bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Carbon Dioxide on Cerebral Autoregulation During Sevoflurane-based Anesthesia in Patients With Type 2 Diabetes
Authors: van den Dool Rokus E.C. , Immink Rogier V. , van der Ster Björn J.P. , Hermanides Jeroen , Hollmann Markus W. , Preckel Benedikt , van Lieshout Johannes J. , Sperna Weiland Nicolaas H. 
Published: August 2021

Background:
Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO2) (cerebrovascular CO2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO2 reactivity and the CA-CO2 relationship.

Methods:
We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO2, blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia.

Results:
In both control and DM patients, awake CO2 reactivity was smaller (2.8%/mm Hg CO2) than during sevoflurane anesthesia (3.9%/mm Hg; P<0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO2) in controls than in DM patients (1.8 deg./mm Hg CO2; P<0.001) in both awake and sevoflurane-anesthetized states.

Conclusions:
The CA-CO2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects.
An Analysis of Online Ratings of Pediatric Orthopaedic Surgeons
Authors: Jay Jordan H. , Runge Nicholas E. , Vergara Franz H. , Sabatini Coleen S. , Oni Julius K. 
Published: August 2021

Background:
Patients continue to utilize physician review websites (PRWs) to assist in their selection of a health care provider. Studies on PRWs and how they affect patient care have recently become popular in the literature. This study analyzes PRW ratings of a previously unexamined subspecialty, pediatric orthopaedic surgeons.

Methods:
Three hundred ninety-nine randomly selected Pediatric Orthopaedic Society of North America member’s PRW ratings were examined from May 4, 2020 to July 18, 2020. Healthgrades.com, Vitals.com, RateMDs.com, and Google.com were reviewed. Number of ratings and average ratings (0 to 5.0) were recorded. Provider sex, years in practice (0 to 10, 11 to 20, and 21+), practice type (academic, private), geographic location (Northeast, Southeast, Midwest, Southwest, West), degree (Medical Doctor, Doctor of Osteopathic Medicine), and fellowship training (yes, no) were recorded. Kruskal-Wallis testing was performed to determine factors affecting positive surgeon ratings.

Results:
98.5% (393) of Pediatric Orthopaedic Society of North America surgeons were rated on a PRW at least once and were highly rated with an average rating of 4.14 of 5.0. Surgeons in practice 1 to 10 years had higher ratings than those in practice 11 to 20 and 21+ years, on Healthgrades.com (P=0.049) and RateMDs.com (P=0.011). Academic surgeons were found to have higher ratings than those in private practice on Google.com (P=0.007). Sex, region of practice, degree type, and fellowship training status did not have an effect on online ratings across all PRWs.

Conclusions:
Pediatric orthopaedic surgeons are frequently and highly rated, similar to other orthopaedic subspecialties. Surgeons in practice 1 to 10 years were found to have statistically higher ratings on some websites. Academic surgeons were found to have statistically higher ratings on some websites.
Physeal Abnormalities in Children With High-risk Neuroblastoma Intensively Treated With/Without 13-Cis-Retinoic Acid
Authors: Koh Kyung-Nam , Jeon Ji Young , Park Soo-Sung , Im Ho Joon , Kim Hyery , Kang Michael Seungcheol 
Published: August 2021

Background:
This study aimed to investigate the presence of physeal abnormality and its effect on growth in children with high-risk neuroblastoma treated by intensive multimodal treatment with/without 13-cis-retinoic acid (13-CRA).

Methods:
Fifteen patients diagnosed with high-risk neuroblastomas at the age of 1 to 10 years, who received treatment such as high-dose chemotherapy and autologous stem cell transplantation with/without 13-CRA, and with complete data during their >2-year follow-up were retrospectively reviewed. The physeal abnormalities were investigated by whole-body magnetic resonance imaging, serially performed every 3 to 6 months. The patients’ height growth was also investigated and compared with that of age-and-sex-matched patients with brain tumors who also underwent high-dose chemotherapy and autologous stem cell transplantation.

Results:
Six of 15 patients presented multifocal physeal abnormalities during follow-up, and all lesions occurred in patients with 13-CRA use. The lesions in 3 patients completely resolved spontaneously without any adverse effect on growth, but some lesions in the other 3 patients progressed to disturb the bony growth. Height growth of matched patients with brain tumors were not significantly different, and none of the matched controls showed definite bony deformity during the follow-up.

Conclusions:
Some children who were treated for high-risk neuroblastomas experienced multifocal physeal insults, probably due to the use of 13-CRA. Most lesions resolved spontaneously, but some led to bony deformity. If the lesions are not followed by premature physeal closure, there seems to be no further adverse effect of 13-CRA on leg length growth. Routine periodic screening for physeal status is needed for the patients with high-risk neuroblastomas using 13-CRA.

