bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity
Authors: Zunhammer Matthias , Schweizer Lauren M. , Witte Vanessa , Harris Richard E. , Bingel Ulrike , Schmidt-Wilcke Tobias
Published: June 2016

The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher–Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations.
Acute Biventricular Interaction in Pediatric Patients Implanted with Continuous Flow and Pulsatile Flow LVAD: A Simulation Study
Authors: Di Molfetta Arianna , Ferrari Gianfranco , Iacobelli Roberta , Fresiello Libera , Pilati Mara , Toscano Alessandra , Filippelli Sergio , Morelli Stefano , Amodeo Antonio
Published: June 2016

Left ventricular assist devices (LVADs) are used to bridge pediatric patients till transplantation. However, the LVADs effects on right ventricular (RV) function are controversial. This work aims at studying the ventricular interdependency in the presence of continuous (c-) and pulsatile (p-) flow LVAD in pediatric patients using a lumped parameter model including the representation of the septum. Five pediatric patients’ data were used to simulate patients’ baseline. The effects on LV and RV functions, energetics, preloads and afterloads of different c-LVAD speeds, p-LVAD rate, p-LVAD systole duration, p-LVAD filling and ejection pressures were simulated. c-LVAD and p-LVAD unload the LV decreasing the LV external work and improving the LV ventriculo-arterial coupling and these effects are more evident increasing the c-LVAD speed and the p-LVAD rate. Continuous-LVAD and p-LVAD decrease the RV afterload, increase the RV ejection fraction and improve the RV ventriculo-arterial coupling. The changes in RV function are inversely proportional to the degree of the interventricular septum leftward shift that increased by increasing the LVAD contribution. The study of the interventricular interaction could lead to the development of a dedicated algorithm to optimize LVAD setting in pediatric population.
Outcomes of Various Treatment Strategies for Patients with Continuous-Flow Ventricular Assist Device Thrombosis: A Retrospective Analysis
Authors: Ertugay Serkan , Engin Cagatay , Daylan Ahmet , Pektok Erman , Ozturk Pelin , Nalbantgil Sanem , Zoghi Mehdi , Yagdi Tahir , Ozbaran Mustafa
Published: June 2016

Pump thrombosis is associated with high morbidity and mortality in patients with a continuous-flow left ventricular assist device. Although it has been defined clearly, the diagnosis and treatment of this complication still remain controversial. Between 2010 and 2014, 163 consecutive patients (mean age: 50.7 ± 13 years, 84% males, median duration of support: 277 (2–1077) days) were implanted a continuous-flow left ventricular assist device. Prospectively collected data of all patients who had at least one pump thrombosis event have been analyzed, retrospectively. Twenty-one pump thrombosis events were observed in 15 patients (9.2%, 0.137 events/patient-year). Median duration of support at the time of first pump thrombosis event was 259 (8–585) days. Overall mortality was 40% (6/15), and overall procedural success was 71.4% (15/21) in our entire cohort. The cause of mortality was hemorrhagic stroke in those who had medical treatment (n = 5), and sepsis and right ventricular failure in the other who had pump exchange. Pump exchange was performed in five patients, of which four survived. Glycoprotein IIb/IIIa antagonists are not beneficial in medical treatment of pump thrombosis. Medical treatment methods including unfractionated heparin and thrombolytics may completely resolve the thrombus and save some patients from pump exchange. In patients where medical treatment does not result in complete thrombus resolution within a reasonable period, and a donor heart is not available, pump exchange is the ultimate solution. Further studies are needed for optimal dosing of thrombolytics to decrease the rate of side effects.
Intravenous lipid emulsions in the critically ill: an update
Authors: Manzanares William , Langlois Pascal L. , Hardy Gil
Published: June 2016

Purpose of review

Purpose of the review is to summarize recent research addressing the role of intravenous lipid emulsions (IVLEs) in the critically ill.

Recent findings

Soybean oil-based IVLEs, which are high in the omega-6 polyunsaturated fatty acids, have been largely used in parenteral nutrition over the last several decades. However, it is now generally accepted that the higher content of phytosterols and polyunsaturated fatty acids in soybean oil IVLE may adversely affect the immunological and inflammatory status of the critically ill. In the last few years, alternative IVLEs with lower soybean oil content have been associated with important improvements in clinical outcomes, such as mortality, mechanical ventilation days, and ICU length of stay. Olive oil and fish oil IVLEs have been reported to reduce the incidence of infections, with no clear benefits in other clinical outcomes. Despite the promising results with these new parenteral nutrition strategies, the optimum composition, dosage and indication for alternative IVLEs still remain controversial. Nevertheless, according to current knowledge alternative IVLEs may be associated with improved clinical outcomes and should be considered in critically ill patients requiring parenteral nutrition.

There is a growing body of evidence suggesting that improved clinical outcomes can be achieved with selective use of alternative IVLEs in parenteral nutrition regimens for the critically ill. More high quality trials are needed, to better evaluate the efficacy of alternative IVLEs.
Update on perioperative acute kidney injury
Authors: Goren Or , Matot Idit
Published: June 2016

Purpose of review

In this review, we discuss the latest updates on perioperative acute kidney injury (AKI) and the specific considerations that are relevant to different surgeries and patient populations.

