from 1995 to 2019 using the apolipoprotein E knockout mouse to study atherosclerosis, data were extracted from 360 unique studies in which a gene was experimentally perturbed to impact plaque size or composition and analyzed using Ingenuity Pathway Analysis software. TREM1 (triggering receptor expressed on myeloid cells) signaling and LXR/RXR (liver X receptor/retinoid X receptor) activation were identified as the top atherosclerosis-associated pathways in mice (both
P
<1.93×10
−
4
, TREM1 implicated early and LXR/RXR in late atherogenesis). The top upstream regulatory network in mice (sc-58125, a COX2 inhibitor) linked 64.0% of the genes into a single network. The pathways and networks identified in mice were interrogated by testing for associations between the genetically predicted gene expression of each mouse pathway-identified human homolog with clinical atherosclerosis in a cohort of 88 660 human subjects. Homologous human pathways and networks were significantly enriched for gene-atherosclerosis associations (empirical
P
<0.01 for TREM1 and LXR/RXR pathways and COX2 network). This included 12(60.0%) TREM1 pathway genes, 15(53.6%) LXR/RXR pathway genes, and 67(49.3%) COX2 network genes. Mouse analyses predicted, and human study validated, the strong association of COX2 expression (
PTGS2
) with increased likelihood of atherosclerosis (odds ratio, 1.68 per SD of genetically predicted gene expression;
P
=1.07×10
−
6
).

Conclusions:
PRESCIANT (Preclinical Science Integration and Translation) leverages published preclinical investigations to identify high-confidence pathways, networks, and regulators of human disease.
Association between diabetes and keratoconus—a systematic review and meta-analysis
Authors: Akowuah Prince K , Arthur Christabel , Otabil Fredrick A , Ofori Collins A , Osei-Poku Kofi , Fummey Jeremiah , Boadi Prince , Dadzie Emmanuella E 
Published: November 2021

Purpose To assess the association between diabetes mellitus and keratoconus. Methods PubMed, Google Scholar, Web of Science, and Scopus databases were searched for literature on the association between diabetes and keratoconus. The last literature search was conducted on April 4, 2021. A secondary form of the literature search was conducted by manually scanning the reference list of retrieved eligible articles. Included studies were cohort, case-control, or cross-sectional study design that used odds ratio or risk ratio to evaluate the relationship between keratoconus and diabetes. Egger's test was used to assess the presence of publication bias. The quality of eligible studies was assessed using the Newcastle-Ottawa Scale. Results Nine studies (six case-control and three cohort studies) published between 2000 and 2021 were included. The total number of keratoconus patients and controls were 27,311 and 53,732. respectively. Meta-analysis revealed no significant association between diabetes mellitus and keratoconus; the pooled odds ratio was 0.87 (95% confidence interval: 0.66–1.14; p = 0.314). There was significant heterogeneity ( Q (df = 7) = 33.36, p < 0.001; I 2  = 79.01, p < 0.001). Age of participants ( p < 0.0001), study design ( p < 0.001), and sample size ( p = 0.024) were significant sources of heterogeneity. There was no evidence of publication bias. Conclusion The current meta-analysis revealed no significant association between diabetes mellitus and keratoconus. Well-designed longitudinal prospective studies are, however, needed to investigate any association between diabetes mellitus and keratoconus.
Conjunctivitis as a sign of persistent SARS-COV-2 infection? An observational study and report of late symptoms
Authors: Vallejo-Garcia Jose Luis , Balia L , Raimondi R , Rustioni G , Camesasca FI , Borgia A , Fossati G , Confalonieri F , Legrottaglie EF , Casari E , Sandri MT , Vinciguerra P 
Published: November 2021

