bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point-of-care ultrasound for the pediatric regional anesthesiologist and pain specialist: a technique review
Authors: Kars Michelle S , Gomez Morad Andrea , Haskins Stephen C , Boublik Jan , Boretsky Karen 
Published: September 2020

Point-of-care ultrasound (PoCUS) has been well described for adult perioperative patients; however, the literature on children remains limited. Regional anesthesiologists have gained interest in expanding their clinical repertoire of PoCUS from regional anesthesia to increasing numbers of applications. This manuscript reviews and highlights emerging PoCUS applications that may improve the quality and safety of pediatric care.
In infants and children, lung and airway PoCUS can be used to identify esophageal intubation, size airway devices such as endotracheal tubes, and rule in or out a pulmonary etiology for clinical decompensation. Gastric ultrasound can be used to stratify aspiration risk when nil-per-os compliance and gastric emptying are uncertain. Cardiac PoCUS imaging is useful to triage causes of undifferentiated hypotension or tachycardia and to determine reversible causes of cardiac arrest. Cardiac PoCUS can assess for pericardial effusion, gross ventricular systolic function, cardiac volume and filling, and gross valvular pathology. When PoCUS is used, a more rapid institution of problem-specific therapy with improved patient outcomes is demonstrated in the pediatric emergency medicine and critical care literature.
Overall, PoCUS saves time, expedites the differential diagnosis, and helps direct therapy when used in infants and children. PoCUS is low risk and should be readily accessible to pediatric anesthesiologists in the operating room.
Long-term outcomes of brainstem arteriovenous malformations after different management modalities: a single-centre experience
Authors: Chen Yu , Li Ruinan , Ma Li , Meng Xiangyu , Yan Debin , Wang Hao , Ye Xun , Jin Hengwei , Li Youxiang , Gao Dezhi , Sun Shibin , Liu Ali , Wang Shuo , Chen Xiaolin , Zhao Yuanli 
Published: September 2020

ObjectiveThe aims of this study are to clarify the long-term outcomes of brainstem arteriovenous malformations (AVMs) after different management modalities.MethodsThe authors retrospectively reviewed 61 brainstem AVMs in their institution between 2011 and 2017. The rupture risk was represented by annualised haemorrhagic rate. Patients were divided into five groups: conservation, microsurgery, embolisation, stereotactic radiosurgery (SRS) and embolisation+SRS. Neurofunctional outcomes were evaluated by the modified Rankin Scale (mRS). Subgroup analysis was conducted between different management modalities to compare the long-term outcomes in rupture or unruptured cohorts.ResultsAll of 61 brainstem AVMs (12 unruptured and 49 ruptured) were followed up for an average of 4.5 years. The natural annualised rupture risk was 7.3%, and the natural annualised reruptured risk in the ruptured cohort was 8.9%. 13 cases were conservative managed and 48 cases underwent intervention (including 6 microsurgery, 12 embolisation, 21 SRS and 9 embolisation+SRS). In the selection of interventional indication, diffuse nidus were often suggested conservative management (p=0.004) and nidus involving the midbrain were more likely to be recommended for intervention (p=0.034). The risk of subsequent haemorrhage was significantly increased in partial occlusion compared with complete occlusion and conservative management (p<0.001, p=0.036, respectively). In the subgroup analysis, the follow-up mRS scores of different management modalities were similar whether in the rupture cohort (p=0.064) or the unruptured cohort (p=0.391), as well as the haemorrhage-free survival (p=0.145). In the adjusted Bonferroni correction analysis of the ruptured cohort, microsurgery and SRS could significantly improve the obliteration rate compared with conservation (p<0.001, p=0.001, respectively) and SRS may have positive effect on avoiding new-onset neurofunctional deficit compared with microsurgery and embolisation (p=0.003, p=0.003, respectively).ConclusionsIntervention has similar neurofunctional outcomes as conservation in these brainstem AVM cohorts. If intervention is adopted, partial obliteration should be avoided because of the high subsequent rupture risk.Trial registration numberNCT04136860.
Genomic and Epigenomic Landscaping Defines New Therapeutic Targets for Adenosquamous Carcinoma of the Pancreas
Authors: Lenkiewicz Elizabeth , Malasi Smriti , Hogenson Tara L. , Flores Luis F. , Barham Whitney , Phillips William J. , Roesler Alexander S. , Chambers Kendall R. , Rajbhandari Nirakar , Hayashi Akimasa , Antal Corina E. , Downes Michael , Grandgenett Paul M. , Hollingsworth Michael A. , Cridebring Derek , Xiong Yuning , Lee Jeong-Heon , Ye Zhenqing , Yan Huihuang , Hernandez Matthew C. , Leiting Jennifer L. , Evans Ronald M. , Ordog Tamas , Truty Mark J. , Borad Mitesh J. , Reya Tannishtha , Von Hoff Daniel D. , Fernandez-Zapico Martin E. , Barrett Michael T. 
Published: September 2020

