bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results from 404 drug-induced sleep endoscopies with probability ramp control: lessons for pharmacokinetic design of DISE protocols
Authors: Mandel Jeff E. , Atkins Joshua H. 
Published: May 2020

Introduction:
Drug-induced sleep endoscopy (DISE) employs a drug such as propofol to allow observation of airway collapse to predict success in surgical interventions for obstructive sleep apnea. A number of protocols have been published for the administration of propofol during DISE, but these protocols do not make use of pharmacokinetic modeling to estimate the propofol concentration at airway collapse and the probability distribution for this quantity. We hypothesized that this information could be used to improve the delivery of propofol during DISE.

Methods:
Deidentified data from 404 patients sedated with Probability Ramp Control was analyzed. The estimated effect site concentration at the time of airway collapse (ECac) was fit to a gamma distribution. Correlation between ECac and age/weight were performed using Spearman ρ. This probability distribution was utilized to assess the ability of a published protocol to produce airway collapse in a reasonable duration in a representative cohort of patients.

Results:
The parameters of the gamma distribution were a=8.3 (95% confidence interval, 7.2–9.5), b=0.58 (95% confidence interval, 0.51–0.67). The mean ECac was 4.8±1.7 µg/mL; 95% of ECac fell in the range 2.4–8.5 µg/mL. ECac was uncorrelated with age (ρ=−0.06, P=0.27) and weight (ρ=−0.11, P=0.03). The previously published protocol displayed variability across the cohort and failed to achieve effect site concentrations sufficient for the least sensitive patients in our cohort.

Conclusions:
Effect site propofol concentrations at the time of airway collapse during DISE span a wide range with a skewed distribution. The lack of correlation with either age or weight suggests that the pharmacokinetic model is sufficient for describing the effect of age and weight on propofol dosing. The impact of these factors on propofol dosing during DISE is examined, and workable solutions to this clinical challenge are proposed.
SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IMAGE COMPENSATION OF THE CHORIOCAPILLARIS INDUCES ARTIFACTS
Authors: Ledesma-Gil Gerardo , Fernandez-Avellaneda Pedro , Spaide Richard F. 
Published: May 2020

Purpose:
To analyze swept-source optical coherence angiography slab images acquired at the default level for the choriocapillaris from the Zeiss PLEX Elite 9000 before and after using a previously described imaging compensation technique.

Methods:
Eyes of normal subjects, in their 20 seconds and 30 seconds, were evaluated. Angiographic slab images, 20 µm in thickness, were taken at the default location of 29 to 49 µm below the retinal pigment epithelium. These images were evaluated, as were images that underwent a published compensation technique that adjusts for light penetration to the sampled layer. Each set of images was threshold at 1 SD below the mean. Visual comparison of the swept-source optical coherence angiography images along with a quantitative analysis using a novel parameter known as multiscale structural similarity index, a measure of image similarity, was performed.

Results:
Eleven eyes of 11 subjects were evaluated. The default location, 29 µm to 49 µm below the retinal pigment epithelium, showed the granular choriocapillaris appearance. Visual comparison showed that the compensation technique altered the appearance of the thresholded images, creating the appearance of new deficits while causing others to disappear. The mean multiscale structural similarity index for the original versus thresholded images and original versus thresholded compensated was 0.49 and 0.34, respectively, representing a statistically significant difference.

Conclusion:
The findings of this study show that the use of a commonly used imaging compensation technique can have undesired effects on the image, and its use should be carefully considered. A model explaining the cause of such changes in the choriocapillaris swept-source optical coherence angiography images is presented.
Free-Floating DMEK in the Host Anterior Chamber: Surgical Management
Authors: Menassa Nardine , Pagano Luca , Gadhvi Kunal A. , Coco Giulia , Kaye Stephen B. , Levis Hannah J. , Romano Vito 
Published: May 2020

Purpose:
To describe a method to visualize and manage a completely detached Descemet membrane endothelial keratoplasty (DMEK) tissue scroll in the anterior chamber.

Methods:
A 56-year-old male patient with pseudophakic bullous keratopathy, who underwent uncomplicated DMEK surgery, had a complete graft detachment diagnosed at 1-week follow-up. The graft was reattached using a new technique, that is, the free-floating graft was stained in the anterior chamber with trypan blue, immediately followed by air injection to separate the host stroma from the dye. The stained DMEK graft was opened by gentle tapping and attached to the host stroma by air tamponade.