Purpose To investigate if symptomatic conjunctivitis during the recovery phase of the disease could be associated to a persistent presence of SARS-CoV-2 in the upper respiratory tract. Secondary end points were to analyze the presence of SARS-CoV-2 in the conjunctiva of ocular symptomatic patients and to record the presence of ocular disturbances at this point of the disease. Methods An observational study including consecutive COVID19 patients treated at Humanitas Clinical and Research Hospital who were attending for nasopharyngeal swab to confirm the resolution of SARS-CoV-2 infection and end of isolation. We examined 129 consecutive patients from May to June 2020. The primary end point was to determine if symptomatic conjunctivitis at this point of the disease could be associated to a persistent presence of SARS-CoV-2 in the upper respiratory tract. Secondary end points were to analyze the presence of SARS-CoV-2 in the conjunctiva of ocular symptomatic patients and to record the presence of ocular disturbances at this point of the disease. Results One hundred twenty eight patients were included, 9.38% had conjunctivitis, none resulted positive to conjunctival PCR swab test, while two of them had positive nasopharyngeal result. Mean time elapsed since the first COVID-19 positive swab to the time of examination was 6 weeks (  ± 3). The only significant association was the presence of conjunctivitis with older age (65.3  ±  12.7 vs 56.7  +  13.5. p  =  0.046). Nasopharyngeal swab resulted positive in 22 patients (17.19%). While 88 patients (68.2%) did not have any ocular complain during their COVID19 disease. The 40 patients (31.8%) reporting ocular disturbances complained about: redness (25.43%), tearing (19.53%), burning (18.35%), foreign body sensation (17.18%), itching (15.62%), and discharge (12.5%). Conclusion This study showed that late conjunctivitis cannot be considered as a marker of persistent infection when patients are sent to confirm the resolution of SARS-CoV-2 infection.
A Systematic Review and Meta-Analysis of 12-Month Patency After Intervention for Iliofemoral Obstruction Using Dedicated or Non-Dedicated Venous Stents
Authors: Majeed Ghulam M. , Lodhia Krishan , Carter Jemima , Kingdon Jack , Morris Rachael I. , Gwozdz Adam , Saratzis Athanasios , Saha Prakash 
Published: November 2021

Background: Endovascular stenting of the deep venous system has been proposed as a method to treat patients with symptomatic iliofemoral outflow obstruction. The purpose of this systematic review and meta-analysis was to compare the effectiveness of this treatment at 1-year following the development of dedicated venous stents. Method and results: We searched MEDLINE and EMBASE for studies evaluating the effectiveness of venous stent placement. Data were extracted by disease pathogenesis: non-thrombotic iliac vein lesions (NIVL), acute thrombotic (DVT), or post-thrombotic syndrome (PTS). Main outcomes included technical success, stent patency at 1 year and symptom relief. A total of 49 studies reporting outcomes in 5154 patients (NIVL, 1431; DVT, 950; PTS, 2773) were included in the meta-analysis. Technical success rates were comparable among groups (97%-100%). There were no periprocedural deaths. Minor bleeding was reported in up to 5% of patients and major bleeding in 0.5% upon intervention. Transient back pain was noted in 55% of PTS patients following intervention. There was significant heterogeneity between studies reporting outcomes in PTS patients. Primary and cumulative patency at 1 year was: NIVL—96% and 100%; DVT—91% and 97%; PTS (stents above the ligament)—77% and 94%, and; PTS (stents across the ligament)—78% and 94%. There were insufficient data to compare patency outcomes of dedicated and nondedicated venous stents in patients with acute DVT. In NIVL and PTS patients, stent patency was comparable at 1 year. There was inconsistency in the use of validated tools for the measurement of symptoms before and after intervention. When reported, venous claudication, improved in 83% of PTS patients and 90% of NIVL patients, and ulcer healing occurred in 80% of PTS patients and 32% of NIVL patients. Conclusions: The first generation of dedicated venous stents perform comparably in terms of patency and clinical outcomes to non-dedicated technologies at 1 year for the treatment of patients with NIVL and PTS. However, significant heterogeneity exists between studies and standardized criteria are urgently needed to report outcomes in patients undergoing deep venous stenting.
Clinical Indoor Running Gait Analysis May Not Approximate Outdoor Running Gait Based on Novel Drone Technology
Authors: Lafferty Lindsay , Wawrzyniak John , Chambers Morgan , Pagliarulo Todd , Berg Arthur , Hawila Nour , Silvis Matthew 
Published: November 2021

Background: Traditional running gait analysis is limited to artificial environments, but whether treadmill running approximates overground running is debated. This study aimed to compare treadmill gait analysis using fixed video with outdoor gait analysis using drone video capture. Hypothesis: Measured kinematics would be similar between natural outdoor running and traditional treadmill gait analysis. Study Design: Crossover study. Level of Evidence: Level 2. Methods: The study population included cross-country, track and field, and recreational athletes with current running mileage of at least 15 km per week. Participants completed segments in indoor and outdoor environments. Indoor running was completed on a treadmill with static video capture, and outdoor segments were obtained via drone on an outdoor track. Three reviewers independently performed clinical gait analysis on footage for 32 runners using kinematic measurements with published acceptable intra- and interrater reliability. Results: Of the 8 kinematic variables measured, 2 were found to have moderate agreement indoor versus outdoor, while 6 had fair to poor agreement. Foot strike at initial contact and rearfoot position at midstance had moderate agreement indoor versus outdoor, with a kappa of 0.54 and 0.49, respectively. The remaining variables: tibial inclination at initial contact, knee flexion angle initial contact, forward trunk lean full gait cycle, knee center position midstance, knee separation midstance, and lateral pelvic drop at midstance were found to have fair to poor agreement, ranging from 0.21 to 0.36. Conclusion: This study suggests that kinematics may differ between natural outdoor running and traditional treadmill gait analysis. Clinical Relevance: Providing recommendations for altering gait based on treadmill gait analysis may prove to be harmful if treadmill analysis does not approximate natural running environments. Drone technology could provide advancement in clinical running recommendations by capturing runners in natural environments.
Youth Athlete Development Models: A Narrative Review
Authors: Varghese Mathew , Ruparell Sonia , LaBella Cynthia 
Published: November 2021

