Τρίτη 27 Ιουνίου 2017

The Complexity of Simple – Bringing Order to Complex Systems by Chris Hicks

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  The ability to simplify means to eliminate the unnecessary so that the necessary may speak –Hans Hofmann We live in complex times.  Resuscitation has gone endovascular, microvascular, mitochondrial.  EPR, ED-ECMO, REBOA–it’s a fascinating time to be a Resuscitationist.  But the more we advance the resuscitation agenda, the more we learn how complex critical illness […]

EMCrit by Chris Hicks.



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A population level atlas of Mus musculus craniofacial skeleton and automated image-based shape analysis

Abstract

Laboratory mice are staples for evo/devo and genetics studies. Inbred strains provide a uniform genetic background to manipulate and understand gene–environment interactions, while their crosses have been instrumental in studies of genetic architecture, integration and modularity, and mapping of complex biological traits. Recently, there have been multiple large-scale studies of laboratory mice to further our understanding of the developmental basis, evolution, and genetic control of shape variation in the craniofacial skeleton (i.e. skull and mandible). These experiments typically use micro-computed tomography (micro-CT) to capture the craniofacial phenotype in 3D and rely on manually annotated anatomical landmarks to conduct statistical shape analysis. Although the common choice for imaging modality and phenotyping provides the potential for collaborative research for even larger studies with more statistical power, the investigator (or lab-specific) nature of the data collection hampers these efforts. Investigators are rightly concerned that subtle differences in how anatomical landmarks were recorded will create systematic bias between studies that will eventually influence scientific findings. Even if researchers are willing to repeat landmark annotation on a combined dataset, different lab practices and software choices may create obstacles for standardization beyond the underlying imaging data. Here, we propose a freely available analysis system that could assist in the standardization of micro-CT studies in the mouse. Our proposal uses best practices developed in biomedical imaging and takes advantage of existing open-source software and imaging formats. Our first contribution is the creation of a synthetic template for the adult mouse craniofacial skeleton from 25 inbred strains and five F1 crosses that are widely used in biological research. The template contains a fully segmented cranium, left and right hemi-mandibles, endocranial space, and the first few cervical vertebrae. We have been using this template in our lab to segment and isolate cranial structures in an automated fashion from a mixed population of mice, including craniofacial mutants, aged 4–12.5 weeks. As a secondary contribution, we demonstrate an application of nearly automated shape analysis, using symmetric diffeomorphic image registration. This approach, which we call diGPA, closely approximates the popular generalized Procrustes analysis (GPA) but negates the collection of anatomical landmarks. We achieve our goals by using the open-source advanced normalization tools (ANT) image quantification library, as well as its associated R library (ANTsR) for statistical image analysis. Finally, we make a plea to investigators to commit to using open imaging standards and software in their labs to the extent possible to increase the potential for data exchange and improve the reproducibility of findings. Future work will incorporate more anatomical detail (such as individual cranial bones, turbinals, dentition, middle ear ossicles) and more diversity into the template.



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Rheumatoid nodule on cytology



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Sculptors, Architects, and Painters Conceive of Depicted Spaces Differently

Abstract

Sculptors, architects, and painters are three professional groups that require a comprehensive understanding of how to manipulate spatial structures. While it has been speculated that they may differ in the way they conceive of space due to the different professional demands, this has not been empirically tested. To achieve this, we asked architects, painters, sculptors, and a control group questions about spatially complex pictures. Verbalizations elicited were examined using cognitive discourse analysis. We found significant differences between each group. Only painters shifted consistently between 2D and 3D concepts, architects were concerned with paths and spatial physical boundedness, and sculptors produced responses that fell between architects and painters. All three differed from controls, whose verbalizations were generally less elaborate and detailed. Thus, for the case of sculptors, architects, and painters, profession appears to relate to a different spatial conceptualization manifested through a systematically contrasting way of talking about space.



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Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma

Abstract

The oral proteasome inhibitor ixazomib (Ninlaro®) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study). A significantly longer time to progression and favourable hazard ratios for PFS were observed across all prespecified subgroups, including patients with high cytogenetic risk. Overall response was achieved in a significantly higher proportion of patients receiving ixazomib- than placebo-based treatment. Ixazomib had a manageable tolerability profile in patients with MM. Ixazomib is the first orally-administered proteasome inhibitor approved for patients with MM, and in combination with lenalidomide and dexamethasone represents an important new option for use in patients with relapsed and/or refractory MM who have previously received at least one prior therapy.



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Chemotherapy-induced cardiomyopathy caused by Pemetrexed

Summary

Chemotherapy-related cardiac toxicity is a rare but serious adverse event in patients with cancer. Thus far, no case of serious cardiac toxicity of pemetrexed has been reported. We describe the case of a patient with advanced lung cancer and cardiomyopathy due to pemetrexed. A 59-year-old woman visited our hospital, and we found abnormal findings on a chest radiograph. She was diagnosed as having stage IV lung adenocarcinoma. Chemotherapy with cisplatin and pemetrexed every 3 weeks was initiated. After four cycles of chemotherapy, maintenance chemotherapy with pemetrexed was administered every 3 weeks. During the seventeenth cycle of pemetrexed, she had shortness of breath in her daily life. A chest radiograph showed an enlarged cardiothoracic ratio (66%), and the transthoracic echocardiogram demonstrated expansion of the left ventricle (diastolic diameter, 67 mm), severe global hypokinesis, and reduced left ventricular ejection fraction (28%). The coronary angiogram showed no coronary constriction. There was no delayed accumulation on the contrast-enhanced cardiac magnetic resonance imaging scan. After right heart catheterization, pathological results of a myocardial biopsy from the ventricular septum indicated no cardiac muscle hypertrophy, cardiac fibrosis, inflammatory cell infiltration, or myocyte disarray. Eventually, she was diagnosed as having pemetrexed-induced cardiomyopathy. Pemetrexed was discontinued, and furosemide, enalapril, and carvedilol were started. Then her symptoms and cardiac function improved. Early detection and discontinuation of causative agents are the most important treatment strategies in similar patients. Diuretics, angiotensin-conversion enzyme inhibitors, and beta-blockers may be effective for treating heart failure.



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The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Three Year Trends in Veterans Health Administration Utilization and Costs after Traumatic Brain Injury Screening among Veterans with Mild Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Journal of Neurotrauma , Vol. 0, No. 0.


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A novel strategy with combined assays for detection of anti-neutrophil cytoplasmic antibody (ANCA) in clinically ANCA-negative granulomatosis with polyangiitis patients

Granulomatosis with polyangiitis (GPA) that is localized to the upper airway presents a diagnostic challenge because of a tendency towards anti-neutrophil cytoplasmic antibody (ANCA)-negativity. The purpose of this study was to investigate whether positivity of ANCA detection might be elicited with combined use of enzyme-linked immunosorbent assay (ELISA) kits.

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Unique Infectious Strategy of H5N1 Avian Influenza Virus Is Governed by the Acid-Destabilized Property of Hemagglutinin

Viral Immunology , Vol. 0, No. 0.


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The Breast Cancer Screening “Arcade” and the “Whack-A-Mole” Efforts to Reduce Access to Screening

The effort to reduce access to breast cancer screening has been going on for decades. As each piece of misinformation has been published, scientific responses have exposed the fallacies, but then new “alternative facts” are generated. The effort has been compared to the arcade game “Whack-a-Mole” in which one false argument is addressed only to have a new one “pop up” to replace it. This has ranged from the false claim that early detection would have no effect on breast cancer, to the fallacious idea that early detection was leading to early deaths among young women, to the more recent false suggestion that tens of thousands of breast cancers found by mammography would disappear if left undetected.