Result:
This technique allowed sufficient staining of DMEK tissue to further evaluate and correct the graft orientation inside the anterior chamber without compromising the stroma. The DMEK graft was attached 1 week after the reattachment procedure. The cornea cleared confirming the functionality of the endothelial cells.

Conclusions:
The technique described may be useful in the cases of complete detachment of DMEK tissue and poor visualization of the DMEK tissue orientation. Staining with trypan blue under a “protective” air bubble can provide sufficient visualization to ensure the unfolding of DMEK tissue and reduce the risk of host stromal staining.
Pseudomonas aeruginosa Isolates From a Cohort of Mexican Children With Cystic Fibrosis Show Adaptation to a Chronic Phenotype
Authors: Rosales-Reyes Roberto , Rodríguez-Alvarado Marian , Lezana-Fernández José Luis , Sánchez-Lozano Joselin Yleana , Gayosso-Vázquez Catalina , Jarillo-Quijada Ma Dolores , Toledano-Tableros José Eduardo , Arredondo-Mercado Martha Jimena , Alcántar-Curiel María Dolores , Lincopan Nilton , Vidal Jorge E. , Lascurain Ricardo , Valvano Miguel A. , Santos-Preciado José Ignacio 
Published: May 2020

Background:
Long-term persistence of Pseudomonas aeruginosa in the lung of individuals with cystic fibrosis (CF) is associated with progressive selection of diverse genotypes and phenotypes. This bacterial adaptation leads to chronic infection and increased morbidity and mortality. The aim of this study was to establish the prevalence, clonal relatedness, antimicrobial susceptibility and virulence-associated phenotypes of P. aeruginosa isolates in a cohort of 50 Mexican children with CF-associated chronic lung infection.

Methods:
Clonal relatedness of P. aeruginosa isolates was verified by pulsed-field gel electrophoresis. The antimicrobial susceptibility was determined by an automated system that performs bacterial identificación and antibiotic susceptibility testing (VITEK 2) and/or broth microdilution method. Biofilm formation was quantified with the crystal violet method; swarming motility was measured on soft agar, and susceptibility to normal human serum determined by reduction of colony formed units (CFUs).

Results:
High prevalence of P. aeruginosa colonization among Mexican children with CF was confirmed; 20% (10/49) of clones identified showed a multidrug-resistant phenotype and 8.2% (4/49) an extensive drug resistance phenotype; 26.5% (13/49) of the isolates were resistant to colistin, 42.9% (21/49) presented a phenotype of adaptation associated with chronic infection and 79.6% (39/49) showed increased ability to survive in normal human serum.

Conclusions:
This cohort of children with CF reveals that colonizing P. aeruginosa strains predominantly display resistance to several first-line antibiotics, although most isolates were susceptible to meropenem and tobramycin; 42.9% of isolates showed a phenotype consistent with adaptation to chronic lung infection.
Screening Algorithms to Reduce Burden of Pediatric HIV Testing
Authors: Clemens Sara L. , Macneal Kenneth D. , Alons Catharina L. , Cohn Jennifer E. 
Published: May 2020

Background:
The accuracy of symptom screening to identify children eligible for further HIV testing in generalized epidemics has been examined in several studies. We performed a systematic review and meta-analysis of these studies.

Methods:
We screened 5 databases and abstracts from 4 HIV/AIDS conferences. Studies were included if they were performed in clinical settings, included children of 0–15 years old, and used a signs/symptoms screen to determine eligibility for HIV testing. The primary outcomes were sensitivity and specificity of the screening tools. A meta-analysis was performed to evaluate the utility of a screening tool in the outpatient setting.

Results:
Our search returned 5529 database results and approximately 6700 conference abstracts, of which 36 articles were reviewed and 7 met criteria for inclusion. All were prospective or cross-sectional studies that developed and/or validated a screening tool to identify children at higher risk for being HIV infected. Sensitivity of the screening tools ranged from 71% to 96%, whereas specificity ranged from 25% to 99%. Meta-analysis of studies evaluating outpatient screening tools revealed a sensitivity of 81.4%, with a specificity of 69.4% for detecting HIV infection.