Recent findings

AKI diagnosis is constantly evolving. New biomarkers detect AKI early and shed a light on the possible cause of AKI. Hypotension, even for a short duration, is associated with perioperative AKI. The debate on the deleterious effects of chloride-rich solutions is still far from conclusion. Remote ischemic preconditioning is showing promising results in the possible prevention of perioperative AKI. No definite data show a beneficiary effect of statins, fenoldepam, or sodium bicarbonate in preventing AKI.

Perioperative AKI is prevalent and associated with significant morbidity and mortality. Considering the lack of effective preventive or therapeutic interventions, this review focuses on perioperative AKI: measures for early diagnosis, defining risks and possible mechanisms, and summarizing current knowledge for intraoperative fluid and hemodynamic management to reduce risk of AKI.
Deficiency in Mucosa‐associated Lymphoid Tissue Lymphoma Translocation 1
Authors: Charbit‐Henrion Fabienne , Jeverica Anja K. , Bègue Bernadette , Markelj Gasper , Parlato Marianna , Avčin Simona Lucija , Callebaut Isabelle , Bras Marc , Parisot Mélanie , Jazbec Janez , Homan Matjaz , Ihan Alojz , Rieux‐Laucat Frédéric , Stolzenberg Marie‐Claude ,   GENIUS Group, Ruemmele Frank M. , Avčin Tadej , Cerf‐Bensussan Nadine
Published: June 2016

Objective:

Early‐onset inflammatory bowel diseases can result from a wide spectrum of rare mendelian disorders. Early molecular diagnosis is crucial in defining treatment and in improving life expectancy. Herein we aimed at defining the mechanism of an immunodeficiency‐polyendrocrinopathy and enteropathy‐X‐linked (IPEX)–like disease combined with a severe immunodeficiency in 2 siblings born from distantly related parents.

Methods:

Whole exome sequencing was performed on blood‐extracted genomic DNA from the 2 affected children and their parents on the genomic platform of Institut IMAGINE. Candidate gene mutation was identified using the in‐house software PolyWeb and confirmed by Sanger sequencing. Protein expression was determined by western blot. Flow cytometry was used to assess consequences of the mutation on lymphocyte phenotype and nuclear factor‐kappa B (NF‐κB) activation at diagnosis and after treatment by hematopoietic stem cell transplantation.

Results:

We identified a homozygous missense mutation in mucosa‐associated lymphoid tissue lymphoma translocation 1 gene (MALT1), which precluded protein expression. In keeping with the known function of MALT1, NF‐κB–dependent lymphocyte activation was severely impaired. Moreover, there was a drastic reduction in Forkhead box P3 (FOXP3) regulatory T cells accounting for the IPEX‐like phenotype. Following identification of the mutation, both children received hematopoietic stem cell transplantation, which permitted full clinical recovery. Immunological workup at 6 and 12 months after transplantation showed normal NF‐κB activation and correction of regulatory T cells frequency.

Conclusions:

Along with FOXP3, interleukin 2 receptor alpha chain (IL2RA), and cytotoxic T‐lymphocyte protein 4 precursor (CTLA‐4) mutations, MALT1 deficiency should now be considered as a possible cause of IPEX‐like syndrome associated with immunodeficiency that can be cured by hematopoietic stem cell transplantation.
A Quality Improvement Initiative to Improve Patient Adherence to Vitamin Supplementation in Cystic Fibrosis
Authors: Garavaglia Lisa , Duncan Christina , Toucheque Malorie , Farley Allilene , Moffett Kathryn S.
Published: June 2016

Objectives:

Patients with cystic fibrosis (CF) and pancreatic insufficiency are prescribed fat‐soluble vitamins, although compliance remains low. Our objective was to identify patient and caregiver knowledge deficits regarding vitamin supplementation, provide targeted education, and examine serum vitamin levels pre‐and posteducation.

Methods:

This prospective quality improvement study involved 118 patients. A vitamin knowledge survey was given to patients/caregivers during a clinic visit, education was provided targeting knowledge deficits, and the survey was re‐administered at the next clinic visit. Serum vitamin levels were collected at pre‐ and postsurvey.

Results:

Results showed significant pre‐post increases for patient and caregiver knowledge scores, and significant decreases in self‐reported nonadherence to vitamin use and number of reported barriers affecting adherence. A significant change in vitamin E level to therapeutic range post‐education was demonstrated.

Conclusions:

Our brief, targeted educational interventions regarding vitamin supplementation showed utility in a routine clinic setting.
A New Formulation of Oral Viscous Budesonide in Treating Paediatric Eosinophilic Oesophagitis
Authors: Oliva Salvatore , Rossetti Danilo , Papoff Paola , Tiberti Antonio , Rossi Paolo , Isoldi Sara , Amil Dias Jorge , Lucarelli Sandra , Cucchiara Salvatore
Published: June 2016

Objectives:

Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single‐centre, open‐label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE.