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Relationship between obstructive sleep apnea and neuroimaging signatures of cerebral small vessel disease in community-dwelling older adults. The Atahualpa Project

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Publication date: Available online 27 June 2017
Source:Sleep Medicine
Author(s): Oscar H. Del Brutto, Robertino M. Mera, Mauricio Zambrano, Pablo R. Castillo
Background/Objectives: Evidence of a relationship between obstructive sleep apnea (OSA) and neuroimaging signatures of cerebral small vessel disease (SVD) is limited. The present study aimed to evaluate this association in older adults living in rural Ecuador, where small vessel disease is a major pathogenetic mechanism underlying stroke.MethodsA representative random sample of Atahualpa residents aged ≥60 years enrolled in the Atahualpa Project neuroimaging substudy underwent a single-night diagnostic polysomnography. We evaluated whether OSA associates with severity of white matter hyperintensities (WMH), silent lacunar infarctions and deep cerebral microbleeds, using multivariate models adjusted for relevant confounders.ResultsOf 351 candidates, 104 (30%) were randomly selected. Of these, 97 individuals (mean age 72.3±7 years, 65% women) had adequate recordings and were included. Mean apnea/hypopnea index was 13.8 ± 14.1 episodes per hour; 27 persons (28%) had ≥15 episodes per hour and were considered to have moderate-to-severe OSA. Moderate-to-severe WMH were noticed in 25 individuals (25.8%), silent lacunar infarctions in 22 (22.7%) and deep cerebral microbleeds in 12 (12.4%). In multivariate models, OSA was associated with moderate-to-severe WMH (OR: 3.94; 95% C.I.: 1.09 – 14.97; p=0.037), but not with silent lacunar infarctions (p=0.195) or deep cerebral microbleeds (p=0.405). A linear regression model confirmed the independent association between the apnea/hypopnea index and moderate-to-severe WMH (β: -8.81, 95% C.I.: -16.51 to -1.11; p=0.025).ConclusionsIndividuals with moderate-to-severe OSA are almost four times more likely to have diffuse subcortical damage of vascular origin than those with none-to-mild OSA, independently of demographics and cardiovascular risk factors.



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CASE STUDY: Amber & Fred

Hear about the amazing transformation in Amber & Fred’s oral health when they began using my Complete Mouth Care System. Amber overcame extreme anxiety about dental visits and Fred, for the first time in his life, has been commended on his oral health! Curious about my Complete Mouth Care System? Learn more with my free … Continue reading CASE STUDY: Amber & Fred

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The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Three Year Trends in Veterans Health Administration Utilization and Costs after Traumatic Brain Injury Screening among Veterans with Mild Traumatic Brain Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Neurodegeneration in the Spinal Ventral Horn Prior to Motor Impairment in Cervical Spondylotic Myelopathy

Journal of Neurotrauma , Vol. 0, No. 0.


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Characterizing and Defining “Infantile Liver Failure”

No abstract available

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Pediatric Autoimmune Hepatitis: What Do You Do When First-line Therapy Fails?

No abstract available

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Early Empiric Antibiotic Use Is Associated With Delayed Feeding Tolerance in Preterm Infants: A Retrospective Analysis

imageABSTRACT: The causative factors of neonatal feeding intolerance are poorly understood, but potentially related to clinical practices such as empiric antibiotic usage. The objective of this study was to evaluate whether early empiric antibiotic exposure negatively affects preterm infants’ enteral feeding tolerance. Data from infants without risk factors for sepsis, 500 to 1499 g birth weight and 24 to 34 weeks gestational age were analyzed. The primary outcomes were the empiric antibiotic exposure effects on the infants’ total parenteral nutrition usage duration and prevalence of necrotizing enterocolitis (NEC). Among the 901 infants included, 67 were exposed to early empiric antibiotic. A 50% increase in parenteral nutrition usage duration and a 4-fold greater prevalence of NEC was seen in the early empiric antibiotic-exposed neonates, when compared with control infants (P 

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Biomarkers of Environmental Enteric Dysfunction: The Good, the Bad, and the Ugly

No abstract available

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Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease

imageObjective: Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. Methods: This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). Results: The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P 

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Second-line Agents in Pediatric Patients With Autoimmune Hepatitis: A Systematic Review and Meta-analysis

imageBackground and Aims: Ten percent to 20% of children with autoimmune hepatitis (AIH) require second-line therapy to achieve remission. Although current guidelines exist on first-line management, evidence for second-line therapy in treatment-refractory patients is lacking. Our aim was to perform a systematic review and meta-analysis of the efficacy and safety of second-line treatments used in this population. Methods: Electronic and manual searches were used to identify potential studies for inclusion. Studies were selected based on reported response rates to second-line therapies in children who failed response to prednisone and azathioprine. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Meta-analysis using weighted estimate of response rates at 6 months was performed for each treatment option. Heterogeneity was assessed. Results: Fifteen studies of 76 pediatric patients with AIH were included in the review. Overall response rates at 6 months were estimated as 36% for mycophenolate mofetil (MMF) (N = 34, 95% confidence interval [CI] (16–57)), and 50% for tacrolimus (N = 4, 95% CI (0–100%)) and 83% for cyclosporine (N = 15, 95% CI (66%–100%)). Adverse effects were most frequent with cyclosporine (64% experiencing at least 1 adverse effect) followed by tacrolimus (54%) and MMF (48%). Pooled estimates of adverse events were 78% for cyclosporine (95% CI (54%–100%)), 42% for tacrolimus (95% CI (0%–85%)) and 45% for MMF (95% CI (25%–68%)). Sensitivity analyses were not performed due to small sample size. Conclusions: Cyclosporine had the highest response rate at 6 months in children with standard-treatment-refractory AIH; however, it also had the highest rate of adverse events. MMF was the second most efficacious option with a low adverse effect rate.

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Giant Pelvic Cyst in 16-Year-Old Boy With Bloody Diarrhea: Atypical Presentation of Colonic Adenocarcinoma

imageNo abstract available

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Intestinal Metaplasia of the Esophagus in Children With Esophageal Atresia

imageObjectives: Patients with esophageal atresia/tracheoesophageal fistula (EA-TEF) can develop Barrett esophagus as a long-term consequence of their condition. Intestinal metaplasia (IM), a risk factor for developing adenocarcinoma of the esophagus, has not been well characterized in the pediatric population. Methods: Retrospective review of patients with EA-TEF followed at 3 academic pediatric centers between the years 1997 and 2014. Results: Among 542 children and adolescents, 1.3% (7 patients, 5 girls) were diagnosed with IM based on endoscopy and pathology. Six of the patients had EA-TEF type C, whereas the last patient had a “long gap” type A atresia. Patients were diagnosed with gastric metaplasia either before the IM diagnosis in 4 patients or concomitantly in 3. The median (range) age of diagnosis for gastric metaplasia was 7.9 (range 2–17.2) and for IM 10.9 (2–17.2) years. Gastroesophageal reflux (GER) symptoms were nonspecific. Five patients were on proton pump inhibitor therapy for symptomatic GER at the time of diagnosis of IM. 2 of the 7 patients had previously undergone Nissen fundoplication. One patient, who had undergone a Nissen fundoplication, was restarted on proton pump inhibitor once the diagnosis of IM was made. All patients had repeated endoscopy and dysplasia was not observed with a median follow-up of 1.7 (range 1–4.9) years. Conclusions: IM occurs in patients with EA-TEF, some as young as 2 years. Therefore, early endoscopic surveillance should be considered in this GER-prone population.

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Eosinophilic Esophagitis and Celiac Disease: A True Association or Coincidence?

No abstract available

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Treatment of Functional Abdominal Pain With Antidepressants: Benefits, Adverse Effects, and the Gastroenterologist's Role

imageObjectives: Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians’ prescribing patterns. Methods: Retrospective review (2005–2013) children (5–21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Results: Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Conclusions: Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.

