bluuebunny/crossref_metadata_2025 huggingface dataset:
OTME-21. The role of Glioblastoma associated mesenchymal stem cells in immune suppression
Authors: Dharma Sanam Sahjram , Barone Tara , Figel Sheila , Birkemeier Meaghan , Zhang Yali , Fenstermaker Robert , Ciesielski Michael
Published: July 2021

Glioblastoma (GBM) is an aggressive brain cancer, with an overall survival of 14.6 months. The tumor microenvironment in GBM plays major roles in immunosuppression and modulation of the response to therapies. GBM patients with higher levels of mesenchymal stem like cells (G-MSC) show poor overall survival as compared to patients with no/lower G-MSC levels. Our lab found that levels of G-MSC corelate with CD4+ T cells in humans and murine models of GBM, and with immunosuppressive molecules like PTGS2, the gene for cyclooxygenase 2. To investigate the mechanism by which G-MSCs promote immunosuppression, we isolated G-MSCs from an orthotopic mouse model of GBM and subjected them to RNASeq analysis to obtain an unbiased picture of transcriptomic changes occurring upon activation. We identified changes in multiple immune modulating pathways involving antigen presentation, leukocyte migration and activation, and immune checkpoints. Our findings indicate that G-MSCs represent a key immune modulating faction in the microenvironment. Further dissection of the role of these cells in immune modulation will aid us in understanding the biology of the brain tumor microenvironment and identifying potential combination therapies.
Density-Functional Theory of Atoms and Molecules
Authors: Parr Robert G. , Weitao Yang
Published: July 2021

This book is a rigorous, unified account of the fundamental principles of the density-functional theory of the electronic structure of matter and its applications to atoms and molecules. Containing a detailed discussion of the chemical potential and its derivatives, it provides an understanding of the concepts of electronegativity, hardness and softness, and chemical reactivity. Both the Hohenberg-Kohn-Sham and the Levy-Lieb derivations of the basic theorems are presented, and extensive references to the literature are included. Two introductory chapters and several appendices provide all the background material necessary beyond a knowledge of elementary quantum theory. The book is intended for physicists, chemists, and advanced students in chemistry.
De-democratization and the Politics of Knowledge: Unpacking the Cultural Marxism Narrative
Authors: Paternotte David , Verloo Mieke
Published: July 2021

The politics of knowledge matter to the current wave of de-democratization in Europe. Building on Walby’s social complexity theory, this article highlights the dynamics between epistemic configurations and contemporary politics. Focusing on academic institutions, and taking gender studies as an illustration, this article shows that actors opposing (social) sciences and academia not only aim to dismantle existing institutions of knowledge production but also promote a new politics of truth. In this, the Cultural Marxism master frame operates as a diagnosis and a prognosis frame, providing the base for attacks on academia and for a strategy of profound transformation of the realm of knowledge in Europe.
Factors associated with new persistent opioid use after ankle sprain: a cross-sectional analysis
Authors: Gossett Timothy D. , Finney Fred T. , Hu Hsou Mei , Waljee Jennifer F. , Brummett Chad M. , Walton David M. , Talusan Paul G. , Holmes James R.
Published: July 2021

Background:

Chronic opioid use is a growing crisis in the United States. The authors examined the risk factors associated with new persistent opioid use in patients who had nonoperatively treated ankle sprains and offer evidence-based treatment recommendations for practitioners.

Methods:

A United States insurance claims database was used to select patients who underwent nonoperative treatment of an ankle sprain between January 2008 and December 2016. The authors examined opioid prescribing 1 yr before diagnosis and 6 mo after and defined new persistent opioid use as prescription fulfillment between 91 and 180 days after injury. We evaluated the effect of patient factors and amount prescribed on the likelihood of new persistent opioid use and the probability of refill within 30 days using logistical regression analysis.

Results:

A total opioid dose of 150 mg oral morphine equivalents (OMEs) prescribed within 7 days of diagnosis was the greatest modifiable risk factor for new persistent opioid use [adjusted odds ratio (aOR) 1.38, 95% confidence interval (CI), 1.28 to 1.49, P<0.001] and for likelihood of refill within 30 days (aOR, 2.22, 95% CI, 2.10 to 2.35, P<0.001). Additional factors included tobacco use, medical comorbidities, and certain pain and mental health disorders.

Conclusions:

New persistent opioid use is common in patients who had nonoperatively treated acute ankle sprains and is linked to identifiable patient and prescribing factors. Factors associated with new persistent opioid use include high initial prescribed dose, tobacco use, medical comorbidities, and certain pain and mental health disorders. These factors were also associated with a higher probability of refill. There is strong evidence-based support for the treatment of these injuries without opioids.

Level of Evidence:

Level III.
Efficacy of Intraoperative Neuromonitoring Using Transcranial Motor-Evoked Potentials for Degenerative Cervical Myelopathy
Authors: Funaba Masahiro , Kanchiku Tsukasa , Yoshida Go , Imagama Shiro , Kawabata Shigenori , Fujiwara Yasushi , Ando Muneharu , Yamada Kei , Taniguchi Shinichirou , Iwasaki Hiroshi , Tadokoro Nobuaki , Takahashi Masahito , Wada Kanichiro , Yamamoto Naoya , Shigematsu Hideki , Kobayashi Kazuyoshi , Yasuda Akimasa , Ushirozako Hiroki , Ando Kei , Hashimoto Jun , Morito Shinji , Takatani Tsunenori , Tani Toshikazu , Matsuyama Yukihiro
Published: July 2021

Study Design.