Abstract

Adenosquamous cancer of the pancreas (ASCP) is a subtype of pancreatic cancer that has a worse prognosis and greater metastatic potential than the more common pancreatic ductal adenocarcinoma (PDAC) subtype. To distinguish the genomic landscape of ASCP and identify actionable targets for this lethal cancer, we applied DNA content flow cytometry to a series of 15 tumor samples including five patient-derived xenografts (PDX). We interrogated purified sorted tumor fractions from these samples with whole-genome copy-number variant (CNV), whole-exome sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analyses. These identified a variety of somatic genomic lesions targeting chromatin regulators in ASCP genomes that were superimposed on well-characterized genomic lesions including mutations in TP53 (87%) and KRAS (73%), amplification of MYC (47%), and homozygous deletion of CDKN2A (40%) that are common in PDACs. Furthermore, a comparison of ATAC-seq profiles of three ASCP and three PDAC genomes using flow-sorted PDX models identified genes with accessible chromatin unique to the ASCP genomes, including the lysine methyltransferase SMYD2 and the pancreatic cancer stem cell regulator RORC in all three ASCPs, and a FGFR1-ERLIN2 fusion associated with focal CNVs in both genes in a single ASCP. Finally, we demonstrate significant activity of a pan FGFR inhibitor against organoids derived from the FGFR1-ERLIN2 fusion–positive ASCP PDX model. Our results suggest that the genomic and epigenomic landscape of ASCP provide new strategies for targeting this aggressive subtype of pancreatic cancer.

Significance:
These data provide a unique description of the ASCP genomic and epigenomic landscape and identify candidate therapeutic targets for this dismal cancer.
Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib
Authors: Sun Yuting , Meyers Brooke A. , Czako Barbara , Leonard Paul , Mseeh Faika , Harris Angela L. , Wu Qi , Johnson Sarah , Parker Connor A. , Cross Jason B. , Di Francesco Maria Emilia , Bivona Benjamin J. , Bristow Christopher A. , Burke Jason P. , Carrillo Caroline C. , Carroll Christopher L. , Chang Qing , Feng Ningping , Gao Guang , Gera Sonal , Giuliani Virginia , Huang Justin K. , Jiang Yongying , Kang Zhijun , Kovacs Jeffrey J. , Liu Chiu-Yi , Lopez Anastasia M. , Ma Xiaoyan , Mandal Pijus K. , McAfoos Timothy , Miller Meredith A. , Mullinax Robert A. , Peoples Michael , Ramamoorthy Vandhana , Seth Sahil , Spencer Nakia D. , Suzuki Erika , Williams Christopher C. , Yu Simon S. , Zuniga Andy M. , Draetta Giulio F. , Marszalek Joseph R. , Heffernan Timothy P. , Kohl Nancy E. , Jones Philip 
Published: September 2020

