bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound and Magnetic Responsive Drug Delivery Systems for Cardiovascular Application
Authors: Qian Bei , Zhao Qiang , Ye Xiaofeng 
Published: July 2020

Abstract:
With the increasing insight into molecular mechanisms of cardiovascular disease, a promising solution involves directly delivering genes, cells, and chemicals to the infarcted myocardium or impaired endothelium. However, the limited delivery efficiency after administration fails to reach the therapeutic dose and the adverse off-target effect even causes serious safety concerns. Controlled drug release via external stimuli seems to be a promising method to overcome the drawbacks of conventional drug delivery systems (DDSs). Microbubbles and magnetic nanoparticles responding to ultrasound and magnetic fields respectively have been developed as an important component of novel DDSs. In particular, several attempts have also been made for the design and fabrication of dual-responsive DDS. This review presents the recent advances in the ultrasound and magnetic fields responsive DDSs in cardiovascular application, followed by their current problems and future reformation.
Role of Bempedoic Acid in Dyslipidemia Management
Authors: Kelly Michael S. , Sulaica Elisabeth M. , Beavers Craig J. 
Published: July 2020

Abstract:
Statins remain the preferred agent to reduce low-density lipoprotein cholesterol (LDL-C) and lower atherosclerotic cardiovascular disease (ASCVD) risk. Additional nonstatin agents are recommended to further lower LDL-C among patients at high-risk of ASCVD or those with heterozygous familial hypercholesterolemia, despite statin therapy. Patients unable to tolerate recommended doses of statin therapy due to adverse effects, including statin-associated muscle symptoms, may also require additional nonstatin agents to lower LDL-C and ASCVD risk. Bempedoic acid is a first-in-class, once-daily oral agent, recently approved as monotherapy and in combination with ezetimibe, as an adjunct to maximally tolerated statin therapy in patients with ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering. Its novel mechanism is reported to avoid adverse muscle symptoms associated with statins. The effectiveness and safety of bempedoic acid and bempedoic acid/ezetimibe combination have been reported in multiple phase 2 and 3 trials. In this review, we report the lipid-lowering effects associated with bempedoic acid, and the safety profile from multiple clinical trials. Based on available data, bempedoic acid significantly lowers LDL-C and other atherogenic lipoprotein measures, and high-sensitivity C-reactive protein when added to background lipid-lowering therapy in patients with and without statin intolerance. Overall safety of bempedoic acid seems to be comparable to placebo, except for increased serum uric acid and tendon rupture. Ongoing clinical trials assessing the long-term safety and cardiovascular outcomes will provide additional insight into the role of bempedoic acid as an adjunct lipid-lowering medication.
AABIP Evidence-informed Guidelines and Expert Panel Report for the Management of Indwelling Pleural Catheters
Authors: Miller Russell J. , Chrissian Ara A. , Lee Y.C. Gary , Rahman Najib M. , Wahidi Momen M. , Tremblay Alain , Hsia David W. , Almeida Francisco A. , Shojaee Samira , Mudambi Lakshmi , Belanger Adam R. , Bedi Harmeet , Gesthalter Yaron B. , Gaynor Margaret , MacKenney Karen L. , Lewis Sandra Z. , Casal Roberto F. 
Published: July 2020

Background:
While the efficacy of Indwelling pleural catheters for palliation of malignant pleural effusions is supported by relatively robust evidence, there is less clarity surrounding the postinsertion management.

Methods:
The Trustworthy Consensus-Based Statement approach was utilized to develop unbiased, scientifically valid guidance for the management of patients with malignant effusions treated with indwelling pleural catheters. A comprehensive electronic database search of PubMed was performed based on a priori crafted PICO questions (Population/Intervention/Comparator/Outcomes paradigm). Manual searches of the literature were performed to identify additional relevant literature. Dual screenings at the title, abstract, and full-text levels were performed. Identified studies were then assessed for quality based on a combination of validated tools. Appropriateness for data pooling and formation of evidence-based recommendations was assessed using predetermined criteria. All panel members participated in development of the final recommendations utilizing the modified Delphi technique.

Results:
A total of 7 studies were identified for formal quality assessment, all of which were deemed to have a high risk of bias. There was insufficient evidence to allow for data pooling and formation of any evidence-based recommendations. Panel consensus resulted in 11 ungraded consensus-based recommendations.

