bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular allergy: update on clinical trials
Authors: Bielory Leonard , Schoenberg Dovid 
Published: July 2019

Purpose of reviewThe purpose of this article is to provide an update on the advances made through recent clinical trials regarding the treatment of the signs and symptoms of allergic conjunctivitis and its associated conditions.Recent findingsRecent studies have demonstrated significant advancement in the various forms of immunotherapy treatments. Nutritional interventions such as probiotics have surfaced as a viable complementary treatment option. Novel delivery methods such as contact lenses have been further studied along with a new tacrolimus formulation to improve ocular levels of the drug.SummaryCurrently, the primary advances in treatment for allergic conjunctivitis has shifted from new ophthalmic agents to immunotherapy and improvement of drug delivery. This includes the classic subcutaneous and sublingual and the novel epicutaneous and intralymphatic immunotherapy delivery systems as well as an edible rice vaccine. New targets for treatment have spurred research into new antagonist drugs such as (OC000459), a prostaglandin D2 antagonist. The Marinosolv formulation using tacrolimus shows promise and may be considered for other ophthalmic agents in the future. Other nonpharmacological treatments such as stenting and mechanical barrier gel have demonstrated their usefulness in treating ocular symptoms.
Population Kinetics of 0.9% Saline Distribution in Hemorrhaged Awake and Isoflurane-anesthetized Volunteers
Authors: Nyberg Joakim , Li Husong , Wessmark Pehr , Winther Viktor , Prough Donald S. , Kinsky Michael P. , Svensén Christer H. 
Published: July 2019

Abstract

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background
Population-based, pharmacokinetic modeling can be used to describe variability in fluid distribution and dilution between individuals and across populations. The authors hypothesized that dilution produced by crystalloid infusion after hemorrhage would be larger in anesthetized than in awake subjects and that population kinetic modeling would identify differences in covariates.

Methods
Twelve healthy volunteers, seven females and five males, mean age 28 ± 4.3 yr, underwent a randomized crossover study. Each subject participated in two separate sessions, separated by four weeks, in which they were assigned to an awake or an anesthetized arm. After a baseline period, hemorrhage (7 ml/kg during 20 min) was induced, immediately followed by a 25 ml/kg infusion during 20 min of 0.9% saline. Hemoglobin concentrations, sampled every 5 min for 60 min then every 10 min for an additional 120 min, were used for population kinetic modeling. Covariates, including body weight, sex, and study arm (awake or anesthetized), were tested in the model building. The change in dilution was studied by analyzing area under the curve and maximum plasma dilution.

Results
Anesthetized subjects had larger plasma dilution than awake subjects. The analysis showed that females increased area under the curve and maximum plasma dilution by 17% (with 95% CI, 1.08 to 1.38 and 1.07 to 1.39) compared with men, and study arm (anesthetized increased area under the curve by 99% [0.88 to 2.45] and maximum plasma dilution by 35% [0.71 to 1.63]) impacted the plasma dilution whereas a 10-kg increase of body weight resulted in a small change (less than1% [0.93 to 1.20]) in area under the curve and maximum plasma dilution. Mean arterial pressure was lower in subjects while anesthetized (P < 0.001).

Conclusions
In awake and anesthetized subjects subjected to controlled hemorrhage, plasma dilution increased with anesthesia, female sex, and lower body weight. Neither study arm nor body weight impact on area under the curve or maximum plasma dilution were statistically significant and therefore no effect can be established.
Changes in Pediatric Spine Surgery Patterns Over the Last 10 Years Among ABOS Part II Candidates
Authors: Nielsen Ena , Andras Lindsay M. , Hosseinzadeh Pooya , Mignemi Megan , Sawyer Jeffrey R. , Flynn John M. , Albanese Stephen , Skaggs David L. 
Published: July 2019

Study Design.
A retrospective review of prospectively collected data.

Objective.
Our purpose was to evaluate the volume of pediatric spine cases being done by surgeons applying for American Board of Orthopaedic Surgeons (ABOS) certification.

Summary of Background Data.
Pediatric orthopedic surgery has become increasingly subspecialized over the past decade.

Methods.
Data were reviewed from the ABOS for surgeons undergoing part II of ABOS certification between 2004 and 2014. Applicants were divided into pediatric orthopedic surgeons and spine surgeons based on their self-declared subspecialty for the ABOS Part II examination. A total of 102,424 cases were reviewed to identify spine cases performed on patients <18 years old.