Methods:

We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post‐treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks.

Results:

At the end of PVB trial, endoscopy showed macroscopic remission in 32 patients (88.9%), whereas at histology median pre‐ and post‐treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15–100) to 2.9 (range: 0–30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance‐pH were treated also with proton pump inhibitors. No significant difference between pre‐/post‐treatment morning cortisol levels occurred.

Conclusions:

The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo‐controlled clinical trials would provide more information about dosing, efficacy, and long‐term safety of this formulation, specifically designed for the oesophagus.
Improving Management of Behavioral and Psychological Symptoms of Dementia in Acute Care
Authors: McConnell Eleanor S. , Karel Michele J.
Published: June 2016

As the prevalence of Alzheimer disease and related dementias increases, dementia-related behavioral symptoms present growing threats to care quality and safety of older adults across care settings. Behavioral and psychological symptoms of dementia (BPSD) such as agitation, aggression, and resistance to care occur in nearly all individuals over the course of their illness. In inpatient care settings, if not appropriately treated, BPSD can result in care complications, increased length of stay, dissatisfaction with care, and caregiver stress and injury. Although evidence-based, nonpharmacological approaches to treating BPSD exist, their implementation into acute care has been thwarted by limited nursing staff expertise in behavioral health, and a lack of consistent approaches to integrate behavioral health expertise into medically focused inpatient care settings. This article describes the core components of one evidence-based approach to integrating behavioral health expertise into dementia care. This approach, called STAR-VA, was implemented in Veterans' Health Administration community living centers (nursing homes). It has demonstrated effectiveness in reducing the severity and frequency of BPSD, while improving staff knowledge and skills in caring for people with dementia. The potential for adapting this approach in acute care settings is discussed, along with key lessons learned regarding opportunities for nursing leadership to ensure consistent implementation and sustainability.
Experience of Psychiatric Mental Health Nurse Practitioners in Public Mental Health
Authors: Phoenix Bethany J. , Hurd Manton , Chapman Susan A.
Published: June 2016

Expansion of health insurance coverage under the Accountable Care Act has meant that millions of people are now insured for mental health treatment, but with no significant increase in the mental health workforce. Services of psychiatric mental health nurse practitioners (PMHNPs) may be best utilized to improve access to and quality of public mental health services if the financial, political, scope of practice, and treatment model barriers that limit their ability or willingness to practice in these settings are better understood. This article reports qualitative results from a study that assessed barriers and best practices in the use of PMHNPs in county mental health services in California. Results indicate that PMHNPs are valued for their “whole person” perspective, collaborative approach, and interpersonal communication skills, but that significant knowledge gaps, regulatory constraints, and bureaucratic barriers in public mental health systems inhibit PMHNPs from practicing at the top of their scope.
Psychometric Properties of the Kessler 10 Scale in Chinese Parents of Children With Cancer
Authors: Bu Xiu-qing , You Li-ming , Li Yong , Liu Ke , Zheng Jing , Yan Tie-bin , Chen Shao-xian , Zhang Li-feng
Published: June 2016

Background:

The Kessler Psychological Distress Scale (K10) has been widely used in rating psychological distress in general and clinical populations. However, whether it can be used in parents of children with cancer is unknown. Still lacking is the evidence on its reliability and validity in culturally diverse groups.

Objective:

The aim of this study was to translate the K10 into Mandarin Chinese and test its psychometric properties (especially the factor structure) of the Chinese version (C-K10) in parents of children with cancer.

Methods:

By convenience sampling, 2 samples of parents of children with cancer (sample I, n = 206, and sample II, n = 103) were surveyed in Guangzhou, China. Sample I completed the C-K10, and the internal consistency reliability and exploratory factor analysis of the C-K10 were estimated. Sample II completed the C-K10, the State Subscale of State-Trait Anxiety Inventory, and the Zung Self-rating Depression Scale; confirmatory factor analysis and concurrent validity estimates were completed.

Results:

The C-K10 demonstrated strong internal consistency reliability (Cronbach’sα= .93). Both exploratory and confirmatory factor analyses supported a 2-factor structure (ie, anxiety and depression). The concurrent validity was moderate with Pearson correlations greater than 0.50 (P< .001).

Conclusion:

The C-K10 demonstrated very acceptable reliability and validity in screening psychological distress in Chinese parents of children with cancer.