Conclusion:
This manuscript was developed to provide clinicians with guidance on the management of patients with indwelling pleural catheters placed for palliation of malignant pleural effusions. Through a systematic and rigorous process, management suggestions were developed based on the best available evidence with augmentation by expert opinion when necessary. In addition, these guidelines highlight important gaps in knowledge which require further study.
Sucrase‐isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders
Authors: Deb Chirajyoti , Campion Stephani , Derrick Veronica , Ruiz Vanessa , Abomoelak Bassam , Avdella Angelina , Zou Baiming , Horvath Karoly , Mehta Devendra I. 
Published: July 2020

ABSTRACTObjectives:The aim of the study was to determine prevalence and characterize sucrase‐isomaltase (SI) gene variants of congenital sucrase‐isomaltase deficiency in non‐Hispanic white pediatric and young adult patients with functional gastrointestinal disorders (FGIDs), and abnormal sucrase activity on histologically normal duodenal biopsy.Methods:Clinical symptoms and disaccharidase activities data were collected for an abnormal (low) sucrase (≤25.8 U, n = 125) activity group, and 2 normal sucrase activity groups with moderate (≥25.8–≤55 U, n = 250) and high (>55 U, n = 250) sucrase activities. SI gene variants were detected by next‐generation sequencing of DNA from formalin‐fixed paraffin‐embedded tissues of these patients. FGIDs symptoms based on Rome IV criteria and subsequent clinical management of abnormal sucrase activity cases with pathogenic SI gene variants were analyzed.Results:Thirteen SI gene variants were found to be significantly higher in abnormal sucrase cases with FGIDs symptoms (36/125, 29%; 71% did not have a pathogenic variant) compared to moderate normal (16/250, 6.4%, P < 0.001) or high normal (5/250, 2.0%, P < 0.001) sucrase groups. Clinical management data were available in 26 of abnormal sucrase cases, and only 10 (38%) were correctly diagnosed and managed by the clinicians. Concomitant lactase deficiency (24%; 23/97) and pan‐disaccharidase deficiency (25%; 13/51) were found in the abnormal sucrase group.Conclusions:Heterozygous and compound heterozygous mutations in the SI gene were more prevalent in cases with abnormal sucrase activity presenting with FGIDs, and normal histopathology. This suggests heterozygous pathogenic variants of congenital sucrase‐isomaltase deficiency may present as FGIDs. Concomitant lactase or pan‐disaccharidase deficiencies were common in abnormal sucrase cases with SI gene variants.
Prevalence and Predictors of Compromised Bone Mineral Density in Pediatric Eosinophilic Esophagitis
Authors: Henderson Anna F. , Khan Soofia M. , Hornung Lindsey N. , Mukkada Vincent A. , Kalkwarf Heidi J. 
Published: July 2020

ABSTRACTObjectives:The aim of the study was to determine whether patients with eosinophilic esophagitis (EoE) have lower bone mineral density (BMD) than expected and if bone deficits are more pronounced in subgroups of patients according to comorbidities (atopic disease and joint hypermobility) or treatments (dietary restriction, medication exposure).Study Design:Retrospective chart review was performed to obtain clinical data, including length of diagnosis, comorbidities, and methods of treatment for patients with EoE ages 3 to 21 years who had a lumbar spine dual‐energy x‐ray absorptiometry scan performed between 2014 and 2017. BMD was standardized by calculation of age, sex, and race‐specific z scores.Results:A total of 269 patients met study criteria. The mean BMD z score (−0.55, 95% confidence interval: −0.68, −0.42) was lower than expected (P < 0.0001), and the prevalence of low BMD z score (≤−2.0) was higher than expected (8.5%, 95% confidence interval: 5.2%–11.9%, P < 0.0001). In multivariable regression models, BMD z scores were −0.27 lower among those following an elimination diet and −0.65 lower among those with any lifetime use of a proton pump inhibitor (93% of the sample). There was no association with swallowed steroid use.Conclusions:In our sample, pediatric patients with EoE had a slightly lower BMD z score compared to peers, and the prevalence of low BMD was higher than expected. Taken cautiously given the limitations of our sample, risk factors for bone deficits included any lifetime use of proton pump inhibitor and a restrictive elimination diet, but not swallowed steroid use. Larger prospective studies are needed to better characterize risk factors for low BMD to help inform screening, selection of therapies, and provide appropriate anticipatory guidance for patients with EoE.
Nephrocalcinosis and Renal Dysfunction in Pediatric Intestinal Failure
Authors: Roberts Amin J. , Belza Christina , Wales Paul W. , Courtney‐Martin Glenda , Harvey Elizabeth , Avitzur Yaron 
Published: July 2020

