bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variability in Hospital Costs of Adult Spinal Deformity Care
Authors: Jacobs Karel , Dewilde Thibault , Vandoren Cindy , Cardoen Brecht , Vansteenkiste Nancy , Scheys Lennart , Roodhooft Filip , Moke Lieven , Kesteloot Katrien 
Published: March 2020

Study Design.
Retrospective, single-center analysis.

Objective.
To calculate the total clinical hospital cost of the Adult Spinal Deformity (ASD) care trajectory, to explain cost variability by patient and surgery characteristics, and to identify areas of process improvement opportunities.

Summary of Background Data.
ASD is associated with a high financial and clinical burden on society. ASD care thus requires improved insights in costs and its drivers as a critical step toward the improvement of value, i.e., the ratio between delivered health outcome and associated costs.

Methods.
Patient characteristics and surgical variables were collected following ethical approval in a cohort of 139 ASD patients, treated between December, 2014 and January, 2018. Clinical hospital costs were calculated, including all care activities, from initial consultation to 1 year after initial surgery (excl. overhead) in a university hospital setting. Multiple linear regression analysis was performed to analyze the impact of patient and surgical characteristics on clinical costs.

Results.
75.5% of the total clinical hospital cost (€27,865) was incurred during initial surgery with costs related to the operating theatre (80.3%), nursing units (11.9%), and intensive care (2.9%) being the largest contributors. 57.5% of the variation in total cost could be explained in order of importance by surgical invasiveness, age, coronary disease, single or multiple-staged surgery, and mobility status. Revision surgery, unplanned surgery due to complications, was found to increase average costs by 87.6% compared with elective surgeries (€ 44,907 (± € 23,429) vs. € 23,944 (± € 7302)).

Conclusion.
This study identified opportunities for process improvement by calculating the total clinical hospital costs. In addition, it identified patient and treatment characteristics that predict 57.5% of cost variation, which could be taken into account when developing a payment system. Future research should include outcome data to assess variation in value.

Level of Evidence: 4
Evaluating the Minimal Clinically Important Difference of EQ-5D-3L in Patients With Degenerative Lumbar Spinal Stenosis
Authors: Burgstaller Jakob M. , Wertli Maria M. , Ulrich Nils H. , Pichierri Giuseppe , Brunner Florian , Farshad Mazda , Porchet François , Steurer Johann , Gravestock Isaac 
Published: March 2020

Study Design.
Analysis of a prospective, multicenter cohort study.

Objective.
The aim of our study was to compare thresholds of published minimal clinically important differences (MCID) for the three-level EuroQol-5D health survey (EQ-5D-3L) summary index (range −0.53 to 1.00) with our anchor-based estimate and evaluate how useful these thresholds are in determining treatment success in patients undergoing surgery for degenerative lumbar spinal stenosis (DLSS).

Summary of Background Data.
MCID values for EQ-5D-3L are specific to the underlying disease and only three studies have been published for DLSS patients reporting different values.

Methods.
Patients of the multicenter Lumbar Stenosis Outcome Study with confirmed DLSS undergoing first-time decompression or fusion surgery with 12-month follow-up were enrolled in this study. To calculate MCID we used the Spinal Stenosis Measure satisfaction subscale as anchor.

Results.
For this study, 364 patients met the inclusion criteria; of these, 196 were very satisfied, 72 moderately satisfied, 43 somewhat satisfied, and 53 unsatisfied 12 months after surgery. The MCID calculation estimated for EQ-5D-3L a value of 0.19. Compared with published MCID values (ranging from 0.30 to 0.52), our estimation is less restrictive.

Conclusions.
In patients with LSS undergoing surgery, we estimated an MCID value for EQ-5D-3L summary index of 0.19 with the help of the average change anchor-based method, which we find to be the most suitable method for assessing patient change scores.

Level of Evidence: 3
The Treatment of Perioperative Spinal Cord Injury With Hyperbaric Oxygen Therapy
Authors: Wilson Jamie R. F. , Schiavo Simone , Middleton William J. , Massicotte Eric M. , De Moraes Marcus V. , Katznelson Rita 
Published: March 2020

Study Design.
Case report (level IV evidence).