Implications for Practice:

This study provides evidence that the C-K10 is a valid tool that can be used in clinical settings to screen for psychological distress in Chinese parents of children with cancer.
Magnesium Deficiency
Authors: Hruby Adela , McKeown Nicola M.
Published: June 2016

Low magnesium intake has been implicated in a broad range of cardiometabolic conditions, including diabetes, hypertension, and cardiovascular disease. Dietary magnesium and total body magnesium status are widely used but imperfect biomarkers in serum magnesium. Despite serum magnesium’s limitations, it is nevertheless observed to be lower in those with cardiometabolic disease than in generally healthy people. Although some 50% of Americans do not meet recommended levels of magnesium intake, the extent of prevalent magnesium deficiency is unknown. Given magnesium’s role in a multitude of chronic conditions that are increasingly common across the globe, here, we summarize recently published literature reporting prevalent hypomagnesaemia in generally representative populations and in populations with type 2 diabetes mellitus, metabolic syndrome, and obesity. On the basis of these studies, we estimate that up to a third of the general population may be magnesium deficient and that outside of acute clinical encounters or hospitalization, hypomagnesaemia is likely frequently overlooked in general clinical practice.
The Latest Dietary Guidelines Spat
Authors: Rowe Sylvia B. , Alexander Nick
Published: June 2016

With the release of the eighth Dietary Guidelines for Americans, nutrition communicators may feel overwhelmed by the growing complexity, both in terms of dietary science and politics. In this article, the guidelines and the evolving communication challenges are reviewed, along with obstacles to public understanding of the government’s dietary advice and the sometimes-unacknowledged communication successes. Observers’ critiques of the policy document emanating from the scientific report are discussed, The article explores some of the unintended consequences encountered in trying to communicate evolving dietary science and evolving dietary guidance. Finally, some bottom-line, simple suggestions are offered for communicating in an environment of increasingly complex political, environmental, and scientific circumstances.
Microbial Contamination of Contact Lens Storage Cases During Daily Wear Use
Authors: Dantam Jaya , McCanna David Joseph , Subbaraman Lakshman N. , Papinski Dominik , Lakkis Carol , Mirza Aftab , Berntsen David A. , Morgan Philip , Nichols Jason J. , Jones Lyndon W.
Published: June 2016

Purpose

To evaluate contact lens (CL) storage case contamination when used with four different CL care solutions during daily wear of three different CL materials.

Methods

A parallel, prospective, bilateral, randomized clinical trial (n = 38) was conducted. Subjects were randomly assigned to use one of three CL materials (etafilcon A, senofilcon A, or galyfilcon A) on a daily wear basis. Subsequently, each subject randomly used one of four different CL care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and CLEAR CARE) for 2 weeks, along with their respective storage cases. After every 2-week period, their storage cases were collected and the right and left wells of each storage case were randomized for two procedures: (1) microbial enumeration by swabbing the storage case surface and (2) evaluation of biofilm formation (multipurpose solution cases only) using a crystal violet staining assay.

Results

More than 80% of storage cases were contaminated when used in conjunction with the four CL care solutions, irrespective of the CL material worn. Storage cases maintained with CLEAR CARE (mean Log colony forming units (CFU)/well ± SD, 2.0 ± 1.0) revealed significantly (p < 0.001) greater levels of contamination, compared to those maintained with Biotrue (1.3 ± 0.8) and RevitaLens OcuTec (1.2 ± 0.8). Predominantly, storage cases were contaminated with Gram-positive bacteria (≥80%). There were significant differences (p = 0.013) for the levels of Gram-negative bacteria recovered from the storage cases maintained with different CL care solutions. Storage cases maintained with OPTI-FREE PureMoist (0.526 ± 0.629) showed significantly higher biofilm formation (p = 0.028) compared to those maintained with Biotrue (0.263 ± 0.197).

Conclusions

Levels of contamination ranged from 0 to 6.4 Log CFU/storage case well, which varied significantly (p < 0.001) between different CL care solutions, and storage case contamination was not modulated by CL materials.
Developing a Very Low Vision Orientation and Mobility Test Battery (O&M-VLV)
Authors: Finger Robert P. , Ayton Lauren N. , Deverell Lil , O’Hare Fleur , McSweeney Shane C. , Luu Chi D. , Fenwick Eva K. , Keeffe Jill E. , Guymer Robyn H. , Bentley Sharon A.
Published: June 2016

Purpose

This study aimed to determine the feasibility of an assessment of vision-related orientation and mobility (O&M) tasks in persons with severe vision loss. These tasks may be used for future low vision rehabilitation clinical assessments or as outcome measures in vision restoration trials.

Methods

Forty legally blind persons (mean visual acuity logMAR 2.3, or hand movements) with advanced retinitis pigmentosa participated in the Orientation & Mobility—Very Low Vision (O&M-VLV) subtests from the Low Vision Assessment of Daily Activities (LoVADA) protocol. Four categories of tasks were evaluated: route travel in three indoor hospital environments, a room orientation task (the “cafe”), a visual exploration task (the “gallery”), and a modified version of the Timed Up and Go (TUG) test, which assesses re-orientation and route travel. Spatial cognition was assessed using the Stuart Tactile Maps test. Visual acuity and visual fields were measured.

Results

A generalized linear regression model showed that a number of measures in the O&M-VLV tasks were related to residual visual function. The percentage of preferred walking speed without an aid on three travel routes was associated with visual field (p < 0.01 for all routes) whereas the number of contacts with obstacles during route travel was associated with acuity (p = 0.001). TUG-LV task time was associated with acuity (p = 0.003), as was the cafe time and distance traveled (p = 0.006 and p < 0.001, respectively). The gallery score was the only measure that was significantly associated with both residual acuity and fields (p < 0.001 and p = 0.001, respectively).