ABSTRACTBackground:Outcomes of pediatric intestinal failure (PIF) have improved recently, with other comorbidities, such as increased echogenicity/nephrocalcinosis on ultrasound (US) in long‐term survivors now evident. We evaluated the significance of nephrocalcinosis over time in PIF and its impact on renal function.Methods:Retrospective analysis on a cohort of PIF patients was performed. Presence of nephrocalcinosis and/or increased renal echogenicity (identified on US), estimated glomerular filtration rate (eGFR; ml · min−1 · 1.73 m−2), renal tubular function, PN volume (ml · kg−1 · day−1) and PN exposure time (hours/day) were reviewed annually over a follow‐up period of 2 years. Outcomes in the nephrocalcinosis versus normal US groups were compared.Results:Forty patients (28 boys, median age 2.7 years) were followed for 2 years. Fifteen (38%) had either increased echogenicity or nephrocalcinosis (group 1) at initial US. US were normal in the remaining 25 (62%) on initial assessment (group 2). eGFR did not differ between group 1 and group 2 at baseline (118 vs 133, P = 0.51) and year 2 (130 vs 131, P = 1.00). The percentage of patients with abnormal markers of tubular function was similar in both groups at year 2 (high urine calcium: creatinine 33 versus 30, P = 0.83; high urine calcium: citrate 39 versus 42, P = 0.87; low urine citrate: creatinine 15 versus 17, P = 1.00; high urine oxalate: creatinine 39 versus 25, P = 0.77).Conclusions:A large proportion of PIF patients with a history of parenteral nutrition (PN) exposure have nephrocalcinosis and/or increased echogenicity on US. Over a 2‐year follow‐up period, however, these abnormalities had no impact on eGFR or renal tubular function.
Cardiovascular Risk Assessment in Children With Chronic Cholestatic Liver Diseases
Authors: Janowski Kamil , Obrycki Łukasz , Litwin Mieczysław , Czubkowski Piotr , Wierzbicka-Rucińska Aldona , Gliwicz-Miedzińska Dorota , Jankowska Irena , Kostewicz Krzysztof , Socha Piotr 
Published: July 2020

ABSTRACT

Objectives:
Chronic cholestatic liver diseases are often associated with disturbed lipid metabolism, which may potentially increase cardiovascular (CV) risk but the evidence is scarce. The aim of the study was to assess factors associated with increased CV risk in children with Alagille syndrome (AGS) and biliary atresia (BA).

Methods:
We investigated 17 patients with AGS, ages 11.0 years (8.4–13.4) and 19 with BA, ages 13.5 years (10.4–15.1) in whom we performed thorough biochemical assessment including lipid profiles and oxidative stress biomarkers, blood pressure (BP)—systolic, diastolic and mean, carotid intima-media thickness (cIMT), and pulse wave velocity (PWV).

Results:
There were abnormal lipid profiles in 82% of children with AGS and 52.6% with BA. In AGS group, we observed significantly higher levels of TC, LDL C, APO B, lower glutathione concentration and glutathione peroxidase activity and lower blood pressure, lower cIMT (P = 0.02), cIMT-SDS (P = 0.04), and PWV (P = 0.04). We, however, observed elevated blood pressure in 2/19 patients with BA and none-with AGS (BA vs AGS: P = 0.12), whereas cIMT-SDS was increased only in 2/17 patients with AGS and in 6/19 with BA (P = 0.24), and abnormal PWV-SDS values were detected in 3/17 of AGS and 8/19 of BA patients (P = 0.15). Neither presence of dyslipidemia nor Lp-X correlated with vascular parameters.

Conclusions:
Children with BA and AGS may present with increased cardiovascular risk factors but vascular parameters are not directly related to lipid abnormalities. cIMT and BP should be considered for clinical practice in these cholestatic disorders so as to determine individuals with potential CV risk.
Physical Function and Frailty Tools in Mortality Prediction of Middle-Aged Adults With HIV
Authors: Pelloquin Regan , Abdo Mona , MaWhinney Samantha , Jankowski Catherine M. , Erlandson Kristine M. 
Published: July 2020

Background:
Frailty and physical function impairments occur at an earlier than expected age in people with HIV (PWH). The goal of this study was to determine which tools or combination of tools assessing frailty/physical function were most predictive of mortality in a middle-aged population of PWH.