Objective.
To describe a potential novel application of hyperbaric oxygen therapy (HBOT) in the successful treatment of a postoperative spinal cord injury.

Summary of Background Data.
A 68-year-old man presented with an acute spinal cord injury (ASIA impairment scale D), on the background of degenerative lower thoracic and lumbar canal stenosis. He underwent emergent decompression and instrumented fusion (T9–L5), with an uncomplicated intraoperative course and no electrophysiological changes. Immediate postoperative assessment demonstrated profound bilateral limb weakness (1/5 on the Medical Research Council [MRC] grading scale, ASIA impairment scale B), without radiological abnormality.

Methods.
Conventional medical management (hypertension, level 2 care) was instigated with the addition of Riluzole, with no effect after 30 hours. At 36 hours 100% oxygen at 2.8 atmospheres was applied for 90 minutes, and repeated after 8 hours, with a further three treatments over 48 hours.

Results.
The patient demonstrated near-immediate improvement in lower limb function to anti-gravity (MRC grading 3/5) after one treatment. Motor improvement continued over the following treatments, and after 2 weeks the patient was ambulatory. At 4 months, the patient demonstrated normal motor function with no sphincteric disturbance.

Conclusion.
The application of HBOT contributed to the immediate and sustained improvement (ASIA B to ASIA E) in motor recovery after postoperative spinal cord injury. HBOT may represent a new avenue of therapy for spinal cord injury, and requires further prospective investigation.

Level of Evidence: 4
miR-29a-5p Targets SATB2 and Regulates the SIRT1/Smad3 Deacetylation Pathway to Inhibit Thoracic Ligamentum Flavum Cell Osteogenesis
Authors: Feng Fabo , Qiu Haiyan , Zhu Danjie , Xiaolin Li , Ning Huiquan , Yang Di 
Published: March 2020

Study Design.
Experimental analysis of the thoracic ligamentum flavum cell osteogenic differentiation process.

Objective.
This study aimed to explore the role of miR-29a-5p and special AT-rich sequence-binding protein 2 (SATB2) in a pathological osteogenic process.

Summary of Background Data.
Thoracic ossification of the ligamentum flavum (TOLF) is an uncommon disease wherein ligaments within the spine undergo progressive ossification, resulting in stenosis of the spinal canal and myelopathy. MiR-29a-5p was found to be downregulated in ligament cells from ossified ligament tissue in a previous study. However, whether miR-29a-5p is involved in the process of TOLF has not been investigated.

Methods.
The expression of miR-29a-5p in ligament tissues or in the context of TOLF osteogenic cell differentiation was measured via qRT-PCR. Alkaline phosphatase activity assay and Alizarin red staining were used to analyze cellular osteogenesis. The protein-level expression of SATB2, SIRT1, and Smad3 were measured via immunohistochemistry or western blotting. Dual luciferase reporter assays and western blotting were used to confirm that miR-29a targets SATB2.

Results.
SATB2 was found to be upregulated and miR-29a-5p was downregulated in TOLF tissue. We additionally observed decreased miR-29a-5p expression during the process of TOLF osteogenic cell differentiation, and there was a marked reduction in the expression of key mediators of osteogenesis when miR-29a-5p was overexpressed. Consistent with this, when miR-29a-5p was inhibited this led to enhanced osteogenic cell differentiation of these cells. We further found miR-29a-5p to directly target and suppress the expression of SATB2. Knock-down of SATB2 was sufficient to reduce the ability of miR-29a-5p to inhibit osteogenesis, and this also led to decreased SIRT1 expression and Smad3 acetylation.

Conclusion.
Together our findings indicate that miR-29a-5p is able to prevent thoracic ligamentum flavum cell osteogenesis at least in part via targeting SATB2 and thereby suppressing the SIRT1/Smad3 deacetylation pathway.