A prospective multicenter observational study.

Objective.

To elucidate the efficacy of transcranial motor-evoked potentials (Tc(E)-MEPs) in degenerative cervical myelopathy (DCM) surgery by comparing cervical spondylotic myelopathy (CSM) to cervical ossification of the posterior longitudinal ligament (OPLL) and investigate the timing of Tc(E)-MEPs alerts and types of interventions affecting surgical outcomes.

Summary of Background Data.

Although CSM and OPLL are the most commonly encountered diseases of DCM, the benefits of Tc(E)-MEPs for DCM remain unclear and comparisons of these two diseases have not yet been conducted.

Methods.

We examined the results of Tc(E)-MEPs from 1176 DCM cases (840 CSM /336 OPLL) and compared patients background by disease, preoperative motor deficits, and the type of surgical procedure. We also assessed the efficacy of interventions based on Tc(E)-MEPs alerts. Tc(E)-MEPs alerts were defined as an amplitude reduction of more than 70% below the control waveform. Rescue cases were defined as those in which waveform recovery was achieved after interventions in response to alerts and no postoperative paralysis.

Results.

Overall sensitivity was 57.1%, and sensitivity was higher with OPLL (71.4%) than with CSM (42.9%). The sensitivity of acute onset segmental palsy including C5 palsy was 40% (OPLL/CSM: 66.7%/0%) whereas that of lower limb palsy was 100%. The most common timing of Tc(E)-MEPs alerts was during decompression (63.16%), followed by screw insertion (15.79%). The overall rescue rate was 57.9% (OPLL/CSM: 58.3%/57.1%).

Conclusion.

Since Tc(E)-MEPs are excellent for detecting long tract injuries, surgeons need to consider appropriate interventions in response to alerts. The detection of acute onset segmental palsy by Tc(E)-MEPs was partially possible with OPLL, but may still be difficult with CSM. The rescue rate was higher than 50% and appropriate interventions may have prevented postoperative neurological complications.

Level of Evidence: 3
Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach
Authors: Nishikimi Mitsuaki , Yagi Tsukasa , Shoaib Muhammad , Takegawa Ryosuke , Rasul Rehana , Hayashida Kei , Okuma Yu , Yin Tai , Choudhary Rishabh C. , Becker Lance B. , Kim Junhwan
Published: July 2021

OBJECTIVES:

Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival.

DESIGN:

Clinical case control study followed by translational laboratory study.

SETTING:

Research institution.

PATIENTS/SUBJECTS:

Adult cardiac arrest patients and male Sprague-Dawley rats.

INTERVENTIONS:

Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle.

MEASUREMENTS AND MAIN RESULTS:

We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect.

CONCLUSIONS:

Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.
Viral Micro-RNAs Are Detected in the Early Systemic Response to Injury and Are Associated With Outcomes in Polytrauma Patients
Authors: Vicente Diego , Schobel Seth A. , Anfossi Simone , Hensman Hannah , Lisboa Felipe , Robertson Henry , Khatri Vivek , Bradley Matthew J. , Shimizu Masayoshi , Buchman Timothy G. , Davis Thomas A. , Dente Christopher J. , Kirk Allan D. , Calin George A. , Elster Eric A.
Published: July 2021

OBJECTIVES:

To evaluate early activation of latent viruses in polytrauma patients and consider prognostic value of viral micro-RNAs in these patients.

DESIGN:

This was a subset analysis from a prospectively collected multicenter trauma database. Blood samples were obtained upon admission to the trauma bay (T0), and trauma metrics and recovery data were collected.

SETTING:

Two civilian Level 1 Trauma Centers and one Military Treatment Facility.

PATIENTS:

Adult polytrauma patients with Injury Severity Scores greater than or equal to 16 and available T0 plasma samples were included in this study. Patients with ICU admission greater than 14 days, mechanical ventilation greater than 7 days, or mortality within 28 days were considered to have a complicated recovery.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Polytrauma patients (n = 180) were identified, and complicated recovery was noted in 33%. Plasma samples from T0 underwent reverse transcriptase-quantitative polymerase chain reaction analysis for Kaposi’s sarcoma–associated herpesvirus micro-RNAs (miR-K12_10b and miRK-12-12) and Epstein-Barr virus–associated micro-RNA (miR-BHRF-1), as well as Luminex multiplex array analysis for established mediators of inflammation. Ninety-eight percent of polytrauma patients were found to have detectable Kaposi’s sarcoma–associated herpesvirus and Epstein-Barr virus micro-RNAs at T0, whereas healthy controls demonstrated 0% and 100% detection rate for Kaposi’s sarcoma–associated herpesvirus and Epstein-Barr virus, respectively. Univariate analysis revealed associations between viral micro-RNAs and polytrauma patients’ age, race, and postinjury complications. Multivariate least absolute shrinkage and selection operator analysis of clinical variables and systemic biomarkers at T0 revealed that interleukin-10 was the strongest predictor of all viral micro-RNAs. Multivariate least absolute shrinkage and selection operator analysis of systemic biomarkers as predictors of complicated recovery at T0 demonstrated that miR-BHRF-1, miR-K12-12, monocyte chemoattractant protein-1, and hepatocyte growth factor were independent predictors of complicated recovery with a model complicated recovery prediction area under the curve of 0.81.