Abstract

Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK pathway. SHP2 inhibition has demonstrated tumor growth inhibition in RTK-activated cancers in preclinical studies. The long-term effectiveness of tyrosine kinase inhibitors such as the EGFR inhibitor (EGFRi), osimertinib, in non–small cell lung cancer (NSCLC) is limited by acquired resistance. Multiple clinically identified mechanisms underlie resistance to osimertinib, including mutations in EGFR that preclude drug binding as well as EGFR-independent activation of the MAPK pathway through alternate RTK (RTK-bypass). It has also been noted that frequently a tumor from a single patient harbors more than one resistance mechanism, and the plasticity between multiple resistance mechanisms could restrict the effectiveness of therapies targeting a single node of the oncogenic signaling network. Here, we report the discovery of IACS-13909, a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway. IACS-13909 potently impeded proliferation of tumors harboring a broad spectrum of activated RTKs as the oncogenic driver. In EGFR-mutant osimertinib-resistant NSCLC models with EGFR-dependent and EGFR-independent resistance mechanisms, IACS-13909, administered as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferation in vitro and caused tumor regression in vivo. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFRi-resistant NSCLC.

Significance:
These findings highlight the discovery of IACS-13909 as a potent, selective inhibitor of SHP2 with drug-like properties, and targeting SHP2 may serve as a therapeutic strategy to overcome tumor resistance to osimertinib.
Iron and Cancer: 2020 Vision
Authors: Torti Suzy V. , Torti Frank M. 
Published: September 2020

Abstract
New and provocative insights into the relationships between iron and cancer have been uncovered in recent years. These include delineation of connections that link cellular iron to DNA repair, genomic integrity, and oncogenic signaling as well as the discovery of ferroptosis, a novel iron-dependent form of cell death. In parallel, new molecules and pathways that regulate iron influx, intracellular iron trafficking, and egress in normal cells, and their perturbations in cancer have been discovered. In addition, insights into the unique properties of iron handling in tumor-initiating cells (cancer stem cells), novel contributions of the tumor microenvironment to the uptake and regulation of iron in cancer cells, and new therapeutic modalities that leverage the iron dependence of cancer have emerged.
Genetic Colorectal Cancer and Adenoma Risk Variants Are Associated with Increasing Cumulative Adenoma Counts
Authors: Sullivan Brian A. , Qin Xuejun , Redding Thomas S. , Gellad Ziad F. , Stone Anjanette , Weiss David , Madison Ashton N. , Sims Kellie J. , Williams Christina D. , Lieberman David , Hauser Elizabeth R. , Provenzale Dawn 
Published: September 2020

Abstract

Background:
The genetic basis for most individuals with high cumulative lifetime colonic adenomas is unknown. We investigated associations between known colorectal cancer–risk single-nucleotide polymorphisms (SNP) and increasing cumulative adenoma counts.

Methods:
The Cooperative Studies Program #380 screening colonoscopy cohort includes 612 selected participants age 50 to 75 with genotyped blood samples and 10 years of clinical follow-up. We evaluated 41 published “colorectal cancer–risk SNPs” for associations with individual cumulative adenoma counts or having ≥10 cumulative adenomas. SNPs were analyzed singly or combined in a polygenic risk score (PRS). The PRS was constructed from eight published SNPs associated with multiple adenomas, termed “adenoma-risk SNPs.”

Results:
Four colorectal cancer–risk SNPs were associated with increasing cumulative adenoma counts (P &lt; 0.05): rs12241008 (gene: VTI1A), rs2423279 (BMP2/HAO1), rs3184504 (SH2B3), and rs961253 (FERMT1/BMP2), with risk allele risk ratios of 1.31, 1.29, 1.24, and 1.23, respectively. Three colorectal cancer–risk SNPs were associated with ≥10 cumulative adenomas (P &lt; 0.05), with risk allele odds ratios of 2.09 (rs3184504), 2.30 (rs961253), and 1.94 (rs3217901). A weighted PRS comprised of adenoma-risk SNPs was associated with higher cumulative adenomas (weighted rate ratio = 1.57; P = 0.03).

Conclusions:
In this mostly male veteran colorectal cancer screening cohort, several known colorectal cancer–risk SNPs were associated with increasing cumulative adenoma counts and the finding of ≥10 cumulative adenomas. In addition, an increasing burden of adenoma-risk SNPs, measured by a weighted PRS, was associated with higher cumulative adenomas.