Level of Evidence: N/A
A Simple and Robust Liquid Chromatography With Tandem Mass Spectrometry Analytical Method for Therapeutic Drug Monitoring of Plasma and Cerebrospinal Fluid Polymyxin B1 and B2
Authors: Wang Peile , Zhang Qiwen , Qin Zifei , Xing Han , Xu Min , Pei Hui , Yang Jing , Zhang Xiaojian 
Published: March 2020

Background:
Polymyxin B is used as the last treatment resort for multidrug-resistant gram-negative bacterial infections. This study aimed to develop and validate a simple and robust liquid chromatography with tandem mass spectrometry analytical method for therapeutic drug monitoring of plasma and cerebrospinal fluid (CSF) polymyxin B1 and B2.

Methods:
Plasma and CSF polymyxin B1 and B2 were chromatographically separated on a Thermo Hypersil GOLD aQ C18 column and detected using electrospray ionization+ mode coupled with multiple reaction monitoring. Blood and CSF samples for pharmacokinetic analysis were collected from 15 polymyxin B-treated patients.

Results:
The calibration curve showed acceptable linearity over 0.2–10 mcg/mL for polymyxin B1 and 0.05–2.5 mcg/mL for B2 in the plasma and CSF, respectively. After validation, according to the Food and Drug Administration (FDA) method validation guideline, this method was applied for polymyxin B1 and B2 quantification in over 100 samples in a clinical study.

Conclusions:
A simple and robust method to measure polymyxin B1 and B2 in human CSF was first exploited and validated with good sensitivity and specificity, and successfully applied in polymyxin B pharmacokinetic analysis and therapeutic monitoring in Chinese patients.
Is Salivary Busulfan the Cause of Oral Mucositis and the Changes in Salivary Antioxidant Enzymes After Hematopoietic Cell Transplantation?
Authors: de Paula Eduardo Fernanda , Bezinelli Letícia Mello , Carvalho Danielle L. C. , Ferreira Mariana Henriques , Gobbi Marcella , Rosin Flavia C. P. , dos Santos Ferreira Carlos Eduardo , Sodre da Costa Lidiane Soares , Hamerschlak Nelson , Corrêa Luciana 
Published: March 2020

Background:
To determine whether the busulfan (Bu) present in saliva during hematopoietic cell transplantation (HCT) conditioning correlates with oral mucositis and the changes in salivary antioxidant enzymes.

Methods:
Bu levels in the plasma and saliva of 19 patients who received HCTs were quantified. Salivary flow and salivary superoxide dismutase and catalase activities were measured during HCT. For the toxicity analysis of salivary Bu, an in vitro assay was conducted by exposing human keratinocytes to artificial saliva containing Bu.

Results:
Plasma and salivary Bu concentrations were very similar (rho = 0.92, P < 0.001). Salivary Bu concentration correlated with the degree of oral mucositis severity (rho = 0.391, P = 0.029) and was inversely proportional to salivary superoxide dismutase and catalase activities (rho = −0.458, P = 0.036; rho = −0.424, P = 0.043, respectively). Cells exposed to Bu-containing saliva had fewer viable cells (P < 0.01) and more apoptotic cells (P = 0.001) than those exposed to non–Bu-containing saliva.

Conclusions:
Bu found in saliva during HCT conditioning was correlated with severe oral mucositis and the reduction in salivary antioxidative activity. Furthermore, Bu can be toxic to keratinocytes.
Increased dipeptidyl peptidase-4 accelerates chronic stress-related thrombosis in a mouse carotid artery model
Authors: Jin Xianglan , Jin Chunzi , Nakamura Kae , Jin Tiefeng , Xin Minglong , Wan Ying , Yue Xueling , Jin Shengyu , Wang Hailong , Inoue Aiko , Nan Yongshan , Lin Zhenhua , Kuzuya Masafumi , Cheng Xian Wu 
Published: March 2020

Objective:
Exposure to chronic psychosocial stress is a risk factor for metabolic cardiovascular disorders. Given that dipeptidyl peptidase-4 (DPP-4) has an important role in human pathobiology, we investigated the role of DPP-4 in stress-related thrombosis in mice, focusing on oxidative stress and the von Willebrand factor (vWF)-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13).