Conclusions

The O&M-VLV was designed to capture key elements of O&M performance in persons with severe vision loss, which is a population not often studied previously. Performance on these tasks was associated with both binocular visual acuity and visual field. This new protocol includes assessments of orientation, which may be of benefit in vision restoration clinical trials.
Small Bowel Adenocarcinoma Frequently Exhibits Lynch Syndrome–associated Mismatch Repair Protein Deficiency But Does Not Harbor Sporadic MLH1 Deficiency
Authors: Xia Michelle , Singhi Aatur D. , Dudley Beth , Brand Randall , Nikiforova Marina , Pai Reetesh K.
Published: June 2016

Universal screening for Lynch syndrome has been advocated for colorectal carcinoma but its utility in small bowel adenocarcinoma has not been reported. We analyzed a consecutive series of 71 small bowel adenocarcinomas identified over an 8-year period for DNA mismatch repair (MMR) protein expression to (1) compare the clinicopathologic features of small bowel adenocarcinoma stratified into MMR-deficient (MMRD) and MMR-proficient (MMRP) groups and (2) examine the patterns of MMR protein expression in small bowel adenocarcinoma compared with colorectal carcinoma. Six of 71 (8.5%) small bowel adenocarcinomas and 149 of 1291 (11.5%) colorectal carcinomas demonstrated MMRD. The 6 MMRD small bowel adenocarcinomas had the following expression pattern: 3 with concurrent loss of MSH2 and MSH6, 1 with isolated loss of MSH6, and 2 with concurrent loss of MLH1 and PMS2 in patients with a family history suggestive of genetic cancer susceptibility. Histopathology suggestive of MMR protein deficiency as proposed by the revised Bethesda guidelines was commonly seen in both MMRP (63%) and MMRD (67%) small bowel adenocarcinomas (P>0.05). MMRD small bowel adenocarcinoma more frequently demonstrated abnormalities of MSH2 and/or MSH6 (4/6, 67%) compared with MMRD colorectal carcinoma (23/149, 15%) (P=0.01). None of the MMRD small bowel adenocarcinomas harbored the BRAF V600E mutation, whereas 60% of MMRD colorectal carcinomas were positive for BRAF V600E with concurrent loss of MLH1 and PMS2 expression. Small bowel adenocarcinoma more frequently harbored Lynch syndrome–associated MMRD compared with colorectal carcinoma, providing support for screening of small bowel adenocarcinoma to identify patients at risk for Lynch syndrome. In contrast to colorectal carcinoma, sporadic MLH1 deficiency is not seen in small bowel adenocarcinoma. Clinicopathologic and histologic features do not distinguish between MMRP and MMRD small bowel adenocarcinoma indicating that universal screening in small bowel adenocarcinoma is necessary to detect patients at risk for Lynch syndrome.
pSTAT3/pSTAT5 Signaling Patterns in Molecularly Defined Subsets of Myeloproliferative Neoplasms
Authors: Sakr Hany , Clark Schneider Kelli , Murugesan Gurunathan , Bodo Juraj , Hsi Eric D. , Cook James R.
Published: June 2016

BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by recurrent mutations in JAK2, CALR, and MPL, each of which has been reported to alter JAK/STAT signaling pathways. This report characterizes JAK/STAT signaling patterns in molecularly defined subsets of MPN utilizing immunohistochemistry for pSTAT3 and pSTAT5. Analysis of 30 BCR/ABL1-negative, nonpolycythemia vera MPN identified 15 (50%) with JAK2 V617F, 2 with MPL mutations (7%), and 8 with CALR mutations (27%). All mutations were mutually exclusive, except for 1 case with concurrent JAK2 V617F and CALR mutations. pSTAT3 staining in megakaryocyte nuclei was found in 4 cases (13%) and was not significantly associated with mutation status. pSTAT5 staining in megakaryocyte nuclei was found in 16 cases (53%), as was significantly associated with JAK2 V617F versus CALR mutation (P=0.009). Erythroid staining for pSTAT5 was seen exclusively in “triple-negative (TN)” cases lacking JAK2 V617F, MPL, and CALR mutations (P=0.006, TN vs. other genotypes), and pSTAT5 staining in megakaryocyte nuclei was seen in 2 TN cases. pSTAT5 staining in TN MPN suggests that other unknown abnormalities in this pathway may contribute to the pathogenesis of these cases. Furthermore, the demonstration of distinct STAT staining patterns in molecularly defined MPN suggests that these mutations result in divergent signaling events that may contribute to the biological and prognostic differences in these molecular subsets of MPN.
Distinct Clinicopathologic and Genetic Features of 2 Histologic Subtypes of Intrahepatic Cholangiocarcinoma
Authors: Hayashi Akimasa , Misumi Kento , Shibahara Junji , Arita Junichi , Sakamoto Yoshihiro , Hasegawa Kiyoshi , Kokudo Norihiro , Fukayama Masashi
Published: June 2016