Methods:
Using electronic health records, we determined survival, death, or loss to follow-up for 359 PWH, aged 45–65 years originally enrolled in a 2009–2010 cross-sectional cohort study. The predictive accuracy of various physical function measures [frailty score, Veterans Aging Cohort Study (VACS) index, 400-m walk, Short Physical Performance Battery (SPPB), grip strength, and falls] were compared using integrated time-dependent receiver operating characteristic area under the curve (AUC) in single variable models. Two-variable models were compared with the best single-variable model to determine if AUC improved with additional physical function variables.

Results:
At 8-year follow-up, frailty, 400-m walk pace, SPPB, chair rise pace, VACS score, and falls were associated with increased hazard of mortality; grip strength was only predictive in sex-adjusted models. The VACS index and 400-m walk pace were the best individual predictors of mortality with time-dependent receiver operating characteristic AUC scores of 0.82, followed by SPPB (0.73), chair-rise pace (0.68), falls (0.65), frailty (0.63), and grip strength (0.55). Addition of the 400-m walk to VACS index yielded the only significant improvement in the prediction of survival compared with the VACS index alone (P = 0.04).

Conclusion:
Our study highlights several clinically applicable physical function measures predictive of mortality in middle-aged PWH that can be tailored to specific patient subpopulations and clinical or research encounters.
Brief Report: Cystatin C-Based Estimation of Glomerular Filtration Rate and Association With Atherosclerosis Imaging Markers in People Living With HIV
Authors: McClean Mitchell , Buzkova Petra , Budoff Matthew , Estrella Michelle , Freiberg Matthew , Hodis Howard N. , Palella Frank , Shikuma Cecilia , Post Wendy S. , Gupta Samir 
Published: July 2020

Introduction:
Reduced estimated glomerular filtration rate (eGFR) is associated with increased risk of cardiovascular disease among people living with HIV (PLWH). It is unclear whether eGFR equations incorporating cystatin C (CysC) measurements are more predictive of preclinical cardiovascular disease than those using only creatinine (Cr).

Objectives:
The study aimed to determine which of the 3 Chronic Kidney Disease Epidemiology (CKD-EPI) eGFR equations is most associated with carotid intima media thickness (CIMT) and coronary artery calcium (CAC) score.

Methods:
This cross-sectional analysis of pooled data from 3 large cohorts compared the associations between the 3 CKD-EPI eGFR equations (Cr, CysC, and Cr-CysC) with CIMT and CAC score using multivariable regression analysis. eGFR and CIMT were analyzed as continuous variables. CAC scores were analyzed as a binary variable (detectable calcification versus nondetectable) and as a log10 Agatston score in those with detectable CAC.

Results:
Thousand four hundred eighty-seven participants were included, and of these 910 (562 HIV+ and 348 HIV−) had CIMT measurements and 366 (296 HIV+ and 70 HIV−) had CAC measurements available. In HIV− participants, GFR estimated by any CKD-EPI equation did not significantly correlate with CIMT or CAC scores. When PLWH were analyzed separately including HIV-specific factors, only GFR estimated using Cr-Cys C correlated with CIMT [β= −0.90, 95% CI: (−1.67 to −0.13) μm; P = 0.023]. Similarly, eGFR correlated with Agatston scores only when using cystatin C-based eGFR [β= −8.63, 95% CI: (−16.49 to −0.77) HU; P = 0.034]. Associations between other eGFR formulas and CAC did not reach statistical significance.

Conclusions:
In PLWH, preclinical atherosclerosis may be more closely correlated with eGFR using formulae that incorporate CysC measurements than Cr alone.
Office-Based Forehead Flaps
Authors: Beederman Maureen , Jaffe Jennifer , Kuchta Kristine , Warner Jeremy 
Published: July 2020

Background
Forehead flaps are one of the workhorse flaps for nasal reconstruction, especially for large defects involving the nasal tip, ala, or multiple nasal subunits. Forehead flaps are often performed on older patients who have accompanying comorbidities and who may be at higher risk for anesthetic complications. The aim of this retrospective study was to compare the safety and success of forehead flap nasal reconstruction in 2 different clinical settings: those performed under local anesthesia in an office-based procedure room, compared with those performed in the operating room under either general anesthesia or intravenous sedation.

