bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scheimpflug Imaging of the Danish Cohort of Patients With Wilson Disease
Authors: Telinius Niklas , Ott Peter , Sandahl Thomas , Hjortdal Jesper 
Published: May 2019

Purpose:
The purpose of this study was to investigate the use of anterior segment imaging in diagnosing Kayser–Fleischer rings in patients with Wilson disease.

Methods:
In a tertiary center for Wilson disease, patients were examined with a Pentacam HR Scheimpflug-based tomography device in addition to conventional slit-lamp examination. The inferior part of the cornea was analyzed using both a built-in densitometry module and ImageJ.

Results:
Thirty-one patients with Wilson disease (78% of all Danish patients) were included, resulting in 83 examinations over a 5-year period. Ten had a manifest Kayser–Fleischer ring in the inferior part of the cornea on at least 1 examination, 5 had other causes of peripheral corneal scatter, and 16 had normal examinations. The built-in densitometry module performed poorly in discriminating between the presence and absence of a Kayser–Fleischer ring. However, analysis of the images in ImageJ and calculation of a normalized signal (peak posterior value/peak anterior value) with a cutoff value set to 1 detected 28 of 31 Kayser–Fleischer rings and resulted in 96% sensitivity and 95% specificity. In 12 patients who underwent 3 or more examinations during the period, changes in the normalized signal seemed to reflect the efficiency of the treatment, although more studies are needed for this conclusion.

Conclusions:
ImageJ-based analysis of Pentacam images has a high sensitivity in detecting Kayser–Fleischer rings and can be used as a diagnostic procedure for Wilson disease and may be a tool to monitor the disease in an objective manner.
Treatment of Tinnitus Using Theta Burst Based Repetitive Transcranial Magnetic Stimulation—A Single Blinded Randomized Control Trial
Authors: Godbehere Joanna , Sandhu Jaswinder , Evans Alexander , Twigg Victoria , Scivill Ian , Ray Jaydip , Barker Anthony 
Published: May 2019

Objective:
To determine whether theta burst repetitive transcranial magnetic stimulation is an effective treatment for chronic tinnitus compared with a control stimulus.

Study Design:
A two-arm, single-blind, randomized controlled trial comparing an active treatment group to a placebo control group.

Setting:
Neurotology department of a tertiary referral center.

Patients:
Forty new and existing patients with chronic unilateral or bilateral tinnitus were recruited from specialist hearing and balance clinics.

Interventions:
The subjects were randomized into two groups representing the treatment and sham subcategories. Two 40 second trains, 15 minutes apart of transcranial stimulation was provided using a super rapid stimulator (2.2. Tesla, Magstim Inc., Wales, UK) using a circular delivery coil. Treatment was provided over 5 consecutive days.

Main Outcome Measure:
Tinnitus functional index (TFI) scores were recorded before treatment, immediately after treatment, 2 weeks, and at 4 weeks following treatment and compared.

Results:
TFI scores were analyzed using the Shapiro–Wilk test and found to be normally distributed. A paired Student t test was then performed. Both the active treatment group and control group had a significant improvement in their TFI scores following treatment; however, there was no significant difference between active treatment and sham treatment groups.

Conclusion:
This study demonstrated a significant placebo effect following treatment with sham therapy and may suggest that repetitive transcranial magnetic stimulation does not have a therapeutic use in treating chronic tinnitus.
Hearing Results of Surgery for Acquired Atresia of the External Auditory Canal
Authors: Stultiens Joost J.A. , Huygen Patrick L.M. , Oonk Anne M.M. , Mylanus Emmanuel A.M. , Kunst Henricus P.M. , Hol Myrthe K.S. , Cremers Cor W.R.J. , Mulder Jef J.S. , Pennings Ronald J.E. 
Published: May 2019

Objective:
To evaluate short- and long-term hearing results of surgery for acquired atresia of the external auditory canal (EAC) in a large patient cohort and to define preoperative audiometric conditions useful for patient counseling.

Study Design:
Retrospective cohort study.

Setting:
Academic tertiary referral center.

Patients:
Seventy-eight ears from 72 patients with postinflammatory acquired atresia of the EAC who underwent canal- and meatoplasty were included. Patients with involvement of the ossicular chain, (syndromic) external ear malformations, or congenital aural atresia were excluded.

Intervention:
Canal- and meatoplasty.