CONCLUSIONS:

Viral micro-RNAs were detected within hours of injury and correlated with poor outcomes in polytrauma patients. Our findings suggest that transcription of viral micro-RNAs occurs early in the response to trauma and may be associated with the biological processes involved in polytrauma-induced complicated recovery.
Coronavirus Disease 2019 and Cardiometabolic Disease
Authors: Kim Chan W. , Aronow Wilbert S. , Frishman William H.
Published: July 2021

Cardiometabolic disease describes a combination of metabolic abnormalities that increases the risk of type 2 diabetes and cardiovascular diseases, including pathological changes such as insulin resistance, hyperglycemia, dyslipidemia, abdominal obesity, and hypertension, and environmental risk factors such as smoking, sedentary lifestyle, poor diet, and poverty. As the number of coronavirus disease 2019 (COVID-19) patients continues to rise, type 2 diabetes, cardiovascular disease, hypertension, and obesity, all components of, or sequelae of cardiometabolic disease, were identified among others as key risk factors associated with increased mortality in these patients. Numerous studies have been done to further elucidate this relationship between COVID-19 and cardiometabolic disease. Cardiometabolic disease is associated with both increased susceptibility to COVID-19 and worse outcomes of COVID-19, including intensive care, mechanical ventilation, and death. The proinflammatory state of cardiometabolic disease specifically obesity, has been associated with a worse prognosis in COVID-19 patients. There has been no evidence to suggest that antihypertensives and antidiabetic medications should be discontinued in COVID-19 patients but these patients should be closely monitored to ensure that their blood pressure and blood glucose levels are stable. Assessment of vaccination efficacy in cardiometabolic disease patients is also discussed.
Reading Aloud, Self-Regulation, and Early Language and Cognitive Development in Northern Brazil
Authors: Piccolo Luciane da Rosa , Weisleder Adriana , Oliveira João B. A. , Mazzuchelli Denise S. R. , Lopez Aline Sá , Neto Walfrido D. , Cates Carolyn B. , Mendelsohn Alan L.
Published: July 2021

Objectives:

In this study, we examined (1) whether a reading aloud intervention, Universidade do Bebê (UBB), had impacts on self-regulation; (2) whether effects on child outcomes were mediated by self-regulation; and (3) whether effects of UBB were explained through a sequential pathway of impact, including cognitive stimulation in the home, parent-child interactive reading, and self-regulation.

Methods:

We performed a cluster randomized controlled trial of UBB in child care centers serving low-income children (mean age 37.4 months; SD = 6.5) in Northern Brazil. The child care centers were randomized to receive UBB or standard care (control). Families in UBB could borrow children's books weekly and participate in monthly workshops focused on reading aloud. Parent-child dyads (n = 484, intervention = 232, control = 252) were evaluated at baseline and 9 months later on: child self-regulation, vocabulary, intelligence quotient (IQ), working memory, and phonological memory and measures of cognitive stimulation in the home and parent-child interactive reading. Multilevel analyses accounted for baseline performance, sociodemographics, and clustering within centers and sites.

Results:

The UBB group showed significantly higher self-regulation (Cohen's d = 0.25), compared with the control group, particularly in the subdomains of Attention (d = 0.24) and Impulse Control (d = 0.21). Previously shown impacts of UBB on receptive vocabulary, IQ, and working memory were mediated by self-regulation. Effects of UBB on self-regulation and child outcomes were partially explained through cognitive stimulation in the home and parent-child interactive reading.

Conclusion:

Self-regulation represents an important mechanism by which reading aloud interventions affect language and cognitive outcomes. Investigators should consider the role of self-regulation when refining interventions, seeking to prevent poverty-related disparities.
Agreement and repeatability of corneal tomography in healthy eyes using a new swept-source OCT, a rotating Scheimpflug camera, and a dual Scheimpflug–Placido system
Authors: Herber Robert , Lenk Janine , Pillunat Lutz E. , Raiskup Frederik
Published: July 2021

Purpose:

To investigate the accordance and repeatability of tomographic parameters measured by a new swept-source optical coherence tomographer (SS-OCT, ANTERION), a rotating Scheimpflug camera (RSC, Pentacam), and a dual Scheimpflug-Placido system (DSP, Galilei G6).

Setting:

Department of Ophthalmology of University of Hospital Carl Gustav Carus, Dresden, Germany.

Design:

Prospective reliability analysis.

Methods:

Normal tomography was ensured by bilaterally evaluating appropriated parameters using RSC. All subjects received 3 consecutive measurements on each device by the same operator and in the uniform order RSC, SS-OCT, and DSP. Anterior (ACP) and posterior (PCP) corneal parameters such as flat and steep keratometry and corneal thickness were analyzed. Repeatability was assessed by using a coefficient of repeatability (CoR) and a coefficient of variation. Agreement between RSC and SS-OCT and between RSC and DSP were shown by Bland-Altman plots.