Methods
A retrospective chart review was performed on all patients who underwent forehead flap reconstruction between the years of 2011 and 2018 by the senior author. Patient demographics, operative details, and postoperative complications were recorded and analyzed. Patients were followed for 1 year postoperatively or until the end of the study period. Patients were excluded if they had an accompanying unrelated cosmetic procedures performed during first-stage forehead flap reconstruction.

Results
A total of 96 forehead flaps were performed, 35 of which (36.5%) were done in an office-based procedure room using local anesthesia only. Patient ages ranged from 45 to 92 years, with an average age of 71.9 years. The majority of flaps (n = 81, 85.3%) were divided at the second-stage procedure. There was no statistically significant difference in time elapsed between first- and second-stage procedures between groups (procedure room: 22.6 days; operating room: 23.8 days). There were 13 total postoperative complications (13.5%), but there was no statistically significant difference in complication rate between groups (office-based: 3 complications, 8.6%; operating room: 10 complications, 16.4%).

Conclusions
Our data suggest that forehead flap reconstruction can be done safely with acceptable postoperative results when performed under local anesthesia in an office-based outpatient setting.
Paranasal Augmentation With Composite Graft Transfer in Overresection of Alar Base and Nostril Contracture
Authors: Yen Cheng-I , Chang Chun-Shin , Chen Hung-Chang , Yang Shih-Yi , Chang Shu-Yin , Yang Jui-Yung , Chuang Shiow-Shuh , Hsiao Yen-Chang 
Published: July 2020

Background
Many Asian patients desire a narrower nasal base with less flaring of the alar lobules. However, patients who underwent multiple rhinoplasty surgeries with nostril contracture or an overreduction of the alar base may experience nostril contracture and deformity, which may lead to further airway obstruction. We present a technique that combines paranasal augmentation with composite chondrocutaneous graft transfer to overcome this problem.

Methods
Nine patients underwent composite chondrocutaneous graft transfer to the soft triangle or alar base combined with paranasal augmentation using preshaped porous polyethylene implants to correct nostril contracture and airway obstruction between September of 2014 and May of 2018. Preoperative and postoperative alar base distances and cross-sectional areas of the nostrils were measured and compared.

Results
The average thickness of paranasal augmentation was 5.5 mm (range, 4.0–7.0 mm). Eighteen composite grafts were located over the soft triangle (n = 3) and the alar base (n = 15). The average number of composite grafts for each person was 2 (range, 1–4). All composite grafts survived totally or partially, and no graft failed. The average follow-up was 10.9 months (range, 3–28 months). The alar base increased 13.9% (range, 2.2%–23.9%), and the nostril area increased an average of 78.1% (range, 4.5%–316.8%) postoperatively. Patients had satisfactory aesthetic and functional outcomes.

Conclusions
Combining paranasal augmentation and composite graft transfer increased the cross-sectional area of the external valve and improved nostril contracture and airway obstruction after the overresection of the alar base or nose contracture after multiple rhinoplasty surgeries.
Understanding the clinical manifestations of 16p11.2 deletion syndrome: a series of developmental case reports in children
Authors: Fetit Rana , Price David J. , Lawrie Stephen M. , Johnstone Mandy 
Published: July 2020

Background
Copy number variants (CNVs) are genetic rearrangements, such as deletions and duplications, which result in a deviation from the normal number of copies of a given gene segment. CNVs are implicated in many neuropsychiatric disorders. Deletions of the human chromosomal region 16p11.2 are one of the most common genetic linkages to autism spectrum disorders (ASD). However, ASD is not the only presenting feature, and many patients with 16p11.2 deletions present with a variable clinical spectrum.

Methods
To better understand the nature and presentation of the syndrome throughout development, we present three different, unrelated clinical cases of children with 16p11.2 deletion and provide a detailed description of their clinical manifestations.

Results
Cognitive and motor impairments were characteristic of all three patients with 16p11.2 deletion, despite the differences in the extent and clinical presentation of impairment. Two patients had a clinical diagnosis of ASD and one showed several ASD traits. In addition, two patients also had severe speech and language impairments, which is in line with previous reports on 16p11.2 phenotypes. Although epilepsy and obesity have been frequently associated with 16p11.2 deletion, only one patient had a diagnosis of epilepsy and none of the three cases were obese.

Conclusion
This variation in clinical phenotype renders correct clinical interpretation and diagnosis challenging. Therefore, it is critical to elucidate the variable clinical phenotypes of rare CNVs, including 16p11.2 deletions, to help guide clinical monitoring and counselling of patients and families.