Context: Physical activity has shown to be beneficial for the overall physical and mental health of youth. There has been an increasing focus on youth sports moving from a recreational activity to becoming a launching pad for participation at elite levels. Several models of athlete development have emerged to guide specialized and nonspecialized athletes at an age-appropriate level, taking into consideration their physical and mental development. The purpose of this review is to summarize the current evidence and theoretical models regarding youth athlete development and discuss broader initiatives for sports participation and future directions for the field. Evidence Acquisition: An electronic databases search, including PubMed, Google Scholar, ScienceDirect, National Institutes of Health, UpToDate, and Springer was conducted. Articles from 1993 to 2021 were included. The search terms long term athlete development, LTAD model, youth physical development, youth athlete development, sports specialization, and pediatric athlete, among others, were used. Study Design: Narrative review. Level of Evidence: Levels 4 and 5. Results: Several models of youth athlete development are discussed in this article. More recent models have built on previous models to incorporate more age- and development-specific recommendations; however, no singular model could be identified as the gold standard for youth athlete development, especially given the lack of empirical data to support these models. Conclusion: Youth athlete development currently consists of several theoretical models, each with their own strengths and weaknesses, that can guide the training of young athletes to maximize their performance. Those involved in this process—physicians, athletic trainers, coaches, physical educators, and parents—should understand these various models and trial their various features to see what works best for their individual athlete with consideration given to factors such as their stage of development. Ultimately, more empirical data are required to definitively state which is the optimal approach.
Incidence Rates of Surgery After Knee MRI: Association According to Referring Physician Type and Patient’s Age and Sex
Authors: Naqvi Syed R. , Beavis R. Cole , Mondal Prosanta , Bryce Rhonda , Leswick David A. 
Published: November 2021

Background: The utility of magnetic resonance imaging (MRI) in the primary care setting is uncertain, with a perception that there is less likelihood for surgery after MRI ordered by general practitioners (GPs) when compared with orthopaedic surgeons and sports medicine physicians. Additionally, the influence of patient age and sex on subsequent surgical intervention is currently unknown. Purpose/Hypothesis: The purpose of this study was to compare surgical incidence after MRI referrals by orthopaedic surgeons, GPs, and sports medicine physicians, including a subset analysis for GP patients based on type of approval given by the radiologist. The authors also wanted to explore the association of age and sex on subsequent surgical intervention. They hypothesized that surgical incidence after MRI ordered by orthopaedic surgeons and sports medicine physicians would be higher than after MRI ordered by GPs. Study Design: Cohort study; Level of evidence, 3. Methods: Knee MRI referrals by the 3 physician cohorts during May to December 2017 were assessed. For GP patients, the types of approval or recommendation from a radiologist were categorized. Subsequent surgical intervention status was then compared among referral groups up to 2 years after MRI. Associations of age and sex with surgical occurrence were also assessed. Chi-square test, analysis of variance, and univariate/multivariable logistic regression were used for statistical analysis. Results: Overall, 407 referrals were evaluated (GP, n = 173; orthopaedic, n = 176; sports medicine, n = 58). Surgical incidence was not significantly higher for orthopaedic and sports medicine than GP referrals at 3 months (10%, 3%, and 6%, respectively; P = .23), 6 months (20%, 17%, and 15%; P = .49), and 2 years (30%, 35%, and 24%; P = .25). Surgical incidence for GP patients was higher after discussion with a radiologist or when evaluating specific pathology on prior imaging versus less defined reasons (30.4% vs 15.7%, respectively; P = .03). Surgical incidence was lower for older patients (11% vs 31% for >60 years vs all other age groups combined; P = .002), and women were less likely to undergo surgery than men (22% vs 35%, respectively; P = .008). Conclusion: Surgical incidence after MRI was likely appropriately lower for older patients. Lower incidence for female patients is of uncertain cause and warrants further study.