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Increased Fat Absorption From Enteral Formula Through an In-line Digestive Cartridge in Patients With Cystic Fibrosis

imageObjectives: Supplemental enteral nutrition (EN) is used by approximately 12% of people with cystic fibrosis (CF). The objective of this study was to evaluate the safety, tolerability, and fat absorption of a new in-line digestive cartridge (Relizorb) that hydrolyzes fat in enteral formula provided to patients with CF. Methods: Patients with CF receiving EN participated in a multicenter, randomized, double-blind, crossover trial with an open-label safety evaluation period. Plasma omega-3 fatty acid (FA) concentrations were measured and used as markers of fat absorption. Gastrointestinal symptoms were recorded to evaluate safety and tolerability. Information regarding the effect of EN on appetite and breakfast consumption was also collected. Results: Before study entry, participants had received EN for a mean of 6.6 years at a mean volume of approximately 800 mL, yet had a mean body mass index of only 17.5 kg/m2 and omega-3 FA plasma concentrations were only 60% of levels found in normal healthy subjects. Compared with placebo, cartridge use resulted in a statistically significant 2.8-fold increase in plasma omega-3 FA concentrations. There were no adverse experiences associated with cartridge use, and a decrease in the frequency and severity of most symptoms of malabsorption was observed with cartridge use. Participants reported increased preservation of appetite and breakfast consumption with cartridge use compared with their pre-study regimen. Conclusions: Use of this in-line digestive cartridge was safe and well tolerated, and resulted in significantly increased levels of plasma omega-3 FA used with enteral formula, suggesting an overall increased fat absorption.

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Yield of Endoscopy in Pediatric Gastroparesis

imageObjectives: The aim of the study was to quantify the diagnostic yield of upper endoscopy in children with gastroparesis and to develop a clinical model for gastroparesis using common symptoms and screening blood tests. Methods: We retrospectively reviewed charts of 196 patients of age 4 to 18 years evaluated for gastroparesis between 2009 and 2013. All patients completed a standard solid-phase gastric emptying scan and upper endoscopy within a 12-month period. We analyzed gross and histologic endoscopy findings. Symptom-based data were collected on dyspeptic symptoms and classic “red-flag” symptoms. Results: Seventy patients with gastroparesis and 126 controls were included. Clinically significant endoscopic findings were noted in 35% of controls (44/126) and 43% of gastroparetics (30/70), P = 0.345. Concordance between gross and histologic findings was low at 50%. Histologic findings included gastritis 60% (17/28), esophagitis 39% (11/28), and duodenitis 7% (2/28). In univariate and multivariate analyses, there was no meaningful correlation between symptoms and/or screening laboratory values and diagnosis of gastroparesis. Conclusions: Clinically significant endoscopy findings were common in both controls and gastroparetics. As more than one-third of patients had findings on endoscopy, we conclude that upper endoscopy remains an important part of the evaluation process of patients with dyspeptic symptoms and suspected gastroparesis. As gross abnormalities were frequently not present with histologic changes, routine biopsy is required. There was no association between studied symptoms and the presence of gastroparesis. A comprehensive evaluation of children with dyspeptic symptoms requires endoscopy with biopsy and solid-phase gastric emptying scan to determine the underlying diagnosis.

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Commercial Probiotic Products: A Call for Improved Quality Control. A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics

imageABSTRACT: Probiotics have been proposed for a number of indications ranging from the hypothetical long-term immunomodulatory effects to proven benefits in the management of different clinical conditions. An increasing number of commercial products containing probiotics are available. In those products, irrespective if it is food, food supplement, medical food, or drug, the probiotic microorganisms have to be present in a sufficient number by the end of the shelf-life, to pass through the gastrointestinal tract resisting acid and bile, to colonize the gut, and to retain functional properties required to obtain the suggested beneficial effect. Finally, it should be contamination-free. Studies organized worldwide and summarized in this article have shown that inconsistencies and deviations from the information provided on the product label are surprisingly common. Frequently strains are misidentified and misclassified, products are occasionally contaminated, sometimes with even facultative or obligatory pathogens, strains are not viable, the labeled number of colonies cannot be verified, or the functional properties are diminished to the extent that preclude the proposed health benefit. As the probiotic preparations are commonly used for a wide range of conditions, the aim of the Working Group was to summarize results of the studies looking into the quality of the probiotic products and to raise the awareness of the important issue of their quality control. Based on the results obtained, we strongly suggest a more stringent quality control process. This process should ensure that the probiotic content as mentioned on the label meets the actual content throughout the shelf life of the product, while no contamination is present.

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Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea

imageObjectives: We aimed to improve the knowledge of pathogenic mutations in sporadic cases of congenital chloride diarrhea (CCD) and emphasize the importance of functional studies to define the effect of novel mutations. Methods: All member 3 of solute carrier family 26 (SLC26A3) coding regions were sequenced in 17 sporadic patients with CCD. Moreover, the minigene system was used to analyze the effect of 2 novel splicing mutations. Results: We defined the SLC26A3 genotype of all 17 patients with CCD and identified 12 novel mutations. Using the minigene system, we confirmed the in silico prediction of a complete disruption of splicing pattern caused by 2 of these novel mutations: the c.971+3_971+4delAA and c.735+4_c.735+7delAGTA. Moreover, several prediction tools and a structure-function prediction defined the pathogenic role of 6 novel missense mutations. Conclusions: We confirm the molecular heterogeneity of sporadic CCD adding 12 novel mutations to the list of known pathogenic mutations. Moreover, we underline the importance, for laboratories that offer molecular diagnosis and genetic counseling, to perform fast functional analysis of novel mutations.

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Evaluation of Carbapenem Resistance Mechanisms and Its Association with Pseudomonas aeruginosa Infections in the Northwest of Iran

Microbial Drug Resistance , Vol. 0, No. 0.


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Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood: Results From the MAL-ED Study

imageObjectives: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. Methods: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age- and sex-specific z scores for mannitol and lactulose recoveries and the L:M ratio. Results: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex-specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. Conclusions: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M-z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

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Giant Pelvic Cyst in 16-Year-Old Boy With Bloody Diarrhea: Atypical Presentation of Colonic Adenocarcinoma

imageNo abstract available

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Pediatric Autoimmune Hepatitis: What Do You Do When First-line Therapy Fails?

No abstract available

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Characterizing and Defining “Infantile Liver Failure”

No abstract available

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Early Empiric Antibiotic Use Is Associated With Delayed Feeding Tolerance in Preterm Infants: A Retrospective Analysis

imageABSTRACT: The causative factors of neonatal feeding intolerance are poorly understood, but potentially related to clinical practices such as empiric antibiotic usage. The objective of this study was to evaluate whether early empiric antibiotic exposure negatively affects preterm infants' enteral feeding tolerance. Data from infants without risk factors for sepsis, 500 to 1499 g birth weight and 24 to 34 weeks gestational age were analyzed. The primary outcomes were the empiric antibiotic exposure effects on the infants' total parenteral nutrition usage duration and prevalence of necrotizing enterocolitis (NEC). Among the 901 infants included, 67 were exposed to early empiric antibiotic. A 50% increase in parenteral nutrition usage duration and a 4-fold greater prevalence of NEC was seen in the early empiric antibiotic-exposed neonates, when compared with control infants (P 

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Biomarkers of Environmental Enteric Dysfunction: The Good, the Bad, and the Ugly

No abstract available

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Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease

imageObjective: Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. Methods: This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). Results: The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P 

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Second-line Agents in Pediatric Patients With Autoimmune Hepatitis: A Systematic Review and Meta-analysis

imageBackground and Aims: Ten percent to 20% of children with autoimmune hepatitis (AIH) require second-line therapy to achieve remission. Although current guidelines exist on first-line management, evidence for second-line therapy in treatment-refractory patients is lacking. Our aim was to perform a systematic review and meta-analysis of the efficacy and safety of second-line treatments used in this population. Methods: Electronic and manual searches were used to identify potential studies for inclusion. Studies were selected based on reported response rates to second-line therapies in children who failed response to prednisone and azathioprine. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Meta-analysis using weighted estimate of response rates at 6 months was performed for each treatment option. Heterogeneity was assessed. Results: Fifteen studies of 76 pediatric patients with AIH were included in the review. Overall response rates at 6 months were estimated as 36% for mycophenolate mofetil (MMF) (N = 34, 95% confidence interval [CI] (16–57)), and 50% for tacrolimus (N = 4, 95% CI (0–100%)) and 83% for cyclosporine (N = 15, 95% CI (66%–100%)). Adverse effects were most frequent with cyclosporine (64% experiencing at least 1 adverse effect) followed by tacrolimus (54%) and MMF (48%). Pooled estimates of adverse events were 78% for cyclosporine (95% CI (54%–100%)), 42% for tacrolimus (95% CI (0%–85%)) and 45% for MMF (95% CI (25%–68%)). Sensitivity analyses were not performed due to small sample size. Conclusions: Cyclosporine had the highest response rate at 6 months in children with standard-treatment-refractory AIH; however, it also had the highest rate of adverse events. MMF was the second most efficacious option with a low adverse effect rate.