Methods and results:
Male mice randomly assigned to nonstress and 2-week immobilized-stress groups underwent iron chloride3 (FeCl3)-induced carotid artery thrombosis surgery for morphological and biochemical studies at specific times. On day 14 post-stress/surgery, stress had enhanced the lengths and weights of arterial thrombi, with alterations of plasma DPP-4, plasminogen activation inhibitor-1 and ADAMTS13. The stressed mice had increased levels of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, monocyte chemoattractant protein-1, gp91phox, p22phox, matrix metalloproteinase-2 (MMP-2), MMP-9, cathepsins S and K mRNAs and/or proteins, and reduced levels of endothelial nitric oxide synthase, catalase and superoxide dismutase-1 mRNAs and/or proteins. Stress also accelerated arterial endothelial cell damage. The DPP-4 inhibitor anagliptin ameliorated the stress-induced targeted molecular and morphological changes and thrombosis. In vitro, DPP-4 inhibition also mitigated the alterations in the targeted ADAMTS13 and other oxidative and inflammatory molecules in human umbilical vein endothelial cells in response to H2O2.

Conclusion:
DPP-4 inhibition appeared to improve the FeCl3-induced thrombosis in mice that received stress, possibly via the improvement of ADAMTS13 and oxidative stress, suggesting that DPP-4 could become a novel therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disorders.
Retinal arterial remodeling in patients with pheochromocytoma or paraganglioma and its reversibility following surgical treatment
Authors: Gosk-Przybyłek Maria , Doroszko Adrian , Dobrowolski Piotr , Warchoł-Celińska Ewa , Harazny Joanna , Bińczyk Ewelina , Szymanek Katarzyna , Pęczkowska Mariola , Kabat Marek , Toutounchi Sadegh , Gałązka Zbigniew , Górnicka Barbara , Szaflik Jerzy , Januszewicz Magdalena , Klisiewicz Anna , Hoffman Piotr , Lenders Jacques W.M. , Eisenhofer Graeme , Szaflik Jacek P. , Schmieder Roland E. , Prejbisz Aleksander , Januszewicz Andrzej 
Published: March 2020

Objective:
Structural abnormalities in resistance arteries are a hallmark of patients with hypertension. In hypertensive patients with pheochromocytoma or paraganglioma (PPGL), it is still a matter of debate whether structural vascular changes are because of elevated blood pressure (BP) or to toxic effects of elevated circulating catecholamines. Hence, the aim of our study was to assess whether catecholamine excess and/or elevated BP affect the structure of small retinal arteries in patients with catecholamine-producing tumors.

Methods:
The study included 27 patients with PPGL and 27 hypertensive patients. All patients underwent biochemical tests for catecholamine excess, echocardiography and analyses of scanning-laser-Doppler-flowmetry (SLDF) both at baseline and 12 months following surgical resection of PPGL.

Results:
Baseline retinal arterial diameter, arterial wall thickness and wall cross sectional area (WCSA) were higher in patients with PPGL as compared with subjects without PPGL (arterial diameter: 110 ± 16.5 vs. 99.5 ± 10.8 μm, wall thickness: 16.3 ± 6.0 vs. 13.5 ± 4.0 μm, WCSA: 4953.9 ± 2472.8 vs. 3784.1 ± 1446.3 μm2, P < 0.05). Significant correlations were noted between wall thickness and WCSA and echocardiographic parameters assessing diastolic and systolic function of left ventricle. No correlations between retinal parameters, BP level and plasma concentrations of metanephrines were observed. In patients with PPGL, there were postoperative decreases in wall thickness (16.4 ± 15.8 vs. 14.8 ± 4.7 μm; P = 0.011) and WLR (0.42 ± 0.13 vs. 0.37 ± 0.10; P = 0.003) at 12 months after surgical removal of tumors.