Level of Evidence:
Level IV—prognostic study.
Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy
Authors: Wang Yuan-Yuan , Han Zhen-Hui , Wang Yu-Li , Liao Ying , Zhang Chun-Yu , Liu Ping , Tang Chao-Shu , Du Jun-Bao , Jin Hong-Fang , Huang Ya-Qian 
Published: August 2021

Abstract

Background:
Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.

Methods:
This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics.

Results:
A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = −2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = −2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039–1.387, P = 0.013).

Conclusions:
Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
Drug Levels Associated With Optimal Discrimination Between Remission and Nonremission and Comparison of Antibody Assays During First Year of Stable Infliximab Maintenance Therapy in Inflammatory Bowel Disease
Authors: Dorn-Rasmussen Maria , Buhl Sine , Brynskov Jørn , Bay Jakob T. , Bolstad Nils , Klausen Tobias W. , Warren David J. , Ainsworth Mark A. , Steenholdt Casper 
Published: August 2021

Background:
To implement therapeutic drug monitoring–based strategies for infliximab (IFX) in inflammatory bowel disease, the authors assessed IFX levels for optimal discrimination between remission and nonremission and compared assays for anti-IFX antibodies (Abs).

Methods:
The retrospective cohort comprised 163 bionaive patients with inflammatory bowel disease who received stable IFX maintenance therapy (5 mg/kg every 8 weeks [q8w]) for 1 year. The clinical and biochemical remission status was assessed at all infusions (weeks 14-22-30-38-46-54), and IFX and anti-IFX Abs were estimated using a time-resolved fluorometric assay (n = 690; 88% of infusions). Samples positive for anti-IFX Abs or IFX levels < limit of detection (n = 102) were analyzed by 2 binding assays [enzyme-linked immunosorbent assay (ELISA)] and functional reporter gene assay/drug-tolerant enzyme immunoassay.

Results:
At all assessed time points, IFX levels were more than double in patients presenting clinical or biochemical remission. An IFX concentration of 4.5 mcg/mL was associated with clinical remission during the entire first year of therapy [sensitivity 54% (49–59), specificity 73% (67–78), AUCROC 0.65 (0.60–0.69), P < 0.0001]; these values were comparable with biochemical remission. Exploratory assessments for endoscopic remission (n = 131) were performed at the discretion of the treating physician. Anti-IFX Abs were associated with undetectable IFX and treatment failure [OR 2.9 (1.4–6.0), P < 0.01], irrespective of persistency or transiency. All performed assays detected anti-IFX Abs were picked up by all assays in ∼2/3 of samples. Binding assays demonstrated a higher sensitivity to anti-IFX Abs.

Conclusions:
IFX at ∼5 mcg/mL was associated with clinical and biochemical remission during the first year of maintenance therapy. During this phase of therapy, standard binding assays are appropriate for therapeutic drug monitoring.
Clinical characteristics, practice patterns, and outcomes of patients with acute severe hypertension visiting the emergency department
Authors: Kim Byung Sik , Kim Hyun-Jin , Lyu Minhyung , Kim Wook-Dong , Lee Yonggu , Kim Miso , Lee Suein , Park Jin-Kyu , Shin Jinho , Shin Hyungoo , Kim Changsun , Shin Jeong-Hun 
Published: August 2021

Objectives:
Data regarding acute severe hypertension, a life-threatening condition encountered in the emergency department, are limited. We aimed to identify the characteristics, practice patterns, and outcomes of patients with acute severe hypertension in the emergency department.

Methods:
This cross-sectional study at a tertiary referral centre included patients aged at least 18 years who were admitted to the emergency department between January 2016 and December 2019 for acute severe hypertension, which was defined as SBP at least 180 mmHg and/or DBP at least 100 mmHg.

Results:
Of 172 105 patients who visited the emergency department, 10 219 (5.9%) had acute severe hypertension. Of them, 2506 (24.5%) patients had acute hypertension-mediated organ damage (HMOD), and these patients had more cardiovascular risk factors than did patients without HMOD. Additionally, 4137 (40.5%) patients were admitted, and nine (0.1%) died in the emergency department. The overall 3-month, 1-year, and 3-year mortality rates were 4.8, 8.8, and 13.9%, respectively. In patients with HMOD, the 1-year mortality rate was 26.9%, and patients lost to follow-up had a significantly higher 1-year mortality rate than those who were followed up (21.3 vs. 10.5%, respectively, P < 0.001).