Main Outcome Measures:
Mean pure-tone averages of thresholds at 0.5, 1, 2, and 3 kHz (PTA0.5,1,2,3) for air conduction (AC), bone conduction, and air-bone gap (ABG) were calculated preoperatively and at short-term (≤0.55 yr) and long-term follow-up (>0.55 yr). Additionally, the numbers of ears with a closed ABG ≤10 dB and ≤20 dB, and with Social hearing (defined as: AC PTA0.5,1,2,3 ≤35 dB) were assessed.

Results:
At short-term follow-up AC PTA0.5,1,2,3 improved by 18 dB. Social hearing was obtained in 81% of the ears. Postoperatively, 35% of the ears had a closed ABG ≤10 dB, 83% was closed ≤20 dB. During follow-up, significant deterioration of 5 to 7 dB occurred for AC thresholds at 0.25, 0.5, and 1 kHz.

Conclusions:
Surgery for acquired atresia of the EAC is often beneficial. This study suggests overall advantageous surgery when the preoperative indication criteria ABG PTA0.5,1,2,3 >20 dB and AC PTA0.5,1,2,3 >35 dB are applied.
A New Lateral Wall Electrode: Evaluation of Surgical Handling, Radiographic Placement, and Histological Appraisal of Insertion Trauma
Authors: Rivas Alejandro , Yawn Robert J. , Kim Ana H. , Driscoll Colin , Cullen Robert , Rebscher Stephen J. , Isaacson Brandon 
Published: May 2019

Objective:
To describe histologic and radiographic findings associated with insertion of a new lateral wall electrode in human temporal bones, as well as quantify the ease of insertion as characterized by multiple cochlear implant surgeons.

Setting:
Multi-institutional cadaveric study.

Methods:
The Slim J electrode was inserted in cadaveric temporal bones via a standard mastoidectomy and facial recess approach. Insertion was performed by five cochlear implant surgeons with no previous experience with the Slim J electrode array. Electrode array insertion was performed via a round window, an extended round window, or a cochleostomy approach. Intracochlear trauma, and angular insertion depth was assessed histologically and radiologically, respectively, after placement of the Slim J electrode array.

Results:
Scala tympani insertion was accomplished in all 40 specimens. Thirty-eight specimens (95%) showed minimal trauma (Esrhaghi grade 0 or 1). One patient had rupture of basilar membrane (grade 2 trauma) at 380 degrees. One patient had grade 4 trauma with scalar translocation beginning at 210 degrees. The mean angular insertion depth was 416.4 degrees (range: 338.7–509.2 degrees, SD 44 degrees). Surgical handling was described as easy in 38 cases (95%).

Conclusion:
In a human cadaveric model the lateral wall Slim J electrode produced minimal intracochlear trauma that was positioned completely within the scala tympani in 97.5% of cases.
Drafting a Surgical Procedure Using a Computational Anatomy Driven Approach for Precise, Robust, and Safe Vestibular Neuroprosthesis Placement—When One Size Does Not Fit All
Authors: Seppen Bart F. , van Hoof Marc , Stultiens Joost J. A. , van den Boogert Thomas , Guinand Nils , Guyot Jean-Philippe , Kingma Herman , Fornos Angelica Pérez , Handschuh Stephan , Glueckert Rudolf , Jacobi Linda , Schrott-Fischer Annelies , Chacko Lejo Johnson , van de Berg Raymond 
Published: May 2019

Objective:
To design and evaluate a new vestibular implant and surgical procedure that should reach correct electrode placement in 95% of patients in silico.

Design:
Computational anatomy driven implant and surgery design study.

Setting:
Tertiary referral center.

Participants:
The population comprised 81 patients that had undergone a CT scan of the Mastoid region in the Maastricht University Medical Center. The population was subdivided in a vestibular implant eligible group (28) and a control group (53) without known vestibular loss.

Interventions:
Canal lengths and relationships between landmarks were calculated for every patient. The relationships in group-anatomy were used to model a fenestration site on all three semicircular canals. Each patient's simulated individual distance from the fenestration site to the ampulla was calculated and compared with the populations average to determine if placement would be successful.

Main Outcome Measures:
Lengths of the semicircular canals, distances from fenestration site to ampulla (intralabyrinthine electrode length), and rate of successful electrode placement (robustness).