Results:

This study included 30 randomly selected eyes of 30 healthy participants. CoR of ACP did not exceed 0.5 diopters. There were no statistically significant differences in repeatability of ACP obtained from the 3 devices (P > .05). For PCP and corneal thickness, there was statistically significant higher repeatability mostly found for SS-OCT as opposed to RSC and DSP (P < .05). For a wide range of analyzed parameters, there were large limits of agreement (95% LoA) found between the devices.

Conclusions:

The SS-OCT showed highly repeatable measurements in healthy subjects regarding anterior, posterior, and corneal thickness parameters. Repeatability of ACP did not differ between the devices. A mostly wide range of 95% LoA prevents interchangeability between the devices.
Shifts in Attitudes and Intentions to Practice Following Medication-Assisted Treatment Training
Authors: Phelps Paula , Domenech Rodríguez Melanie M. , Alvarez María de la Caridad , Johnson Jeffrey L.
Published: July 2021

Purpose

The Idaho State University Physician Assistant (PA) program was one of the first PA programs in the country to incorporate medication-assisted treatment (MAT) into its curriculum. This manuscript documents the impact of the course.

Methods

In the spring and summer of 2018, 61 students and 12 local providers enrolled in an elective MAT course developed by Idaho State University. All completed the training. At the end of the course, only the students submitted reflective essays.

Results

A review and coding of the essays indicated that MAT education increased knowledge about addiction and resulted in self-reported decreases in negative attitudes towards people with addictions.

Conclusion

PA programs can support communities' increased capacity to offer MAT. A widely available course appears to result in important gains in both knowledge and attitude.
Use of a Knee Orthosis to Advance Motor Control in a 3-Year-Old with Achondroplasia: A Case Report
Authors: Parent-Nichols Jennifer , Chamberlain Deborah
Published: July 2021

Introduction

Children with achondroplasia experience numerous impairments in body structure and function, including hypotonicity, weakness, joint laxity/hypermobility, skeletal malalignment, and delays in gross motor development. Atypical patterns of movement are often used to compensate for short limbs, weakness, laxity at the joints, and bony malalignment. As a result of these atypical patterns, pain and self-restricted movement frequently begin at a young age. Surgical interventions are the general recommendation to address progressive deformity and resultant pain. Lower-limb bracing to address alignment and motor control in children with other diagnoses that include hypotonia has had positive results, including improved alignment and gross motor skills, but has not been explored in children with achondroplasia.

Materials and Methods

A 3-year-old child with achondroplasia participated in an intervention using a neoprene knee orthosis with hyperextension resistance at the knee combined with a play-based, proprioceptive-intensive home exercise program. We hypothesized that the knee orthosis would increase proprioceptive input, improve alignment, and have a positive effect on gross motor skill acquisition and refinement. Early training may also have a positive impact on potential future pain and disability.

Results

Improvements in alignment and motor control were seen in this child after 12 weeks of this intervention but were not initially sustained. After an additional 6 weeks of intervention, significant progress was demonstrated in lower-limb alignment and motor control, as evidenced by independent use of proper movement patterns. Delay in gross motor skill was reduced from 27% to 22%.

Discussion

Motor skills training in proper alignment with aid of neoprene knee orthosis resulted in positive gains for a 3-year old with achondroplasia.

Conclusion

This intervention may be helpful for other children with achondroplasia who experience hypotonia, malalignment, and atypical movement patterns. Sufficient amounts of practice and intensity are recommended for permanent motor learning to occur.
Sleep and quality of life in lung cancer patients and survivors
Authors: Martin Rachel E. , Loomis Dianne M. , Dean Grace E.
Published: July 2021

Background:

Lung cancer patients and survivors are vulnerable to disturbed sleep and impaired quality of life (QOL) across the continuum of illness. Few studies have sought to identify predictors of QOL using well-validated measures of both sleep quality and QOL in this population.

Purpose:

The purpose of this study was to examine factors associated with lung cancer that are predictive of QOL in adult lung cancer patients and survivors in the outpatient setting.

Method:

Cross-sectional data collected exclusively in the outpatient setting from three lung cancer clinics in the Northeastern United States were pooled and analyzed. The pooled sample (N = 103) data included cancer type and stage, body mass index, Pittsburgh Sleep Quality Index, and Functional Assessment of Cancer Treatment-Lung information.

Results:

Significant correlations between sleep quality, lung cancer symptom severity, and QOL were observed. Sleep quality and lung cancer symptoms were found to be statistically significant predictors of QOL. No significant differences in QOL were found based on cancer type or recruitment source. Demographic factors and cancer stage were also not predictive of overall QOL.

Conclusions:

Lung cancer symptoms and sleep quality were important determinants of QOL in this pooled sample of lung cancer patients and survivors.