Conclusion:
The mortality rate in patients with acute severe hypertension in the emergency department is high, especially in patients with HMOD. Evaluation of HMOD, investigating the underlying causes, and adequate follow-up are mandatory to improve the outcomes in these patients. This study emphasizes the need for disease-specific guidelines that include detailed acute treatment strategies and follow-up management for acute severe hypertension.
Independent relationships between renal mechanisms and systemic flow, but not resistance to flow in primary hypertension in Africa
Authors: Malan Nico , Norton Gavin R. , Peterson Vernice R. , Yusuf Suraj M. , Libhaber Elena , Libhaber Carlos D. , Mmopi Keneilwe N. , Bello Hamza , Masiu Mohlabani , Da Silva Fernandes Daniel , Tade Grace , Mthembu Nonhlanhla , Peters Ferande , Dessein Patrick H. , Sareli Pinhas , Woodiwiss Angela J. 
Published: August 2021

Aims:
Whether renal mechanisms of hypertension primarily translate into increases in systemic vascular resistance (SVR) in all populations is uncertain. We determined whether renal mechanisms associate with either increases in SVR (and impedance to flow) or systemic flow in a community of African ancestry.

Method:
In a South African community sampled across the full adult age range (n = 546), we assessed stroke volume (SV), peak aortic flow (Q), SVR, characteristic impedance (Zc) and total arterial compliance (TAC) from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures. Renal changes were determined from creatinine clearance (glomerular filtration rate, GFR) and fractional Na+ excretion (FeNa+) (derived from 24-h urine collections).

Results:
Independent of confounders (including MAP and pressures generated by the product of Q and Zc), SV (and hence cardiac output) (P < 0.0001) and Q (P < 0.01), but not SVR, Zc or TAC (P = 0.09–0.20) were independently associated with decreases in both GFR (index of nephron number) and FeNa+. Through an interactive effect (P < 0.0001), the impact of GFR on SV or Q was strongly determined by FeNa+ and vice versa. The relationship between the GFR-FeNa+ interaction and either SV or Q was noted in those above or below 50 years of age, although neither GFR, FeNa+ nor the interaction were independently associated with SVR, Zc or TAC at any age.

Conclusion:
Across the full adult lifespan, in groups of African ancestry, renal mechanisms of hypertension translate into increases in systemic flow rather than into resistance or impedance to flow.
EVALUATION OF ARTIFICIAL INTELLIGENCE–BASED QUANTITATIVE ANALYSIS TO IDENTIFY CLINICALLY SIGNIFICANT SEVERE RETINOPATHY OF PREMATURITY
Authors: Li Jie , Huang Kaide , Ju Rong , Chen Yuanyuan , Li Mengyu , Yang Shijun , Wang Yue , Dong Wentao , Liu Miao , Chen Sizhu , Leng Hongmei , Zhong Jie 
Published: August 2021

Purpose:
To evaluate the screening potential of a deep learning algorithm–derived severity score by determining its ability to detect clinically significant severe retinopathy of prematurity (ROP).

Methods:
Fundus photographs were collected, and standard panel diagnosis was generated for each examination by combining three independent image-based gradings. All images were analyzed using a deep learning algorithm, and a quantitative assessment of retinal vascular abnormality (DeepROP score) was assigned on a 1 to 100 scale. The area under the receiver operating curve and distribution pattern of all diagnostic parameters and categories of ROP were analyzed. The correlation between the DeepROP score and expert rank ordering according to overall ROP severity of 50 examinations was calculated.

Results:
A total of 9,882 individual examinations with 54,626 images from 2,801 infants were analyzed. Fifty-six examinations (0.6%) demonstrated Type 1 ROP and 54 examinations (0.5%) demonstrated Type 2 ROP. The DeepROP score had an area under the receiver operating curve of 0.981 for detecting Type 1 ROP and 0.986 for Type 2 ROP. There was a statistically significant correlation between the expert rank ordering of overall disease severity and the DeepROP score (correlation coefficient 0.758, P < 0.001). When hypothetical referral cutoff score of 35 was selected, all cases of severe ROP (Type 1 and Type 2 ROP) was captured and 8,562 eyes (87.6%) with no or mild ROP were excluded.

Conclusion:
The DeepROP score determined by deep learning algorithm was an objective and quantitative indicator for the severity of ROP, and it had potential in automated detecting clinically significant severe ROP.
Lower Cognitive Function in Patients With Functionally and Structurally Severe Glaucoma: The LIGHT Study
Authors: Yoshikawa Tadanobu , Obayashi Kenji , Miyata Kimie , Saeki Keigo , Ogata Nahoko 
Published: August 2021

Precis:
This cross-sectional study of 172 patients with glaucoma showed that functional and structural glaucoma damage was significantly associated with cognitive impairment independent of age and visual acuity.

Purpose:
The aim of this study was to determine whether functional and structural glaucoma damage is associated with cognitive function.