Conclusion:
This is the first study to demonstrate that catecholamine excess is related to thickening of retinal arteries independent of BP and reversible after surgical cure. These data support a role of catecholamines in vascular remodeling in PPGL patients.
Deep-layer Microvasculature Dropout in Preperimetric Glaucoma Patients
Authors: Suh Min Hee , Na Jeong Ho , Zangwill Linda M. , Weinreb Robert N. 
Published: March 2020

Purpose:
To compare disease severity between preperimetric primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature dropout.

Materials and Methods:
Ninety-four eyes of 94 preperimetric POAG patients with β-zone parapapillary atrophy (βPPA) were categorized according to the presence of deep-layer microvasculature dropout defined as a complete loss of microvasculature within the choroid or scleral flange on optical coherence tomography angiography. Parameters representing disease severity, that is, visual field (VF) mean deviation (MD), global and sectoral (6-sector) retinal nerve fiber layer (RNFL) thickness, and other factors including age, focal lamina cribrosa (LC) defect, width of βPPA with and without Bruch membrane (BM) (βPPA+BM and βPPA−BM), and optic disc hemorrhage were compared between eyes with and without dropout.

Results:
Deep-layer microvasculature dropout was observed in 33 preperimetric POAG eyes (35.1%). Eyes with dropout had significantly thinner RNFL in all areas except the inferonasal sector, worse VF MD, and higher prevalence of focal LC defect, and larger βPPA−BM (P<0.05), whereas the 2 groups did not differ in age, disc hemorrhage, or βPPA+BM width (P>0.05). In the multivariable logistic regression, worse VF MD [odds ratio (OR), 1.485; P=0.045], thinner RNFL (OR, 1.141; P<0.001), and higher prevalence of focal LC defect (OR, 6.673; P<0.001) were significantly associated with dropout.

Conclusions:
Deep-layer microvasculature dropout was observed in a considerable number of preperimetric POAG eyes, and worse disease severity was associated with dropout. Future studies elucidating the pathogenic role of deep-layer microvasculature dropout in the development and progression of glaucoma are warranted.
Foveal Avascular Zone Measurement Via Optical Coherence Tomography Angiography and its Relationship With the Visual Field in Eyes With Open-angle Glaucoma
Authors: Igarashi Ryoko , Ochiai Shun , Togano Tetsuya , Sakaue Yuta , Suetake Aki , Iikawa Ryu , Honma Yurie , Miyamoto Daiki , Fukuchi Takeo 
Published: March 2020

Precis:
The foveal avascular zone (FAZ) in optical coherence tomography angiography is significantly correlated with retinal inner layer thickness, Humphrey field analyzer (HFA) 10-2 sensitivity threshold, and mean deviation (MD) value in open-angle glaucoma patients.

Purpose:
The purpose of this study was to measure the FAZ area using optical coherence tomography angiography and investigate its relationship with retinal inner layer thickness and visual field defects in eyes with open-angle glaucoma.

Participants and Methods:
A total of 52 eyes with open-angle glaucoma from 52 patients. FAZ area was measured using optical coherence tomography angiography in angio-macula mode. Thicknesses of retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), and ganglion cell complex (GCC) were determined using a 7 mm×7 mm macular (V) map via 3D-OCT. Correlations of FAZ area with sensitivity threshold measurements, foveal threshold (FT), and MD value in the HFA10-2 visual field were analyzed for each inner retinal layer.

Results:
FAZ area was 0.26±0.07 mm2; overall mean thicknesses were 19.14±6.55 μm (RNFL), 57.34±5.93 µm (GCL+IPL), and 75.87±10.96 μm (GCC); mean FT was 35.23±3.15 dB, and sensitivity threshold was 20.81±7.22 dB in the HFA10-2 visual field. FAZ area was significantly correlated with the thickness of individual retinal layers in the entire field (RNFL, P<0.001; GCL+IPL, P<0.001; GCC, P<0.001), sensitivity threshold (P=0.01), FT (P<0.001), and MD value (P=0.011).