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Intestinal Metaplasia of the Esophagus in Children With Esophageal Atresia

imageObjectives: Patients with esophageal atresia/tracheoesophageal fistula (EA-TEF) can develop Barrett esophagus as a long-term consequence of their condition. Intestinal metaplasia (IM), a risk factor for developing adenocarcinoma of the esophagus, has not been well characterized in the pediatric population. Methods: Retrospective review of patients with EA-TEF followed at 3 academic pediatric centers between the years 1997 and 2014. Results: Among 542 children and adolescents, 1.3% (7 patients, 5 girls) were diagnosed with IM based on endoscopy and pathology. Six of the patients had EA-TEF type C, whereas the last patient had a "long gap" type A atresia. Patients were diagnosed with gastric metaplasia either before the IM diagnosis in 4 patients or concomitantly in 3. The median (range) age of diagnosis for gastric metaplasia was 7.9 (range 2–17.2) and for IM 10.9 (2–17.2) years. Gastroesophageal reflux (GER) symptoms were nonspecific. Five patients were on proton pump inhibitor therapy for symptomatic GER at the time of diagnosis of IM. 2 of the 7 patients had previously undergone Nissen fundoplication. One patient, who had undergone a Nissen fundoplication, was restarted on proton pump inhibitor once the diagnosis of IM was made. All patients had repeated endoscopy and dysplasia was not observed with a median follow-up of 1.7 (range 1–4.9) years. Conclusions: IM occurs in patients with EA-TEF, some as young as 2 years. Therefore, early endoscopic surveillance should be considered in this GER-prone population.

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Eosinophilic Esophagitis and Celiac Disease: A True Association or Coincidence?

No abstract available

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Treatment of Functional Abdominal Pain With Antidepressants: Benefits, Adverse Effects, and the Gastroenterologist's Role

imageObjectives: Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. Methods: Retrospective review (2005–2013) children (5–21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Results: Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Conclusions: Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.

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Increased Fat Absorption From Enteral Formula Through an In-line Digestive Cartridge in Patients With Cystic Fibrosis

imageObjectives: Supplemental enteral nutrition (EN) is used by approximately 12% of people with cystic fibrosis (CF). The objective of this study was to evaluate the safety, tolerability, and fat absorption of a new in-line digestive cartridge (Relizorb) that hydrolyzes fat in enteral formula provided to patients with CF. Methods: Patients with CF receiving EN participated in a multicenter, randomized, double-blind, crossover trial with an open-label safety evaluation period. Plasma omega-3 fatty acid (FA) concentrations were measured and used as markers of fat absorption. Gastrointestinal symptoms were recorded to evaluate safety and tolerability. Information regarding the effect of EN on appetite and breakfast consumption was also collected. Results: Before study entry, participants had received EN for a mean of 6.6 years at a mean volume of approximately 800 mL, yet had a mean body mass index of only 17.5 kg/m2 and omega-3 FA plasma concentrations were only 60% of levels found in normal healthy subjects. Compared with placebo, cartridge use resulted in a statistically significant 2.8-fold increase in plasma omega-3 FA concentrations. There were no adverse experiences associated with cartridge use, and a decrease in the frequency and severity of most symptoms of malabsorption was observed with cartridge use. Participants reported increased preservation of appetite and breakfast consumption with cartridge use compared with their pre-study regimen. Conclusions: Use of this in-line digestive cartridge was safe and well tolerated, and resulted in significantly increased levels of plasma omega-3 FA used with enteral formula, suggesting an overall increased fat absorption.

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Yield of Endoscopy in Pediatric Gastroparesis

imageObjectives: The aim of the study was to quantify the diagnostic yield of upper endoscopy in children with gastroparesis and to develop a clinical model for gastroparesis using common symptoms and screening blood tests. Methods: We retrospectively reviewed charts of 196 patients of age 4 to 18 years evaluated for gastroparesis between 2009 and 2013. All patients completed a standard solid-phase gastric emptying scan and upper endoscopy within a 12-month period. We analyzed gross and histologic endoscopy findings. Symptom-based data were collected on dyspeptic symptoms and classic "red-flag" symptoms. Results: Seventy patients with gastroparesis and 126 controls were included. Clinically significant endoscopic findings were noted in 35% of controls (44/126) and 43% of gastroparetics (30/70), P = 0.345. Concordance between gross and histologic findings was low at 50%. Histologic findings included gastritis 60% (17/28), esophagitis 39% (11/28), and duodenitis 7% (2/28). In univariate and multivariate analyses, there was no meaningful correlation between symptoms and/or screening laboratory values and diagnosis of gastroparesis. Conclusions: Clinically significant endoscopy findings were common in both controls and gastroparetics. As more than one-third of patients had findings on endoscopy, we conclude that upper endoscopy remains an important part of the evaluation process of patients with dyspeptic symptoms and suspected gastroparesis. As gross abnormalities were frequently not present with histologic changes, routine biopsy is required. There was no association between studied symptoms and the presence of gastroparesis. A comprehensive evaluation of children with dyspeptic symptoms requires endoscopy with biopsy and solid-phase gastric emptying scan to determine the underlying diagnosis.

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Commercial Probiotic Products: A Call for Improved Quality Control. A Position Paper by the ESPGHAN Working Group for Probiotics and Prebiotics

imageABSTRACT: Probiotics have been proposed for a number of indications ranging from the hypothetical long-term immunomodulatory effects to proven benefits in the management of different clinical conditions. An increasing number of commercial products containing probiotics are available. In those products, irrespective if it is food, food supplement, medical food, or drug, the probiotic microorganisms have to be present in a sufficient number by the end of the shelf-life, to pass through the gastrointestinal tract resisting acid and bile, to colonize the gut, and to retain functional properties required to obtain the suggested beneficial effect. Finally, it should be contamination-free. Studies organized worldwide and summarized in this article have shown that inconsistencies and deviations from the information provided on the product label are surprisingly common. Frequently strains are misidentified and misclassified, products are occasionally contaminated, sometimes with even facultative or obligatory pathogens, strains are not viable, the labeled number of colonies cannot be verified, or the functional properties are diminished to the extent that preclude the proposed health benefit. As the probiotic preparations are commonly used for a wide range of conditions, the aim of the Working Group was to summarize results of the studies looking into the quality of the probiotic products and to raise the awareness of the important issue of their quality control. Based on the results obtained, we strongly suggest a more stringent quality control process. This process should ensure that the probiotic content as mentioned on the label meets the actual content throughout the shelf life of the product, while no contamination is present.

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Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea

imageObjectives: We aimed to improve the knowledge of pathogenic mutations in sporadic cases of congenital chloride diarrhea (CCD) and emphasize the importance of functional studies to define the effect of novel mutations. Methods: All member 3 of solute carrier family 26 (SLC26A3) coding regions were sequenced in 17 sporadic patients with CCD. Moreover, the minigene system was used to analyze the effect of 2 novel splicing mutations. Results: We defined the SLC26A3 genotype of all 17 patients with CCD and identified 12 novel mutations. Using the minigene system, we confirmed the in silico prediction of a complete disruption of splicing pattern caused by 2 of these novel mutations: the c.971+3_971+4delAA and c.735+4_c.735+7delAGTA. Moreover, several prediction tools and a structure-function prediction defined the pathogenic role of 6 novel missense mutations. Conclusions: We confirm the molecular heterogeneity of sporadic CCD adding 12 novel mutations to the list of known pathogenic mutations. Moreover, we underline the importance, for laboratories that offer molecular diagnosis and genetic counseling, to perform fast functional analysis of novel mutations.

