bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Experience With Endoscopic Ultrasound‐guided Coil Placement for Pediatric Gastric Variceal Hemostasis
Authors: Barakat Monique T. , Foley Megan A. , Gugig Roberto 
Published: December 2020

ABSTRACTBackground:Gastric variceal (GV) bleeding is among the most morbid sequelae of portal hypertension, with mortality ranging from 30% to 50%. Pediatric data focused on endoscopic approaches to management are needed. The present study represents the first pediatric case series of endoscopic ultrasound (EUS)‐guided coil placement within feeding vessels as monotherapy for management of GV bleeding.Methods:Using our prospectively maintained endoscopy database, we identified patients 18 years and younger who underwent EUS‐guided coil placement for management of GV bleeding from 2008 to 2018. Demographics, indication, procedural interventions/findings, and available clinical outcomes data were analyzed.Results:Twelve patients (median age 15, range 11–18 years) underwent EUS‐guided coil placement for GV bleeding. All had portal hypertension, with EV in 58.3% and prior GV bleeding with attempted endoscopic management in 75%. Coil placement was accomplished using a linear echoendoscope and a 19‐gauge needle. A mean of 2.75 (± 0.43) coils were placed in each patient (4, 6, 8, and 10 mm Nester Embolization Coils, Cook Medical, Bloomington, Indiana, USA). Immediate hemostasis was achieved in all patients, and 25% of patients developed recurrent gastric varices at a median of 5.5 months following the initial EUS‐guided coil placement (range 4–6 months) over the median 12 month follow‐up period.Conclusions:The present study establishes the feasibility and efficacy of EUS‐guided coil placement as monotherapy for GV bleeding in children and adolescents. The technique was technically successful, with primary hemostasis achieved in all patients. EUS‐guided embolization with coils may represent an alternative to current approaches for management of highly morbid GV bleeding.
Diagnostic Accuracy of the Rome IV Criteria for the Diagnosis of Functional Gastrointestinal Disorders in Children
Authors: Velasco‐Benítez Carlos A. , Gómez‐Oliveros Lina F. , Rubio‐Molina Lina M. , Tovar‐Cuevas José R. , Saps Miguel 
Published: December 2020

ABSTRACTThe diagnosis of functional gastrointestinal disorders (FGIDs) centers on symptoms‐based criteria (Rome criteria). The last edition of the criteria was published in 2016. Still, few data on its validity support its use in children. We conducted a study aimed at determining the diagnostic accuracy of the Rome IV criteria through the application of questionnaires (Questionnaire of Pediatric Gastrointestinal Symptoms‐Rome IV QPGS‐IV) to diagnose FGIDs in children. We hypothesized that the Rome IV criteria has adequate diagnostic accuracy supporting its use for diagnosing FGIDs in children.Methods:School children ages 10 to 18 years from Cali (Colombia) completed the Spanish version of the QPGS‐IV. Children with FGIDs were matched with a group of children without FGIDs. Both groups had a medical consultation with a blinded experienced pediatric gastroenterologist (criterion standard) who provided his diagnosis. The questionnaire‐based diagnoses were compared with the consultation's diagnoses.Results:Of 487 schoolchildren surveyed with the QPGS‐IV, 97 (20.8%) had FGIDs. Eighty‐nine with FGIDs were matched with 92 children without FGIDs (mean age 13.1 years [±1.3]). We found a higher prevalence of FGIDs during the medical visit than using the self‐report QPGS‐IV (66.3% vs 49.2%, P = 0.001), mainly in abdominal pain disorders (19.3% vs 10.5%, P = 0.013). The Rome IV diagnostic criteria using the QPGS‐IV had a sensitivity of 75% (95% confidence interval, 59–79) and 90% specificity (95% confidence interval, 83–98). Positive predictive value is 85.8%, and negative predictive value is 79.9%.Conclusion:Our study suggests that the QPGS‐IV has adequate diagnostic accuracy.
A Trial of an Anamnesis‐based Score Applied as a Diagnostic Tool for Cow's Milk Protein Allergy in Children
Authors: Muñoz‐Urribarri Ana , Sabrá Aderbal , Sabrá Selmá , Condorhuamán Yovani M. 
Published: December 2020