Results.
Between 2004 and 2014, the total number of ABOS part II pediatric candidates increased significantly, from a low of 15 to a high of 44 (r

2
= 0.68, P = 0.001). During this time frame, there has been no significant increase in the total number of pediatric spine cases reported (r

2
= 0.09, P = 0.19). In 2004, 46.5% (33/71) of the pediatric spine cases were done by spine surgeons, which decreased to 17.3% (28/162) in 2014. Conversely in 2004, 53.5% (38/71) of pediatric spine cases were done by pediatric orthopedists, which increased to 82.7% (134/162) in 2014. The number of pediatric candidates performing pediatric spine cases decreased 35% from 2004 to 2014, but the percentage performing >20 spine cases during their candidate year has increased from 0% to 7% (r

2
= 0.31, P = 0.04).

Conclusion.
The share of pediatric spine surgeries performed by pediatric candidates has increased from 54% in 2004 to 83%, with a corresponding fall in the share surgeries performed by spine candidates (47% to >17%). The percentage of pediatric candidates performing more than 20 spine cases/year increased from 0% to 7%, reflecting a trend of spine subspecialization within pediatric surgery.

Level of Evidence: 3
Sagittal Reconstruction and Clinical Outcome Using Traditional ACDF, Versus Stand-alone ACDF Versus TDR
Authors: Katsuura Yoshihiro , York Philip J. , Goto Rie , Yang Jingyan , Vaishnav Avani S. , McAnany Steven , Albert Todd , Iyer Sravisht , Gang Catherine Himo , Qureshi Sheeraz A. 
Published: July 2019

Study Design.
Systematic review.

Objective.
To determine the difference in postoperative sagittal alignment when single level cervical radiculopathy or myelopathy is treated with an anterior cervical discectomy and fusion (ACDF) using a structural graft and plate, a stand-alone ACDF, or a total disc arthroplasty (TDR). We also wanted to determine if postoperative sagittal alignment impacted clinical outcomes in this patient population.

Summary of Background Data.
Although there are several accepted techniques for interbody reconstruction during single level anterior cervical surgery, little is known on the impact of any of them on segmental and regional sagittal alignment.

Methods.
A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines of the PubMed, Embase, and Cochrane databases. Only studies which contained pre and postoperative C2–7 Cobb angles as well as Neck Disability Index (NDI) scores following single level traditional ACDF with plate and cage, stand-alone ACDF, or TDR with at least 1 year follow up were included.

Results.
There were 12 publications that fulfilled the inclusion criteria with a total of 658 patients. Cluster regression analysis showed no difference between treatment arms at each respective time-point or in the overall change in NDI from preoperative to postoperative (P = 0.88). Cluster regression analysis showed no difference between treatment arms at each respective time point or in the overall change in lordosis from pre-op to post-op (P = 0.93).

Conclusion.
This review provides evidence that while NDI scores improved across all devices, there was no significant difference in NDI improvement or C2–7 Cobb angle change between single level traditional ACDF, stand-alone ACDF, or TDR. Although TDR has not been considered a lordosis producing operation, our investigation shows it does not differ significantly in sagittal profile from other cervical fusion techniques. Moreover, we show that the NDI score improved, regardless of device implanted.

Level of Evidence: 1
Predictors of Poor Global Alignment and Proportion Score After Surgery for Adult Spinal Deformity
Authors: Ohba Tetsuro , Ebata Shigeto , Oba Hiroki , Koyama Kensuke , Yokomichi Hiroshi , Haro Hirotaka 
Published: July 2019

Study Design.
Retrospective observational study of a cohort of consecutive patients.

Objective.
To determine 1) the correlation between clinical and radiographic outcomes and Global Alignment and Proportion (GAP) score, and 2) which preoperative parameters predominantly influence the risk for poor GAP scores.

Summary of Background Data.
Although numerous investigators have indicated their criteria for sagittal correction, it is still not unusual to observe poor outcome or complications even after ideal correction. The recently developed GAP score indicates spinopelvic alignment and setting surgical goals according to the score might decrease the prevalence of mechanical complications. However, there is no clear evidence of correlation between the GAP score and clinical outcomes, or which patient factors are preoperative predictors of poor postoperative GAP score.