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Apropos: “Gut Microbiota Differences in Children From Distinct Socioeconomic Levels Living in the Same Urban Area in Brazil”

No abstract available

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Allergic Interstitial Nephritis Masquerading as Pyelonephritis in a Pediatric Patient With Crohn Disease

imageNo abstract available

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Age and Sex Normalization of Intestinal Permeability Measures for the Improved Assessment of Enteropathy in Infancy and Early Childhood: Results From the MAL-ED Study

imageObjectives: The aim of the study was to describe changes in intestinal permeability in early childhood in diverse epidemiologic settings. Methods: In a birth cohort study, the lactulose:mannitol (L:M) test was administered to 1980 children at 4 time points in the first 24 months of life in 8 countries. Data from the Brazil site with an incidence of diarrhea similar to that seen in the United States and no growth faltering was used as an internal study reference to derive age- and sex-specific z scores for mannitol and lactulose recoveries and the L:M ratio. Results: A total of 6602 tests demonstrated mannitol recovery, lactulose recovery, and the L:M ratio were associated with country, sex, and age. There was heterogeneity in the recovery of both probes between sites with mean mannitol recovery ranging for 1.34% to 5.88%, lactulose recovery of 0.19% to 0.58%, and L:M ratios 0.10 to 0.17 in boys of 3 months of age across different sites. We observed strong sex-specific differences in both mannitol and lactulose recovery, with boys having higher recovery of both probes. Alterations in intestinal barrier function increased in most sites from 3 to 9 months of age and plateaued or diminished from 9 to 15 months of age. Conclusions: Alterations in recovery of the probes differ markedly in different epidemiologic contexts in children living in the developing world. The rate of change in the L:M-z ratio was most rapid and consistently disparate from the reference standard in the period between 6 and 9 months of age, suggesting that this is a critical period of physiologic impact of enteropathy in these populations.

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Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh

imageObjectives: Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. Methods: In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. Results: EED prevalence (L:M > 0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or α-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and α-1 antitrypsin (r = 0.33, P 

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Outpatient Liver Biopsy in Children: Safety, Feasibility, and Economic Impact

ABSTRACT: Liver biopsy is a valuable tool. Even though outpatient liver biopsies are routinely performed in adults, there are no clear recommendations on its safety and feasibility in children. We reviewed the records of children who underwent a percutaneous liver biopsy at our institution between January 2005 and June 2015. A total of 626 biopsies were performed on 497 patients (250 boys, median age 6 [0.2–19.3] years). Abnormal liver function tests for investigation 288 (46%) was the most common indication. Thirty (4.8%) biopsies had complications, most common being subcapsular hematoma 14 of 30 (46.7%). Complications were identified within 8 hours of the biopsy in all patients. Approach, needle size, or number of passes did not affect the complication rate. Bleeding-related complications were not related to the international normalized ratio. Performing liver biopsies on an outpatient basis would have saved 60 beds/AU$ 80,000/year. The present study suggests that if an observation period of 8 hours is instituted, outpatient liver biopsies can be performed safely in children.

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Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment

imageObjectives: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. Methods: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing–driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters. Results: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P 

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Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh

imageObjectives: Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. Methods: In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool, and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis and partial least squares regression. Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. Results: EED prevalence (L:M > 0.07) was 39.0%; 60% had elevated acute phase proteins (C-reactive protein >5 mg/L or α-1 acid glycoprotein >100 mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and α-1 antitrypsin (r = 0.33, P 

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Outpatient Liver Biopsy in Children: Safety, Feasibility, and Economic Impact

ABSTRACT: Liver biopsy is a valuable tool. Even though outpatient liver biopsies are routinely performed in adults, there are no clear recommendations on its safety and feasibility in children. We reviewed the records of children who underwent a percutaneous liver biopsy at our institution between January 2005 and June 2015. A total of 626 biopsies were performed on 497 patients (250 boys, median age 6 [0.2–19.3] years). Abnormal liver function tests for investigation 288 (46%) was the most common indication. Thirty (4.8%) biopsies had complications, most common being subcapsular hematoma 14 of 30 (46.7%). Complications were identified within 8 hours of the biopsy in all patients. Approach, needle size, or number of passes did not affect the complication rate. Bleeding-related complications were not related to the international normalized ratio. Performing liver biopsies on an outpatient basis would have saved 60 beds/AU$ 80,000/year. The present study suggests that if an observation period of 8 hours is instituted, outpatient liver biopsies can be performed safely in children.

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Filaggrin and Periostin Expression Is Altered in Eosinophilic Esophagitis and Normalized With Treatment

imageObjectives: Previous data have suggested that filaggrin (FLG) and periostin (POSTN) genes may be dysregulated in eosinophilic esophagitis (EoE). We aimed to further evaluate the expression patterns of FLG and POSTN proteins in esophageal tissue samples of patients with EoE, as compared to those of patients with gastroesophageal reflux disease (GERD) and normal controls. Methods: A total of 61 prospectively collected cases, including 40 children with EoE and 21 children with GERD, and a control group of 14 sex- and age-matched healthy children were enrolled. Patients with EoE were treated with skin testing–driven elimination diet and/or corticosteroids. The immunohistochemical expression of FLG and POSTN was evaluated in esophageal biopsies obtained from patients and controls, and the results were correlated with EoE-related clinicopathological parameters. Results: Positive FLG and negative POSTN staining were observed in all esophageal biopsies from normal controls. In contrast, FLG and POSTN stained negative and positive, respectively, in all pretreatment biopsies obtained from patients with EoE, whereas FLG and POSTN stained positive in 57.1% and 95.2% of GERD cases, respectively (P 

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Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.

Acute kidney injury after cardiac surgery is associated with increased morbidity and mortality. Methods for measuring urine output in real time may better ensure renal perfusion perioperatively in contrast to the current standard of care where urine output is visually estimated after empiric epochs of time. In this study, we describe an accurate method for monitoring urine output continuously during cardiopulmonary bypass. This may provide a means for setting patient-specific targets for blood pressure and cardiopulmonary bypass flow as a potential strategy to reduce the risk for acute kidney injury. (C) 2017 International Anesthesia Research Society

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Quadratus Lumborum Spares Paravertebral Space in Fresh Cadaver Injection.

No abstract available

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In Response.

No abstract available

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To the Editor.

No abstract available

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Enhanced Recovery After Surgery: Current Controversies and Concerns.

No abstract available

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An Automated Critical Event Screening and Notification System to Facilitate Preanesthesia Record Review.

BACKGROUND: Anesthesia information management systems make prior anesthesia records readily available for review when patients return for a subsequent procedure but may create a problem of too much documentation to review in a limited amount of time. We implemented a screening tool to facilitate the identification of critical documentation for review. METHODS: An algorithm was developed to electronically search prior anesthesia records for predefined critical events and flag records containing these events. Our web-based daily case schedule was modified to contain a warning message for any patient on the schedule who has a prior record flagged by the system, in addition to a preexisting hyperlink to view the relevant record. A retrospective analysis was performed to determine the impact of the warning messages on the frequency with which the care team reviewed these records before providing anesthesia care. RESULTS: The screening algorithm flagged 13% of archived cases as critical. There were 3329 and 3369 cases in the 6 months before and after system implementation, respectively, that had prior critical records available for review at that time. One or more of these critical records were viewed before the subsequent case start in 39% vs 59% (P

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To the Editor.

No abstract available

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In Response.

No abstract available

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In Response.

No abstract available

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Anesthetic Management of Narcolepsy Patients During Surgery: A Systematic Review.