Impact:
Future work will seek to validate these findings in different populations and then augment current colorectal cancer risk prediction tools with precancerous, adenoma genetic data.
Racial and Ethnic Differences in Sarcoma Incidence Are Independent of Census-Tract Socioeconomic Status
Authors: Diessner Brandon J. , Weigel Brenda J. , Murugan Paari , Zhang Lin , Poynter Jenny N. , Spector Logan G. 
Published: September 2020

Abstract

Background:
Epidemiologic analyses of sarcoma are limited by the heterogeneity and rarity of the disease. Utilizing population-based surveillance data enabled us to evaluate the contribution of census tract-level socioeconomic status (CT-SES) and race/ethnicity on sarcoma incidence rates.

Methods:
We utilized the Surveillance, Epidemiology, and End Results program to evaluate associations between CT-SES and race/ethnicity on the incidence rates of sarcoma. Incidence rate ratios and 99% confidence intervals were estimated from quasi-Poisson models. All models were stratified by broad age groups (pediatric: &lt;20 years, adult: 20–65 years, older adult: 65+ years) and adjusted for sex, age, and year of diagnosis. Within each age group, we conducted analyses stratified by somatic genome (fusion-positive and fusion-negative sarcomas) and for subtypes with &gt;200 total cases. A P value less than 0.01 was considered statistically significant.

Results:
We included 55,415 sarcoma cases in 35 sarcoma subtype–age group combinations. Increasing CT-SES was statistically significantly associated with 11 subtype–age group combinations, primarily in the older age group strata (8 subtypes), whereas malignant peripheral nerve sheath tumors in adults were associated with decreasing CT-SES. Nearly every sarcoma subtype–age group combination displayed racial/ethnic disparities in incidence that were independent of CT-SES.

Conclusions:
We found race/ethnicity to be more frequently associated with sarcoma incidence than CT-SES. Our findings suggest that genetic variation associated with ancestry may play a stronger role than area-level SES-related factors in the etiology of sarcoma.

Impact:
These findings provide direction for future etiologic studies of sarcomas.
Predictors of Mortality by Sex and Race in Heart Failure With Preserved Ejection Fraction: ARIC Community Surveillance Study
Authors: Sharma Kavita , Mok Yejin , Kwak Lucia , Agarwal Sunil K. , Chang Patricia P. , Deswal Anita , Shah Amil M. , Kitzman Dalane W. , Wruck Lisa M. , Loehr Laura R. , Heiss Gerardo , Coresh Josef , Rosamond Wayne D. , Solomon Scott D. , Matsushita Kunihiro , Russell Stuart D. 
Published: September 2020

Background
Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all‐cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study.

Methods and Results

Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1‐year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06–1.52 [
P
=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64–0.97 [
P
=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race.

Conclusions
In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex‐ and race‐based differences in predictors of mortality may help strategize targeted management of HFpEF.
Changes in Vestibular Function in Patients With Head-and-Neck Cancer Undergoing Chemoradiation
Authors: Hülse Roland , Stuck Boris A. , Hörmann Karl , Rotter Nicole , Nguyen Julia , Aderhold Christoph , Schell Angela 
Published: September 2020

Introduction: While the cochleotoxicity of cisplatin has been well investigated, less is known about the effects of platinum-based chemotherapy on the vestibular system. In particular, there is a lack of prospective studies using modern laboratory vestibular testing that examine the effects of cisplatin on the semicircular canals and on the otolith organs. The aim of the present study was, therefore, to investigate the vestibulotoxic effect of cisplatin in patients with head and neck tumors who are undergoing chemoradiation. Methods: Forty-five patients undergoing cisplatin-based chemoradiation for head and neck cancer received a vestibular assessment consisting of anamnesis, a horizontal video head impulse test (vHIT), ocular and cervical vestibular evoked myogenic potential testing, as well as pure tone audiometry. This assessment was performed before therapy, 6 weeks after therapy, and 3 months after therapy. Results: Video head impulse test showed a significantly reduced median gain 6 weeks after chemoradiation. In addition, significantly more refixational saccades could be detected after therapy. Vestibular evoked myogenic potential testing results also revealed significant changes, whereas pure tone audiometry did not. None of the patients mentioned “dizziness” during the follow-up examinations. Conclusion: We demonstrated a vestibulotoxic effect of cisplatin-based chemoradiation in patients with head and neck cancer. Future studies are needed to better understand cisplatin-induced vestibulotoxicity and to identify possible vestibuloprotective substances. Still, before and after chemoradiation, patients should undergo not only auditory testing but also vestibular testing in order to detect potential vestibular loss as soon as possible and to quickly initiate vestibular physiotherapy.
Strategies and Controversies in the Treatment With Carbon Dioxide Laser of Laryngeal Hemangioma: A Case Series and Review of the Literature
Authors: Mesolella Massimo , Allosso Salvatore , Mansueto Gelsomina , Fuggi Mariano , Motta Gaetano 
Published: September 2020