Methods.
We included 128 consecutive patients treated with spinal correction surgery who had a minimum 2-year follow-up. The correlations between clinical outcomes, increased proximal junctional angle, and GAP score were determined. Univariate and multivariate logistic regression analyses were conducted to clarify potential preoperative risk factors for poor GAP score.

Results.
Based on total GAP score, 32 (25%) patients were grouped into proportioned, 50 (39.1%) into moderately disproportioned, and 44 (34.3%) into severely disproportioned spinopelvic alignment. Our present study showed a significantly positive correlation between Oswestry Disability Index, increased proximal junctional angle 2 years after surgery, and total GAP score. Uni and multivariate regression analysis showed a large global tilt was a risk factor for a poor GAP score and that the risk for a poor GAP score increased with ageing.

Conclusions.
Because GAP score correlated with Oswestry Disability Index and increased proximal junctional angle 2 years after surgery, GAP score might define targets for sagittal spinopelvic alignment for favorable outcomes of corrective spinal surgery. A large preoperative global tilt is a potential predictor of poor postoperative GAP score.

Level of Evidence: 3
Mechanical Ventilation Guided by Electrical Impedance Tomography in Children With Acute Lung Injury
Authors: Rosemeier Isabel , Reiter Karl , Obermeier Viola , Wolf Gerhard K. 
Published: July 2019

Objectives:
To provide proof-of-concept for a protocol applying a strategy of personalized mechanical ventilation in children with acute respiratory distress syndrome. Positive end-expiratory pressure and inspiratory pressure settings were optimized using real-time electrical impedance tomography aiming to maximize lung recruitment while minimizing lung overdistension.

Design:
Prospective interventional trial.

Setting:
Two PICUs.

Patients:
Eight children with early acute respiratory distress syndrome (< 72 hr).

Interventions:
On 3 consecutive days, electrical impedance tomography-guided positive end-expiratory pressure titration was performed by using regional compliance analysis. The Acute Respiratory Distress Network high/low positive end-expiratory pressure tables were used as patient’s safety guardrails. Driving pressure was maintained constant. Algorithm includes the following: 1) recruitment of atelectasis: increasing positive end-expiratory pressure in steps of 4 mbar; 2) reduction of overdistension: decreasing positive end-expiratory pressure in steps of 2 mbar until electrical impedance tomography shows collapse; and 3) maintaining current positive end-expiratory pressure and check regional compliance every hour. In case of derecruitment start at step 1.

Measurements and Main Results:
Lung areas classified by electrical impedance tomography as collapsed or overdistended were changed on average by –9.1% (95% CI, –13.7 to –4.4; p < 0.001) during titration. Collapse was changed by –9.9% (95% CI, –15.3 to –4.5; p < 0.001), while overdistension did not increase significantly (0.8%; 95% CI, –2.9 to 4.5; p = 0.650). A mean increase of the positive end-expiratory pressure level (1.4 mbar; 95% CI, 0.6–2.2; p = 0.008) occurred after titration. Global respiratory system compliance and gas exchange improved (global respiratory system compliance: 1.3 mL/mbar, 95% CI [–0.3 to 3.0], p = 0.026; Pao
2: 17.6 mm Hg, 95% CI [7.8–27.5], p = 0.0039; and Pao
2/Fio
2 ratio: 55.2 mm Hg, 95% CI [27.3–83.2], p < 0.001, all values are change in pre vs post).

Conclusions:
Electrical impedance tomography-guided positive end-expiratory pressure titration reduced regional lung collapse without significant increase of overdistension, while improving global compliance and gas exchange in children with acute respiratory distress syndrome.
Advanced cutaneous squamous cell carcinoma: how is it defined and what new therapeutic approaches are available?
Authors: Soura Efthymia , Gagari Eleni , Stratigos Alexander 
Published: July 2019

Purpose of review
Despite the overall excellent survival rates in patients with cutaneous squamous cell carcinoma (cSCC), advanced cutaneous SCCs are associated with high patient morbidity and mortality. Therefore, important unmet clinical needs persist: identifying high risk patients and choosing optimal treatment approaches.