BACKGROUND: Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness, sleep paralysis, and/or hypnagogic/hypnopompic hallucinations, and in some cases cataplexy. The response to anesthetic medications and possible interactions in narcolepsy patients is unclear in the perioperative period. In this systematic review, we aim to evaluate the current evidence on the perioperative outcomes and anesthetic considerations in narcolepsy patients. METHODS: Electronic literature search of Medline, Medline in-process, Embase, Cochrane Database of Systematic Reviews databases, international conference proceedings, and abstracts was conducted in November 2015 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guideline. A total of 3757 articles were screened using a 2-stage strategy (title-abstract followed by full text). We included case studies/series, cohort studies, and randomized controlled trials of narcolepsy patients undergoing surgical procedures under anesthesia or sedation. Preoperative narcolepsy symptoms and sleep study data, anesthetic technique, and perioperative complications were extracted. Screening of articles, data extraction, and compilation were conducted by 2 independent reviewers and any conflict was resolved by the senior author. RESULTS: A total of 19 studies including 16 case reports and 3 case series were included and evaluated. The majority of these patients received general anesthesia, whereas a small percentage of patients received regional anesthesia. Reported complications of narcolepsy patients undergoing surgeries were mainly related to autonomic dysregulation, or worsening of narcolepsy symptoms intra/postoperatively. Narcolepsy symptoms worsened only in those patient populations where the preoperative medications were either discontinued or reduced (mainly in obstetric patients). In narcolepsy patients, use of depth of anesthesia monitoring and total intravenous technique may have some advantage in terms of safety profile. Several patients undergoing neurosurgery involving the hypothalamus or third or four ventricles developed new-onset narcolepsy. CONCLUSIONS: We found a paucity of prospective clinical trials in this patient population, as most of the studies were case reports or observational studies. Continuation of preoperative medications, depth of anesthesia monitoring, use of multimodal analgesia with short-acting agents and regional anesthesia techniques were associated with favorable outcomes. Obstetric patients may be at greater risk for worsening narcolepsy symptoms, possibly related to a reduction or discontinuation of medications. For neurosurgical procedures involving the hypothalamus or third and fourth ventricle, postoperative considerations should include monitoring for symptoms of narcolepsy. Future studies are needed to better define perioperative risks associated with anesthesia and surgery in this population of patients. (C) 2017 International Anesthesia Research Society

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Loss of Resistance Syringe: A Substitute for Cuff Pressure Manometer.

No abstract available

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Recommendations for Procedural Sedation Clinical Trials.

No abstract available

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Dural Puncture Epidural Technique: Not So Fast.

No abstract available

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In Response.

No abstract available

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Imaging Guidance for Thoracic Epidural Catheter Placement.

No abstract available

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Intraoperative Detection of Persistent Endoleak by Detecting Residual Spontaneous Echocardiographic Contrast in the Aneurysmal Sac During Thoracic Endovascular Aortic Repair.

Persistent endoleaks may lead to adverse events after endovascular aortic repair. We prospectively examined the relationship between intraoperative residual spontaneous echocardiographic contrast (SEC) within the aneurysmal sac and the incidence of postoperative endoleaks in 60 patients undergoing thoracic endovascular aortic repair. Patients with SEC had a higher incidence of postoperative endoleaks than did patients without SEC within a few days postoperatively (60.0% vs 12.5%, respectively; P

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Validation of a Real-Time Minute-to-Minute Urine Output Monitor and the Feasibility of Its Clinical Use for Patients Undergoing Cardiac Surgery.

Acute kidney injury after cardiac surgery is associated with increased morbidity and mortality. Methods for measuring urine output in real time may better ensure renal perfusion perioperatively in contrast to the current standard of care where urine output is visually estimated after empiric epochs of time. In this study, we describe an accurate method for monitoring urine output continuously during cardiopulmonary bypass. This may provide a means for setting patient-specific targets for blood pressure and cardiopulmonary bypass flow as a potential strategy to reduce the risk for acute kidney injury. (C) 2017 International Anesthesia Research Society

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Quadratus Lumborum Spares Paravertebral Space in Fresh Cadaver Injection.

No abstract available

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Inhibition of Androgen Receptor Nuclear Localization and Castration Resistant Prostate Tumor Growth by Pyrroloimidazole-Based Small Molecules

The androgen receptor (AR) is a ligand-dependent transcription factor that controls the expression of androgen-responsive genes.  A key step in androgen action, which is amplified in castration resistant prostate cancer (CRPC), is AR nuclear translocation. Small molecules capable of inhibiting AR nuclear localization could be developed as novel therapeutics for CRPC. We developed a high throughput screen and identified two structurally-related pyrroloimidazoles that could block AR nuclear localization in CRPC cells. We show that these two small molecules, 3-(4-ethoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (EPPI) and 3-(4-chlorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (CPPI) can inhibit the nuclear localization and transcriptional activity of AR and reduce the proliferation of AR-positive but not AR-negative prostate cancer cell lines.  EPPI and CPPI did not inhibit nuclear localization of the glucocorticoid receptor or the estrogen receptor, suggesting they selectively target AR.  In LNCaP tumor xenografts, CPPI inhibited the proliferation of relapsed LNCaP tumors.  These findings suggest that EPPI and CPPI could serve as lead structures for the development of therapeutic agents for CRPC.



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Inhibition of Megakaryocyte Differentiation by Antibody-Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC Induced Thrombocytopenia

Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADCs), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and Trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MKs) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an in vitro system in which human hematopoietic stem cells (HSCs) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcRIIA on MKs. Blocking the interaction of T-DM1 with FcRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was co-localized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia.



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A small molecule inhibitor of WEE1, AZD1775, synergizes with olaparib by impairing homologous recombination and enhancing DNA damage and apoptosis in acute leukemia.

Although some patients with acute leukemia have good prognoses, the prognosis of adult and pediatric patients who relapse or cannot tolerate standard chemotherapy is poor. Inhibition of WEE1 with AZD1775 has been shown to sensitize cancer cells to genotoxic chemotherapies including cytarabine in AML and T-ALL. Inhibition of WEE1 impairs homologous recombination by indirectly inhibiting BRCA2. Thus, we sought to determine if AZD1775 could sensitize cells to the PARP1/2 inhibitor olaparib. We found that combined treatment with AZD1775 and olaparib was synergistic in AML and ALL cells, and this combination impaired proliferative capacity upon drug withdrawal. AZD1775 impaired homologous recombination in olaparib-treated cells resulting in enhanced DNA damage accumulation and apoptosis induction. This combination enhanced disease control and increased survival in a murine AML model. Furthermore, we demonstrated that combined treatment with AZD1775 and olaparib reduces proliferation and colony formation and increases apoptosis in AML patient samples. In aggregate, these studies raise the possibility of rational combinations of targeted agents for leukemia in patients for whom conventional chemotherapeutics may not be effective or well tolerated.



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ADA-07 suppresses solar ultraviolet-induced skin carcinogenesis by directly inhibiting TOPK

Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the mitogen-activated protein kinase (MAPK) cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs, and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK.



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Evaluation and Design of Genome-Wide CRISPR/SpCas9 Knockout Screens

The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols. In this study, we re-analyze 17 genome-scale knockout screens in human cell lines from three research groups using three different genome-scale gRNA libraries. Using the Bayesian Analysis of Gene Essentiality (BAGEL) algorithm to identify essential genes, we refine and expand our previously defined set of human core essential genes from 360 to 684 genes. We use this expanded set of reference Core Essential Genes (CEG2) plus empirical data from six CRISPR knockout screens to guide the design of a sequence-optimized gRNA library, the Toronto KnockOut version 3.0 (TKOv3) library. We then demonstrate the high effectiveness of the library relative to reference sets of essential and nonessential genes as well as other screens using similar approaches. The optimized TKOv3 library, combined with the CEG2 reference set, provide an efficient, highly optimized platform for performing and assessing gene knockout screens in human cell lines.



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Genome-Wide Associations for Water-Soluble Carbohydrate Concentration and Relative Maturity in Wheat Using SNP and DArT Marker Arrays

Improving water-use efficiency by incorporating drought avoidance traits into new wheat varieties is an important objective for wheat breeding in water-limited environments. This study uses genome wide association studies (GWAS) to identify candidate loci for water-soluble carbohydrate accumulation, an important drought-avoidance characteristic in wheat. Phenotypes from a multi-environment trial with experiments differing in water availability and separate single nucleotide polymorphism (SNP) and diversity arrays technology (DArT) marker sets were used to perform the analyses. Significant associations for water-soluble carbohydrate accumulation were identified on chromosomes 1A, 1B, 1D, 2D and 4A. Notably, these loci did not collocate with the major loci identified for relative maturity. Loci on chromosome 1D collocated with markers previously associated with the high molecular weight glutenin Glu-D1 locus. Genetic x environmental interactions impacted the results strongly, with significant associations for carbohydrate accumulation only identified in the water-deficit experiments. The markers associated with carbohydrate accumulation may be useful for marker assisted selection of drought tolerance in wheat.