Patients and Methods:
This was a cross-sectional analysis comprising 172 patients with glaucoma with a mean age of 70.6 years. Functional glaucoma severity was evaluated according to the visual field mean deviation (MD) (severe, MD ≤−12 dB; mild, MD >−12 dB), and structural glaucoma severity was determined based on circumpapillary retinal nerve fiber layer thickness. The main outcome measure was cognitive impairment defined by a Mini-Mental State Examination (MMSE) score of ≤26 and MMSE-blind score of ≤16.

Results:
The prevalence of patients with cognitive impairment (MMSE score ≤26) was significantly higher in the severe glaucoma group than in the mild glaucoma group (33.3% vs. 15.7%; P=0.010, respectively). Similar results were obtained in the analyses with MMSE-blind score of ≤16 (14.7% vs. 1.4%; P=0.003, respectively). Multivariable logistic regression analysis adjusted for potential confounders, including age, body mass index, education, visual acuity, hypertension, diabetes, and depressive symptoms, indicated a higher odds ratio (OR) for cognitive impairment (MMSE score ≤26) in patients with severe glaucoma than in those with mild glaucoma (OR, 2.62; 95% confidence interval, 1.006-6.84; P=0.049) and in relation to a 10-μm thinning of the retinal nerve fiber layer (OR, 1.42; 95% confidence interval, 1.05-1.93; P=0.025).

Conclusion:
Functional and structural glaucoma damage was significantly associated with lower cognitive function independent of age and visual acuity in a glaucoma cohort.
Performance in Real World- and Virtual Reality-Based Spatial Navigation Tasks in Patients With Vestibular Dysfunction
Authors: Biju Kevin , Wei Eric X. , Rebello Elliott , Matthews Jacob , He Qiliang , McNamara Timothy P. , Agrawal Yuri 
Published: August 2021

Objective:
This study evaluated whether vestibular dysfunction is associated with reduced spatial navigation performance.

Study Design:
Cross-sectional study.

Setting:
Otolaryngology Clinic in the Johns Hopkins Outpatient Center and an analogous virtual reality (VR) environment.

Patients:
Eligible patients had diagnosis of unilateral or bilateral vestibular loss. Matched healthy controls were recruited at 1:1 ratio.

Interventions:
The navigation task involved a route-based or place-based strategy in both real world and VR environments.

Main Outcome Measures:
Navigation performance was measured by distance travelled relative to optimal distance (i.e., path ratio) and the Judgments of Relative Direction (JRD) task, whereby participants had to recall relative angular distances between landmarks.

Results:
The study sample included 20 patients with vestibular loss (mean age: 61 yrs, SD: 10.2 yrs) and 20 matched controls (mean age: 60 yrs, SD: 10.4 yrs). Patients with vestibular loss travelled significantly greater distance using both route-based (path ratio 1.3 vs. 1.0, p = 0.02) and place-based (path ratio 2.6 vs. 2.0, p = 0.03) strategies in the real world. Overall, participants performed worse in virtual reality compared to real world in both path ratio (2.2 vs. 1.7; p = 0.04) and JRD error (78° vs. 67°; p < 0.01). Furthermore, while controls exhibited significant positive correlations between real world and VR performance in place-based (β = 0.75; p < 0.001) and JRD tasks (β = 0.70; p < 0.001), patients with vestibular loss exhibited no similar correlations.

Conclusions:
The vestibular system appears to play a role in navigation ability during both actual and virtual navigation, suggesting a role for static vestibular signals in navigation performance.
Four-Hour Delayed Gadolinium-Enhanced 3D-FLAIR MR Imaging Highlights Intralabyrinthine Micro-Schwannomas
Authors: Kurata Natsuko , Kawashima Yoshiyuki , Ito Taku , Ooka Tomoki , Tsutsumi Takeshi 
Published: August 2021

Objective:
To demonstrate the clinical significance of 4-hour delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery (delayed 3D-FLAIR) in patients with intralabyrinthine schwannoma (ILS).

Patients:
Three patients who were clinically diagnosed with ILS.

Interventions:
All patients underwent audiological examinations and magnetic resonance imaging (MRI) scans. The MR-protocol included axial MR cisternography, immediate gadolinium-enhanced T1-weighted sequence, and heavily T2-weighted 3D-FLAIR prior to and 4 hours after the intravenous administration of gadolinium contrast medium.

Main Outcome Measures:
All MR images were visually inspected.

Results:
In all three patients with ILS, delayed 3D-FLAIR MRI demonstrated a strong signal of cochlear fluid surrounding the tumor, which highlighted a tumor region that lacked signals.

Conclusions:
Delayed 3D-FLAIR MRI may serve as a novel diagnostic tool for the early detection of intralabyrinthine micro-schwannoma. The findings also shed light on the pathophysiology of ILS.