Previous studies have identified 2 clinically significant morphologic subtypes of intrahepatic cholangiocarcinoma (ICC) on the basis of anatomic location and/or histologic appearances. Recognizing that these classification schemes are not always applicable practically, this study aimed to establish a novel classification system based on mucin productivity and immunophenotype and to determine the rationale of this classification by examining the clinicopathologic and genetic characteristics of the 2 subtypes defined by this method. We retrospectively investigated 102 consecutive ICC cases and classified them on the basis of mucin productivity and immunophenotype (S100P, N-cadherin, and NCAM). We found that 42 and 56 cases were classified as type 1 and type 2 ICCs, respectively, and only 4 cases were of indeterminate type. Type 1 ICC, generally characterized by mucin production and diffuse immunoreactivity to S100P, arose less frequently in chronic liver diseases and showed higher levels of serum CEA and CA 19-9 than did type 2 ICC, which generally showed little mucin production and exhibited immunoreactivity to N-cadherin and/or NCAM. Type 1 ICC was characterized by several pathologic features, including higher frequencies of perineural invasion and lymph node metastasis. Although the log-rank test demonstrated that type 1 ICC had significantly worse survival, the multivariate Cox regression analysis showed no prognostic significance of this histologic subtype. Genetic analyses revealed that KRAS mutation was significantly more frequent in type 1 ICC, whereas IDH mutation and FGFR2 translocation were restricted to type 2 ICC. In conclusion, the present classification of ICC based on mucin productivity and immunophenotype identified 2 subtypes with clinicopathologic significance.
Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor–Positive Subset of Triple-Negative Breast Cancers
Authors: Mills Anne M. , E. Gottlieb Chelsea , M. Wendroth Scott , M. Brenin Christiana , Atkins Kristen A.
Published: June 2016

Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonapocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for apocrine breast carcinoma. All pure apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for apocrine carcinomas and 56.7 years for NA-TNC. All apocrine carcinomas and no NA-TNC were AR positive. The proportions of apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired.
Pathologic Response of HER2-positive Gastric Cancer to Trastuzumab-based Chemotherapy
Authors: Urabe Masayuki , Ushiku Tetsuo , Seto Yasuyuki , Fukayama Masashi
Published: June 2016

Trastuzumab-based chemotherapy is now a standard approach for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. However, histopathologic changes after treatment have yet to be elucidated. This study aims to characterize the histologic response of gastric cancer to trastuzumab treatment and its correlation with HER2 status. Twenty-one advanced HER2-positive gastric cancers treated with trastuzumab-based chemotherapy, including 10 surgically resected specimens and 11 biopsy samples from patients with inoperable tumors, were evaluated for the histologic responses and HER2 status of residual cells. We also reviewed, as controls, 10 cases undergoing surgical resection of tumors after chemotherapy without trastuzumab. Complete and partial histologic responses were obtained in 2 and 8 of the surgical cases, respectively. HER2-positive neoplastic cells were recognized at least focally in the 8 cases. Notably, the proportion of HER2-positive cells was always higher in superficial (mucosal/submucosal) layers than in deeper layers. Three specimens contained HER2-positive neoplastic cells exclusively in the superficial area or intravascular space, whereas deeply invasive or metastatic components almost completely disappeared or were HER2 negative when still present. In contrast, HER2-negative cells or residual tumor cells in control cases tended to survive as well or better in deeply invasive areas or in metastases than in superficial areas. Biopsy samples from nonoperative patients remained HER2 positive after treatment in 8 of 11 patients. Our observations suggest that HER2-positive neoplastic cells tend to survive within superficial areas or intravascular spaces after trastuzumab therapy, even when deeply invasive or metastatic lesions responded well to therapy.
ETV6-NTRK3 Is Expressed in a Subset of ALK-Negative Inflammatory Myofibroblastic Tumors
Authors: Alassiri Ali H. , Ali Rola H. , Shen Yaoqing , Lum Amy , Strahlendorf Caron , Deyell Rebecca , Rassekh Rod , Sorensen Poul H. , Laskin Janessa , Marra Marco , Yip Stephen , Lee Cheng-Han , Ng Tony L.
Published: June 2016