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Two Variants in SLC24A5 Are Associated with "Tiger-Eye" Iris Pigmentation in Puerto Rican Paso Fino Horses

A unique eye color, called tiger-eye, segregates in the Puerto Rican Paso Fino Horse breed and is characterized by a bright yellow, amber, or orange iris. Pedigree analysis identified a simple autosomal recessive mode of inheritance for this trait. A genome-wide association study with 24 individuals identified a locus on ECA 1 reaching genome wide significance (Pcorrected =1.32 x 10-5). This ECA1 locus harbors the candidate gene, Solute Carrier Family 24 (Sodium/Potassium /Calcium Exchanger), Member 5 (SLC24A5), with known roles in pigmentation in humans, mice, and zebrafish. Humans with compound heterozygous mutations in SLC24A5 have oculocutaneous albinism type 6 (OCA6) which is characterized by dilute skin, hair, and eye pigmentation as well as ocular anomalies. Twenty tiger-eye horses were homozygous for a non-synonymous mutation in Exon 2 (p.Phe91Tyr) of SLC24A5 (called here Tiger-eye 1), which is predicted to be deleterious to protein function. Additionally, eight of the remaining 12 tiger-eye horses heterozygous for the p.Phe91Tyr variant were also heterozygous for a 628bp deletion encompassing all of Exon 7 of SLC24A5 (c.875-340_1081+82del) which we will call here the Tiger-eye 2 allele. None of the 122 brown-eyed horses were homozygous for either tiger-eye associated allele or were compound heterozygotes. Further, neither variant was detected in 196 horses from four related breeds, not known to have the tiger-eye phenotype. Here we propose that two mutations in SLC24A5 affect iris pigmentation in tiger-eye Puerto Rican Paso Fino horses. Further, unlike OCA6 in humans, the Tiger-eye 1 mutation in its homozygous state or as a compound heterozygote (Tiger-eye 1/ Tiger-eye 2), do not appear to cause ocular anomalies or change in coat color in the Puerto Rican Paso Fino horse.



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Inhibition of autophagy prevents cadmium-induced prostate carcinogenesis

Inhibition of autophagy prevents cadmium-induced prostate carcinogenesis

British Journal of Cancer 117, 56 (27 June 2017). doi:10.1038/bjc.2017.143

Authors: Deeksha Pal, Suman Suman, Venkatesh Kolluru, Sophia Sears, Trinath P Das, Houda Alatassi, Murali K Ankem, Jonathan H Freedman & Chendil Damodaran



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Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia

Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia

British Journal of Cancer 117, 136 (27 June 2017). doi:10.1038/bjc.2017.148

Authors: Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai & Kapaettu Satyamoorthy



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A randomized cross-over study of the effects of lidocaine on motor and sensory evoked potentials during spinal surgery

Lidocaine has emerged as a useful adjuvant anesthetic agent for cases requiring intraoperative monitoring of motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs). A previous retrospective study suggested that lidocaine could be used as a component of propofol-based intravenous anesthesia without adversely affecting MEP or SSEP monitoring, but did not address the effect of addition of lidocaine on the MEP and SSEP signals of individual patients.

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Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

British Journal of Cancer 117, 65 (27 June 2017). doi:10.1038/bjc.2017.140

Authors: Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen & Arne Östman



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Inhibiting p53 acetylation reduces cancer chemotoxicity

Chemotoxicity due to unwanted p53 activation in the bone marrow remains an unmet clinical challenge. Doxorubicin, a first-line chemotherapy drug, often causes myelosuppression in patients, thus limiting its effectiveness. In this study, we discovered that C646, a reversible p300 inhibitor, downregulates p53 transcription and selectively protects non-cancerous cells from p53-dependent apoptosis. C646 treatment blocked acetylation of specific lysine residues that regulate p53 activity. Exploitation of differential p53 genetic backgrounds between human hematopoietic and colorectal cancer cells improved the therapeutic index of doxorubicin with C646 cotreatment. C646 administration in mice afflicted with p53 mutant tumors protected them from doxorubicin-induced neutropenia and anemia while retaining anti-tumor efficacy. We deduce that temporary and reversible inhibition of p53 acetylation in cancer subjects, especially those with p53-mutant tumors, may protect them from severe chemotoxicity while allowing treatment regimens to effectively proceed.

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Nrf2 mutagenic activation drives hepatocarcinogenesis

Nrf2, a master regulator of oxidative stress, is considered a prominent target for prevention of hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide. Here we report that Nrf2 deficient mice resisted diethylnitrosamine (DEN)-induced hepatocarcinogenesis without affecting P450-mediated metabolic activation of DEN. Nrf2 expression, nuclear translocation, and transcriptional activity were enhanced in liver tumors. Overactivated Nrf2 was required for hepatoma growth in DEN-induced HCC. Following DEN treatment, Nrf2 genetic disruption reduced expression of pentose phosphate pathway (PPP)-related enzymes, the depletion of which has been associated with an amelioration of HCC incidence. Conversely, enhanced Nrf2 activity was attributable to alterations in the ability to bind its endogenous inhibitor Keap1. Our findings provide a mechanistic rationale for Nrf2 blockade to prevent and possibly treat liver cancer.

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The effect of dual-sided breast surgery on breast asymmetry: a retrospective clinical evaluation study

Almost every female shows some degree of breast asymmetry. Complete correction of asymmetry is not achievable; the best a surgeon can deliver is improvement of asymmetry.

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“Isolated long thoracic nerve palsy”: more than meets the eye

Two main hypotheses have been proposed for the pathophysiology of long thoracic nerve (LTN) palsy: nerve compression and nerve inflammation. We hypothesized that critical reinterpretation of electrodiagnostic (EDX) studies and MRIs of patients with a diagnosis of non-traumatic isolated LTN palsy could provide insight into the pathophysiology and potentially, the treatment.

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MRI anatomical preoperative evaluation of the distally-based peroneus brevis muscle flap in reconstructive surgery of the lower limb

The distally-based peroneus brevis muscle flap has proved to be a simple solution for small-to moderate-sized wounds of the lower limb. The length of the muscle belly suitable for coverage is a crucial parameter. In this study we evaluated the capability of 3D-MRI of the lower limb to measure it preoperatively.

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How Many People Work In Your Operating Room? An Assessment of Factors Associated with Instrument Recounts Within Plastic Surgery

Intra-operative instrument recounts are performed in order to avoid retained foreign surgical items. These additional counts, however, beget risks of their own; including prolonged operative times, exposure to radiation, and increased cost. Our study aimed to identify factors that increase the likelihood of instrument recounts during plastic surgery procedures, and use our findings to guide potential solutions for preventing unnecessary recounts across all surgical fields.

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Quantifying Decreased Radiation Exposure From Modern CT Scan Technology and Surveillance Programs of Germ Cell Tumors.

Introduction: Upgrading computerized tomography (CT) scanners to iterative reconstruction techniques (IRT) decreases radiation dose. This reduction, combined with changes in surveillance protocols in clinical stage I testicular cancer (CS1TC) measurably decrease the lifetime attributable risk (LAR) of dying of radiation-associated cancer. Materials and Methods: This IRB-approved study enrolled 24 CS1TC patients who had CT scans on the same Toshiba Aquilion 64 CT before and after IRT software installation. Dose-length product and CT dose index volume were recorded. A physicist calculated effective doses. Radiation doses were compared using the Wilcoxon signed rank test. Median effective dose per scan was multiplied by scan number based on 16 versus 7 scans in 5-year AS protocols to calculate estimated cumulative dose (ECD). LAR of dying of radiation-associated solid tumor was estimated using ECD for a single exposure at age 35 with the excess absolute risk transport model from the BEIR VII analysis of long-term atomic bomb survivors. Results: Median preupgrade and postupgrade effective doses were 12.5 and 7.7 mSv, respectively (P

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EFFECTS OF TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) ON BLOOD VOLUME DISTRIBUTION IN PATIENTS WITH CIRRHOSIS

Cirrhosis is accompanied by portal hypertension with splanchnic and systemic arterial vasodilation, and central hypovolaemia.A transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension, but also causes major haemodynamic changes.