Results:
The canal lengths for the lateral, posterior, and superior canal were respectively 12.1 mm ± 1.07, 18.8 mm ± 1.62, and 17.5 mm ± 1.23, the distances from electrode fenestration site to the ampulla were respectively 3.73 mm ± 0.53, 9.02 mm ± 0.90, and 5.31 mm ± 0.73 and electrode insertions were successful for each respective semicircular canal in 92.6%, 66.7%, and 86.4% of insertions in silico. The implant electrode was subsequently revised to include two more electrodes per lead, resulting in a robustness of 100%.

Conclusions:
The computational anatomy approach can be used to design and test surgical procedures. With small changes in electrode design, the proposed surgical procedure's target robustness was reached.
To Scan or Not to Scan—A Cross-Sectional Analysis of the Clinical Efficacy and Cost-Effectiveness of Audiometric Protocols for Magnetic Resonance Imaging Screening of Vestibular Schwannomas
Authors: Bhargava Eishaan Kamta , Coyle Paula , Wong Billy , Masood Ajmal , Qayyum Asad 
Published: May 2019

Introduction:
Vestibular schwannomas (VS) are a rare cause of asymmetrical hearing loss, and routine screening with magnetic resonance imaging (MRI) can be costly. At present, no consensus exists on what qualifies as “asymmetrical sensorineural hearing loss” (ASNHL) and when a patient should be referred for screening.

Objectives:
1) Evaluation of published audiometric protocols on the basis of sensitivity and specificity when applied to local clinical cohort of patients with ASNHL; 2) determination of clinical risks of missing VS and potential wastes in screening “radiologically normal” cases; 3) assessment of the cost of MRI screening.

Methods:
Cross-sectional study with chart review in a 2-year (2015–2016) cohort of 1059 patients who underwent MRI screening and audiometry indicating sensorineural hearing loss. Fourteen previously published audiometric protocols were assessed for their sensitivity and specificity in guiding radiological diagnosis of VS, and cost analysis was performed.

Results:
6/14 audiometric protocols had a sensitivity greater than 85%. Diagnostic specificity ranged from 22.91 to 82.76%, clinical risks from 0 to 50%, and potential wastes from 17.24 to 77.09%. Average annual cost of screening was £64,069. Application of proposed local screening protocol had a projected cost saving of 32.19%. Cost of screening patients that benefit from treatment was compared with a utility function that quantified expected benefit.

Conclusions:
Development of an easy-to-apply algorithm incorporating high-sensitivity audiometric protocols may result in significant cost saving, with minimal clinical risk of missing cases. There was disparity between screening costs and monetary “benefit” of hearing.
Coronary artery calcium as a predictor of coronary heart disease, cardiovascular disease, and all-cause mortality in Asian-Americans: The Coronary Artery Calcium Consortium
Authors: Orimoloye Olusola A. , Banga Sandeep , Dardari Zeina A. , Uddin S. M. Iftekhar , Budoff Matthew J. , Berman Daniel S. , Rozanski Alan , Shaw Leslee J. , Rumberger John A. , Nasir Khurram , Miedema Michael D. , Blumenthal Roger S. , Blaha Michael J. , Mirbolouk Mohammadhassan 
Published: May 2019

Background
Coronary artery calcium (CAC) has been shown in multiple populations to predict atherosclerotic cardiovascular disease. However, its predictive value in Asian-Americans is poorly described.

Patients and methods
We studied 1621 asymptomatic Asian-Americans in the CAC Consortium, a large multicenter retrospective cohort. CAC was modeled in categorical (CAC = 0; CAC = 1–99; CAC = 100–399; CAC ≥ 400) and continuous [ln (CAC + 1)] forms. Participants were followed over a mean follow-up of 12 ± 4 years for coronary heart disease (CHD) death, cardiovascular disease (CVD) death, and all-cause mortality. The predictive value of CAC for individual outcomes was assessed using multivariable-adjusted Cox regression models adjusted for traditional cardiovascular risk factors and reported as hazard ratios (95% confidence interval).

Results
The mean (SD) age of the population was 54 (11.2) years and 64% were men. The mean 10-year atherosclerotic cardiovascular disease risk score was 8%. Approximately half had a CAC score of 0, whereas 22.5% had a CAC score of greater than 100. A total of 56 deaths (16 CVD and 8 CHD) were recorded, with no CVD or CHD deaths in the CAC = 0 group. We noted a significantly increased risk of CHD [hazard ratio (HR): 2.6 (1.5–4.3)] and CVD [HR: 2.3 (1.8–2.9)] mortality per unit increase in In (CAC + 1). Compared to those with CAC scores of 0, individuals with CAC scores of at least 400 had over a three-fold increased risk of all-cause mortality [HR: 3.3 (1.3–8.6)].