Conclusions:
Few studies have evaluated the use of screening tools for HIV diagnosis in children. Screening tools that exist showed only moderate sensitivity and specificity and missed a substantial number of HIV-infected children in high-prevalence areas. In outpatient settings, the use of a screening tool may help reduce the number of HIV tests needed to identify an HIV-infected child, but at the cost of missed diagnoses. Further studies are needed to determine whether this represents a resource-saving mechanism.
A disintegrin and metalloproteinase domain 17-epidermal growth factor receptor signaling contributes to oral cancer pain
Authors: Scheff Nicole N. , Ye Yi , Conley Zachary R. , Quan Jen Wui , Lam Yat Vong Ronald , Klares Richard , Singh Kamalpreet , Schmidt Brian L. , Aouizerat Bradley E. 
Published: May 2020

Abstract
Cancer cells secrete pronociceptive mediators that sensitize adjacent sensory neurons and cause pain. Identification and characterization of these mediators could pinpoint novel targets for cancer pain treatment. In this study, we identified candidate genes in cancer cell lines that encode for secreted or cell surface proteins that may drive nociception. To undertake this work, we used an acute cancer pain mouse model, transcriptomic analysis of publicly available human tumor-derived cell line data, and a literature review. Cancer cell line supernatants were assigned a phenotype based on evoked nociceptive behavior in an acute cancer pain mouse model. We compared gene expression data from nociceptive and nonnociceptive cell lines. Our analyses revealed differentially expressed genes and pathways; many of the identified genes were not previously associated with cancer pain signaling. Epidermal growth factor receptor (EGFR) and disintegrin metalloprotease domain 17 (ADAM17) were identified as potential targets among the differentially expressed genes. We found that the nociceptive cell lines contained significantly more ADAM17 protein in the cell culture supernatant compared to nonnociceptive cell lines. Cytoplasmic EGFR was present in almost all (>90%) tongue primary afferent neurons in mice. Monoclonal antibody against EGFR, cetuximab, inhibited cell line supernatant-induced nociceptive behavior in an acute oral cancer pain mouse model. We infer from these data that ADAM17-EGFR signaling is involved in cancer mediator-induced nociception. The differentially expressed genes and their secreted protein products may serve as candidate therapeutic targets for oral cancer pain and warrant further evaluation.
Cardiogenic shock: role of invasive cardiology
Authors: Feistritzer Hans-Josef , Thiele Holger , Desch Steffen 
Published: May 2020

Purpose of review
Early revascularization significantly improved the outcome of patients with cardiogenic shock following acute myocardial infarction (AMI). Nevertheless, the mortality remains substantial, ranging between 40 and 50% after 30 days. The present review summarizes the current evidence regarding revascularization strategies, vascular access site and concomitant antiplatelet and antithrombotic treatment in infarct-related cardiogenic shock.

Recent findings
On the basis of the SHOCK trial, early revascularization is the most relevant procedure to improve the outcome of patients with infarct-related cardiogenic shock. The majority of these patients present with multivessel coronary disease. The randomized CULPRIT-SHOCK trial showed that in the emergency setting, percutaneous coronary intervention (PCI) should be confined to the culprit lesion. Regarding vascular access site, no data derived from randomized controlled trials in cardiogenic shock are available. Emergency coronary artery bypass grafting (CABG) is nowadays rarely performed in cardiogenic shock with rates less than 5% but is still a treatment option if coronary anatomy is not amenable to PCI. Regarding antiplatelet treatment, a randomized trial testing the intravenous P2Y12 inhibitor cangrelor versus an oral P2Y12 inhibitor in infarct-related cardiogenic shock is currently being performed.

Summary
Early revascularization is the cornerstone of treatment of infarct-related cardiogenic shock and should be confined to the culprit lesion in the emergency setting.
Propofol alone prevents worsening hepatic encephalopathy rather than midazolam alone or combined sedation after esophagogastroduodenoscopy in compensated or decompensated cirrhotic patients
Authors: Jeong Joonho , Jung Kyoungwon , Seo Kwang Il , Yun Byung Cheol , Han Byung Hoon , Lee Sang Uk , Moon Won 
Published: May 2020

Background
This study was conducted to determine which type and dose of sedative drugs should be given to cirrhotic patients with compensation or decompensation during esophagogastroduodenoscopy (EGD) to prevent hepatic encephalopathy (HE) after sedation.