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Patterns of Adjuvant Therapy Utilization in Uterine Carcinosarcoma Stages I to III: A National Cancer Database Analysis.

Objective: The objective of this study is to characterize patterns of utilization of adjuvant chemotherapy (CT) and radiotherapy (RT) in the posthysterectomy management of uterine carcinosarcoma (UCS) in the United States. Materials and Methods: We queried the National Cancer Database for women diagnosed with UCS between 2004 and 2012 and undergoing hysterectomy. Logistic regression was performed to identify sociodemographic, facility-specific, and treatment-related predictors of receiving multiagent chemotherapy, external beam radiotherapy (EBRT), or brachytherapy (BT). Results: In total 4272 patients were included, with 2 in 5 (40.5%) receiving no adjuvant therapy. Regarding RT, 2357 (55.1%) received neither EBRT nor BT, 929 (21.7%) received EBRT alone, 518 (12.1%) received BT alone, and 468 (11.0%) received EBRT+BT. Most women (70.8%) received no CT, a minority (1.5%) received single-agent CT, and the rest (27.8%) received multiagent chemotherapy. Logistic regression demonstrated disparities in receipt of adjuvant therapies by age, diagnosis year, insurance, facility volume, facility type, stage, and margin status, with patients with positive surgical margins less likely to receive BT. Conclusions: Following hysterectomy for UCS, a large proportion of women receives no CT and no RT in the United States. Multispecialty evaluation is critical for individualization of therapy and may address disparities in this aggressive disease. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Capecitabine and Celecoxib as a Promising Therapy for Thymic Neoplasms.

Objectives: For patients with unresectable or metastatic thymic epithelial neoplasms, few therapy options are available and outcomes are poor. This case series demonstrates that the combination of capecitabine and celecoxib may be a promising therapeutic option for these patients. Materials and Methods: The current report describes the outcomes of 5 patients with thymic neoplasms treated on a drug-drug interaction study of capecitabine and celecoxib in patients with advanced solid malignancies (NCT01705106) conducted at the University of Chicago, plus a sixth patient treated with the same regimen outside of the protocol. Results: Six patients with thymic neoplasms were treated with capecitabine 1000 mg/m2 twice daily and celecoxib 200 mg twice daily, day 1 to day 14 on a 21-day cycle. This included 3 patients with thymic carcinoma, 1 with thymic neuroendocrine tumor, and 2 with thymomas. Objective response rates were noted in 3 of 6 patients. Two of the 3 thymic carcinoma patients had complete responses, and the third had a partial response. Best response for the other patients included stable disease for both thymoma patients and progressive disease for the thymic neuroendocrine patient. Other than grade 3 palmar-plantar erythrodysesthesia, which developed in 4 of 6 patients and required dose reductions, the regimen was well tolerated. Conclusions: This case series suggests that capecitabine plus celecoxib may be an effective and well-tolerated treatment option for patients with thymic carcinoma. Further studies should be carried out to establish the efficacy of capecitabine plus celecoxib in thymic carcinoma, and to determine whether monotherapy with capecitabine would be similarly effective. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Predictors of Local Recurrence in Patients With Myxofibrosarcoma.

Objectives: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR. Materials and Methods: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as 5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR. Results: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049). Conclusions: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Re: Gaskill CS, Awan JA, Watts CR, Awan SN. Acoustic and perceptual classification of within-sample normal, intermittently dysphonic, and consistently dysphonic voice types. J Voice. 2016;31:218–228

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Publication date: Available online 26 June 2017
Source:Journal of Voice
Author(s): Philipp Aichinger, Gernot Kubin




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Re: Gaskill CS, Awan JA, Watts CR, Awan SN. Acoustic and perceptual classification of within-sample normal, intermittently dysphonic, and consistently dysphonic voice types. J Voice. 2016;31:218–228

Publication date: Available online 26 June 2017
Source:Journal of Voice
Author(s): Philipp Aichinger, Gernot Kubin




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Lateral cervical approach for supracricoid partial laryngectomy

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Publication date: Available online 27 June 2017
Source:American Journal of Otolaryngology
Author(s): Giuseppe Spriano, Giuseppe Mercante, Giovanni Cristalli, Raul Pellini, Fabio Ferreli
IntroductionThe supracricoid partial laryngectomy has been described for the treatment of T3 laryngeal glottic and supraglottic tumors as well as upfront and salvage surgery. Good oncological and functional outcomes are expected, while the post-operative rehabilitation can be quite difficult for the patient. Early and late complications can occur especially in salvage surgery. Neck dissection according to the T stage is often associated with the resection of the primary tumor.ObjectiveTo verify the feasibility of a minimally invasive procedure for supracricoid partial laryngectomy by adopting the lateral cervical approach.Methods/resultsA 61-year old man affected by a cT3N0 glottic cancer already treated 10years prior with radiotherapy for oropharyngeal cancer underwent supracricoid laryngectomy using the lateral approach. The key point of the procedure was a subfascial dissection with the harvesting of anterior cervical flap including skin, fat, platysma, fascia superficialis, anterior jugular veins, homo- and sterno-hyoid muscles.ConclusionSupracricoid laryngectomy by a lateral approach is feasible and safe; it allows to perform a simultaneous neck dissection and the removal of the entire laryngeal specimen preserving ample healthy tissue compared to the classic anterior approach.



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Open Journal of Genetics Vol.7,No.2 (June 2017)

Multivariate Based Variability within Diverse Indian Mustard (Brassica juncea L.) Genotypes
Genetic Diversity, Agro-Morphology, Brassica juncea L., PCA Analysis
Paper Information Full Paper: PDF (Size:3142KB)
DOI: 10.4236/ojgen.2017.72007

Single Chain Fragment Variables Antibody binding to EGF Receptor in the Surface of MCF7 Breast Cancer Cell Line: Application and Production Review
Single Chain Fragment Variable, Epidermal Growth Factor Receptor, MCF-7, Phage Display Technology
Paper Information Full Paper: PDF (Size:1027KB)
DOI: 10.4236/ojgen.2017.72008



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Treatment of laryngopharyngeal reflux using a sleep positioning device: A prospective cohort study

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Publication date: Available online 27 June 2017
Source:American Journal of Otolaryngology
Author(s): William S. Tierney, Scott L. Gabbard, Claudio F. Milstein, Michael S. Benninger, Paul C. Bryson
ObjectiveLaryngopharyngeal reflux (LPR) symptoms are often resistant to management and cause significant quality of life impairment to patients with this disease. This study assesses the utility of a sleep-positioning device (SPD) in treating LPR.DesignSingle center prospective cohort study.SettingTertiary medical centerParticipants27 adult patients with diagnosed laryngopharyngeal reflux.InterventionAn SPD consisting of a two-component wedge-shaped base pillow and a lateral positioning body pillow (Medcline, Amenity Health Inc.) was given to patients with a diagnosis of LPR. Subjects slept using the device for at least 6h per night for 28 consecutive nights.Main outcomesPrimary outcomes were Nocturnal Gastroesophageal Reflux Symptom Severity and Impact Questionnaire (N-GSSIQ) and the Reflux Symptoms Index (RSI) survey instrument. Each was collected at baseline, after 14, and after 28days of SPD use.Results27 patients (19 female and 8 male; age 57.1±12.8, BMI 29.0±8.1) were recruited. At baseline mean N-GSSIQ was 50.1±22.4 and mean RSI of 29.6±7.7. Repeated measure analysis showed that subjects' total N-GSSIQ scores decreased by an average of 19.1 (p=0.0004) points by two weeks and 26.5 points by 4weeks (p<0.0001). RSI decreased an average of 5.3 points by 2weeks (p=0.0425) and an average of 14.0 points by 4weeks (p<0.0001).ConclusionsIn patients with LPR, SPD treatment significantly improves self-reported symptoms of nocturnal reflux as well as symptoms specific to LPR. These results support the therapeutic efficacy of a SPD for patients with LPR.



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