Conclusion
Although Asian-Americans are a relatively low-risk group, CAC strongly predicts CHD, CVD, and all-cause mortality beyond traditional risk factors. These findings may help address existing knowledge gaps in CVD risk prediction in Asian-Americans.
Emerging single-cell tools are primed to reveal functional and molecular heterogeneity in malignant hematopoietic stem cells
Authors: Shepherd Mairi S. , Kent David G. 
Published: May 2019

Purpose of review
The recent emergence of single-cell technologies has permitted unprecedented insight into the molecular drivers of fate choice in blood stem and progenitor cells. This review gives a broad overview of current efforts to understand the molecular regulators of malignant hematopoietic stem cells (HSCs) at the single-cell level.

Recent findings
The large-scale adoption of single-cell approaches has allowed extensive description of the transcriptional profiles and functional properties of single HSCs. These techniques are now beginning to be applied to malignant HSCs isolated directly from patients or from mouse models of malignancy. However, these studies have generally struggled to pinpoint the functional regulators of malignant characteristics, since malignant HSCs often differ in more than one property when compared with normal HSCs. Moreover, both normal and malignant populations are complicated by HSC heterogeneity.

Summary
Despite the existence of single-cell gene expression profiling tools, relatively few publications have emerged. Here, we review these studies from recent years with a specific focus on those undertaking single-cell measurements in malignant stem and progenitor cells. We anticipate this to be the tip of the iceberg, expecting the next 2–3 years to produce datasets that will facilitate a much broader understanding of malignant HSCs.
Hematopoietic-cell transplantation for lymphoma in the era of genetically engineered cellular therapy: it's not quite time to scrap the old vehicle for the new car
Authors: Scordo Michael , Lin Richard J. , Sauter Craig S. 
Published: May 2019

Purpose of reviewSecond-line platinum-based salvage chemotherapy followed by high-dose chemotherapy and autologous hematopoietic-cell transplantation (AHCT) has remained the standard of care (SOC) for relapsed and primary refractory (r/r) diffuse large B-cell lymphoma (DLBCL) for greater than 2 decades. In the postrituximab era, this strategy has yielded disappointing outcomes for r/r patients with curability in less one-quarter of the patients by intention-to-treat.Recent findingsGiven the Food and Drug Administration (FDA) approval of chimeric antigen receptor (CAR) modified T cells directed against CD19 (CD19 CAR T) for DLBCL following two lines of therapy and/or failed AHCT, encouragement with this therapy in the second line for r/r patients has naturally prompted randomized phase III studies against the aforementioned SOC. The predominant hurdle to procession to AHCT is chemotherapy sensitivity after platinum-based salvage therapy.SummaryIn this review, we will discuss recent investigations to improve response rates in r/r DLBCL with the intent of proceeding to potentially curative AHCT, as well as investigations to decrease progression post-AHCT. In addition, data regarding currently FDA approved CD19 CAR T cells will be reviewed. Within 2–3 years, we will know if the multicenter/multinational studies of CD19 CAR T will replace SOC salvage therapy and AHCT in the second-line. The role of allogeneic HCT will also be briefly reviewed in the context of these therapies.
Decrement in Cellular Iron and Reactive Oxygen Species, and Improvement of Insulin Secretion in a Pancreatic Cell Line Using Green Tea Extract
Authors: Koonyosying Pimpisid , Uthaipibull Chairat , Fucharoen Suthat , Koumoutsea Evangelia Vlachodimitropoulou , Porter John B. , Srichairatanakool Somdet 
Published: May 2019

Objectives
We have investigated the efficacy of mono- and combined therapy with green tea extract (GTE) in mobilizing redox iron, scavenging reactive oxygen species (ROS), and improving insulin production in iron-loaded pancreatic cells.

Methods
Rat insulinoma pancreatic β-cells were iron-loaded using culture medium supplemented with either fetal bovine serum or ferric ammonium citrate and treated with various doses of GTE for epigallocatechin-3-gallate (EGCG) equivalence and in combination with iron chelators. Cellular iron, ROS, and secretory insulin were measured.