Implications for practice:

Patients and survivors of lung cancer require routine screening for sleep disturbance, lung cancer symptoms, and QOL needs. Nurse practitioners can help improve QOL in this population by screening for and treating sleep disturbance and lung cancer symptoms.
A Power Tracking Algorithm for Early Detection of Centrifugal Flow Pump Thrombosis
Authors: Slaughter Mark S. , Schlöglhofer Thomas , Rich Jonathan D. , Brown Michael C. , Kadrolkar Abhijit , Ramos Veronica , Stadler Robert W. , Uriel Nir , Mahr Claudius , Sauer Andrew J.
Published: July 2021

Logfiles from the HeartWare HVAD System provide operational pump trend data to aid in patient management. Pump thrombosis is commonly associated with increases in the logfile power that may precede the clinical presentation. A Power Tracking algorithm was developed to detect significant deviations in pump power that may be associated with pump thrombus (PT). The Power Tracking algorithm was applied retrospectively to logfiles captured in the ENDURANCE, ENDURANCE Supplemental, and LATERAL clinical trials. From a combined dataset of 896 patients, available logfiles with suspected PT (n = 70 events in 60 patients) and available logfiles from patients without adverse events (AEs) (n = 106 patients, consisting of 27.4 patient-years of monitoring) were organized into two cohorts. The Power Tracking algorithm detected PT cases on or before the recorded AE date with a sensitivity of 85.7%, with detection occurring an average of 3.9 days before clinical presentation. The algorithm averaged one false alarm for every 6.85 patient-years of monitoring from logfiles without AEs. The favorable performance of the Power Tracking algorithm may enable earlier detection of pump thrombosis and allow early medical management versus surgical intervention.
The different facets of sickle cell disease-related pulmonary hypertension
Authors: Prohaska Clare C. , Machado Roberto F.
Published: July 2021

Purpose of review

Sickle cell disease (SCD), one of the most common genetic diseases in the world, is characterized by repeated episodes of hemolysis and vaso-occlusion. Hemolytic anemia is a risk factor for the development of pulmonary hypertension, and currently SCD-related pulmonary hypertension is classified as World Health Organization group 5 pulmonary hypertension. Patients with SCD-related pulmonary hypertension have unique hemodynamics, multiple comorbidities, and distinct phenotypes that may contribute to the development of pulmonary hypertension.

Recent findings

SCD-related pulmonary hypertension is defined as a mean pulmonary artery pressure >20 mmHg, a pulmonary artery occlusion pressure ≤15 mmHg and relatively low pulmonary vascular resistance (>2 Wood units) rather than the traditional definition of ≥3 Wood units, an important distinction due to a baseline high-cardiac output state in the setting of chronic anemia and low vascular resistance. Diastolic dysfunction is frequently identified in this patient population and right heart catheterization is essential to determine if combined pre- and postcapillary pulmonary hypertension is present. Thromboembolism is common among patients with SCD, and screening for chronic thromboembolic pulmonary hypertension is essential. Data regarding advanced therapies are limited. Primary treatment options include targeting correction of their primary hemoglobinopathy as well as aggressive management of underlying comorbid conditions.

SCD-related pulmonary hypertension is common among patients with SCD and is associated with increased mortality. A high index of suspicion is warranted during evaluation to identify all potential factors that may be contributing to disease.
Effects of Provocative Testing on Phase III Migrating Motor Complex in Children
Authors: Damrongmanee Alisara , El-Chammas Khalil , Fei Lin , Liu Chunyan , Santucci Neha , Kaul Ajay
Published: July 2021

Objectives:

Antroduodenal manometry (ADM) is used to evaluate antral and small intestinal motility, with the presence of phase III migrating motor complexes (MMCs) indicating an intact enteric neuromuscular system. The lack of evidence-based or consensus-driven established norms for MMC in fasting phase and after provocative testing marks a major limitation in the interpretation of ADM studies. We aimed to determine the characteristics of MMC in fasting and post-provocative phase in children.

Methods:

Data from subjects ages <20 years with ADM results evaluated at neuro-gastroenterology and Motility Disorders Center, Cincinnati Children's Hospital Medical Center from January 2018 to March 2019 were analyzed.

Results:

Forty-eight ADM tracings that did not demonstrate abnormal patterns were included; the mean age was 10.00 ± 5.72 years and 50% were male. Indications for ADM included: vomiting (27.1%), feeding intolerance (27.1%), abdominal pain (16.6%), nausea (14.6%), and abdominal distension (14.6%). Thirty-seven percent of subjects had enteral access for feeds. During fasting, one-third of all MMC originated in the antrum. Azithromycin-induced MMC occurred in 28% of subjects and two-thirds of these originated in the antrum with antral contractions of significantly higher frequency and amplitude compared to fasting. Octreotide significantly increased frequency, amplitude, and duration of MMC compared to fasting, with 76% originating in the antrum. Both azithromycin and octreotide induced more than one MMC in a third of subjects.

Conclusions:

We describe the characteristics of antral and small intestinal motility during fasting and after provocative testing in children. These values will help standardize our interpretation of pediatric ADM studies.
Creation of a Pediatric Choledocholithiasis Prediction Model
Authors: Cohen Reuven Zev , Tian Hongzhen , Sauer Cary G. , Willingham Field F. , Santore Matthew T. , Mei Yajun , Freeman A. Jay
Published: July 2021

Background:

Definitive non‐invasive detection of pediatric choledocholithiasis could allow more efficient identification of those patients who are most likely to benefit from therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for stone extraction.