ABSTRACTThis study presents an anamnesis‐based questionnaire as a diagnostic tool for cow's milk protein allergy (CMPA) in children. We applied 24 dichotomous yes/no questions to 51 cases diagnosed by oral challenge and 31 controls. All patients were recruited at the pediatric gastroenterologist outpatient practice. Patients with CMPA presented with a family history of atopy/autoimmunity, cesarean delivery, use and/or change of formulas, use of antacids/antibiotics in the first 6 months of life, an overly clean caregiver, multisystem clinical presentation, and the absence of seasonal symptoms. The CMPA group had an average score of 10.4 versus 3.2 for the control group. We identified a cut‐off score of 7, which had 94.4% sensitivity and 96.9% specificity to distinguish CMPA from the control population. Cases were younger and showed different symptoms than controls. This study shows the usefulness of an anamnesis‐based clinical score to guide the diagnosis of CMPA in children.
Acute Fluctuant Neurological Symptoms in Stable Chronic Cryptococcus gattii Cryptococcomas
Authors: Lennon Matthew , Tudehope Fiona , McCready Michael , Jude Martin 
Published: December 2020

Background:
Cryptococcus, a yeast-like fungus, is the most common cause of fungal meningitis worldwide. The Cryptococcus gattii variety is concentrated in Australia has a greater propensity to infect immunocompetent hosts, cause meningitis and form crytococcomas. This case presents a novel disease complication, that is, acute neurological symptoms without seizures, disease progression or reactivation.

Case Presentation:
A 58-year-old immunocompetent male was brought to the emergency department with dysarthria and right arm paraesthesias. Computed tomography of the brain brain and magnetic resonance imaging revealed no stroke but found several previously identified crytococcomas that demonstrated no interval change. Blood tests and lumbar puncture found only a low cryptococcal antigen complex titer (CRAG) (1:10) and a negative cell culture. He had remained compliant on his maintenance fluconazole therapy and had no immunocompromise or seizure activity. He was initially treated as a relapse of cryptococcal disease and restarted on induction therapy but after the cell culture returned negative and the symptoms resolved over the following days he was reverted back to maintenance therapy.

Discussion and Conclusions:
Central nervous system cryptococcomas are difficult to treat, chronic infections, that in our patient had lasted over 10 years despite treatment compliance. A true cryptococcal meningitis relapse is indicated by positive cell cultures in previously sterile fluid but cryptococcoma progression is measured by serial magnetic resonance imaging or computed tomography scans. In the case of progression or relapse induction and consolidation therapy should be restarted. Our patient demonstrated neither relapse nor progression but presented with a novel disease complication of acute fluctuating neurology in chronic stable cryptococcomas.
Predictors of Good Outcomes in Stroke Thrombolysis Guided by Tissue-Window
Authors: Zhang Xianxian , Wang Dapeng , Wang Hui , Cai Xiuying , Shi Haicun , Fang Qi 
Published: December 2020

Background:
Recently studies suggested that assessment of tissue-window can effectively guide thrombolysis in acute ischemic stroke patients with unknown time of onset or late presenting. This study aimed to evaluate predictors of good outcomes from thrombolysis in these patients.

Methods:
Acute ischemic stroke patients received thrombolysis guided by computed tomography perfusion (CTP) from October 2018 to August 2019 were reviewed. Baseline characteristics and outcomes were collected. Good outcomes were defined as modified Rankin scale scores of 0 to 2 at 90 days. Logistic regression analysis was performed and the receiver operating characteristics analysis was used to determine cut-off values for the predictors of outcomes.

Results:
Sixty-three patients were enrolled. The median age was 64 (interquartile range 57.75 to 72.5) years. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 8 (interquartile range 3 to 13) and 41 (65.1%) patients had a good outcome at 90 days. Multivariate regression analysis showed smaller perfusion lesion (the sum of ischemic penumbra and infarcted core) (odds ratio: 0.961; 95% confidence interval, 0.931-0.992; P=0.013) and lower baseline NIHSS score (odds ratio: 0.759; 95% confidence interval, 0.644-0.895; P=0.001) were significant predictors for good outcomes. Receiver operating characteristics analysis was utilized to define optimal cut-off values for perfusion lesion [cut-off, 59 mL; area under curve (AUC), 0.761; sensitivity, 0.57; specificity, 0.93; P=0.001], ischemic penumbra (cut-off, 43.5 mL; AUC, 0.761; sensitivity, 0.62; specificity, 0.90; P=0.001), infarcted core (cut-off, 9.5 mL; AUC, 0.665; sensitivity, 0.43; specificity, 0.93; P=0.035), and baseline NIHSS score (cut-off, 8.5; AUC, 0.880; sensitivity, 0.81; specificity, 0.88; P<0.001).