Results
The rat insulinoma pancreatic cells took up iron from fetal bovine serum more rapidly than ferric ammonium citrate. After treatment with GTE (0.23–2.29 μg EGCG equivalent), cellular levels of iron and ROS were dose dependently decreased. Importantly, secretory insulin levels were increased nearly 2.5-fold with 2.29 μg of EGCG equivalent GTE, indicating a recovery in insulin production.

Conclusions
Green tea EGCG ameliorated oxidative damage of iron-loaded β-cells by removing redox iron and free radicals and attenuating insulin production. The impact can result in the restoration of pancreatic functions and an increase in insulin production. Green tea extract exerts iron-chelating, free-radical scavenging, and pancreato-protective effects in the restoration of β-cell functions, all of which we believe can increase insulin production in diabetic β-thalassemia patients.
Hepatic Encephalopathy in Children With Acute Liver Failure
Authors: Toney Nicole A. , Bell Michael J. , Belle Steven H. , Hardison Regina M. , Rodriguez‐Baez Norberto , Loomes Kathleen M. , Vodovotz Yoram , Zamora Ruben , Squires Robert H. ,   Pediatric Acute Liver Failure Study Group
Published: May 2019

ABSTRACTBackground:Pediatric acute liver failure (PALF) is a public heath burden, often requiring prolonged hospitalization and liver transplantation. Hepatic encephalopathy (HE) is a complication of PALF with limited diagnostic tools to predict outcomes. Serum neurological markers (neuron‐specific enolase, S100β, and myelin basic protein) can be elevated in traumatic or ischemic brain injury. We hypothesized that these neuromarkers would be associated with the development of HE in PALF.Methods:PALF study participants enrolled between May 2012 and December 2014 by 12 participating centers were the subjects of this analysis. Daily HE assessments were determined by study investigators. Neurological and inflammatory markers were measured using enzyme‐linked immunosorbent assay and MILLIPLEX techniques, respectively. To model encephalopathy, these markers were log2 transformed and individually examined for association with HE using a generalized linear mixed model with a logit link and random intercept.Results:Eighty‐two children had neurological and inflammatory marker levels and HE assessments recorded, with the majority having assessments for 3 days during their illness. An indeterminate diagnosis (29%) was most common and the median age was 2.9 years. Significant associations were observed for HE with S100β (odds ratio 1.16, 95% confidence interval [1.03–1.29], P = 0.04) and IL‐6 (odds ratio 1.24 [1.11–1.38], P = 0.006).Conclusions:Serum S100β and IL‐6 are associated with HE in children with PALF. Measuring these markers may assist in assessing neurological injury in PALF, impacting clinical decisions.
Nutrition Interventions in Pediatric Pancreatitis
Authors: Theodoridis Xenophon , Grammatikopoulou Maria G. , Petalidou Arianna , Stamouli Eleni‐Maria , Fotiadou Iliana , Gkiouras Konstantinos , Bogdanos Dimitrios P. , Dardavessis Theodore 
Published: May 2019

ABSTRACTObjective:Despite the fact that pediatric pancreatitis is an uncommon disease, its prevalence has increased in recent years. Nevertheless, until 4 years ago, the lack of nutritional guidelines for pediatric pancreatitis was evident, with all recommendations being based on clinical practice guidelines (CPGs) for adults. The aim of the present study was to review and critically appraise guidelines for the medical nutrition therapy (MNT) of pediatric pancreatitis.Methods:A comprehensive search was performed in electronic databases (PubMed, Scopus, National Institute for Health and Care Excellence), the International Guidelines Network, BMJ best practice, and the Scottish Intercollegiate Guidelines Network to identify CPGs on the MNT of pediatric pancreatitis. The validated AGREE II tool was used for guidelines appraisal by a team of 3 independent multidisciplinary reviewers.Results:A total of 4 CPGs were retrieved with pediatric pancreatitis MNT information. Out of the 4 advising bodies in total, the joint society paper published by the ESPGHAN/NASPGHAN received the highest score in almost all domains, whereas the Belgian consensus obtained the lowest score in all domains but stakeholder involvement, and was not recommended by 2 out of 3 reviewers.Conclusions:Pediatric pancreatitis guidelines appear heterogenous in quality, rigour, and transparency. Our study points out existing gaps and biases in the CPGs, and delineates the need for improving the domains identified as being of low‐quality.