Recent findings
In recent years, a better understanding of the biology of cSCC and its clinical progression have led to improved staging systems and new promising treatments for advanced disease. Such treatments include PD1 inhibitors, such as cemiplimab, which was recently approved for the treatment of cutaneous SCC, and pembrolizumab whose efficacy in the treatment cSCC is still being investigated. Other treatments, such as epidermal growth factor receptor inhibitors have also been used in the treatment of cSCC with moderate success. Several clinical and histological risk factors are considered key in estimating the risk or recurrence or metastasis in cSCCs and, therefore, influence the appropriate treatment choice and patient monitoring.

Summary
The present study reviews the current definition of advanced cSCC and discusses the new systemic approaches, including checkpoint inhibitors.
Artificial Intelligence Estimates the Importance of Baseline Factors in Predicting Response to Anti-PD1 in Metastatic Melanoma
Authors: Indini Alice , Di Guardo Lorenza , Cimminiello Carolina , De Braud Filippo , Del Vecchio Michele 
Published: July 2019

Objective:
Prognosis of patients with metastatic melanoma has dramatically improved over recent years because of the advent of antibodies targeting programmed cell death protein-1 (PD1). However, the response rate is ~40% and baseline biomarkers for the outcome are yet to be identified. Here, we aimed to determine whether artificial intelligence might be useful in weighting the importance of baseline variables in predicting response to anti-PD1.

Methods:
This is a retrospective study evaluating 173 patients receiving anti-PD1 for melanoma. Using an artificial neuronal network analysis, the importance of different variables was estimated and used in predicting response rate and overall survival.

Results:
After a mean follow-up of 12.8 (±11.9) months, disease control rate was 51%. Using artificial neuronal network, we observed that 3 factors predicted response to anti-PD1: neutrophil-to-lymphocyte ratio (NLR) (importance: 0.195), presence of ≥3 metastatic sites (importance: 0.156), and baseline lactate dehydrogenase (LDH) > upper limit of normal (importance: 0.154). Looking at connections between different covariates and overall survival, the most important variables influencing survival were: presence of ≥3 metastatic sites (importance: 0.202), age (importance: 0.189), NLR (importance: 0.164), site of primary melanoma (cutaneous vs. noncutaneous) (importance: 0.112), and LDH > upper limit of normal (importance: 0.108).

Conclusions:
NLR, presence of ≥3 metastatic sites, LDH levels, age, and site of primary melanoma are important baseline factors influencing response and survival. Further studies are warranted to estimate a model to drive the choice to administered anti-PD1 treatments in patients with melanoma.
Molecular Mechanisms of Adipose Tissue Survival during Severe Hypoxia: Implications for Autologous Fat Graft Performance
Authors: Wang Sheri , Gusenoff Jeffrey A. , Rubin J. Peter , Kokai Lauren 
Published: July 2019

Background:
Variable retention outcomes remain a significant issue in autologous fat grafting procedures. Among seemingly similar patients, using identical harvesting procedures, variability in graft retention is noted. Recent data suggest that the inherent characteristics of donor adipose tissue dictate graft healing outcomes. The goal of this study was to elucidate intrinsic qualities of human adipose tissue that confer resistance to ischemic stress to therapeutically target such mechanisms and improve overall results of fat grafts.

Methods:
Whole fat from 5 female patients was cultured in vitro under severe (1% O2) and mild (8% O2) hypoxic conditions. Microarray analysis of 44 hypoxia-related genes was performed. Perilipin was used to visualize viable adipocytes. Macrophage phenotypes were identified using PCR.

Results:
Analysis of adipocyte survival with perilipin suggested improved viability for tissue obtained from high BMI donors. Microarray data revealed a significant positive correlation for induced expression of ANGPTL4, a survival gene, and subject BMI (P = 0.0313) during hypoxic conditions whereas HIF1α and HIF2α genes were negatively correlated with donor BMI (P = 0.0003 and 0.0303). Interestingly, induced differentiation of proinflammatory M1 macrophages was negatively correlated with BMI under hypoxia (P = 0.0177).

Conclusions:
The innate resilience of adipocytes to hypoxia and relative macrophage activation play a crucial role in fat graft retention. This study suggests that adipose tissue from high BMI donors demonstrates greater resistance to hypoxia-induced apoptosis associated with an increased expression of ANGPTL4. Therefore, therapeutic interventions that target this factor may improve clinical adipose graft survival.
Social Media and the Dissemination of Prepublication Data in Surgical Fields
Authors: Akhavan Arya A. , Ndem Idorenyin E. , Kalliainen Loree K. 
Published: July 2019

Background:
This review investigates the use of social media at surgical conferences and possible effects of prepublication data release in surgical fields. Potential risks include patient harm by the preliminary application of research that lacks sufficient peer review, infringements on intellectual property, and loss of “research novelty.”