Methods
We reviewed the medical records of cirrhotic patients consecutively admitted to the hospital and conducted a number connection test (NCT) before and 2 h after EGD with moderate sedation. Sedation was performed using either propofol alone, midazolam alone, or combined propofol + midazolam.

Results
Sixty-seven patients were admitted for a screening EGD. The NCT before and after sedation were not significantly different in the propofol alone (pre-NCT = 47.3 ± 19.71 seconds vs. post-NCT = 49.4 ± 21.79 seconds, P = 0.6389). In the midazolam alone (pre-NCT = 50.3 ± 20.56 vs. post-NCT = 63.7 ± 33.17, P = 0.0021) and in the combined propofol + midazolam (pre-NCT = 47.4 ± 20.99 vs. post-NCT = 60.0 ± 30.79, P = 0.0002), NCT were significantly delayed. The propofol alone group received 52.3 ± 16.31 mg (0.82 ± 0.29 mg/kg). In 45 (67.2%) decompensated patients, only the propofol alone was not significantly different between pre-NCT (49.2 ± 22.92) and post-NCT (52.3 ± 24.90) (P = 0.4548). Serum sodium level was significantly correlated with delta-NCT (r = 0.3594, P = 0.0028).

Conclusion
Propofol alone could be the best sedation strategy for cirrhotic patients with compensation or decompensation without aggravation of covert or overt HE. Hyponatremia could be a risk factor for developing or worsening HE after EGD with sedation.
Low real-world eligibility rates for nonalcoholic steatohepatitis patients for phase 3 clinical trial criteria application in a large academic health system
Authors: Ilagan-Ying Ysabel C. , Xu Jin , Lim Joseph K. , Do Albert 
Published: May 2020

Objective
Nonalcoholic steatohepatitis (NASH) is the most common liver disease in the USA. Clinical trials have stringent study criteria which may limit real-world generalizability. Thus, we studied whether a real-world, university-based cohort of patients could be eligible for a pivotal phase 3 NASH clinical trial.

Methods
We queried Yale-New Haven Health System electronic medical records for patients with a diagnosis of NASH from 2013 to 2017. Of those who received liver biopsy, we extracted demographic, clinical, laboratory, and biopsy data. We compared patient characteristics to enrollment criteria of the Randomized Global Phase 3 Study to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment.

Results
Of 14 403 patients with NASH, 478 (3.3%) completed liver biopsy, of whom 237 (49.6%) had histological confirmation by a gastrointestinal pathologist. Histologically-confirmed NASH patients were 51.1 ± 13.2 years old, 56.5% female, 69.6% white race, and 24.6% had cirrhosis. In this group, 68 (28.7%) patients met all inclusion criteria, 87 (36.7%) had no exclusions, and 34 (14.4%) met all enrollment criteria. Other than cirrhosis, common reasons for ineligibility were presence of medical comorbidity (n = 83) or laboratory abnormalities (n = 47). Multiple logistic regression did not reveal significant predictors of eligibility.

Conclusion
Within a university-based cohort of NASH patients, few met phase 3 clinical trial enrollment criteria, mostly due to low rates of liver biopsy. Of those with histologic confirmation, 14.4% met enrollment criteria. Validation of generalizability for safety and efficacy of NASH investigational agents in real-world populations is needed.
Circadian rhythms of mineral metabolism in chronic kidney disease–mineral bone disorder
Authors: Egstrand Søren , Olgaard Klaus , Lewin Ewa 
Published: May 2020

Purpose of review
The circadian rhythms have a systemic impact on all aspects of physiology. Kidney diseases are associated with extremely high-cardiovascular mortality, related to chronic kidney disease–mineral bone disorder (CKD–MBD), involving bone, parathyroids and vascular calcification. Disruption of circadian rhythms may cause serious health problems, contributing to development of cardiovascular diseases, metabolic syndrome, cancer, organ fibrosis, osteopenia and aging. Evidence of disturbed circadian rhythms in CKD–MBD parameters and organs involved is emerging and will be discussed in this review.