Conclusion:
FAZ area was significantly negatively correlated with retinal inner layer thickness, sensitivity threshold, FT, and MD value in the HFA10-2 visual field.
Accuracy of intraocular lens power calculation methods when targeting low myopia in monovision
Authors: Turnbull Andrew M.J. , Hill Warren E. , Barrett Graham D. 
Published: March 2020

Purpose:
To investigate the accuracy of IOL power calculation methods for refractive targets of myopia compared with emmetropia.

Setting:
Lions Eye Institute, Perth, Australia.

Design:
Retrospective analysis.

Methods:
Patients undergoing bilateral, sequential cataract surgery with a plan of modest monovision were analyzed. Target refraction was plano (distance eye) and −1.25 diopters (D) (near eye). Prediction error was determined by comparing the actual postoperative refraction with the predicted postoperative refraction, calculated by the Barrett Universal II (BUII), Hill-RBF version 2.0 (Hill-RBF 2.0), Haigis, Holladay 1, SRK/T, and Hoffer Q formulas. The dataset was divided into distance and near eye subgroups. Mean and median absolute error and percentage of eyes within ±0.25, ±0.50, ±0.75, and ±1.00 D of refractive target were compared.

Results:
The study included 88 consecutive patients. There was a consistent trend for lower refractive accuracy in the near eyes. BUII and Hill-RBF 2.0 were the most accurate overall and least affected by this phenomenon, with 1 (1.1%) and 4 (4.6%) fewer eyes, respectively, in the near subgroup achieving ±0.50 D of target. Haigis and SRK/T were most affected, with 14 (15.9%) and 11 (12.5%) fewer near eyes achieving ±0.50 D of target (P < .05). Holladay 1 and Hoffer Q occupied the middle ground, with 6 (6.8%) and 9 (10.2%) fewer near eyes achieving ±0.50 D of target.

Conclusions:
IOL-power calculation formulas appear to be less accurate when targeting myopia compared with emmetropia. BUII and Hill-RBF 2.0 represented good options when planning pseudophakic monovision as they were least affected by this phenomenon and can be used for both distance and near eyes.
Management of Malignant Vulval Melanoma: A Retrospective Case Series and Review of the Literature
Authors: Platt Sarah , Coleridge Sarah , Hughes Geoff , Donkers Hannah , Wiggans Alison , Frost Jonathan , Rolland Phil , Julian Sophia , Morrison Jo , Pawade Joya , Patel Amit , Newton Claire 
Published: March 2020

Objectives
The aims of the study were to evaluate clinicopathologic features, management, and outcomes in vulval melanoma and to review the literature.

Materials and Methods
Data were collected retrospectively on patients with vulval melanoma from 2001 to 2017 in 5 gynecological oncology cancer centers (Bristol, Taunton, Truro, Plymouth, and Cheltenham). SPSS software was used for univariate and multivariate statistical analysis. Disease-specific median survival was calculated using Kaplan-Meier curves.

Results
Forty-four patients with vulval melanoma were included, with a median age of 71 years. Forty-three of 44 had wide local excision with full inguinal lymphadenectomy if abnormal lymph nodes. Seven patients had sentinel lymph nodes. However, 2 patients with negative sentinel lymph nodes had distant recurrences within 16 months.
On univariate analysis, presence of ulceration (p = .012), perineural invasion (p = .03), and area of lesion (p = .016) were associated with risk of recurrence but only presence of microsatellites (p = .01) was associated with risk of death.
There were 31 deaths (70%): 29 (94%) of 31 from melanoma and 28 (64%) of 44 recurrences: 17 local (10 groin, 7 vulval) and 9 distant. Overall median survival was 32.5 months (95% CI, 17.8–46.5 months) and median recurrence-free survival 12.6 months (95% CI, 7.7–17.4 months).

Conclusions
This retrospective multicenter study highlights the high recurrence rate and poor prognosis of vulval melanoma. Lymph node surgery did not make any difference to recurrence-free survival or overall survival. The presence of microsatellites was associated with a statistically increased risk of death.