Methods:
A literature review of the current use of social media in dispersion of prepublication data was performed. Current submission guidelines for surgical conferences and journals were analyzed for data release embargos and social media use policies.

Results:
Conference abstract guidelines mentioned data embargos half of the time and the use of social media less than one third of the time. Eighty percentage of journal instructions to authors contained guidelines on both.

Conclusions:
In nonsurgical fields, the appropriateness of the use of social media to release prepublication data is increasingly being discussed. Little guidance exists on how surgical conference attendees should use social media while at conferences. Given the potential for patient harm and negative impact on intellectual property and attribution, further discussion is warranted.

Introducción:
Esta crítica investiga el uso de las redes sociales en las conferencias quirúrgicas y los efectos posibles de los datos pre-publicados en cirugía. Los riesgos probables incluyen: daño al paciente causado por la aplicación prematura de las investigaciones sin bastante análisis, violación de la propiedad intelectual, y perdido de “novedad de investigación.”

Metodología:
Un repaso fue hecho sobre el rol de las redes sociales en la propagación de los datos pre-publicados. Las normas actuales para la entrega de las conferencias y los periódicos quirúrgicos claves fueron analizadas por las reglas gobernando el uso de las redes sociales y los embargos del lanzamiento de datos.

Resultados:
Las reglas generales sobre la entrega de abstractos para las conferencias mencionaron los embargos de datos la mitad del tiempo mientras que estas mismas reglas mencionaron el uso de las redes sociales menos que un tercio el tiempo. 80% de las instrucciones de los periódicos dirigidas a los autores tuvieron las reglas generales sobre los dos: los embargos de datas y las redes sociales.

Conclusiones:
En las especialidades non-quirúrgicas, la pertinencia del uso de las redes sociales para lanzar el dato pre-publicado es discutida con más frecuencia. No existen normas sobre cómo se usan las redes sociales durante las conferencias. Dado el daño potencial al paciente y el impacto negativo en la propiedad y la atribución intelectuales, más discusión está obligatoria.
Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vaccination Against Respiratory Syncytial Virus: A Multicenter Questionnaire Study
Authors: Wilcox Christopher R. , Calvert Anna , Metz Jane , Kilich Eliz , MacLeod Rachael , Beadon Kirsten , Heath Paul T. , Khalil Asma , Finn Adam , Snape Matthew D. , Vandrevala Tushna , Nadarzynski Tom , Coleman Matthew A. , Jones Christine E. 
Published: July 2019

Introduction:
Respiratory syncytial virus (RSV) is a common cause of infant hospitalization and mortality. With multiple vaccines in development, we aimed to determine: (1) the awareness of RSV among pregnant women and healthcare professionals (HCPs), and (2) attitudes toward clinical trials and routine implementation of antenatal RSV vaccination.

Methods:
Separate questionnaires for pregnant women and HCPs were distributed within 4 hospitals in South England (July 2017–January 2018).

Results:
Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unknown) were analyzed. Most pregnant women (88%) and midwives (66%) had no/very little awareness of RSV, unlike obstetricians (14%). Among pregnant women, 29% and 75% would likely accept RSV vaccination as part of a trial, or if routinely recommended, respectively. Younger women (16–24 years), those of 21–30 weeks’ gestation, and with experience of RSV were significantly more likely to participate in trials [odds ratio (OR): 1.42 (1.72–9.86); OR: 2.29 (1.22–4.31); OR: 9.07 (1.62–50.86), respectively]. White-British women and those of 21–30 weeks’ gestation were more likely to accept routinely recommended vaccination [OR: 2.16 (1.07–4.13); OR: 2.10 (1.07–4.13)]. Obstetricians were more likely than midwives to support clinical trials [92% vs. 68%, OR: 2.50 (1.01–6.16)] and routine RSV vaccination [89% vs. 79%, OR: 4.08 (1.53–9.81)], as were those with prior knowledge of RSV, and who deemed it serious.

Conclusions:
RSV awareness is low among pregnant women and midwives. Education will be required to support successful implementation of routine antenatal vaccination. Research is needed to understand reasons for vaccine hesitancy among pregnant women and HCPs, particularly midwives.