Conclusions:
This study suggested that smaller perfusion lesion and lower baseline NIHSS score may be helpful to predict favorable prognosis of stroke patients who receive thrombolysis guided by tissue-window.
A Case Series of Acute Hemorrhagic Leukoencephalitis
Authors: Podduturi Varsha , Blessing Melissa M. , Joseph David M. , Ross Jennifer L. , Sandberg Glenn D. 
Published: December 2020

Abstract
Acute hemorrhagic leukoencephalitis (AHL) is an acute, hemorrhagic demyelinating disease thought to be caused by an immune-mediated process. Acute hemorrhagic leukoencephalitis is both diagnostically challenging and fatal in the majority of cases. We present two cases of AHL unexpectedly diagnosed at autopsy. These cases demonstrate the often nonspecific and challenging nature of AHL clinical presentation, review neuropathological mimics, and emphasize the importance of considering this diagnosis in the forensic setting.
Research Priorities for U.K. Pediatric Critical Care in 2019: Healthcare Professionals’ and Parents’ Perspectives
Authors: Tume Lyvonne N. , Menzies Julie C. , Ray Samiran , Scholefield Barnaby R. 
Published: December 2020

OBJECTIVES:
The Paediatric Intensive Care Society Study Group conducted a research prioritization exercise with the aim to identify and agree research priorities in Pediatric Critical Care in the United Kingdom both from a healthcare professional and parent/caregiver perspective.

DESIGN:
A modified three-round e-Delphi survey, followed by a survey of parents of the top 20 healthcare professional priorities.

SETTING:
U.K. PICUs.

PATIENTS:
U.K. PICU healthcare professionals who are members of the professional society and parents and family members of children, with experience of a U.K. PICU admission.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Forty-nine healthcare professional submitted topics in round 1, 98 participated in round 2, and 102 in round 3. These topics were categorized into eight broad domain areas, and within these, there were 73 specific topics in round 2. At round 3, 18 topics had a mean score less than 5.5 and were removed, leaving 55 topics for ranking in round 3. Ninety-five parents and family members completed the surveys from at least 17 U.K. PICUs. Both parents and healthcare professional prioritized research topics associated with the PICU workforce. Healthcare professional research priorities reflected issues that impacted on day-to-day management and practice. Parents’ prioritized research addressing acute situations such as infection identification of and sepsis management or research addressing long-term outcomes for children and parents after critical illness. Parents prioritized research into longer term outcomes more than healthcare professional. Parental responses showed clear support for the concept of research in PICU, but few novel research questions were proposed.

CONCLUSIONS:
This is the first research prioritization exercise within U.K. PICU setting to include parents’ and families’ perspectives and compare these with healthcare professional. Results will guide both funders and future researchers.
Evaluation of Hip Pain and Management of Toxic Synovitis in the Ultrasound Era
Authors: Takundwa Prisca , Chen Lei , Malik Rabia N. 
Published: December 2020

Abstract
The cause of acute onset hip pain in children can be difficult to determine. Once trauma is excluded, the workup revolves around determining whether there is a hip effusion and eliminating orthopedic emergencies. Point-of-care-ultrasound can be used as an adjunct in the workup. In this article, we review (1) differential diagnosis of hip pain, with a focus on toxic synovitis; (2) the evaluation of a hip for the presence of effusion, including the point-of-care ultrasound technique; and (3) the management of toxic synovitis.
Risk Factors for Spinal Structural Damage in a Chinese Cohort With Ankylosing Spondylitis
Authors: Kong Weiping , Jefferies Caroline , Learch Thomas J. , Gan Xiaowei , Zhu Feng , Zhang Nan , Jin Dier , Zhang Yingze , Tao Qingwen , Yan Xiaoping , Ishimori Mariko L. , Weisman Michael H. 
Published: December 2020

Objectives
A cross-sectional study was conducted in 270 Chinese patients with ankylosing spondylitis (AS) in order to identify potential risk factors for severity of spinal structural damage.

Methods
Two hundred seventy AS patients fulfilled the Modified New York Criteria. Computed tomography (CT) was used to scan sacroiliac and hip joints, and radiography was used to scan anteroposterior and lateral lumbar spine, as well as lateral cervical spine. Bath Ankylosing Spondylitis Radiology Index and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were scored in duplicate.

Results
One hundred eighty-three patients had low mSASSS (mSASSS, <10), and 87 patients had high mSASSS (mSASSS, ≥10). Univariate analysis revealed that AS age of onset, body mass index (BMI), smoking duration, duration of symptoms, diagnostic delay, hip involvement, and sacroiliitis grade were significantly associated with the risk of having high mSASSS after adjustment (all p's < 0.05). Hip involvement interacted significantly with BMI and smoking duration in a graded manner. Particularly, relative to patients with low BMI-negative hip involvement, those with high BMI-negative hip involvement, low BMI-positive hip involvement, and high BMI-positive hip involvement had a 1.94-fold, 3.29-fold, and 5.07-fold increased risk of high mSASSS (95% confidence interval, 0.84–4.47, 1.37–7.89, and 1.97–13.06, p = 0.118, 0.008, and 0.001, respectively). Finally, a nomogram graph based on 7 significant risk factors was generated with substantial prediction accuracy (concordance index, 0.906).