Objective:

To craft a pediatric choledocholithiasis prediction model using a combination of commonly available serum laboratory values and ultrasound results.

Methods:

A retrospective review of laboratory and imaging results from 316 pediatric patients who underwent intraoperative cholangiogram or ERCP due to suspicion of choledocholithiasis were collected and compared to presence of common bile duct stones on cholangiography. Multivariate logistic regression with supervised machine learning was used to create a predictive scoring model. Monte‐Carlo cross‐validation was used to validate the scoring model and a score threshold that would provide at least 90% specificity for choledocholithiasis was determined in an effort to minimize non‐therapeutic ERCP.

Results:

Alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, and common bile duct diameter via ultrasound were found to be the key clinical variables to determine the likelihood of choledocholithiasis. The dictated specificity threshold of 90.3% yielded a sensitivity of 40.8% and overall accuracy of 71.5% in detecting choledocholithiasis. Positive predictive value was 71.4% and negative predictive value was 72.1%.

Conclusion:

Our novel pediatric choledocholithiasis predictive model is a highly specific tool to suggest ERCP in the setting of likely choledocholithiasis.
Skull Base Vagal Schwannoma
Authors: Xiong Lei , Wang Chong , Liu Huan , Feng Zhien
Published: July 2021

Skull base vagal nerve schwannoma (VNS) is relatively uncommon and poses a challenge to surgeons. Although schwannomas are benign and slowly growing neoplasms arising from Schwann cells, they may cause significant dysfunction by causing the surrounding structures compression or infiltrating vital structures such as the skull base, the orbit, and the cranial nerves. These tumors are resistant to radiotherapy and chemotherapy. Complete surgical removal is the optimal treatment modality, with recurrence being rare. The authors report a case of a 58-year-old man with an extensive VNS involving the left jugular foramen and parapharyngeal space. The clinical presentation, surgical management, and outcomes of VNS are discussed.
Single Segment Neo-Bandeau Fronto-Orbital Advancement in Children With Craniosynostosis: Technique Adaptation and Craniometric Analysis
Authors: Zapatero Zachary D. , Zimmerman Carrie E. , Kosyk Mychajlo S. , Kalmar Christopher L. , Carlson Anna R. , Humphries Laura S. , Lang Shih-Shan , Swanson Jordan W.
Published: July 2021

Fronto-orbital advancement (FOA) of the anterior skull and orbital bandeau is standard of care for craniosynostosis with anterior morphology. Fronto-orbital retrusion, temporal hollowing, and bony contour irregularities are commonly seen in long-term follow-up. In this study, we report several technical adaptations of a new FOA technique described in Fearon et al that help facilitate adaptation of the single-segment neo-bandeau FOA technique in preparation of use in younger patients, and perform a craniometric analysis of the technique. Five consecutive patients who underwent the single-segment neo-bandeau FOA in 2020 with available pre- and post-operative three-dimensional head computed tomography scans were studied. Using Materialise Mimics (Materialise, Ghent, Belgium), cranial length, cranial height, cranial widths, and intracranial volume were measured. Two (40%) patients were male and all were non-Hispanic White with a median age at surgery of 18.6 months (interquartile range 10.4–45.7). Three patients (60%) had bicoronal or other multi-suture craniosynostosis, and 1 each had metopic and sagittal craniosynostosis. Intraoperatively measured intracranial pressure decreased from 17.8 mmHg (R 13.0–20.0) before craniectomy to 4.8 mmHg (R 2.0–11.0; P = 0.038) after craniectomy. Anterior cranial width increased postoperatively (mean 92.6 mm; R 74.9–111.5 versus 117.6 mm; R 109.8–135.2, P = 0.005). Intracranial volume increased from preoperative (mean 1211 cm3; R 782–1949 cm3) to postoperative (1387 cm3; R 1022–2108 cm3; P = 0.009). The authors find in this small sample that a single-segment neo-bandeau FOA demonstrates volumetric expansion similar to conventional FOA techniques and is feasible in infants under 1 year of age.
The Role of Extracellular Vesicles Secreted From Thermal Stress-Induced Adipose-Derived Stem Cells on Bone Regeneration
Authors: Akdeniz-Dogan Zeynep , Sendur Samet , Karademir-Yilmaz Betul , Bugdayci Onur , Cilingir-Kaya Ozlem Tugce , Yilmaz-Goler Ayse M. , Gunduz Oguzhan , Celebiler Ozhan B.
Published: July 2021

Purpose:

Extracellular vesicles (EVs) are responsible for intercellular communication. Mesenchymal stem cell-derived vesicles have been shown to have similar properties as functional mesenchymal stem cells. The aim of this study was to compare the therapeutic benefit of EVs obtained from adipose tissue-derived stem cells (ADSC) on bone repair whereas using ß-tricalcium phosphate (ß-TCP) biomaterial as a carrier.

Materials and Method:

A single critical size bone defect of 8 mm in diameter was created on the right side of rat calvarium using a custom-made punch needle. Animals were randomly divided into 5 groups: group 1 (no treatment), group 2 (bone graft), group 3 (ß-TCP + ADSC), group 4 (ß-TCP + EV), group 5 (ß-TCP). Eight weeks later, animals were sacrificed and histologic and radiologic evaluation was performed.