Inflammatory myofibroblastic tumor (IMT) is a genetically heterogenous tumor of the viscera and soft tissues, with multiple molecular features having been demonstrated in this tumor type. About 50% of cases harbor an anaplastic lymphoma kinase (ALK) gene rearrangement, and recent studies have described novel fusions involving the ROS1 and PDGFRβ genes in a subset of ALK-negative cases. However, the molecular features of the remaining subset of cases are not yet defined. We report a case of a large, highly aggressive IMT of the lung in a 17-year-old girl. This case was molecularly characterized through whole-genome and transcriptome sequencing. Subsequently, we investigated a cohort of 15 ALK-negative IMTs of various anatomic sites. All cases were screened using fluorescence in situ hybridization (FISH) for rearrangement of the ETV6 locus and with reverse transcription polymerase chain reaction (RT-PCR) for the ETV6-NTRK3 fusion transcript. Whole-genome and transcriptome sequencing revealed an ETV6-NTRK3 fusion transcript in our index case. This was confirmed by FISH studies for ETV6 gene rearrangement, as well as by RT-PCR. In addition, 2 additional cases in our cohort demonstrated ETV6 rearrangement by FISH. The presence of ETV6-NTRK3 fusion transcript was demonstrated by RT-PCR in one of these additional cases. In summary, we demonstrate the expression of the ETV6-NTRK3 fusion oncogene in a small subset of IMTs, lending further support to the role of oncogenic tyrosine kinases in the pathophysiology of this tumor type. Our data also further expand the growing spectrum of tumor types expressing the ETV6-NTRK3 fusion.
Symptom-Guided Emergency Department Discharge Instructions for Children With Concussion
Authors: Brooks Talia M. , Smith Marissa M. , Silvis Renee M. , Lerer Trudy , Mulvey Christine Henry , Maitland Ralynne , Dunn Amy L. , Logan Kelsey , Smith Sharon R.
Published: June 2016

Objectives

The objective was to evaluate the use and utility of a novel set of emergency department discharge instructions (DIs) for concussion based on a child's ongoing symptoms: symptom-guided DIs (symptom DIs). Differences in clinical outcomes were also assessed.

Methods

A convenience sample of 114 children aged 7 to 17 years presenting to an urban pediatric emergency department with a complaint of concussion was assembled. Children were randomized to standard DIs or symptom DIs. Children completed a graded symptom checklist (GSC) and completed daily the GSC for 1 week. Telephone follow-up was performed at 7 days after enrollment using a standardized survey.

Results

Fifty-eight children received the symptom DIs, and 56 received the standard DIs. Rates of use were similar with reported rates of 92% for symptom DIs and 84% for standard DIs. Caregivers with symptom DIs reported that the DIs were more helpful in determining when their child could return to school and physical activity (P < 0.05) than caregivers with standard DIs. Children continued to have postconcussive symptoms days and weeks after their injury with 44% of children with symptom DIs and 51% of children with standard DIs reporting symptoms on the GSC at 1 week.

Conclusions

Both study groups reported frequent use of the DIs. Caregivers with symptom DIs found them particularly helpful in determining when their child could return to school and physical activity. Larger-scale investigations are needed to further develop instructions that are easy to use and that may decrease the postconcussive period.
Treatment of Severe Hypervolemic Hyponatremia in a Child With Pneumonia
Authors: Genoni Teresa , Tenconi Rossana , Bertolozzi Giuseppe , Laicini Emanuela Anna , Tardini Giacomo , Vianello Federica , Leva Ernesto , Milani Gregorio Paolo , Fossali Emilio Filippo
Published: June 2016

A 21-month-old boy came to our attention because of pneumonia. His weight increased before presentation, and his blood test results showed hyponatremia (116 mEq/L), low plasma osmolarity (241 mOsm/L), and high urine osmolarity (435 mOsm/L). He was treated with 0.9% sodium chloride solution and intravenous furosemide, and sodium levels rose up to 135 mEq/L in 36 hours. No standard treatment is available for severe hyponatremia in children. The use of vaptans in pediatric patients is described in literature, but it lacks evidence about safety and effectiveness. We suggest that furosemide administration plus salt replacement is effective in restoring normal values of plasma sodium concentration in severe euvolemic and hypervolemic hyponatremia.
Essentials of PEM Fellowship Part 2: The Profession in Entrustable Professional Activities
Authors: Hsu Deborah , Nypaver Michele , Fein Daniel M. , McAneney Constance , Santen Sally , Nagler Joshua , Zuckerbraun Noel , Roskind Cindy Ganis , Reynolds Stacy , Zaveri Pavan , Stankovic Curt , House Joseph B. , Langhan Melissa , Titus M. Olivia , Dahl-Grove Deanna , Klasner Ann E. , Ramirez Jose , Chang Todd , Jacobs Elizabeth , Chapman Jennifer , Lumba-Brown Angela , Thompson Tonya , Mittiga Matthew , Eldridge Charles , Heffner Viday , Herman Bruce E. , Kennedy Christopher , Madhok Manu , Kou Maybelle
Published: June 2016

This article is the second in a 7-part series that aims to comprehensively describe the current state and future directions of pediatric emergency medicine (PEM) fellowship training from the essential requirements to considerations for successfully administering and managing a program to the careers that may be anticipated upon program completion. This article describes the development of PEM entrustable professional activities (EPAs) and the relationship of these EPAs with existing taxonomies of assessment and learning within PEM fellowship. It summarizes the field in concepts that can be taught and assessed, packaging the PEM subspecialty into EPAs.
Critical Review: When the Party is Over: A Systematic Review of Behavioral Interventions for Substance-Using Men Who Have Sex with Men
Authors: Carrico Adam W. , Zepf Roland , Meanley Steven , Batchelder Abigail , Stall Ronald
Published: June 2016