Conclusions
We have identified 7 potential risk factors for the severity of spinal structural damage in Chinese AS patients. Importantly, positive hip involvement, combined with high BMI or long smoking duration, was associated with a remarkably increased risk of having severe spinal structural damage.
Authentication of In Situ Measurements for Thoracic Aortic Aneurysms in Mice
Authors: Ohno-Urabe Satoko , Kukida Masayoshi , Franklin Michael K. , Katsumata Yuriko , Su Wen , Gong Ming C. , Lu Hong S. , Daugherty Alan , Sawada Hisashi 
Published: December 2020

AbstractAortic diameter is a standard parameter for defining disease severity of thoracic aortic aneurysms. In mouse studies, aortic diameters can be measured in situ directly, but this approach has a potential confounder of underestimation due to the absence of physiological arterial blood pressure. In the present study, we developed an in situ approach for authentic aortic measurements. Thoracic aortic aneurysms were induced by beta-aminopropionitrile (BAPN, 0.5% wt/vol) administration in 4-week-old male C57BL/6J mice. Ultrasonography was performed to examine aortic dimensions, and mice with thoracic aortic dilatations were terminated subsequently. After saline perfusion through the left ventricle, periaortic tissues were removed to expose thoracic aortas. Optimal cutting temperature (OCT) compound was injected via the left ventricle to maintain aortic patency. In situ aortic images were captured pre- and post-OCT injection. In mice with severe thoracic aortic aneurysms, smaller aortic diameters were observed prior to OCT injection compared to ultrasound measurements, while aortic diameters in situ after OCT were comparable to diameters measured using ultrasound. A telemetry system demonstrated that maximal luminal pressures during 150 ul of OCT injection were 90 mmHg. Immunostaining for CD31 revealed that endothelial cells were preserved in the intima after OCT injection. These results indicate that OCT injection does not cause aortic damages due to excess pressures. In conclusion, in situ imaging with OCT injection provides authentic aortic measurements without overt aortic damage in mice with thoracic aortic aneurysms.
Characterization of aRAD51C-Silenced High Grade Serous Ovarian Cancer Model During PARP Inhibitor Resistance Development
Authors: Hurley Rachel M. , McGehee Cordelia D. , Nesic Ksenija , Correia Cristina , Weiskittel Taylor M. , Kelly Rebecca L. , Venkatachalam Annapoorna , Hou Xiaonan , Pathoulas Nicholas M. , Meng X. Wei , Kondrashova Olga , Radke Marc R. , Schneider Paula A. , Flatten Karen S. , Peterson Kevin L. , Dobrovic Alexander , Lin Kevin K. , Harding Thomas C , McNeish Iain A. , Ross Christian A. , Wagner Jill M. , Wakefield Matthew J. , Scott Clare L. , Haluska Paul , Wahner Hendrickson Andrea E. , Karnitz Larry M. , Swisher Elizabeth M. , Li Hu , Weroha S. John , Kaufmann Scott H. 
Published: December 2020

ABSTRACTAcquired PARP inhibitor (PARPi) resistance inBRCA1- orBRCA2-mutant ovarian cancer often results from secondary mutations that restore expression of functional protein.RAD51Cis a less commonly studied ovarian cancer susceptibility gene whose promoter is sometimes methylated in the tumor, leading to homologous recombination deficiency and PARPi sensitivity. For this study, the PARPi-sensitive patient-derived xenograft PH039, which lacks demonstrable repair gene mutations but harborsRAD51Cpromoter methylation, was selected for PARPi resistance by repeated 21-day niraparib treatmentsin vivo. PH039 acquired PARPi resistance by the third cycle of treatment and demonstrated unimpeded growth during subsequent exposure to either niraparib or rucaparib. Transcriptional profiling throughout the time course of resistance development showed widespread pathway level changes along with a marked increase inRAD51CmRNA, which reflected loss ofRAD51Cpromoter methylation. Analysis ofRAD51Cmethylation in patient tumor samples from the ARIEL2 Part 1 clinical trial of rucaparib monotherapy likewise indicated that loss ofRAD51Cmethylation prior to on-study biopsy was associated with limited response. Interestingly, the PARPi resistant PH039 model remained platinum sensitive. Collectively, these results not only indicate that PARPi treatment pressure can reverseRAD51Cmethylation and restore RAD51C expression, but also provide an important model for studying the clinical observation that PARPi and platinum sensitivity are sometimes dissociated.
Lipid-based, protein-based, and steric interactions synergize to facilitate transmembrane signaling stimulated by antigen-clustering of IgE receptors
Authors: Bag Nirmalya , Wagenknecht-Wiesner Alice , Lee Allan , Shi Sophia , Holowka David A. , Baird Barbara A. 
Published: December 2020