Results:

Semiquantitative histologic scoring demonstrated significantly higher bone regeneration scores for groups 2, 3, and 4 compared to group 1. Radiologic imaging showed significantly higher bone mineral density for groups 2, 3, and 5 compared to group 1. There were no significant differences between treatment groups in either histologic or radiologic scoring.

Conclusions:

Our data showed that EVs provided from thermally induced ADSCs did not show any significant difference in bone regeneration when compared to ADSCs themselves. Future studies should focus on determining the optimum amount and content of EV application since these vary significantly depending on the microenvironment.
Development of De Novo Donor-specific HLA Antibodies and AMR in Renal Transplant Patients Depends on CYP3A5 Genotype
Authors: Friebus-Kardash Justa , Nela Ejona , Möhlendick Birte , Kribben Andreas , Siffert Winfried , Heinemann Falko Markus , Eisenberger Ute
Published: July 2021

Background.

The single-nucleotide polymorphism CYP3A5 rs776746 is related to a reduction in the metabolizing activity of the CYP3A5 enzyme. People carrying at least one copy of the wild-type allele, defined as CYP3A5 expressers, exhibit higher clearance and lower trough concentrations of tacrolimus than homozygous nonexpressers, and this difference may affect alloimmunization and allograft function.

Methods.

We retrospectively studied 400 kidney transplant recipients treated with a tacrolimus-based immunosuppression regimen to detect CYP3A5 genotype, de novo formation of HLA antibodies and donor-specific antibodies (DSAs), and clinical outcome up to 5 y after transplant.

Results.

We found that 69 (17%) of the 400 patients were CYP3A5 expressers. During the first 3 y after transplant, CYP3A5 expressers tended to have lower tacrolimus trough levels than nonexpressers, although their tacrolimus dosage was as much as 80% higher. De novo DSAs were found more frequently in CYP3A5 expressers than in nonexpressers (13/69 [19%] versus 33/331 [10%], P = 0.02). De novo DSA-free survival rates (P = 0.02) were significantly lower for expressers than for nonexpressers. CYP3A5 genotype had no effect on allograft failure, but CYP3A5 expressers exhibited a significantly higher frequency of antibody-mediated rejection. CYP3A5 expresser status was an independent risk factor for the development of de novo DSAs (relative risk, 2.34, P = 0.01).

Conclusions.

Early detection of CYP3A5 expressers, enabling genotype-based dose adjustment of tacrolimus immediately after renal transplant, may be a useful strategy for reducing the risk of de novo DSA production and antibody-mediated rejection.
Factors Associated With Increased Emergency Department Utilization in Patients With Acute Optic Neuritis
Authors: Muro-Fuentes Elena A. , Moss Heather E.
Published: July 2021

Background:

Symptoms of acute vision loss and eye pain may lead patients with optic neuritis to seek care in the emergency department (ED). Given the availability of lower cost alternatives for providing medical care for optic neuritis, this study aimed to identify factors associated with higher ED utilization.

Methods:

Subjects with acute optic neuritis were identified through a chart review of adults with International Classification of Diseases-9 (ICD-9) or ICD-10 codes for optic neuritis with corresponding gadolinium contrast enhancement of the optic nerve on MRI in the medical record research repository of a tertiary care institution. Subjects were grouped based on the number of ED visits (0–1 and 2–3) within 2 months of either ICD code or MRI. Demographics, characteristics of disease presentation, type and location of medical care, testing (chest imaging, lumbar puncture, optical coherence tomography, spine MRI, visual field, and laboratory tests), treatment, provider specialty of follow-up visits, and duration of care were extracted from the medical record.

Results:

Of 30 acute optic neuritis subjects (age 41 ± 16 years, range 18–76, 53% [16/30] female), 19 had 0–1 ED visit and 11 had 2–3 ED visits. Most subjects were Caucasian, non-Hispanic (47%), followed by Asian (23%), Hispanic/Latino (17%), Black (10%), and others (3%). Subjects had an initial clinical encounter primarily in the outpatient setting (63%) as compared with the ED (37%). The median time from symptom onset to initial clinical encounter was 4 days with a range of 0–13. Subjects were mostly insured through a private insurance (60%), followed by Medicare/Medicaid (23%) and uninsured (17%). Fewer ED visits were associated with an initial clinical encounter in an outpatient setting (P = 0.02, chi-square), but not residential distance from the hospital or insurance type. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). There was no significant difference in the ophthalmic, radiologic, or laboratory testing performed in both groups. Both groups presented in a similar time frame with similar symptoms and clinical signs. Treatment was similar in both groups.

Conclusions:

Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting and thus strategies aimed at facilitating outpatient care may help reduce unnecessary ED visits, although some, such as insurance status, may be difficult to modify. Further study in a larger sample is needed to refine these observations.
Recent trends in the management of depression in persons with cancer
Authors: Panjwani Aliza A. , Li Madeline
Published: July 2021

Purpose of review

Depression is a prevalent comorbidity in cancer that significantly increases the risk for numerous negative health outcomes. This review updates the current evidence base for management of depression in cancer, highlighting new research directions based on the inflammatory hypothesis of depression.