Because problematic patterns of alcohol and other substance use are prevalent drivers of the HIV/AIDS epidemic, comprehensive interventions are needed for substance-using men who have sex with men (SUMSM). We conducted a systematic review of 12 randomized controlled trials (RCTs) of behavioral interventions for reducing condomless anal intercourse (CAI) in SUMSM. Three RCTs observed that cognitive behavioral or motivational interviewing interventions achieved a 24% to 40% decrease in CAI. Interventions also tended to demonstrate greater efficacy for reducing CAI and substance use among those who had lower severity of substance use disorder symptoms. Although behavioral interventions for SUMSM are one potentially important component of biobehavioral HIV/AIDS prevention, further research is needed to examine whether integrative approaches that cultivate resilience and target co-occurring syndemic conditions demonstrate greater efficacy. Multilevel intervention approaches are also needed to optimize the effectiveness of pre-exposure prophylaxis and HIV treatment as prevention with SUMSM.
Infections associated with the use of eculizumab: recommendations for prevention and prophylaxis
Authors: Benamu Esther , Montoya José G.
Published: June 2016

Purpose of review

Eculizumab inhibits complement effector functions and has significantly impacted the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. However, the risks of potentially life-threatening infections, notably with Neisseria spp. in addition to its cost, are major challenges in clinical practice. In this review, we characterize and summarize the infectious complications reported with the use of eculizumab in the context of its typical and expanding indications.

Recent findings

Use of eculizumab is rapidly extending to the fields of transplantation and neurology. Eculizumab has been primarily associated with an increased risk of meningococcal infections. Immunization against its commonest serotypes (ABCWY) is now possible with the advent of the meningococcal B vaccine. A combined ABCWY vaccine is underway. Preventive strategies against breakthrough Neisseria infections should also include chemoprophylaxis. Less is known about the association of eculizumab with other infections as recently reported. Surrogate markers of complement blockade, notably CH50, and eculizumab efficacy may help in the risk assessment of infection.

Eculizumab has opened new horizons in the treatment of complement-mediated disorders. Prophylactic and immunization strategies against the risk of Nesseria spp. infections are sound and feasible. The use of eculizumab is expanding beyond complement-mediated diseases to transplantation and neurological disorders. Further research is needed to better define and stratify the risk of infection and prevention strategies in patients with the latter indications.
Personal protective equipment and improving compliance among healthcare workers in high-risk settings
Authors: Honda Hitoshi , Iwata Kentaro
Published: June 2016

Purpose of review

Personal protective equipment (PPE) protects healthcare workers (HCWs) from infection by highly virulent pathogens via exposure to body fluids and respiratory droplets. Given the recent outbreaks of contagious infectious diseases worldwide, including Ebola virus and Middle Eastern respiratory syndrome, there is urgent need for further research to determine optimal PPE use in high-risk settings. This review intends to provide a general understanding of PPE and to provide guidelines for appropriate use based on current evidence.

Recent findings

Although previous studies have focused on the efficacy of PPE in preventing transmission of pathogens, recent studies have examined the dangers to HCWs during removal of PPE when risk of contamination is highest. Access to adequate PPE supplies is crucial to preventing transmission of pathogens, especially in resource-limited settings. Adherence to appropriate PPE use is a challenge due to inadequate education on its usage, technical difficulties, and tolerability of PPE in the workplace. Future projects aim at ameliorating this situation, including redesigning PPE which is crucial to improving the safety of HCWs.

PPE remains the most important strategy for protecting HCW from potentially fatal pathogens. Further research into optimal PPE design and use to improve the safety of HCWs is urgently needed.
Stigma in Cirrhotic Patients
Authors: Shabanloei Reza , Ebrahimi Hossein , Ahmadi Fazlollah , Mohammadi Eesa , Dolatkhah Roya
Published: June 2016

Stigma is one of the main problems of patients suffering from cirrhosis, and it causes many challenges for the patients and their treatment. The present study aimed to discover and define the perceived stigma by cirrhotic patients. This qualitative study was conducted through a content analysis approach. The participants were 15 patients suffering from cirrhosis. Data were collected via semistructured, in-depth interviews and analyzed on the basis of methods described by Granheme and Landman. During data analysis, stigma was categorized into four categories and 13 subcategories: external representation of social stigma (others' avoidance behaviors, inadmissible tag, discriminative behaviors of treatment personnel, blaming behaviors), internal representation of social stigma (social ostracism, social isolation, curiosity to perceive people's perceptions), external representation of self-stigma (fear of disclosure of illness, threatening situation, difficult emotional relationships), and internal representation of self-stigma (condemned to suffer, self-punishment, self-alienation). Experiencing stigma is common among cirrhotic patients and may affect patients' coping with the illness and treatment. Thus, it is specifically important that treatment personnel know patients' perception, provide comprehensive support for these patients, and plan to enhance public awareness about the disease recommended.