ABSTRACTAntigen (Ag) crosslinking of immunoglobulin E-receptor (IgE-FcεRI) complexes in mast cells stimulates transmembrane (TM) signaling, requiring phosphorylation of the clustered FcεRI by lipid-anchored Lyn tyrosine kinase. Previous studies showed that this stimulated coupling between Lyn and FcεRI occurs in liquid ordered (Lo)-like nanodomains of the plasma membrane and that Lyn binds directly to cytosolic segments of FcεRI that it initially phosphorylates for amplified activity. Net phosphorylation above a non-functional threshold is achieved in the stimulated state, but not in the resting state, and current evidence supports the hypothesis that this relies on disruption by Ag-crosslinking of a balance between Lyn and tyrosine phosphatase activities. However, the structural interactions that underlie the stimulation process remain poorly defined. This study evaluates the relative contributions and functional importance of different types of interactions leading to supra-threshold phosphorylation of Ag-crosslinked IgE-FcεRI in live rat basophilic leukemia (RBL) mast cells. Our high-precision diffusion measurements by Imaging Fluorescence Correlation Spectroscopy (ImFCS) on multiple structural variants of Lyn and other lipid-anchored probes confirm subtle, stimulated stabilization of the Lo-like nanodomains and concomitant sharpening of segregation from liquid-disordered (Ld)-like regions. With other structural variants we determine that lipid-based interactions are essential for access by Lyn leading to phosphorylation of and protein-based binding to clustered FcεRI. By contrast, TM tyrosine phosphatase, PTPα, is excluded from these regions by steric repulsion of TM segments and preference for Ld-like regions. Overall, we establish a synergy of lipid-based, protein-based, and steric interactions underlying functional TM signaling in mast cells.SIGNIFICANCE STATEMENTLipid organization of the plasma membrane is known to be important for facilitating protein interactions in transmembrane signaling. However, the orchestration of these interactions in live cells has been elusive. We employed ImFCS to systemically investigate the interplay of lipids and proteins during signaling in mast cells, initiated as phosphorylation of Ag-crosslinked IgE-FcεRI by lipid-anchored Lyn kinase. We find lipid-based interactions are first required for protein-based phosphorylation of the clustered FcεRI within Lo-like nanodomains. Transmembrane phosphatases must be excluded from these regions, and we find this is mediated by their preference for Ld-like regions and by steric exclusion from the clustered FcεRI proteins. ImFCS provides quantitative characterization of the functional link between features of plasma membrane organization and transmembrane signaling.
Matrix stiffness and blood pressure together regulate vascular smooth muscle cell phenotype switching
Authors: Swiatlowska Pamela , Sit Brian , Feng Zhen , Marhuenda Emilie , Xanthis Ioannis , Zingaro Simona , Ward Matthew , Zhou Xinmiao , Xiao Qingzhong , Shanahan Cathy , Jones Gareth E , Yu Cheng-han , Iskratsch Thomas 
Published: December 2020

AbstractVascular smooth muscle cells (VSMCs) play a central role in the onset and progression of atherosclerosis. In pre-atherosclerotic lesions, VSMCs switch from a contractile to a synthetic phenotype and subsequently remodel the microenvironment, leading to further disease progression. Ageing and associated mechanical changes of the extracellular matrix as well as hypertension are major risk of atherosclerosis. Consequently, we sought here to systematically study the impact of mechanical stimulations on VSMC phenotypic switching, by modulating both stiffness and hydrodynamic pressure. Thereby we find that hemodynamic pressure and matrix stiffness individually affect the VSMC phenotype. However, only the combination of hypertensive pressure and matrix compliance, and as such mechanical stimuli that are prevalent during atherosclerosis, lead to a full phenotypic switch including the formation of matrix degrading podosomes. We further analyse the molecular mechanism in stiffness and pressure sensing and identify a regulation through different, but overlapping pathways, culminating in the regulation of the actin cytoskeleton through cofilin. Altogether, our data shows how different pathological mechanical signals combined, but through distinct pathways accelerate a phenotypic switch that will ultimately contribute to atherosclerotic disease progression.