Introduction: The hemangioma is the most common vascular tumor, involving the head and neck in 60% of cases. It is rare in the larynx. In children, hemangiomas are more frequent on the subglottis, whereas in adults the most common site is the supraglottis. Laryngeal hemangioma with cavernous features isolated to the free edge of the vocal fold is a very rare clinical finding. We present 2 cases of glottic hemangioma. Both patients reported severe hoarseness. Cases: In the first patient, an extensive blue-purple mass was seen on the right vocal cord. The patient was posted for microlaryngeal surgery with carbon dioxide (CO2) laser. Second patient had a large, smooth, flesh-colored polypoid mass emanating from the left vocal cord. The patient was posted for microlaryngeal surgery. After 2 months, both patients showed a considerable voice improvement. Discussion: Vocal cord hemangiomas are very rare, and they usually cause problem in the voice of the patient. A vascular lesion that may mimic a hemangioma may sometimes result from an organizing hematoma following a hemorrhage on the vocal cords due to voice abuse. Laryngeal hemangiomas also need to be distinguished pathologically from polypoidal vascular granulation tissue that may be produced by laryngeal biopsy, intubation, or trauma. Indirect endoscopy is enough to diagnosis. No active treatment is advised for adult laryngeal hemangiomas unless the lesions are symptomatic or show a tendency to involve other parts. There is no uniformly accepted treatment of head and neck hemangiomas. Surgical excision with laser CO2 microlaryngoscopic techniques gives satisfactory results.
Recurrent Intramuscular Hemangioma (Infiltrating Angiolipoma) of the Lower Lip: A Case Report and Review of the Literature
Authors: DeGiovanni Jason C. , Simmonds Jonathan , Lang-Orsini Melanie , Lee Arnold 
Published: September 2020

Objective: To report a case of a recurrent intramuscular hemangioma (IMH) of the lower lip of a 68-year-old female and review the published literature to provide an overview of the presentation, diagnostic strategy, pathological classification, and management of these lesions within the oral cavity. Methods: A case report was conducted by reviewing the documentation at a single institution. A systematic literature review on OVID MEDLINE and PubMed was performed using the MESH terms “intramuscular hemangioma” and “oral cavity,” “tongue,” “cheek,” “buccal,” “gingiva,” and “lip.” Results: A 62-year-old female presented to our institution with a 2 × 2 × 1 cm IMH of the lower lip involving the surrounding orbicularis oris muscle. She underwent a submucosal resection and did well postoperatively. Six and a half years later, she represented to our institution with a new lower lip lesion in the area of her previous resection. Preoperative magnetic resonance imaging showed a new 10 × 11 mm lesion with a well circumscribed central component surrounded by ill-defined tissue. Preoperative angiography showed that the lesion was supplied by vessels branching off the left facial artery, which were embolized. She underwent wide-local excision (WLE) with bilateral advancement flaps and at her 2-month postoperative visit has not had recurrence. Conclusion: Only 39 cases of IMH in the oral cavity have been reported, with only 3 others occurring in the lower lip. Here we add the first case of an IMH of the oral cavity that recurred after primary WLE. The patient was successfully retreated with WLE. At a 3-month follow-up visit, she noted some incompetence with oral secretions and occasional tingling along the incision site but no evidence of recurrence.