Recent findings

Research on pharmacotherapy and psychotherapy for depression in cancer has shown mixed efficacy partly because of methodological issues arising from the phenomenology of depression in cancer. After decades of stagnancy, more recent high-quality clinical trials are beginning to provide an evidence base to guide treatment. Inflammatory cytokine-associated depression is a subtype of depression that may have particular relevance in cancer, opening new avenues to explore therapeutic targets and biobehavioral impacts of interventions, which may improve cancer outcomes.

The continuum of severity in cancer-related depression is important to consider in management approaches. Choice of treatment should be personalized to the patient and their symptom profile as there is currently insufficient evidence to recommend any particular medication or psychotherapy over another. Psychological interventions should be considered first line for mild-to-moderate depression, and pharmacological treatment added for more severe depression, which can be optimally delivered within a collaborative care model.

Video abstract

http://links.lww.com/YCO/A62
Synergistic motion compensation strategies for positron emission tomography when acquired simultaneously with magnetic resonance imaging
Authors: Polycarpou Irene , Soultanidis Georgios , Tsoumpas Charalampos
Published: July 2021

Subject motion in positron emission tomography (PET) is a key factor that degrades image resolution and quality, limiting its potential capabilities. Correcting for it is complicated due to the lack of sufficient measured PET data from each position. This poses a significant barrier in calculating the amount of motion occurring during a scan. Motion correction can be implemented at different stages of data processing either during or after image reconstruction, and once applied accurately can substantially improve image quality and information accuracy. With the development of integrated PET-MRI (magnetic resonance imaging) scanners, internal organ motion can be measured concurrently with both PET and MRI. In this review paper, we explore the synergistic use of PET and MRI data to correct for any motion that affects the PET images. Different types of motion that can occur during PET-MRI acquisitions are presented and the associated motion detection, estimation and correction methods are reviewed. Finally, some highlights from recent literature in selected human and animal imaging applications are presented and the importance of motion correction for accurate kinetic modelling in dynamic PET-MRI is emphasized.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.
Motion estimation and correction for simultaneous PET/MR using SIRF and CIL
Authors: Brown Richard , Kolbitsch Christoph , Delplancke Claire , Papoutsellis Evangelos , Mayer Johannes , Ovtchinnikov Evgueni , Pasca Edoardo , Neji Radhouene , da Costa-Luis Casper , Gillman Ashley G. , Ehrhardt Matthias J. , McClelland Jamie R. , Eiben Bjoern , Thielemans Kris
Published: July 2021

SIRF is a powerful PET/MR image reconstruction research tool for processing data and developing new algorithms. In this research, new developments to SIRF are presented, with focus on motion estimation and correction. SIRF’s recent inclusion of the adjoint of the resampling operator allows gradient propagation through resampling, enabling the MCIR technique. Another enhancement enabled registering and resampling of complex images, suitable for MRI. Furthermore, SIRF’s integration with the optimization library CIL enables the use of novel algorithms. Finally, SPM is now supported, in addition to NiftyReg, for registration. Results of MR and PET MCIR reconstructions are presented, using FISTA and PDHG, respectively. These demonstrate the advantages of incorporating motion correction and variational and structural priors.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.
Investigating the contributions of circadian pathway and insomnia risk genes to autism and sleep disturbances
Authors: Tesfaye Rackeb , Huguet Guillaume , Smiliovich Zoe , Loum Mor Absa , Douard Elise , Jean-Louis Martineau , Martinot Jean Luc , Whelan Rob , Desrivieres Sylvane , Heinz Andreas , Schumann Gunter , Hayward Caroline , Elsabbagh Mayada , Jacquemont Sebastien
Published: July 2021

Sleep disturbance is prevalent in youth with Autism Spectrum Disorder (ASD). Researchers have posited that circadian dysfunction may contribute to sleep problems or exacerbate ASD symptomatology. However, there is limited genetic evidence of this. It is also unclear how insomnia risk genes identified through GWAS in a general population are related to ASD risk and common sleep problems like insomnia in ASD. We investigated the contribution of copy number variants (CNVs) encompassing circadian pathway genes and insomnia risk genes to ASD risk as well as parent reported sleep disturbances in children diagnosed with ASD. We studied 5860 ASD probands and 2092 unaffected siblings from the Simons Simplex Collection and MSSNG database, as well as 7463 individuals from two unselected populations (IMAGEN and Generation Scotland). We identified 320 and 626 rare CNVs encompassing circadian genes and insomnia risk genes respectively. Deletions and duplications with circadian genes were overrepresented in ASD probands compared to siblings and unselected controls. For insomnia-risk genes, deletions (but not duplications) were also associated with ASD. Results remained significant after adjusting for cognitive ability. CNVs containing circadian pathway and insomnia risk genes showed a stronger association with ASD, compared to CNVs containing other genes. Duplications containing circadian genes were associated with shorter sleep duration (22 minutes). Only insomnia risk genes intolerant to haploinsufficiency increased insomnia traits when duplicated. Overall, CNVs encompassing circadian and insomnia risk genes increase ASD risk despite small impacts on sleep disturbances.