Recent findings
Kidney injury induces unstable behavioral circadian rhythm. Potentially, uremic toxins may affect the master-pacemaker of circadian rhythm in hypothalamus. In CKD disturbances in the circadian rhythms of CKD–MBD plasma-parameters, activin A, fibroblast growth factor 23, parathyroid hormone, phosphate have been demonstrated. A molecular circadian clock is also expressed in peripheral tissues, involved in CKD–MBD; vasculature, parathyroids and bone. Expression of the core circadian clock genes in the different tissues is disrupted in CKD–MBD.

Summary
Disturbed circadian rhythms is a novel feature of CKD–MBD. There is a need to establish which specific input determines the phase of the local molecular clock and to characterize its regulation and deregulation in tissues involved in CKD–MBD. Finally, it is important to establish what are the implications for treatment including the potential applications for chronotherapy.
Simultaneous management of disordered phosphate and iron homeostasis to correct fibroblast growth factor 23 and associated outcomes in chronic kidney disease
Authors: Courbon Guillaume , Martinez-Calle Marta , David Valentin 
Published: May 2020

Purpose of review
Hyperphosphatemia, iron deficiency, and anemia are powerful stimuli of fibroblast growth factor 23 (FGF23) production and are highly prevalent complications of chronic kidney disease (CKD). In this manuscript, we put in perspective the newest insights on FGF23 regulation by iron and phosphate and their effects on CKD progression and associated outcomes. We especially focus on new studies aiming to reduce FGF23 levels, and we present new data that suggest major benefits of combined corrections of iron, phosphate, and FGF23 in CKD.

Recent findings
New studies show that simultaneously correcting iron deficiency and hyperphosphatemia in CKD reduces the magnitude of FGF23 increase. Promising therapies using iron-based phosphate binders in CKD might mitigate cardiac and renal injury and improve survival.

Summary
New strategies to lower FGF23 have emerged, and we discuss their benefits and risks in the context of CKD. Novel clinical and preclinical studies highlight the effects of phosphate restriction and iron repletion on FGF23 regulation.
Utility of brain fluorodeoxyglucose PET in children with possible autoimmune encephalitis
Authors: Aydos Uğuray , Arhan Ebru , Akdemir Ümit Özgür , Akbaş Yilmaz , Aydin Kürşad , Atay Lütfiye Özlem , Serdaroğlu Ayşe 
Published: May 2020

Purpose
We aimed to explore the utility and additional clinical contribution of brain fluorodeoxyglucose (FDG) PET imaging for the assessment of children with possible autoimmune encephalitis in comparison to brain MRI.

Materials and methods
We conducted a retrospective analysis of six pediatric patients (all seronegative) between 2014 and 2019 with the initial diagnosis of possible autoimmune encephalitis who had brain FDG PET/CT or PET/MRI and brain MRI during the diagnostic period. Diagnosis of possible autoimmune encephalitis was based on clinical consensus criteria defined by Graus et al. Brain FDG PET images were visually evaluated. Semiquantitative evaluation was also performed by using the statistical parametric mapping (SPM) method.

Results
Cerebrospinal fluid pleiocytosis and electroencephalography abnormality were present in all patients. Mean duration between the onset of symptoms and brain FDG PET imaging was 33 ± 16 days (range: 18–62 days). There were a total of eight brain FDG PET scans (six of PET/MRI and two of PET/CT). In two patients, FDG PET imaging was performed at diagnosis and follow-up. Initial FDG PET and SPM analysis findings were abnormal in all patients (100%), with four demonstrating only hypometabolism. Only a hypermetabolic pattern was seen in one patient, and mixed the hypohypermetabolic pattern was seen in one patient. All patients had metabolic abnormalities in temporal lobes. Additionally, visual and semiquantitative FDG PET findings revealed hypometabolism in extratemporal regions. Brain MRI was abnormal in two patients (33.3%) who had also FDG hypermetabolism in mesial temporal lobes.

Conclusions
Our findings support the usage of fluorine-18-FDG PET/computed tomography (CT)/MRI with quantitative analysis early in the diagnostic work-up of possible autoimmune encephalitis, particularly in those with normal or nonspecific MRI findings. However, it remains a purpose of further studies, if and to what extent FDG PET/CT or integrated FDG PET/MRI with quantitative analysis can improve the diagnostic workup of children with possible autoimmune encephalitis.